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Dehydrogenative Transformation of Alcoholic Substrates in Aqueous Media Catalyzed by an Iridium Complex Having a Functional Ligand with α-Hydroxypyridine and 4,5-Dihydro-1H-imidazol-2-yl Moieties Masato Yoshida, Han Wang, Takuya Shimbayashi and Ken-ichi Fujita *

ID

Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan; [email protected] (M.Y.); [email protected] (H.W.); [email protected] (T.S.) * Correspondence: [email protected]; Tel.: +81-75-753-6827 Received: 29 June 2018; Accepted: 27 July 2018; Published: 31 July 2018







Abstract: A new catalytic system that employs water as an environmentally friendly solvent for the dehydrogenative oxidation of alcohols and lactonization of diols has been developed. In this catalytic system, a water-soluble dicationic iridium complex having a functional ligand that comprises α-hydroxypyridine and 4,5-dihydro-1H-imidazol-2-yl moieties exhibits high catalytic performance. For example, the catalytic dehydrogenative oxidation of 1-phenylethanol in the presence of 0.25 mol % of the iridium catalyst and base under reflux in water proceeded to give acetophenone in 92% yield. Additionally, under similar reaction conditions, the iridium-catalyzed dehydrogenative lactonization of 1,2-benzenedimethanol gave phthalide in 98% yield. Keywords: dehydrogenation; iridium catalyst; functional ligand; alcohol; diol; ketone; lactone; water solvent

1. Introduction From the viewpoint of green sustainable chemistry, it is important to accomplish synthetic organic reactions efficiently using water as a solvent. Because water is incombustible, non-toxic, inexpensive, and easily available in large quantities, it is important that research aims at using water as a solvent for organic synthesis [1–6]; however, it is generally difficult to use water as a solvent in such reactions, especially in reactions that require homogeneous transition metal catalysts. This is probably due to the fact that most homogeneous transition metal catalysts have problems when used in aqueous media, such as (1) instability in water, (2) insolubility in water, and/or (3) inactivity in water. These limitations have prevented the development of methods for catalytic organic synthesis in aqueous media. Recently, with an objective to overcome the aforementioned problems, we developed a homogeneous dicationic iridium catalyst with a bipyridine-based functional ligand, which is highly soluble and stable in water [7]. Additionally, we reported some catalytic systems that were active for the dehydrogenative oxidation reaction of alcohols in aqueous media, for the production of aldehydes, ketones, carboxylic acids, and lactones [8–10]. These achievements were remarkable as uncommon examples of catalytic organic synthesis using water as a solvent [11–22]; however, some issues remained unresolved such as (1) the necessity of using comparatively large amounts of catalyst, (2) the significant effort required to synthesize the functional ligands, and (3) the limited scope of substrates that can be used as a starting material for the dehydrogenative reactions.

Catalysts 2018, 8, 312; doi:10.3390/catal8080312

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catalyst, (2) the significant effort required to synthesize the functional ligands, and (3) the limited scope of substrates that can be used as a starting material for the dehydrogenative reactions. thisstudy, study,we we synthesized a series of iridium complexes bearing a bidentate functional In this synthesized a series of iridium complexes bearing a bidentate functional ligand ligand on based on a pyridine and an imidazoline These catalysts weresuccessfully successfullyapplied appliedto to the based a pyridine and an imidazoline ring.ring. These catalysts were production of ketones and lactones in water using a small amount of catalyst. production of ketones and lactones in water using a small amount of catalyst. 2. Results and Discussion First, a series of dicationic complexes 1–4 were prepared (Figure (Figure 1). 1). Complexes 1 and 2 have bidentate functional ligands ligands that that comprise comprise α-hydroxypyridine α-hydroxypyridine and and 4,5-dihydro-1H-imidazol-2-yl 4,5-dihydro-1H-imidazol-2-yl moieties. Complex Complex 33 does does not not have have hydroxy hydroxy group group in in the the pyridine pyridine ring ring of of the functional functional ligand. ligand. Complex 4 includes methoxy group instead of hydroxy group at the α-position α-position in the the pyridine ring of the functional functional ligand. The structures of these complexes 1–4 were determined by NMR data and elemental analyses. For For example, example, in in the the 11H H NMR NMR analysis analysis of of 11 [23], three signals in the aromatic region at δδ 8.13, 8.13,7.63, 7.63,and and7.33 7.33 ppm, which would be assigned as protons onpyridine the pyridine ring, ppm, which would be assigned as protons on the ring, were were observed. Additionally, of signals assignedtotothe the methylene methylene protons protons in observed. Additionally, two two sets sets of signals thatthat cancan bebeassigned 4,5-dihydro-1H-imidazol-2-yl moiety were were observed observed at at δδ 4.34 and 4.10 ppm as triplet signals with 4,5-dihydro-1H-imidazol-2-yl moiety each integration values corresponding to 2H, clearly clearly indicating indicating the the bidentate bidentate N,N-chelating N,N-chelating nature of the the ligand ligand in in complex complex 1. 1. Details Details of the the procedures procedures for the the preparation preparation of complexes 1–4 and their analytical data are included in the experimental experimental section. All these complexes were highly soluble in water airair or or in water for extended periods of time. we decided to explore water and andstable stableunder under in water for extended periods of Therefore, time. Therefore, we decided to their applications as catalysts for the dehydrogenative oxidation of organic substrates in aqueous explore their applications as catalysts for the dehydrogenative oxidation of organic substrates in media following our previous work on this type reaction. aqueous media following our previous work on of this type of reaction.

Figure 1. 1. The pyridine and and Figure The dicationic dicationic complexes complexes 1–4 1–4 bearing bearing aa bidentate bidentate ligand ligand based based on on pyridine 4,5-dihydro-1H-imidazole-2-yl moieties. moieties. 4,5-dihydro-1H-imidazole-2-yl

Thus, we examined the dehydrogenative oxidation of 1-phenylethanol (5a) to acetophenone Thus, we examined the dehydrogenative oxidation of 1-phenylethanol (5a) to acetophenone (6a) (6a) in aqueous media using the water-soluble iridium complexes 1–4. The results are summarized in aqueous media using the water-soluble iridium complexes 1–4. The results are summarized in in Table 1. Complex 1 and 2 having an α-hydroxypyridine moiety in the functional ligand exhibited Table 1. Complex 1 and 2 having an α-hydroxypyridine moiety in the functional ligand exhibited high high catalytic performance, with the activity of 1 slightly higher than that of 2 (entries 1 and 2). High catalytic performance, with the activity of 1 slightly higher than that of 2 (entries 1 and 2). High yield yield of 6a was accomplished by the employment of a very small amount (0.25 mol %) of both of 6a was accomplished by the employment of a very small amount (0.25 mol %) of both catalyst catalyst 1 and Na2CO3 (entry 1). The presence of hydroxy group at the α-position of the functional 1 and Na2 CO3 (entry 1). The presence of hydroxy group at the α-position of the functional ligand ligand was observed to be indispensable for achieving a high catalytic performance; complex 3 was observed to be indispensable for achieving a high catalytic performance; complex 3 without without a hydroxy group and complex 4 with a methoxy group exhibited poor catalytic activity a hydroxy group and complex 4 with a methoxy group exhibited poor catalytic activity (entries 3 (entries 3 and 4). The importance of hydroxy group at α-position of the pyridine ring in the and 4). The importance of hydroxy group at α-position of the pyridine ring in the functional ligand functional ligand will be discussed later in the explanation of catalytic mechanism (vide infra). When will be discussed later in the explanation of catalytic mechanism (vide infra). When compared with compared with our previously reported catalysts for the dehydrogenative oxidation of alcohols in our previously reported catalysts for the dehydrogenative oxidation of alcohols in aqueous media, aqueous media, complex 1 can be regarded as one of the most effective catalysts [7,9,24]. complex 1 can be regarded as one of the most effective catalysts [7,9,24].

Table 1. Dehydrogenative oxidation of 1-phenylethanol (5a) to acetophenone (6a) in aqueous media using water-soluble iridium complexes 1–4. Catalysts 2018, 2018, 8, 8, x312 Catalysts FOR PEER REVIEW

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Table 1. Dehydrogenative oxidation of 1-phenylethanol (5a) to acetophenone (6a) in aqueous media Table 1. Dehydrogenative oxidation of 1-phenylethanol (5a) to acetophenone (6a) in aqueous media using water-soluble iridium complexes 1–4. using water-soluble iridium 1–4. of 5a (%) a yield of 6a (%) a cat. conv. entry complexes

1

1

92

92

2

2

89

89

3 entry entry

3 cat. cat.

1 4 21 3 42

1 142

conv. of14 conv. of5a5a(%) (%)aa yield yieldof14 of6a 6a(%) (%)aa 2592 92 89

2592 92 89

3 a Determined14 by GC analysis. 8925

8925

24

14

a Determined GC analysis. With an optimal catalyst we further on the14 optimization of basic additive for 3 3 in hand, 14byfocused the dehydrogenative oxidation of 5a to 6a catalyzed by 1. The results are summarized in Table 2. The With an optimal catalyst in hand, we further focused on the optimization of basic additive for 4 resulted in 25 reaction without any basic additive a very low yield of256a (16%). However, addition of a 4 the dehydrogenative oxidation of 5a to 6a catalyzed by 1. The results are summarized in Table 2. variety of bases, such as Na2CO3, aNaOH, NaHCO 3, Li2CO3, K2CO3, and Cs2CO3, considerably Determined analysis. The reaction without any basic additive resulted by in GC a very low yield of 6a (16%). However, addition improved the catalytic activity of 1, with the highest yield of 6a (92%) obtained using 0.25 mol % of of a variety of bases, such as Na2 CO3 , NaOH, NaHCO3 , Li2 CO3 , K2 CO3 , and Cs2 CO3 , considerably Na2CO 3 (entry 2). We catalyst think that the addition of base would to the formation of catalytically With an optimal in hand, we further focused on lead the optimization of basic additive for improved the catalytic activity of 1, with the highest yield of 6a (92%) obtained using 0.25 mol % of active monocationic species. detailed explanation theresults effect are of base will be discussed the dehydrogenative oxidationThe of 5a to 6a catalyzed by 1.ofThe summarized in Table 2.later The Na2 CO3 (entry 2). We think that the addition of base would lead to the formation of catalytically active (vide infra). reaction without any basic additive resulted in a very low yield of 6a (16%). However, addition of a monocationic species. The detailed explanation of the effect of base will be discussed later (vide infra). variety of bases, such as Na2CO3, NaOH, NaHCO3, Li2CO3, K2CO3, and Cs2CO3, considerably Table the 2. Optimization of the of basic additive for the dehydrogenative oxidation of 5ausing to 6a 0.25 catalyzed improved catalytic activity 1,additive with thefor highest yield of 6a (92%) obtained mol Table 2. Optimization of the basic the dehydrogenative oxidation of 5a to 6a catalyzed by% of by 1 in aqueous media. Na2CO 3 (entry 2).media. We think that the addition of base would lead to the formation of catalytically 1 in aqueous active monocationic species. The detailed explanation of the effect of base will be discussed later (vide infra).

Table 2. Optimization of the basic additive for the dehydrogenative oxidation of 5a to 6a catalyzed by 1 in aqueous media.

entry (mol %)%) entry basebase (mol 1 2 3 2 4 5 3 6 entry 7 14 8

1

conv. ofof5a5a(%) conv. (%)aa

none 16 none 1692 Na 2 CO3 (0.25) Na2 CO3 (0.50) 81 Na2CO 3 (0.25) 9283 NaOH (0.50) NaHCO3 (0.50) 82 Na 2CO 3 (0.50) conv. of815a base %) Li(mol 83 (%) a 2 CO3 (0.25) K2 CO3 (0.25) 83 NaOH (0.50) 8386 none 16 Cs 2 CO3 (0.25) a

a a yieldofof yield 6a6a (%)(%)

16 9216 81 8392 82 yield 82 of816a (%) a 83 83 8616

Determined by GC analysis.

NaHCO (0.50) 82 82 25 Na2CO33(0.25) 92 92 To explore the scope of the new catalytic system that employs 1 and Na2 CO3 in aqueous Li22CO 83 82 36 Na CO33 (0.25) (0.50) 81 81 media, various secondary alcohols were subjected to the optimized reaction conditions. The results are summarized in reactions of 83 1-arylethanols bearing K3. 2CO3The (0.25) 83 83 electron-donating and 47 TableNaOH (0.50) 83 electron-withdrawing substituents in the aromatic ring smoothly proceeded to give the corresponding Csmoderate 2CO3 3(0.25) 86Methoxy, N,N-dimethylamino, 86 58 NaHCO (0.50) 82 acetophenone derivatives in to high yields.82 trifluoromethyl, a Determined fluoro, and chloro groups were tolerated in this catalytic system. 1-Indanol and 1-tetralol were also by GC analysis. 6 Li2CO3 (0.25) 83 82 converted into the corresponding ketones in excellent yields. Additionally, 1-phenyl-1-propanol could To explore the7scope ofKthe new catalytic system employs 1 and Na CO3 in catalyst aqueousloading media, be dehydrogenatively oxidized to propiophenone, even a relatively 2CO3 (0.25) 83thatthough 83 2higher various secondary were subjected the optimized reaction conditions. The results are and longer reaction alcohols time were required in thistocase. summarized in Table 3.Cs2The reactions of 1-arylethanols bearing86 electron-donating and 8 CO3 (0.25) 86 a

Determined by GC analysis.

To explore the scope of the new catalytic system that employs 1 and Na2CO3 in aqueous media, various secondary alcohols were subjected to the optimized reaction conditions. The results are summarized in Table 3. The reactions of 1-arylethanols bearing electron-donating and

1-tetralol 1-tetralol were wereacetophenone also also converted converted into intogroups the the corresponding corresponding corresponding ketones ketones in incatalytic excellent excellent yields. yields. Additionally, Additionally, 1-tetralol were also converted into the ketones in excellent yields. Additionally, trifluoromethyl, fluoro, and chloro were tolerated in this system. 1-Indanol and corresponding derivatives in moderate to high yields. Methoxy, N,N-dimethylamino, corresponding derivatives moderate to yields. Methoxy, N,N-dimethylamino, trifluoromethyl, fluoro, and were in this system. 1-Indanol and corresponding acetophenone derivatives in moderate tohigh high yields. Methoxy, N,N-dimethylamino, trifluoromethyl, fluoro, andchloro chloro groups weretolerated tolerated in this catalytic system. 1-Indanol and 1-tetralol wereacetophenone also converted intogroups the in corresponding ketones incatalytic excellent yields. Additionally, corresponding acetophenone derivatives in moderate to high yields. Methoxy, N,N-dimethylamino, 1-phenyl-1-propanol 1-phenyl-1-propanol could could be be dehydrogenatively dehydrogenatively oxidized oxidized to toin propiophenone, propiophenone, even even though though aa 1-phenyl-1-propanol could be dehydrogenatively oxidized to propiophenone, even though 1-tetralol were also converted into the corresponding ketones in excellent yields. Additionally, trifluoromethyl, fluoro, and chloro groups were tolerated in this catalytic system. 1-Indanol and trifluoromethyl, fluoro, and chloro groups were tolerated in this catalytic system. 1-Indanol and 1-tetralol were also converted into the corresponding ketones excellent yields. Additionally, trifluoromethyl, fluoro, and chloro groups were tolerated in this catalytic system. 1-Indanol and 1-tetralol were also converted into the corresponding ketones in excellent yields. Additionally, 1-phenyl-1-propanol could be dehydrogenatively oxidized to propiophenone, even though aa trifluoromethyl, fluoro, and chloro groups were tolerated in this catalytic system. 1-Indanol and relatively relatively higher higher catalyst catalyst loading loading and and longer longer reaction reaction time time were were required required in in this this case. case. relatively higher catalyst loading and longer reaction time were required in this case. 1-phenyl-1-propanol could be dehydrogenatively oxidized to propiophenone, even though 1-tetralol were also converted into the corresponding ketones in excellent yields. Additionally, 1-tetralol were converted the ketones in excellent Additionally, 1-phenyl-1-propanol could be dehydrogenatively propiophenone, though 1-tetralol were also also converted into the corresponding corresponding ketones in excellent yields. Additionally, 1-phenyl-1-propanol could beinto dehydrogenatively oxidized to propiophenone, even though aaa relatively higher catalyst loading and longer reactionoxidized time wereto required in thisyields. case.even 1-tetralol were also converted corresponding ketones in excellent yields. Additionally, relatively higher catalyst loading and longer reaction time were required in this case. 1-phenyl-1-propanol could be dehydrogenatively oxidized to propiophenone, even though 1-phenyl-1-propanol could be dehydrogenatively to propiophenone, even though relatively catalyst loading and longer reaction time were required in case. 1-phenyl-1-propanol could be into dehydrogenatively oxidized to propiophenone, even though aaa relativelyhigher higher catalyst loading andthe longer reactionoxidized time were required inthis this case. 1-phenyl-1-propanol could be dehydrogenatively oxidized to propiophenone, evenketones though a Table Tablehigher 3. 3. Dehydrogenative Dehydrogenative oxidation oxidation of of various various secondary secondary alcohols alcohols to to the thein corresponding corresponding ketones ketones Table 3. oxidation of secondary alcohols to corresponding relatively catalyst loading and longer reaction time were required this case. relatively catalyst loading and reaction time required this relatively higher catalyst loading andlonger longer reaction timewere were required in thiscase. case. Tablehigher 3. Dehydrogenative Dehydrogenative oxidation of various various secondary alcohols to the thein corresponding ketones Catalysts 2018, 8, 312 4 of 12 relatively loading and longer reaction time were required this case. ketones catalyzed catalyzed by by11catalyst 1in in inaqueous aqueous aqueous media. media. catalyzed by media. Table 3. Dehydrogenative oxidation of various secondary alcohols to the corresponding ketones Table Table 3. 3. Dehydrogenative oxidation oxidation of of various secondary secondary alcohols alcohols to to the corresponding corresponding ketones Tablehigher 3.Dehydrogenative Dehydrogenative oxidation ofvarious various secondary alcohols tothe thein corresponding ketones catalyzed by 1 in aqueous media. catalyzed by in aqueous media. catalyzed catalyzed by by in aqueous media. Table 3. Dehydrogenative oxidation of various secondary alcohols to the corresponding ketones catalyzed by1111in inaqueous aqueousmedia. media. Table 3. oxidation Table 3. Dehydrogenative Dehydrogenative oxidationof ofvarious various secondary secondaryalcohols alcoholsto tothe the corresponding correspondingketones ketones Table 3. Dehydrogenative oxidation of various secondary alcohols to the corresponding ketones Table 3. Dehydrogenative oxidation of various secondary alcohols to the corresponding ketones catalyzed by 1 in aqueous media. catalyzed by 1 in aqueous media. catalyzed by 1 in aqueous media. catalyzed by 1 in aqueous media. Table 3. Dehydrogenative oxidation of various secondary alcohols to the corresponding ketones catalyzed by 1 in aqueous media. catalyzed by 1 in aqueous media.

6b 6b 87% 87% (84%) (84%) 6b 6b 87% 87% (84%) (84%) 6b 87% (84%) 6b 6b 87% (84%) 6b87% 87%(84%) (84%) 6b 87% (84%) 6b 6b87% 87%(84%) (84%) 6b 87% (84%) 6b 87% (84%)

6c 6c 95% 95% (92%) (92%) 6c 6c 95% 95% (92%) (92%) 6c 95% (92%) 6c 6c 95% (92%) 6c95% 95%(92%) (92%) 6c 6c 95% (92%) 6c95% 95%(92%) (92%) 6c 95% (92%) 6c 95% (92%)

6d 6d 62% 62% (59%) (59%) 6d 6d 62% 62% (59%) (59%) 6d 62% (59%) 6d 6d 62% (59%) 6d62% 62%(59%) (59%) 6d 62% (59%) 6d 6d62% 62%(59%) (59%) 6d 62% (59%) 6d 62% (59%)

6e 6e 63% 63% (57%) (57%) 6e 6e 63% 63% (57%) (57%) 6e 63% (57%) 6e 6e 63% (57%) 6e63% 63%(57%) (57%) 6e 63% (57%) 6e 6e63% 63%(57%) (57%) 6e 63% (57%) 6e 63% (57%)

6f 6f 83% 83% (74%) (74%) 6f 6f 83% 83% (74%) (74%) 6f 83% (74%) 6f 83% (74%) 6f 6f 83% 83% (74%) (74%) 6f 83% (74%) 6f 6f83% 83%(74%) (74%) 6f 83% (74%) 6f 83% (74%)

6g 6g 80% 80% (75%) (75%) 6g 6g 80% 80% (75%) (75%) (75%) 6g 80% 6g 6g 80% (75%) 6g80% 80%(75%) (75%) 6g 80% (75%) 6g 6g80% 80%(75%) (75%) 6g 80% (75%) 6g 80% (75%)

6h 6h 83% 83% (81%) (81%) 6h 6h 83% 83% (81%) (81%) 6h 83% (81%) 6h 83% (81%) 6h 6h83% 83%(81%) (81%) 6h 83% (81%) 6h 6h83% 83%(81%) (81%) 6h 83% (81%) 6h 83% (81%)

6i 6i 80% 80% (78%) (78%) 6i 6i 80% 80% (78%) (78%) 6i 80% (78%) 6i 80% (78%) 6i 6i80% 80%(78%) (78%) 6i 80% (78%) 6i 6i80% 80%(78%) (78%) 6i 80% (78%) 6i 80% (78%)

a,b a,b a,b 6j 6k 6l 6m 6j 6j80% 80% 80%(75%) (75%) (75%) 6k 6k98% 98% 98%(98%) (98%) (98%) 6l 98% 98% (98%) (98%) 6m 73% 73% (71%) (71%)a,b 6j 6k 6l 6m 6j 80% 80% (75%) (75%) 6k 98% 98% (98%) (98%) 6l 98% 98% (98%) (98%) 6m 73% 73% (71%) (71%) a,b 1 a a,b a,b a,b a,b Yields6j were determined H NMR analysis. Isolated yields are6l shown in the parentheses. 6m 1.073% mol (71%) % of complex 6j 80% (75%) 6k 98% (98%) 6l 98% (98%) 6m 73% (71%) 1H 6j 80% 80% (75%) (75%) 6k 98% 98% (98%) (98%) 6l 98% (98%) (98%) 6m 73% (71%) 6j 80% (75%) by by 6k 98% (98%) 6l98% 98% (98%) 6m 73% (71%) aaa1.0 Yields Yields were were determined determined by by111H H6k NMR NMR analysis. analysis. Isolated Isolatedyields yields yields are are shown shown in inthe the theparentheses. parentheses. parentheses. 1.0 1.0mol mol mol Yields were determined analysis. Isolated are shown in b Reaction Yields were H NMR NMR analysis. mol 1 and Na were used asby catalyst. timeIsolated was 72 h.yields are shown in the parentheses. a 1.0 2 CO3determined a,b a,b a,b a,b 6j 80% (75%) 6k 98% (98%) 6l 98% (98%) 6m 73% (71%) 6j 80% (75%) 6k 98% (98%) 6l 98% (98%) 6m 73% (71%) bbbReaction 6j 80% (75%) 6k 98% (98%) 6l 98% (98%) 6m 73% (71%) 6j 80% (75%) 6k 98% (98%) 6l 98% (98%) 6m 73% (71%) 1 a 1 1 a a % % of of complex complex 1 1 and and Na Na 2 2 CO CO 3 3 were were used used as as catalyst. catalyst. Reaction Reaction time time was was 72 72 h. h. 1 a % of complex 1 and Na 2 CO 3 were used as catalyst. time was 72 h. Yields were determined by H NMR analysis. Isolated yields are shown in the parentheses. 1.0 mol Yields Yields were were determined by by H NMR analysis. analysis. Isolated Isolated yields yields are shown in in the parentheses. 1.0 mol Yields weredetermined determined by3H HNMR NMR analysis. Isolated yieldsare areshown shown in theparentheses. parentheses. 1.0 1.0mol mol b Reaction % of complex 1 and Na2CO were used as catalyst. time was 72 h.the 6j 80% (75%) 6k 98% (98%) 6l 98% (98%) 6m 73% (71%) a,b bbbbReaction 1H % of complex and Na CO were used as catalyst. Reaction time was 72 h. % % of complex 1111and and Na 3313113H were were used used as as catalyst. Reaction time was was 72 72 h. h. Yields were determined by NMR analysis. Isolated yields are shown in the parentheses. 1.0 mol %of ofcomplex complex andNa Na222CO 2CO CO were used ascatalyst. catalyst. Reaction time was 72 h. Yields were by NMR analysis. Isolated yields are shown in the parentheses. Yields weredetermined determined by H NMR analysis. Isolated yieldstime are shown in the parentheses. 1.0 mol A possible mechanism for the dehydrogenative oxidation of alcohols catalyzed by aa1aa1.0 is mol depicted Yields were determined by H NMR analysis. Isolated yields are shown in the parentheses. 1.0 mol 1H NMR analysis. Isolated yields are shown in the parentheses. a 1.0 mol Yields were mechanism determined by A Aof possible possible mechanism mechanism for for the theused dehydrogenative dehydrogenative oxidation oxidation of of alcohols alcohols catalyzed catalyzed by by is is depicted depicted A possible for the oxidation of alcohols 1111is % of complex and Na were used as catalyst. Reaction time was 72 h. % complex 1111and Na 3333were time was 72 h. % of complex andthe Na222CO 2CO CO were usedas ascatalyst. catalyst.bbbbReaction Reaction time was 72 h. catalyzed % of complex and Na CO were used as catalyst. Reaction time was 72 h. in Scheme 1. Firstly, base-promoted elimination of triflic along with theby dissociation of A possible mechanism for the dehydrogenative dehydrogenative oxidation ofacid alcohols catalyzed by is depicted depicted b % of complex 1 andthe Na2base-promoted CO 3 were used aselimination catalyst. Reaction time was 72 h. catalyzed in inScheme Scheme Scheme 1. 1.Firstly, Firstly, Firstly, the the base-promoted base-promoted elimination elimination of of triflic triflic triflic acid acid along along with with the the theby dissociation dissociation of of in 1. of acid along with dissociation of AApossible possible mechanism for the dehydrogenative oxidation of alcohols catalyzed by isisdepicted depicted A mechanism for the oxidation of alcohols 111is possible mechanism for thedehydrogenative dehydrogenative oxidation of alcohols catalyzed by depicted

aquo ligand catalyst 1 would occurelimination to generateofa triflic monocationic coordinatively unsaturated in Scheme 1. from Firstly, the base-promoted acid along with the dissociation of aquo aquo ligand ligand from from catalyst catalyst 11for would would occur occur to to generate generate monocationic monocationic coordinatively coordinatively unsaturated aquo ligand 1for would occur to monocationic coordinatively in Scheme 1.1.from Firstly, the base-promoted elimination of triflic acid along with the dissociation of A possible mechanism the dehydrogenative oxidation of alcohols catalyzed by 1unsaturated is depicted A possible mechanism the dehydrogenative oxidation of alcohols catalyzed 1unit. is A possible mechanism themoiety dehydrogenative oxidation of alcohols catalyzed by 1unsaturated isdepicted depicted in 1. Firstly, the elimination of acid along with dissociation of inScheme Scheme Firstly, thebase-promoted base-promoted elimination ofaaaatriflic triflic acid along withthe theby dissociation of species A having ancatalyst α-pyridonate connected to the 4,5-dihydro-1H-imidazol-2-yl Further, aquo ligand from catalyst 1for would occur to generate generate monocationic coordinatively unsaturated Aligand possible mechanism for the dehydrogenative oxidation of alcohols catalyzed by 1unsaturated is depicted species species A A having having an an α-pyridonate α-pyridonate moiety moiety connected connected to to the the 4,5-dihydro-1H-imidazol-2-yl 4,5-dihydro-1H-imidazol-2-yl unit. unit. species A having an α-pyridonate moiety connected to the 4,5-dihydro-1H-imidazol-2-yl unit. aquo ligand from catalyst 1 would occur to generate a monocationic coordinatively unsaturated in Scheme 1. Firstly, the base-promoted elimination of triflic acid along with the dissociation of in Scheme 1. Firstly, the base-promoted elimination of triflic acid along with the dissociation of aquo from catalyst 1 would occur to generate a monocationic coordinatively in Scheme 1. Firstly, the base-promoted elimination of triflic acid along with the dissociation of aquo ligand from catalyst 1 would occur to generate a monocationic coordinatively unsaturated activation the alcohol substrate would occurconnected through transition state B which produces the ketonic species A of having an α-pyridonate moiety to the 4,5-dihydro-1H-imidazol-2-yl unit. in Scheme 1. Firstly, base-promoted elimination ofaato triflic along with dissociation of Further, Further, activation activation of of the the alcohol alcohol substrate substrate would would occur occur through through transition transition state statethe B B which which produces produces Further, activation of the alcohol substrate occur transition state B produces species A having an α-pyridonate moiety connected to the 4,5-dihydro-1H-imidazol-2-yl unit. aquo ligand from catalyst would occur to generate monocationic coordinatively unsaturated aquo ligand from catalyst 111 would occur to generate monocationic coordinatively unsaturated species A having an α-pyridonate moiety the 4,5-dihydro-1H-imidazol-2-yl unit. aquo ligand from catalyst would occur toconnected generate athrough monocationic coordinatively unsaturated species A having anthe α-pyridonate moiety connected to theacid 4,5-dihydro-1H-imidazol-2-yl unit. product with the concomitant formation of would iridium hydride species C. The final would involve Further, activation of the alcohol substrate would occur through transition statestep B which which produces aquo ligand from catalyst 1 would occur to generate ato monocationic coordinatively unsaturated the the ketonic ketonic product product with with the the concomitant concomitant formation formation of of iridium iridium hydride hydride species species C. C. The The final final step step the ketonic product with the formation of iridium hydride C. The step Further, activation of the alcohol substrate would occur through transition state BB which produces species A having an α-pyridonate moiety connected to the 4,5-dihydro-1H-imidazol-2-yl unit. species A having an α-pyridonate connected the unit. Further, activation the alcohol would occur through transition state which produces species A having an α-pyridonate moiety connected to the 4,5-dihydro-1H-imidazol-2-yl 4,5-dihydro-1H-imidazol-2-yl unit. Further, activation of the alcohol substrate would occur through transition state which produces the protonolysis of of the hydride onsubstrate themoiety iridium center by hydroxy protonspecies on theB functional ligand, ketonic product with the concomitant concomitant formation ofthe iridium hydride species C. The final final step species A having an α-pyridonate moiety connected to the 4,5-dihydro-1H-imidazol-2-yl unit. would would involve involve the the protonolysis protonolysis of of the the hydride hydride on on the theof iridium iridium center center by by the the hydroxy hydroxy proton proton on onstep the the would involve protonolysis of the hydride on the iridium center by hydroxy proton on the the ketonic product with the concomitant formation of iridium hydride species C. The final Further, activation of the alcohol substrate would occur through transition state BB which produces Further, activation of the would occur through transition state B which produces the product with the concomitant formation iridium hydride species C. The final Further, activation of thealcohol alcohol substrate would occur through transition state which produces theketonic ketonic product with theactive concomitant formation of iridium hydride species C. The final step regenerating thethe catalytically unsaturated species A along with release of hydrogen gas. would involve the protonolysis ofsubstrate the hydride on the iridium center by the the hydroxy proton onstep the Further, activation of the alcohol substrate would occur through transition state B which produces functional functional ligand, ligand, regenerating regenerating the the catalytically catalytically active active unsaturated unsaturated species species A A along along with with release release of of functional ligand, regenerating the catalytically active unsaturated species A along with release of would involve the protonolysis of the hydride on the iridium center by the hydroxy proton on the the ketonic product with the concomitant formation of iridium hydride species C. The final step the ketonic product with the concomitant formation of iridium hydride species C. The final step the ketonic product with the concomitant formation of iridium hydride species C.with final would the protonolysis ofofthe hydride on the center by proton on the would involve theregenerating protonolysis the hydride on theiridium iridium center bythe the hydroxy proton onstep the Toinvolve verify the possible mechanism, some experiments were carried out. First, aThe quantitative functional ligand, the catalytically active unsaturated species Ahydroxy along release of the ketonic product with the concomitant formation of iridium hydride species C. The final step hydrogen hydrogen gas. gas. hydrogen functional ligand, regenerating the catalytically active unsaturated species AA along with release of would involve the protonolysis of the hydride on the iridium center by the hydroxy proton on the would involve protonolysis of hydride on the center by the hydroxy proton on functional ligand, the catalytically active unsaturated species A along with release of would involve theregenerating protonolysis ofthe the hydride on theiridium iridium center byWhen the hydroxy proton onthe the functional ligand, regenerating the catalytically active unsaturated species along with release of analysis ofgas. the the evolved hydrogen gas was conducted (Equation (1)). the dehydrogenative hydrogen gas. would involve the protonolysis of the hydride on the iridium center by the hydroxy proton on the To To verify verify the the possible possible mechanism, mechanism, some some experiments experiments were were carried carried out. out. First, First, a a quantitative quantitative To verify the possible mechanism, some experiments were carried out. First, a quantitative hydrogen gas. functional ligand, regenerating the catalytically active unsaturated species A along with release of functional ligand, regenerating the catalytically active unsaturated species A along with release of functional ligand, regenerating the catalytically active unsaturated species A along with release of hydrogen gas. hydrogen gas. oxidation of 1-indanol in aqueous media some on a large scale (10 were mmolcarried scale) was hydrogen To verify the possible mechanism, experiments out.performed, First, a quantitative functional ligand, regenerating the gas catalytically active unsaturated species A along with release of analysis analysis of of the thethe evolved evolved hydrogen hydrogen gas gaswas was was conducted conducted (Equation (Equation (1)). (1)). When When the the dehydrogenative dehydrogenative analysis of the evolved conducted (Equation (1)). When the dehydrogenative To verify possible mechanism, some experiments were carried out. First, quantitative hydrogen gas. hydrogen gas. To possible mechanism, some experiments were carried out. First, aaa quantitative hydrogen gas. Toverify verify the possible mechanism, some experiments were carried out. First, quantitative gas was obtained in 98%hydrogen yield, which almost equimolar amount to that of the ketone product analysis of thethe evolved hydrogen gas was was conducted (Equation (1)). When the dehydrogenative hydrogen gas. oxidation oxidation of of 1-indanol 1-indanol in in aqueous aqueous media media on on a a large large scale scale (10 (10 mmol mmol scale) scale) was was performed, performed, hydrogen hydrogen oxidation of 1-indanol in aqueous media on a large scale (10 mmol scale) was performed, hydrogen analysis of the evolved hydrogen gas was conducted (Equation (1)). When the dehydrogenative To verify the possible mechanism, some experiments were carried out. First, a quantitative To verify the possible mechanism, some experiments were carried out. First, a quantitative analysis of the evolved hydrogen gas was conducted (Equation (1)). When the dehydrogenative To verify the possible mechanism, some experiments were carried out. First, a quantitative analysis of the evolved hydrogen gas was conducted (Equation (1)). When the dehydrogenative (99%). Theofsecond experiment addressed of the monocationic species oxidation 1-indanol in aqueous mediathe on formation a large scale (10 catalytically mmol scale)active was performed, hydrogen To the possible mechanism, some experiments were carried out.of First, a quantitative gas gas was wasverify obtained obtained in in 98% 98% yield, yield, which which was was almost equimolar equimolar amount amount to to that that of of the the ketone ketone product product gas was in 98% yield, which was almost equimolar amount to that the ketone product oxidation of 1-indanol in aqueous media on aconducted large scale (10 mmol scale) was performed, hydrogen analysis of the evolved hydrogen gas (Equation (1)). When the dehydrogenative analysis of the evolved hydrogen gas conducted (Equation (1)). When the dehydrogenative oxidation of 1-indanol in aqueous media on aalmost scale (10 mmol scale) was performed, hydrogen analysis of the evolved hydrogen gas was conducted (Equation (1)). When the dehydrogenative oxidation of 1-indanol in aqueous media on alarge large scale (10 mmol scale) was performed, hydrogen was A (Equation (2)). By treatment of the dicationic catalyst 1 with one equivalent of Na CO at room gas was obtained obtained in the 98% yield, which was almost equimolar amount to that of the ketone product 2 3 analysis of the evolved hydrogen gas was was conducted (Equation (1)). When the dehydrogenative (99%). (99%). The The second second experiment experiment addressed addressed the the formation formation of ofmmol the the catalytically catalytically active active monocationic monocationic (99%). The second experiment addressed the formation of the catalytically active monocationic gas was obtained in 98% yield, which was almost equimolar amount to that of the ketone product oxidation of 1-indanol in aqueous media on a large scale (10 mmol scale) was performed, hydrogen oxidation of 1-indanol in aqueous media on a large scale (10 scale) was performed, hydrogen gas was obtained in 98% yield, which almost equimolar amount to that of the ketone product oxidation of 1-indanol in aqueous media on a large scale (10 mmol scale) was performed, hydrogen gas was obtained in 98% yield, which was almost equimolar amount to that of the ketone product temperature for 10 min, a new monocationic complex 9 having an α-pyridonate ring connected to the (99%). The second experiment addressed the formation of the catalytically active monocationic oxidation of 1-indanol inBy aqueous media on athe large scale (10 mmol scale) was performed, hydrogen species species A A (Equation (Equation (2)). (2)). By By the the treatment treatment of of the the dicationic dicationic catalyst catalyst 1 1 with with one one equivalent equivalent of of Na Na 2CO CO species A (Equation (2)). the treatment of the dicationic catalyst 1 with one equivalent of Na 22CO 333 (99%). The second experiment addressed the formation of the catalytically active monocationic gas was obtained in 98% yield, which was almost equimolar amount to that of the ketone product gas was obtained in 98% yield, which was almost equimolar amount to that of the ketone product (99%). The second experiment addressed the formation of the catalytically active monocationic gas was obtained in 98% yield, which was almost equimolar amount to that of the ketone product (99%). The second experiment addressed formation of the catalytically active monocationic 4,5-dihydro-1H-imidazol-2-yl moiety, whichofisthe closely relatedcatalyst to the species in Scheme 1, was isolated species A (Equation (2)). By the treatment dicationic 1 withAone equivalent of Na 2CO3 gas was obtained in 98% yield, which was almost equimolar amount to that of the ketone product at at room room temperature temperature for for 10 10 min, min, a a new new monocationic monocationic complex complex 9 9 having having an an α-pyridonate α-pyridonate ring ring at room temperature for 10 min, a new monocationic complex 9 having an α-pyridonate ring species A (Equation (2)). By the treatment of the dicationic catalyst 1 with one equivalent of Na 2 CO (99%). The second experiment addressed the formation of the catalytically active monocationic (99%). The second experiment addressed the formation of the catalytically active monocationic species (Equation (2)). the treatment ofof the catalyst 191with equivalent ofofNa 3333 (99%). The second experiment the formation of the catalytically active monocationic species Atemperature (Equation (2)). By the treatment thedicationic dicationic catalyst with one equivalent Na22CO 2CO in 33% A yield. The structure of 9addressed was determined by spectroscopic dataone (see the Supplementary at room forBy 10 min, a new monocationic complex having an α-pyridonate ring (99%). The second experiment addressed the formation of the catalytically active monocationic connected connected to to the the 4,5-dihydro-1H-imidazol-2-yl 4,5-dihydro-1H-imidazol-2-yl moiety, moiety, which which is is closely closely related related to to the the species species A A in in connected to the moiety, which is related to the species in at room temperature for 10 min, new monocationic complex having an α-pyridonate species A (Equation (2)). By the treatment of the dicationic catalyst with one equivalent of Na 2ring CO species A (Equation (2)). By the treatment the dicationic catalyst 191919with one equivalent of Na at for 10 min, aaa new monocationic complex having α-pyridonate species Atemperature (Equation (2)). By the treatment of the dicationic catalyst with onean equivalent of Na2A 2ring CO at room room temperature for 10 min, newof monocationic complex having an α-pyridonate ring 2CO Materials). the catalytic performance of 9 was investigated (Equation (3)). expected, connected toFurther, the 4,5-dihydro-1H-imidazol-2-yl 4,5-dihydro-1H-imidazol-2-yl moiety, which is closely closely related to the As species A in3333 species Atemperature (Equation (2)). By10 the treatment ofmonocationic themoiety, dicationic catalyst 1999with onean equivalent of Na2A CO 3 connected to the 4,5-dihydro-1H-imidazol-2-yl moiety, which is closely related to the species A in at room temperature for 10 min, a new monocationic complex having an α-pyridonate ring at room for min, a new complex having α-pyridonate ring connected to the 4,5-dihydro-1H-imidazol-2-yl which is closely related to the species in at room temperature for 10 min, a new monocationic complex having an α-pyridonate ring connected to the 4,5-dihydro-1H-imidazol-2-yl moiety, which is closely related to the species A in the complex 9 showed high catalytic activity for the dehydrogenation of 1-phenylethanol in water at room temperature for 10 min, a new monocationic complex 9 having an α-pyridonate ring connected to the 4,5-dihydro-1H-imidazol-2-yl moiety, which is closely related to the species A in connected to moiety, is closely A connected tothe the 4,5-dihydro-1H-imidazol-2-yl moiety, which isacetophenone closelyrelated related to the species species Ain in with a loading of4,5-dihydro-1H-imidazol-2-yl 0.25 mol % even in the absence of basewhich to give into a the high yield (90%). connected to the 4,5-dihydro-1H-imidazol-2-yl moiety, which is closely related to the species A in We assume that the results of these reactions (Equations (1)–(3)) strongly support the proposed catalytic cycle that is depicted in Scheme 1.

Scheme 1, was isolated in 33% yield. structure 9 was determined spectroscopic data Scheme 1, was isolated in 33% yield. TheThe structure of 9of determined by by spectroscopic data (see(see Scheme 1, was was isolated in 33% 33% yield. The structure ofwas was determined by spectroscopic spectroscopic data (see Scheme 1, isolated in yield. The structure of 99 was determined by data (see the Supplementary Materials). Further, the catalytic performance of 9 was investigated (Equation the the Supplementary Materials). Further, the the catalytic performance of 9ofwas investigated (Equation Supplementary Materials). Further, catalytic performance 9 was investigated (Equation the Supplementary Materials). Further, the catalytic performance of 9for was investigated (Equation expected, complex 9 showed high catalytic activity dehydrogenation (3)).(3)). As As expected, thethe complex 9 showed high catalytic activity for for thethe dehydrogenation of of (3)). As expected, the complex 9 showed high catalytic activity the dehydrogenation of (3)). As expected, the complex 9loading showedofhigh catalytic activity for absence the dehydrogenation of 1-phenylethanol in water with a 0.25 mol % even in the of base to give 1-phenylethanol in water with a loading of 0.25 mol % even in the absence of base to give 1-phenylethanol in in water water with with aa loading loading of of 0.25 0.25 mol mol % % even even in in the the absence absence of of base base to to give give 1-phenylethanol acetophenone a high yield (90%). assume results of these reactions (Equations (1)–(3)) acetophenone in ain high yield (90%). WeWe assume thatthat thethe results of these reactions (Equations (1)–(3)) acetophenone in a high yield (90%). We assume that the results of these reactions (Equations (1)–(3)) Catalysts 2018, 8, 312 5 of 12 acetophenone in a high yield (90%). We cycle assume that the results of these reactions (Equations (1)–(3)) strongly support proposed catalytic is depicted in Scheme strongly support thethe proposed catalytic cycle thatthat is depicted in Scheme 1. 1. strongly support the proposed catalytic cycle that is depicted in Scheme 1. strongly support the proposed catalytic cycle that is depicted in Scheme 1.

Scheme 1. Possible mechanism of the present dehydrogenative oxidation of alcohols catalyzed by 1. Scheme 1. Possible mechanism of the present dehydrogenative oxidation of alcohols alcohols catalyzed by 1. 1. dehydrogenative oxidation of catalyzed by Scheme 1. Possible mechanism of the present dehydrogenative oxidation of alcohols catalyzed by 1. Scheme 1. Possible mechanism of the present dehydrogenative oxidation of alcohols catalyzed by 1.

(1) (1) (1) (1) (1)

(2) (2) (2)(2) (2)

(3) (3) (3) (3) (3)

a further application ofdehydrogenative the dehydrogenative oxidation system catalyzed by 1, we examined As application ofofthe oxidation system catalyzed by 1, examined the As aAs a further further application the dehydrogenative oxidation system catalyzed bywe 1, examined As a further further application of the the dehydrogenative oxidation system catalyzed bywe 1, we we examined As a application of dehydrogenative oxidation system catalyzed by 1, examined the dehydrogenation of diols in water. Although we have previously reported a similar catalytic dehydrogenation of diols in water. Although we have previously reported a similar catalytic system the the dehydrogenation of diols in water. Although we have previously reported a similar catalytic dehydrogenation of of diols diols in in water. water. Although Although we we have have previously previously reported reported aa similar similar catalytic catalytic the dehydrogenative dehydrogenation system dehydrogenative lactonization using a water-soluble iridium catalyst having for the lactonization using a water-soluble iridium catalystiridium having acatalyst bipyridine-based system for for thethe dehydrogenative lactonization using a water-soluble having a aa system for the dehydrogenative lactonization using a water-soluble iridium catalyst having system for the dehydrogenative lactonization using a water-soluble iridium catalyst having a bipyridine-based functional ligand, a relatively high catalyst loading (1.0–3.0 mol %) was required functional ligand,functional a relatively high catalyst loading (1.0–3.0 mol %) was required in those cases [10]. bipyridine-based ligand, a relatively high catalyst loading (1.0–3.0 molmol %) was required in in bipyridine-based functional ligand, a relatively relatively high catalyst loading (1.0–3.0 %) was was required in bipyridine-based functional ligand, a high catalyst loading (1.0–3.0 mol %) required in Therefore, in this study, we attempted the reactions of various diols using 0.25 mol % of catalyst 1 and Na2 CO3 . The results are summarized in Table 4. A variety of lactones having five- or six-membered ring structures could be obtained in good to excellent yields by conducting the reactions in aqueous media. For the substrates depicted in entries 5–7, two isomers of lactones were obtained. In those

Catalysts 2018, 2018, 8, x FOR REVIEW Catalysts 8, x PEER FOR PEER REVIEW

6 of 126 of 12

those cases [10].PEER Therefore, in this study, we attempted the reactions of various diols using 0.25 mol6 of 12 Catalysts 2018, 8, x FOR REVIEW

those cases [10]. Therefore, in this study, we attempted the reactions of various diols using 0.25 mol % ofCatalysts catalyst 1 and Na2CO 3. The results are summarized in Table 4. A variety of lactones having five2018, 8, x FOR PEER REVIEW 6 of 12 thosethose cases [10]. Therefore, in this study, we results attempted the reactions ofTable various diols using 0.25 mol having cases [10]. Therefore, in we attempted the reactions of various diols using 0.25 mol % of catalyst 1 and Na 2this CO3study, . The are summarized in 4. A variety of lactones Catalysts 2018, 8, PEER REVIEW 66 of 12 Catalysts 2018, 8, xx FOR FOR PEERstructures REVIEW of 12fiveor six-membered ring could be obtained in good to excellent yields by conducting the those cases [10]. Therefore, in this study, we attempted the reactions of various diols using 0.25 mol Catalysts 2018, 8, x FOR REVIEW 6 of 12 2018, 8, x2CO FOR PEER REVIEW 6 of 12 % of% catalyst 1 and 32.CO The results are summarized in Table 4.inAgood variety lactones having ofCatalysts catalyst 1 Na and Na 3.PEER The results arecould summarized in Table 4. A variety of lactones having fiveor six-membered ring structures be obtained to of excellent yields byfiveconducting the those cases [10]. Therefore, in this study, we attempted the reactions of various diols using 0.25 mol reactions in aqueous media. For the substrates depicted in entries 5–7, two isomers of lactones were catalyst 1 and Na 2structures CO 3. could The results are summarized in Table 4. A variety of lactones having fiveor % six-membered ring structures be obtained in good to excellent yields by conducting the orofsix-membered ring could be obtained in good to excellent yields by conducting the reactions in aqueous media. For the substrates depicted in entries 5–7, two isomers of lactones were those cases [10]. Therefore, in study, we attempted the of diols using 0.25 mol those cases [10]. Therefore, in this this study, we attempted the reactions reactions ofAvarious various diols using 0.25 molfive% of8,catalyst 1 cases, and Na 2COproduct 3. in The results are summarized in Table 4. variety of lactones having obtained. In those each was isolated as a mixture of isomers, the ratios of which were those cases [10]. Therefore, this study, we the reactions ofof various diols using 0.25 Catalysts 2018, 312 6mol of 12 those cases [10]. Therefore, in this study, we attempted the reactions ofisomers, various diols using 0.25 molwere or six-membered ring structures could be obtained good to excellent yields by conducting the reactions inof aqueous media. For the substrates depicted inattempted entries 5–7, two isomers lactones were reactions in aqueous media. For the substrates depicted ininentries 5–7, two isomers of lactones obtained. In those each product was isolated as aTable mixture of the ratios ofwere which % catalyst 1 and Na 22cases, CO 33.. The results are summarized in 4. A variety of lactones having five% of catalyst 1 and Na CO The results are summarized in Table 4. A variety of lactones having five1 or six-membered ring could be summarized obtainedininTable good toAexcellent yields by having conducting the determined by H1NMR analysis. % of catalyst and Na 2.structures CO 3. The results are in Table 4. A variety of lactones having five% of catalyst 1 and Na 2 CO 3 The results are summarized 4. variety of lactones five1H obtained. those cases, each product was isolated a depicted mixture of the ratios ofisomers which were obtained. Inaqueous those cases, each product was isolated as a mixture ofto isomers, the ratios of which were the reactions in media. For the substrates inisomers, entries 5–7, two of lactones lactones were determined by NMR analysis. or ring structures could be obtained in excellent by conducting orInsix-membered six-membered ring structures could be as obtained in good good to excellent yields by conducting the reactions in aqueous media. For the substrates depicted into entries 5–7,yields two isomers were The reaction pathway for dehydrogenative lactonization is illustrated in Scheme In the first or ring structures could be obtained in good to excellent yields by2.ofconducting the or six-membered ring structures could be obtained in good excellent yields by conducting the 1six-membered 1H NMR determined by H NMR analysis. determined by analysis. The reaction pathway for dehydrogenative is isomers, illustrated in Scheme Inwere the first reactions in aqueous media. For the substrates depicted in entries 5–7, two isomers of lactones obtained. In those cases, each product was isolated aslactonization aaswould mixture of the ratios of2.which which were reactions in aqueous media. Foras the substrates depicted inathe entries 5–7, two isomers ofdetermined lactones were 1 obtained. In those cases, each product was isolated mixture of isomers, the ratios of were one of the alcohol moieties in the diol substrate be transformed to the aldehyde by cases,step, each product was isolated a mixture of isomers, ratios of which were by reactions in aqueous media. For the substrates depicted in entries 5–7, two isomers of lactones were reactions in1 aqueous media. For the substrates depicted in entries 5–7, two isomers of lactones were byH Theobtained. reaction pathway for dehydrogenative lactonization is illustrated in 2.ratios In2.the first The reaction pathway for dehydrogenative lactonization is illustrated in Scheme the first step, one of the alcohol moieties in the diol substrate would beScheme transformed toIn the aldehyde In those cases, each product was isolated as a mixture of isomers, the of which were obtained. In those cases, each product was isolated as a mixture of isomers, the ratios of which were determined by H NMR analysis. 1 determined H NMR analysis. catalytic dehydrogenation. Then, an intramolecular afford theratios corresponding NMR analysis. obtained. In11by those cases, product was isolated as atransformed mixture of isomers, the of which obtained. In those cases, each product was isolated aswould acyclization mixture ofwould isomers, the ratios of which werewere step, onedetermined of catalytic the moieties in each the diol substrate would be to the aldehyde by step, one of alcohol the alcohol moieties inThen, the diol be transformed toafford the aldehyde by dehydrogenation. an substrate intramolecular cyclization would the corresponding by H NMR analysis. determined by H NMR analysis. The reaction pathway for dehydrogenative lactonization is illustrated in Scheme 2. In the first The reaction pathway for dehydrogenative lactonization is illustrated in Scheme 2. In the 1dehydrogenative hemiacetal. Finally, transformation would occur to generate lactone as a product. 1 determined by H NMR analysis. determined bypathway H NMR analysis. The reaction for dehydrogenative lactonization is illustrated incorresponding Scheme Infirst thefirst first catalytic dehydrogenation. Then, an intramolecular cyclization would afford catalytic dehydrogenation. Then, an intramolecular cyclization would afford the hemiacetal. Finally, dehydrogenative transformation would to the generate lactone as2. a product. The reaction pathway for dehydrogenative lactonization is illustrated in Scheme 2. the The reaction pathway for dehydrogenative lactonization isoccur illustrated incorresponding Scheme 2. In In the first by step, one of the alcohol moieties in the diol substrate would be transformed to aldehyde step, one of the alcohol moieties in the diol substrate would be transformed to the aldehyde by The reaction pathway for dehydrogenative lactonization is illustrated in Scheme 2. In the first The reaction pathway for dehydrogenative lactonization is illustrated in Scheme 2. In the first step, one of the alcohol moieties in the diol substrate would be transformed to the aldehyde by catalytic hemiacetal. Finally, dehydrogenative transformation would occur to generate lactone as a product. hemiacetal. Finally, dehydrogenative transformation would would occur tobe generate lactoneto a product. step, one of alcohol in diol substrate transformed aldehyde by step,catalytic one of the the alcohol moieties moieties in the the diol substrate would be transformed toasthe the aldehyde by dehydrogenation. Then, an intramolecular cyclization would afford the corresponding catalytic dehydrogenation. Then, an intramolecular cyclization would afford the corresponding step, one of the alcohol moieties in the diol substrate would be transformed to the aldehyde by step, one of theThen, alcohol in the diol substrate would transformed to the aldehyde by dehydrogenation. anmoieties intramolecular cyclization wouldbe afford the corresponding hemiacetal. catalytic dehydrogenation. Then, cyclization would afford the corresponding catalytic dehydrogenation. Then, an an intramolecular intramolecular cyclization would afford the corresponding hemiacetal. Finally, dehydrogenative would occur to generate lactone as aa product. catalytic dehydrogenation. Then, antransformation intramolecular cyclization would afford the corresponding hemiacetal. Finally, dehydrogenative transformation would occur to generate lactone as product. catalytic dehydrogenation. Then, an intramolecular cyclization would afford the corresponding Finally, dehydrogenative transformation would occurwould to generate aslactone a product. hemiacetal. Finally, transformation occur generate as hemiacetal. Finally, dehydrogenative dehydrogenative transformation would occur to tolactone generate lactone as aa product. product. hemiacetal. Finally, dehydrogenative transformation would occur to generate lactone a product. hemiacetal. Finally, dehydrogenative transformation would occur to generate lactone as a as product. Scheme 2. Reaction pathway for the dehydrogenative lactonization catalyzed by 1. Scheme 2. Reaction pathway for the dehydrogenative lactonization catalyzed by 1. Scheme 2. Reaction pathway for the lactonization catalyzed by 1. by 1. Scheme 2. Reaction pathway fordehydrogenative the dehydrogenative lactonization catalyzed Catalysts 2018, 8, x FOR PEER 6 of 12 Table 4.REVIEW Dehydrogenative lactonization of diols in aqueous media catalyzed by 1. Table 4. Dehydrogenative lactonization of diols in aqueous media catalyzed by 1. Scheme 2. Reaction pathway for the dehydrogenative lactonization catalyzed by 1. Table 4. Therefore, Dehydrogenative lactonization ofthe diols in aqueous media catalyzed bydiols 1. by 1. Table 4. Dehydrogenative lactonization of diols in aqueous media catalyzed those cases [10]. in thispathway study, we attempted the reactions of various using mol Scheme 2. pathway for dehydrogenative lactonization catalyzed by Scheme 2. Reaction Reaction pathway for thedehydrogenative dehydrogenative lactonization catalyzed by 1. 1. 0.25 Scheme 2. Reaction for lactonization catalyzed Scheme 2. Reaction pathway fordehydrogenative the dehydrogenative lactonization catalyzed by 1. 1. Scheme 2. Reaction pathway forthe the dehydrogenative lactonization catalyzed by 1.by Scheme 2. Reaction pathway for the lactonization catalyzed by 1. % of catalyst 1 and NaTable 2CO3.4.The results are summarized 4. aqueous A variety of lactones having Dehydrogenative lactonizationinofTable diols in media catalyzed by 1. fiveTable 4. lactonization of aqueous media catalyzed by Table 4. Dehydrogenative Dehydrogenative lactonization of diols diols in into aqueous media catalyzed by 1. 1. or six-membered ring structures could lactonization be obtained in good excellent yields by conducting the Table 4. Table Dehydrogenative of diols inaqueous aqueous media catalyzed 4. Dehydrogenative lactonization of diols in aqueous media catalyzed by 1. 1. Table 4. Dehydrogenative lactonization of diols in media catalyzed by 1.by

Table 4.media. Dehydrogenative lactonization of diols in aqueous media catalyzed by 1. were reactions in aqueous For the substrates depicted in entries 5–7, two isomers of lactones obtained. In those cases, each product was isolated as a mixture of isomers, the ratios ofa which were diol product yield (%) entry product yield (%) a entry determined by 1H NMR analysis. diol a a diol product yield (%) entry diol product yield (%) entry The reaction pathway for dehydrogenative lactonization is illustrated in Scheme 2. In the first step, one of the alcohol moieties in the diol substrate would be transformed to the aldehyde by a diol product yield (%) entry aa 1 98the (81) diol product yield (%) entry catalytic dehydrogenation. Then, corresponding diol an intramolecular product cyclization would afford yield (%) entry a(%) a 1 98 (81) product diol diol product yieldyield (%) entryentry a entry diol product yield a (%) hemiacetal. Finally, transformation would occur to generate lactone a product. diol product yieldas (%) entry dehydrogenative 1

98 (81) 98 (81)

1

1 11 1

98 (81) 98 98 (81) (81) 98 (81) 98 (81) 98 (81)

1

OH OH 98 (81) OH OH OH OH 2b 98 (91) 2 b OH7bOH 98 (91) Ph OH b 7b Phfor b 2 Scheme 98 catalyzed (91) 2. Reaction pathway the dehydrogenative lactonization by 1. 2 98 (91) OH OH OH 7b Ph7b Ph OH OH OH OH 2b 98 (91) 98 (91) 2b Table 4. lactonization of diols in aqueous media catalyzed by 1. b 22 bDehydrogenative 98 7bOH 98 (91) (91) Ph OH OH b b 2 98 (91) 2 98 (91) 7b 7b Ph Ph 7b Ph 7b Ph OH 2b 3 98 (91) 78 (73) 1

1

3

3

7b Ph

78 (73) 78 (73)

33

Catalysts 2018, 8, x FOR 3 PEER REVIEW Catalysts diolPEER REVIEWproduct entry2018, 3 8, x FOR

3 3

3

Catalysts 8, x FOR PEER REVIEW Catalysts 2018, 8, x PEER FOR PEER REVIEW Catalysts 2018, 8, x 2018, FOR REVIEW

4 4 3 45 PEER REVIEW Catalysts 2018, 1 8, x FOR Catalysts Catalysts 2018, FOR 8, PEER x FOR PEER REVIEW 5REVIEW 4 8,4 x2018,

78 (73) 78 (73)

78 (73) a yield (%) 78 78 (73) (73) 78 (73) 78 (73)

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d 99 91, (71)82 :99 18(71) 78 (73) (71) 82 : 18 d 7 of 12 98 (81) 9991, d 7 of 12 7 of 12 99 (71) 99 (71)(91, 82 : 18 ) d (91, 82 : 18 ) d: 82 91, 82 18 :d 18 d 91, 8291, :99 18 4 (71) 544 5 5 99 (71) 99 (71) d:)82 (91, :dd)18 d) (91, 82 (91,99 82 : 99 18 4 (71) 91, 82 : 18 18 4 (71) 91, 82 : 18 d d 82 : 18 d 5 b,c 91, 82 : 18 91, 5 OH (91,: 18 82 d:)18 d ) 5 5 (91, 82 d)82 : 18 d) (91, 82 : 18 (91, OH 99, 48 : 52 d 48 : 52 d 6 24b 98 (91) 99 99, (71) 6 Ph (86, 47 : 53 d) 7b (86, 47 : 53 d)d 99, 48d: 52d 99,d: 48 48 52 : 52 6 99, 4899, : 52 (86, 47 : 53 d ) 6 6 6 d d d (86, (86, 47 53 (86, 47 : 53 99, 48 ::)47 52 :d)53 ) 99, 48 : 52 99,d 48 : 52 d 6 6 6 (86, 47 : 53 d) d)47 : 53 d) (86, 4798, : (86, 53 d 45 55 98,: 45 45: :55 55dd 98, 7 73 78 (73) (88,: 52 48 d:)52 d ) 7 (88, 48 (88, 48 : 52 d) 98,d: 45 45 55 :d 55 d 98, 4598, : 55 7 7 1 7 a Yields were determined b 0.5 mol % of complex 1 by H NMR analysis. Isolated yields are shown in parentheses. d 52 :dd)52 d) a Yields were determined by 1H NMR analysis. Isolated yields (88, (88, (88, 48 : 52 are 48 shown in parentheses. 98, 45 ::)48 55 c Reaction time d Ratio of two isomers. a and Na2 CO were used7were as catalyst. 48 h. determined by 1H was NMR analysis. Isolated yields are shown in d parentheses. 45 : 55 98,d 45 : 55 b 30.5 Yields mol % of complex 1 and Na2CO3 were used as catalyst. c 98, Reaction time was 48 h. 7 of complex 1 and Na2CO3 were used as catalyst. c (88, 48 : 52 dtime ) b 0.57 mol % Reaction was 48 h. d Ratio of two isomers. (88, 48 : (88, 52 d)48 : 52 d) d a Ratio 1H NMR analysis. Isolated yields are shown in parentheses. a Yields 1 a Yields 1 of two isomers. Yields were determined by determined H NMR analysis. Isolated yields in parentheses. determined by by H NMR analysis. Isolated yields are99are shown in parentheses. 4 werewere (71)shown b 0.5 mol % of complex 1 and Na2CO3 were used as catalyst. c Reaction time was 48 h. c Reaction b 0.5b mol c Reaction 0.5 mol of complex 1 and Na32CO 3 were as catalyst. % of%Section complex 1 and Na 2CO were usedused as catalyst. timetime was was 48 h.48 h. 3. Experimental a Yields were 1 determined by H NMR analysis. Isolated yields are shown in parentheses. d Ratio of twoSection d Experimental 3. da Ratio 1 a 1 isomers. Ratio of two isomers. of two isomers. Yields by H by NMRH analysis. Isolated Isolated yields are shown in parentheses. Yieldsdetermined were determined NMR analysis. yields are shown in parentheses. b 0.5 were mol % of complex 1 and Na2CO3 were used as catalyst. c Reaction time was 48 h. b 0.5 mol c Reaction b 0.5 c Reaction % mol of complex 1 and Na 2CO3 Na were catalyst. time was 48 was h. 48 h. % of complex 1 and 2CO3used wereasused as catalyst. time 3.1. General d Ratio of two isomers. 3.1. General 3. Experimental d Ratio 3.d Ratio Experimental 3. Experimental of twoSection isomers. of Section twoSection isomers.

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3. Experimental Section 3.1. General 1H

and 13 C{1 H} NMR spectra were recorded on ECX-500 and ECS-400 spectrometers (JEOL, Akishima, Tokyo, Japan) at room temperature. Gas chromatography (GC) analyses were performed on a GC353B gas chromatograph (GL-Sciences, Shinjuku, Tokyo, Japan) with a capillary column [InertCap Pure WAX (GL-Sciences, Shinjuku, Tokyo, Japan)]. Elemental analyses were carried out at the Microanalysis Center of Kyoto University. Silica-gel column chromatography was carried out using Wako-gel C-200 (FUJIFILM Wako Pure Chemical Corporation, Doshoumatchi, Osaka, Japan). The compounds, [Cp*IrCl2 ]2 (Cp* = η5 -pentamethylcyclopentadienyl) [25] and [Cp*Ir(OH2 )3 ](OTf)2 [26] were prepared according to the literature method. The diol 7b was prepared by the reduction of 2-benzoylbenzoic acid using LiAlH4 [10]. The diols 7e–g were prepared by the reduction of the corresponding dicarboxylic acids using BH3 -THF [10]. All other reagents are commercially available and were used as received. 3.2. Preparation of Dicationic Complexes 1–4 In a two-necked round-bottomed flask under argon atmosphere, [Cp*Ir(OH2 )3 ](OTf)2 (1.14 g, 1.68 mmol), 2-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxymethoxypyridine (348 mg, 1.68 mmol), and degassed distilled water (10 mL) were placed. The mixture was stirred at 60 ◦ C for 12 h. After cooling to room temperature, the mixture was washed with CH2 Cl2 (15 mL × 3) and Et2 O (10 mL × 1). Evaporation of the water layer under vacuum gave a crude product of complex 1 as a yellow powder. The product was purified by recrystallization from water (orange crystals, 965 mg, 1.20 mmol, 71%). Analysis: 1 H NMR (400 MHz, methanol-d4 ): δ 8.13 (t, J = 7.2 Hz, 1H, aromatic), 7.63 (d, J = 7.2 Hz, 1H, aromatic), 7.33 (d, J = 8.0 Hz, 1H, aromatic), 4.34 (t, J = 10 Hz, 2H, -N(CH2 )-), 4.10 (t, J = 11 Hz, 2H, -N(CH2 )-), 1.77 (s, 15H, Cp*). 13 C{1 H} NMR (100 MHz, methanol-d4 ): δ 173.2, 165.6, 144.9, 144.8, 123.3(q, CF3 ), 118.2, 117.4, 89.6, 53.8, 47.0, 9.7. 1 H NMR (500 MHz, D2 O): δ 7.97 (dd, J = 8.0 Hz, 7.0 Hz, 1H, aromatic), 7.42 (d, J = 7.0 Hz, 1H, aromatic), 7.23 (d, J = 8.0 Hz, 1H, aromatic), 4.27 (t, J = 10.5 Hz, 2H, -N(CH2 )-), 4.02 (t, J = 10.5 Hz, 2H, -N(CH2 )-), 1.70 (s, 15H, Cp*). 13 C{1 H} NMR (125 MHz, D2 O): δ 172.5, 165.0, 144.1, 143.5, 120.3 (q, JCF = 316 Hz), 117.2, 117.1, 88.6, 53.1, 46.4, 9.27. Anal. Calcd for C20 H26 N3 O8 IrF6 S2 : C, 29.78; H, 3.25; N, 5.21. Found: C, 29.42; H, 3.25; N, 5.14. Complexes 2–4 were prepared by the similar procedures for complex 1. Complex 2 (61%): Analysis: 1 H NMR (400 MHz, methanol-d4 ): δ 8.15 (t, J = 8.0 Hz, 1H, aromatic), 7.92 (d J = 8.0 Hz, 1H, aromatic), 7.35 (d, J = 8.0 Hz, 1H, aromatic), 4.20 (m, 4H, -N(CH2 CH2 )N-), 3.50 (s, 3H, NCH3 ), 1.75 (s, 15H, Cp*). 13 C{1 H} NMR (100 MHz, methanol-d4 ): δ 171.3, 165.7, 144.9, 144.8, 123.3, 120.0, 117.4, 89.8, 56.7, 51.9, 35.7, 9.8. Anal. Calcd for C21 H29 N3 O8 IrF6 S2 •2H2 O: C, 29.40; H, 3.88; N, 4.90. Found: C, 29.50; H, 3.62; N, 4.92. Complex 3 (75%): Analysis: 1 H NMR (400 MHz, methanol-d4 ): δ 9.24 (d, J = 5.2Hz, 1H, aromatic), 8.45 (t, J = 7.6 Hz, 1H, aromatic), 8.23 (d, J = 7.6 Hz, 1H, aromatic), 8.02 (t, J = 6.4 Hz, 1H, aromatic), 4.38 (t, J = 10 Hz, 2H, -N(CH2 )-), 4.18 (t, J = 11 Hz, 2H, -N(CH2 )-), 1.80 (s, 15H, Cp*). 13 C{1 H} NMR (100 MHz, methanol-d4 ): δ 172.5, 154.3, 148.0, 143.2, 132.1, 126.8, 123.3, 89.8, 53.6, 47.4, 9.12. Anal. Calcd for C20 H26 N3 O7 IrF6 S2 : C, 30.38; H, 3.31; N, 5.31. Found: C, 30.29; H, 3.32; N, 5.27. Complex 4 (88%): Analysis: 1 H NMR (400 MHz, methanol-d4 ): δ 8.36 (t, J = 7.6 Hz, 1H, aromatic), 7.80 (d, J = 1.2 Hz, 1H, aromatic), 7.69 (d, J = 9.2 Hz, 1H, aromatic), 4.36 (m, 2H, -N(CH2 -)), 4.13 (m, 2H, -N(CH2 )-), 4.34 (s, 3H, OCH3 ), 1.76 (s, 15H, Cp*). 13 C{1 H} NMR (100 MHz, methanol-d4 ): δ 173.1, 165.9, 146.2, 145.7, 123.4, 119.4, 114.4, 89.9, 59.1, 54.0, 47.1, 9.8. Anal. Calcd for C21 H28 N3 O8 IrF6 S2 •2H2 O: C, 29.44; H, 3.76; N, 4.90. Found: C, 29.72; H, 3.73; N, 4.84. 3.3. General Procedures for the Dehydrogenative Oxidation of 1-Phenylethanol (Tables 1 and 2) In a flask under argon atmosphere, catalyst 1 (0.0025 mmol, 0.25 mol %), 1-phenylethanol (1.0 mmol), degassed distilled water (3.0 mL) and 0.1 M Na2 CO3 aq. (25 µL) were placed. The mixture

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was stirred under reflux for 20 h in an oil bath (135 ◦ C). After cooling to room temperature, the mixture was diluted with THF (10 mL). The conversion of 1-phenylethanol and the yield of acetophenone were determined by GC analysis using biphenyl as an internal standard. 3.4. General Procedure for the Dehydrogenative Oxidation of Secondary Alcohols (Table 3) In a flask under argon atmosphere, catalyst 1 (0.0025 mmol, 0.25 mol %), secondary alcohol (1.0 mmol), degassed distilled water (3.0 mL) and 0.1 M Na2 CO3 aq. (25 µL, 0.0025 mmol, 0.25 mol %) were placed. The mixture was stirred under reflux for 20 h in an oil bath (135 ◦ C). After cooling to room temperature, the produced ketones were isolated by column chromatography on silica-gel (eluent: hexane/ethyl acetate). 40 -Methylacetophenone (6b) [27]: 1 H NMR (400 MHz, CDCl3 ): δ 7.87 (m, 2H, aromatic), 7.26 (m, 2H, aromatic), 2.58 (s, 3H, -COCH3 ), 2.41 (s, 3H, -CH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 197.8, 143.8, 134.7, 129.2, 128.4, 26.5, 21.6. 40 -Methoxyacetophenone (6c) [28]: 1 H NMR (400 MHz, CDCl3 ): δ 7.95 (m, 2H, aromatic), 6.93 (m, 2H, aromatic), 3.87 (s, 3H, OCH3 ), 2.56 (s, 3H, -COCH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 196.8, 163.5, 130.6, 130.3, 114.0, 55.5, 26.3. 40 -(N,N-dimethylamino)acetophenone (6d) [27]: 1 H NMR (400 MHz, CDCl3 ): δ 7.86 (d, J = 6.8 Hz, 2H, aromatic), 6.64 (m, 2H, aromatic), 3.03 (s, 6H), 2.49 (s, 3H). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 196.4, 153.4, 130.5, 125.1, 110.6, 40.0, 26.0. 40 -Trifluoromethylacetophenone (6e) [29]: 1 H NMR (400 MHz, CDCl3 ): δ 8.04 (d, J = 8.4 Hz, 2H, aromatic), 7.71 (d, J = 7.6 Hz, 2H, aromatic), 2.63 (s, 3H, -COCH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 197.1, 139.8, 134.4 (q, JCF = 32.4 Hz), 128.7, 125.8 (d, JCF = 2.8 Hz), 123.7 (q, JCF = 271.8 Hz), 26.9. 40 -Fluoroacetophenone (6f) [29]: 1 H NMR (400 MHz, CDCl3 ): δ 7.94 (m, 2H, aromatic), 7.08 (t, J = 8.8 Hz, 2H, aromatic), 2.54 (s, 3H, -COCH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 196.5, 165.8 (d, JCF = 253.6 Hz), 133.6, 131.0 (d, JCF = 8.5 Hz), 115.6 (d, JCF = 21.9 Hz), 26.5. 40 -Chloroacetophenone (6g) [30]: 1 H NMR (400 MHz, CDCl3 ): δ 7.89 (ddd, J = 8.4, 2.4, 1.6 Hz, 2H, aromatic), 7.42 (dt, J = 8.8, 2.0 Hz, 2H, aromatic), 2.59 (s, 3H, -COCH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 196.7, 139.6, 135.5, 129.6, 128.9, 26.6. 30 -Methylacetophenone (6h) [31]: 1 H NMR (400 MHz, CDCl3 ): δ 7.75 (m, 2H, aromatic), 7.33 (m, 2H, aromatic), 2.57 (s, 3H, -COCH3 ), 2.40 (s, 3H, -CH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 198.4, 138.3, 137.1, 133.9, 128.8, 128.4, 125.6, 26.7, 21.3. 30 -Methoxyacetophenone (6i) [28]: 1 H NMR (400 MHz, CDCl3 ): δ 7.50 (m, 1H, aromatic), 7.45 (m, 1H, aromatic), 7.33 (m, 1H, aromatic), 7.07 (m, 1H, aromatic), 3.81 (s, 3H, -OCH3 ) 2.56 (s, 3H, -COCH3 ). 13 C{1 H} NMR (100 MHz, CDCl ): δ 197.9, 159.8, 138.5, 129.6, 121.1, 119.6, 112.4, 55.4, 26.7. 3 30 -Chloroacetophenone (6j) [31]: 1 H NMR (400 MHz, CDCl3 ): δ 7.88 (m, 1H, aromatic), 7.79 (m, 1H, aromatic), 7.49 (m, 1H, aromatic), 7.37 (t, J = 8.0 Hz, 1H, aromatic), 2.56 (s, 3H, -COCH3 ). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 196.8, 138.6, 134.9, 133.1, 130.0, 128.4, 126.5, 26.7. 1-Indanone (6k) [32]: 1 H NMR (400 MHz, CDCl3 ): δ 7.70 (d, J = 7.6 Hz, 1H, aromatic), 7.54 (m, 1H, aromatic), 7.44 (m, 1H, aromatic), 7.32 (m, 1H, aromatic), 3.09 (t, J = 6.0 Hz, 2H), 2.70–2.63 (m, 2H). 13 C{1 H} NMR (100 MHz, CDCl ): δ 207.0, 155.2, 137.2, 134.6, 127.2, 126.7, 123.6, 36.2, 25.8. 3 α-Tetralone (6l) [32]: 1 H NMR (400 MHz, CDCl3 ): δ 8.01 (m, 1H, aromatic), 7.45 (m, 1H, aromatic), 7.32–7.18 (m, 2H, aromatic), 2.92 (m, 2H), 2.61 (m, 2H), 2.07 (m, 2H). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 198.1, 144.4, 133.2, 132.9, 128.7, 126.9, 126.4, 39.0, 29.5, 23.1. Propiophenone (6m) [31]: 1 H NMR (400 MHz, CDCl3 ): δ 7.95 (m, 2H, aromatic), 7.52 (m, 1H, aromatic), 7.43 (m, 2H, aromatic), 2.99 (q, J = 7.2 Hz, 2H, CH2 CH3 ), 1.21 (t, J = 7.2 Hz, 3H, CH2 CH3 ). 13 C{1 H} NMR (100 MHz, CDCl ): δ 200.8, 136.9, 132.9, 128.6, 128.0, 31.8, 8.3. 3

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3.5. Procedure for the Quantitative Analysis of the Evolved Hydrogen Gas in the Dehydrogenative Oxidation of 1-Indanol (Equation (1)) In a flask connected with a gas burette through a condenser under argon atmosphere, catalyst 1 (20.3 mg, 0.025 mmol), distilled water (30 mL), 0.1 M Na2 CO3 aq. (250 µL) and 1-indanol (1.35 g, 10 mmol) were placed. The mixture was stirred under reflux for 20 h in an oil bath (135 ◦ C). The yield of 1-indanone was determined by 1 H NMR (CDCl3 ) using triphenylmethane as an internal standard. The volume of evolved gas was measured by a gas burette. The molar amount of hydrogen was calculated using the ideal gas law. The purity of evolved hydrogen gas was confirmed by GC analysis (experimental detail is described in the Supplementary Materials). 3.6. Preparation of Monocationic Complex 9 (Equation (2)) In a flask under argon atmosphere, complex 1 (101.6 mg, 0.126 mmol) was placed. 0.1 M Na2 CO3 aq. (1.25 mL) was added and stirred for 10 min at room temperature. Then, the solvent water was evaporated by the vacuum pump and the deposed dark green powder remained. The powder was dissolved in dry CH2 Cl2 and filtered by Celite under argon atmosphere. The filtrate organic layer was washed by distilled water (10 mL × 4) under argon atmosphere, then the solvent was removed by evaporation and the dark green powder was obtained (27.2 mg, 0.041 mmol, 33%). Results of the NMR analysis of complex 9 are shown in the Supplementary Materials. 3.7. General Procedure for the Dehydrogenative Lactonization of Diols (Table 4) In two-necked test tube under argon atmosphere, catalyst 1 (0.0025 mmol, 0.25 mol %), diol (1.0 mmol), distilled water (1.5 mL) and 0.1 M Na2 CO3 aq. (25 µL, 0.0025 mmol, 0.25 mol %) were placed. The mixture was stirred under reflux for 20 h in an oil bath (135 ◦ C). After cooling to room temperature, the solvent was evaporated. The yield of the product was determined by 1 H NMR using 1,3,5-trimethoxybenzene as an internal standard. The product was isolated by silica-gel column chromatography (eluent: hexane/ethyl acetate). Phthalide (8a) [33]: 1 H NMR (500 MHz, CDCl3 ): δ 7.91 (d, J = 7.5 Hz, 1H, aromatic), 7.71 (td, J = 7.5, 1.0 Hz, 1H, aromatic), 7.56–7.52 (m, 2H, aromatic), 5.34 (s, 2H, -CH2 -). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 171.2, 146.6, 134.1, 129.0, 125.6, 125.6, 122.2, 69.7. 3-Phenyl-1(3H)-isobenzofuranone (8b) [34]: 1 H NMR (500 MHz, CDCl3 ): δ 7.97 (d, J = 7.5 Hz, 1H, aromatic), 7.66 (t, J = 7.5 Hz, 1H, aromatic), 7.56 (t, J = 7.5 Hz, 1H, aromatic), 7.41–7.36 (m, 3H, aromatic), 7.34 (d, J = 7.5 Hz, 1H, aromatic), 7.30–7.27 (m, 2H, aromatic). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 170.7, 149.8, 136.5, 134.5, 129.5, 129.4, 129.1, 127.1, 125.8, 125.7, 123.0, 82.9. Naphtho[2,3-c]furan-1(3H)-one (8c) [33]: 1 H NMR (400 MHz, CDCl3 ): δ 8.52 (s, 1H, aromatic), 8.06 (d, J = 8.4 Hz, 1H, aromatic), 7.96 (d, J = 8.4 Hz, 1H, aromatic), 7.92 (s, 1H, aromatic), 7.67 (td, J = 6.8, 1.2 Hz, 1H, aromatic), 7.61 (t, J = 8.0 Hz, 1H, aromatic), 5.5 (s, 2H, -CH2 -). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 171.1, 140.1, 136.3, 133.2, 130.0, 129.1, 128.2, 127.1, 127.1, 123.5, 120.1, 69.8. 1H,3H-Naphtho[1,8-cd]pyran-1-one (8d) [33]: 1 H NMR (400 MHz, CDCl3 ): δ 8.35 (dd, J = 7.6, 0.8 Hz, 1H, aromatic), 8.08 (d, J = 8.0 Hz, 1H, aromatic), 7.81 (d, J = 8.4 Hz, 1H, aromatic), 7.62 (dd, J = 8.0, 7.2 Hz, 1H, aromatic), 7.53 (t, J = 7.2 Hz, 1H, aromatic), 7.34 (dd, J = 7.2, 0.8 Hz, 1H, aromatic), 5.79 (s, 2H, -CH2 -). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 170.3, 139.0, 137.3, 132.7, 131.9, 130.7, 130.2, 128.8, 128.7, 128.6, 128.5, 69.2. 3,4-Dihydro-1H-2-benzopyran-1-one (8ea) [35], 1,4-Dihydro-3H-2-benzopyran-3-one (8eb) [36]: 1 H NMR (500 MHz, CDCl3 ): δ 8.08 (dd, J = 6.4, 0.8 Hz 1H), 7.55 (td, J = 6.0, 1.2 Hz, 1H), 7.41 (t, J = 6.0 Hz, 1H), 7.27 (m, 1H), 4.55 (t, J = 4.8 Hz, 2H), 3.08 (t, J = 4.8 Hz, 2H). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 165.0, 139.5, 133.6, 130.1, 127.5, 127.2, 125.1, 67.2, 27.6. 1 H NMR (400 MHz, CDCl3 ): δ 7.37–7.23 (m, 4H), 5.32 (s, 2H), 3.72 (s, 2H). 13 C{1 H} NMR (100 MHz, CDCl3 ): δ 170.7, 131.5, 130.9, 128.6, 126.9, 124.5, 69.9, 36.1. 6-Methyl-1(3H)-isobenzofuranone (8fa) [33], 5-Methyl-1(3H)-isobenzofuranone (8fb) [33]: 1 H NMR (500 MHz, CDCl3 ): δ 7.70 (s, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 5.27 (s, 2H), 2.50 (s,

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3H). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 171.2, 143.8, 139.1, 135.1, 125.6, 125.3, 121.8, 69.6, 21.1. 1 H NMR (500 MHz, CDCl3 ): δ 7.79 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.29 (s, 1H), 5.29 (s, 2H), 2.47 (s, 3H). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 171.1, 147.1, 145.2, 130.0, 125.3, 122.9, 122.4, 69.4, 21.9. 6-Fluoro-1(3H)-isobenzofuranone (8ga) [37]: 1 H NMR (500 MHz, CDCl3 ): δ 7.58 (dd, J = 2.5, 7.0 Hz, 1H, aromatic), 7.49 (m, 1H, aromatic), 7.42 (td, J = 2.5, 8.5 Hz, 1H, aromatic), 5.32 (s, 2H, -CH2 -). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 170.1 (d, JCF = 3.5 Hz), 163.2 (d, JCF = 248.0 Hz), 142.0, 127.9 (d, JCF = 9.6 Hz), 123.9 (d, JCF = 8.4 Hz), 122.2 (d, JCF = 23.9 Hz), 112.3 (d, JCF = 23.9 Hz), 69.6 (s). 5-Fluoro-1(3H)-isobenzofuranone (8gb) [37]: 1 H NMR (500 MHz, CDCl3 ): δ 7.93 (dd, J = 8.5, 5.0 Hz, 1H, aromatic), 7.25 (td, J = 8.8, 2.0 Hz, 1H, aromatic), 7.20 (dd, J = 7.5, 1.5 Hz, 1H, aromatic), 5.32 (s, 2H, -CH2 -). 13 C{1 H} NMR (125 MHz, CDCl3 ): δ 170.0, 166.7 (d, JCF = 255.1 Hz), 149.4 (d, JCF = 10.8 Hz), 128.2 (d, JCF = 9.5 Hz), 122.0, 117.5 (d, JCF = 23.8 Hz), 109.6 (d, JCF = 23.9 Hz), 69.1 (d, JCF = 3.6 Hz). 4. Conclusions In summary, we have synthesized water-soluble and stable dicationic complexes 1–4 having a bidentate functional ligand that comprises substituted or non-substituted pyridine and 4,5-dihydro-1H-imidazol-2-yl moieties. Among the prepared complexes, derivative 1, which contained an α-hydroxypyridine in the functional ligand, exhibited high catalytic performance in the dehydrogenative oxidation of secondary alcohols to the corresponding ketones in aqueous media. Furthermore, the complex 1 also exhibited high catalytic activity for the dehydrogenative lactonization of diols in aqueous media. For both reactions, lower catalyst loadings were required as compared to the requirement of the previously reported systems. Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4344/8/8/312/s1. Figure S1. Reaction setup for the quantitative analysis of the evolved hydrogen gas. Figure S2. GC analyses of the hydrogen gas. a) The chromatogram of the evolved gas by the reaction of 1-indanol. b) The chromatogram of the standard gas of pure hydrogen. Figure S3. 1 H NMR(D2 O) experiment for detection of the active species. Author Contributions: M.Y. performed the experiments, analyzed the results, and wrote the manuscript. H.W. performed the experiments and analyzed the results. T.S. contributed to analyze the experimental results and write the manuscript. K.F. guided the research, designed the experiments, and wrote the manuscript. Funding: This work was financially supported by JSPS KAKENHI Grant Number JP16H01018 and JP18H04255 in Precisely Designed Catalysts with Customized Scaffolding. Conflicts of Interest: The authors declare no conflicts of interest.

References and Notes 1. 2. 3. 4. 5. 6.

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10.

11. 12.

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17. 18.

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