Supporting Info 20.08.2012

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Aug 20, 2012 - PhIO / HBF4 (48 % in water). Ph. O. O .... The residue is diluted with ether and washed three times with ... 220 µl of HBF4 (1.7 mmol, 1.7 eq.
Supporting information Oxidative cleavage of α-arylaldehydes using iodosylbenzene

Nizam Havare and Dietmar A. Plattner

1

Entry 1: O PhIO/HBF4 (Et2O) no reaction CH2Cl2, r.t.

Method A1

Entry 2

O

O

Ph

O

PhIO / HBF4 (48 % in water) CH2Cl2, 1.5 h, r.t.

Ph

OH

Method B1 In a two-necked flask equipped with two bubble counters, which are connected and filled with the CO2 detection reagent (barium hydroxide) and with the CO detection reagent (PdCl2/HCl in water), respectively, 608 mg of phenylglyoxal (4 mmol, 1 eq.) is in 20 ml CH2Cl2 solved. 1.32 g of iodosylbenzene (6 mmol, 1.5 eq) is added to the solution. Under stirring, 630 µL of tetrafluoroboric acid (4.82 mmol, 1.2 eq., 48% in water) is added within a few minutes dropwise to the suspension. The reaction mixture is stirred for 1.5 hours at room temperature (TLC control after 1.5 hours). After 1.5 hours, BaCO3 and Pd metal precipitated in bubble counter. The reaction mixture is concentrated under reduced pressure. The product is isolated by column chromatography (eluent: cyclohexane:ethyl acetate = 20 / 1 → 10 / 1).

Yield: 73 %

O Ph 1

OH

H-NMR (300 MHz, CDCl3):

δ = 8.13 (d, J = 8.0 Hz, 2H, Ar-H), 7.62 (t, J = 7.4 Hz, 1H, Ar-H), 7.52-7.45 (t, J = 7.4 Hz, 2H, Ar-H).

2

GC/MS-EI m/z(%): 123.1(6), 122.0(100), 106.1(6), 105.0(88), 77.1(38).

Entry 3 OMe Ph

O

1,4-dioxane

O

O

PhIO/HBF4 Et2O Ph

H

+

Ph

OMe

Method A2 In a 100 ml flask, 150 mg of 2-methoxy-2-phenylacetaldehyde (1 mmol, 1 eq.) and 50 mg of 1,4-dichlorobenzene (0.347 mmol) (internal standard) are solved in 10 ml of 1,4-dioxane (abs.) under argon atmosphere. 330 mg of iodosylbenzene (1.5 mmol, 1.5 equiv.) is added. The suspension is stirred for 5 minutes at room temperature. Then, 220 µl of tetrafluoroboric acid ethrerat complex (395 mg, 2.2 mmol, 2.2 eq., 50-55% in ether), diluted with CH2Cl2 (abs.) to the total volume of 10 ml with 1,4-dioxane. This is injected within 10 minutes to the suspension. After 10, 20, 40 and 60 minutes, and finally after 15 hours are taken each 700 µl sample of the reaction environment. (The preparation of GC sample: the sample is first diluted to 2 ml with diethyether, and then washed with saturated sodium thiosulfate. The aqueous solution is removed. The sample is washed then with saturated sodium bicarbonate. The 3

aqueous phase is removed. The organic phase is dried with little sodium sulfate and filtered. After 15 hours, the reaction is processed with the same work up of the samples. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane/ethyl acetate: 10/1).

Yield: 65% (GC-yield), 3% (GC-yield) methyl benzoate (oxidative cleavage product). O Ph

H

Benzaldehyde: 1

H-NMR (300 MHz, CDCl3):

δ = 10.02 (s, 1H, CHO), 7.85 (d, 2H, Ar-H), 7.61 (t, 1H, Ar-H), 7.51 (t, 2H, Ar-H).

O Ph

OMe

Methylbenzoate 1

H-NMR (300 MHz, CDCl3):

δ = 8.028 (d, 2H, Ar-H), 7.56-7.26 (m, 3H, Ar-H), 3.89 (s, -COOCH3).

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Synthesis of 2-methoxy-2-phenylacetaldehyde

OMe Ph

OH

OMe

Oxalyl chloride / DMSO / Et3N CH2Cl2, -78°C, 25 min.

Ph

O

1.26 mL (14.5 mmol, 1.1 eq.) oxalyl chloride is disolved in 60 mL of dichloromethane. The solution is cooled to -78 °C. 2.05 mL of DMSO (28.9 mmol, 2.2 eq.), dissolved in 10 mL of dichloromethane is added dropwise. The solution is stirred 20 min. at -78 ° C. 2 g of 2methoxy-2-phenylethanol (13.1 mmol, 1 eq.) were added dropwise in 7 mL of dichloromethane. The solution is stirred for a further five minutes at -78 °C. Then 9.16 mL of triethylamine is added at the same temperature. The mixture fades a yellow suspension. The reaction mixture is allowed to warm to 0°C and hydrolyzed with 20 mL of water. The aqueous phase is extracted three times with dichloromethane. The combined organic phase is washed once with saturated sodium chloride solution and dried over sodium sulfate. The organic phase is concentrated. The residue is diluted with ether and washed three times with 20 mL of 1% cold HCl solution and once with brine. The organic phase is dried over 5

magnesium sulphate and the solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane/ethyl acetate: 20/1).

Yield: 43% (842 mg)

OMe Ph 1

O

H-NMR (300 MHz, CDCl3):

δ = 9.60 (d, J = 1.5 Hz, 1H, -CHO), 7.46-7.32 (m, 5H, Ar-H), 4.64 (d, J = 1.5 Hz, 1H, PhCH(OCH3)CHO), 3.45 (s, 3H, PhCH(OCH3)CHO).

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Entry 4 O2 N O

O

PhIO / HBF4

Ph

H N

Ph Ph

N

NO2

1.2 g of phenylacetaldehyde (10 mmol, 1 eq.) is dissolved in 30 mL of dioxane-water (15:15). 3.3 g of iodosylbenzene (15 mmol, 1.5 eq.) is added. Under stirring, 1:58 mL of tetrafluoroboric acid (12 mmol, d = 1.4 g / mL, 48% in water) is added dropwise to the suspension. The reaction mixture is stirred for six days at room temperature. After six days, the freshly prepared 2,4-dinitrophenylhydrazine solution is added to give the corresponding hydrazone compound. The precipitate is filtered and washed several times with water. The hydrazone is then dried. Preparation of 2,4-dinitrophenylhydrazine solution: To 3.1 g of 2,4-dinitrophenylhydrazine (11 mmol, 1.1 eq, 70%) are added 11.74 mL of sulfuric acid and 17.6 mL of water. 60 mL tech. Ethanol is then added to hot solution. The solution is stirred for 10 minutes at room temperature.

Yield: 98 % (2.82 g).

O2N H N

Ph N

NO2

1-Benzylidene-2-(2,4-dinitrophenyl)hydrazine 1

H-NMR (300 MHz, DMSO-d6):

δ = 11.7 (bs,1H, -CHNNH-), 8.88 (d, J = 2.7 Hz, 1H, Ar-H), 8.73 (s, 1H, -CHNNH- ), 8.438.36 (dd, J = 2.70 Hz, J = 9.70 Hz, 1H, Ar-H), 8.15-8.10 (d, J = 9.70, 1H, Ar-H), 7.85-7.75 (dd, J = 4.2 Hz, J = 2.06 Hz, 2H, Ar-H), 7.54-7.46 (m, 3H; Ar-H).

7

Entry 5 O

PhIO / HBF4 (48% in H2O)

O

1,4-dioxane / water: 1 / 1

Method B2 170 mg of 2-(naphthalene-6-yl)acetaldehyde (1 mmol, 1 eq.) is dissolved in mixture of 20 ml 1,4-dioxane-water (1:1). And then, 330 mg of iodosylbenzene (1.5 mmol, 1.5 equiv.) is added to the solution. 220 µl of HBF4 (1.7 mmol, 1.7 eq. 48% in water) is added dropwise to the suspension. The suspension is stirred for 6 days at room temperature. The reaction mixture will be clearer with time. After 6 days, the reaction mixture is washed with saturated sodium thiosulfate, and extracted twice with 30 ml diethyl ether. The organic layer dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate: 10 / 1).

Yield: 51%

8

O 1

H- NMR (300 MHz, CDCl3):

10.17 (s, 1H, -CHO), 8.35 (s, 1H, Ar-H), 8.04-7.89 (m, 4H, Ar-H), 7.72-7.56 (m, 2H, Ar-H).

Synthesis of 2-(naphthalene-6-yl)acetaldehyde

AcO OAc OAc I O OH

O

O

CH2Cl2

2.58 g of Dess-Martin reagent (6.1 mmol, 1.18 eq.) is dissolved in 50 ml of dichloromethane under nitrogen atmosphere. 888 mg of 2-(naphthalene-6-yl)ethanol (5.15 mmol, 1 eq.) is added in 40 ml of dichloromethane to the solution. The yellowish reaction mixture is stirred at room temperature for 1.5 hours. A precipitate is observed. After 1.5 hours, the reaction 9

mixture hydrolyzed with saturated sodium bicarbonate solution. The organic phase is separated, and then is extracted with sodium thiosulfate solution (6 g in 100 ml water). The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 1:1). The product is a yellow solid.

Yield: 72 % (630 mg)

O

1

H-NMR (300 MHz, CDCl3):

δ = 9.83 (t, 1H, CHO)), 7.84 (m, 3H, Ar-H), 7.69 (s, 1H, Ar-H), 7.49 (m, 2H, Ar-H), 7.32 (dd, 1H, Ar-H), 3.85 (d, 2H, -CH2CHO).

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Entry 6 Me

O O

O2N

PhIO / BF3 OEt2 1,4-dioxane, r.t., 26 h

Me O2N

In a 50 ml flask, 50 mg of 2-(4-nitrophenyl)propanal (0.280 mmol, 1 eq.) and 50 µL of nheptane (internal standard) (0.360 mmol, d = 0.865 g/ml) are solved in 5 mL of 1,4-dioxane (abs.) under argon atmosphere. 61 mg of iodosylbenzene (0.280 mmol, 1 eq.) is added to the solution. The suspension is stirred for 5 minutes at room temperature. Then, 110 µl of BF3·OEt2 complex (0.42 mmol, 1.5 eq. 48% in ether), diluted to the total volume of 5 ml with 1,4-dioxane, is added dropwise within 10 minutes to the suspension. After 10, 20, 40 and 60 minutes, and finally 26 hours, sample is taken each 300 µl from the reaction mixture. The samples work up: the sample is first diluted to 2 ml with ethyl acetate, and then washed with saturated sodium thiosulfate solution. The aqueous solution is removed. The sample is washed this time with saturated sodium bicarbonate solution. The aqueous phase is removed. The organic phase is dried over little sodium sulfate and filtered. After 26 hours, the reaction is processed with the same treatment of the samples. The solvent is removed. The product is isolated by column chromatography (eluent = cyclohexane / ethyl acetate: 10 / 1).

Yield: 63% (GC-Yield).

O Me O2 N 1

H-NMR (300 MHz, CDCl3):

δ = 8.29 (dt, J = 8.97, J = 1.94, 2H, Ar-H), 8.09 (dt, J = 8.97, J = 2.16, 2H, Ar-H), 2.66 (s, 3H).

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Synthesis of rac-ethyl 3-methyl-3-(4-nitrophenyl)oxirane-2-carboxylate

O Me O2N

Me O O

1) Na, Benzol-Xylol, t-Buthanol 2) Ethyl chloroactetate

OEt O2N

5.52 g of sodium (0.24 mol) in 72 ml benzene (abs.), 7.2 ml of xylene (abs.) and 2.4 ml tbutanol are suspended under argon. Under stirring and ice cooling, a mixture of 20 g (0.12 mmol) 4-nitro-acetophenone and 22 g of ethyl chloroacetate are added to the suspension. The reaction mixture is stirred 24 hours at r. t., and then poured into ice-water. The aqueous phase is separated and extracted several times with toluene. The combined organic phases are washed several times with water and NaHCO3 solution, separated, dried over sodium sulfate and filtered. The solvent is removed. The residue is distilled (bp.(0.23 mbar) = 120 ° C). Yield: 61% (18,24 g, after distillation)

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Me O O OEt O2N 1

H-NMR (400 MHz, CDCl3):

δ = 8.21 (tt, J = 8.99, J = 2.01, 2H, Ar-H), 7.60 (tt, J = 8.99, J = 2.01, 2H, Ar-H), 3.93 (qd, J = 7.16, J = 1.95, 2H, -COOCH2CH3), 3.72 (s, 1H, -C-(O)-CHCOOCH2CH3), 1.78 (s, 3H, CH3C(Ar)-(O)-CH-), 0.97 (t, J = 7.04, 3H, -COOCH2CH3).

Synthesis of rac-sodium 3-methyl-3-(4-nitrophenyl)oxirane-2-carboxylate

Me O O

Me O O OEt

O2N

NaOEt, Wasser

O O2 N

Na

To 1.84 g of sodium (0.08 mol) is added enough ethanol (abs.) in a 100 ml two-necked flask under reflux condenser and argon atmosphere, until formation of clear solution. In an ice bath, 13

18.2 g (0.725 mol) glycid ester is added drop wise. The reaction mixture is stirred 10 min. at r.t. 1.8 ml of water (0.1 mol) added dropwise to solution. This is stirred 10 min. The flask is allowed one day to the crystallization of the product in a refrigerator at 4 °C. The product is filtered after 24 hours, and dried over phosphorus pentoxide.

Yield: 82% (13.65 g).

Me O O O O2 N 1

Na

H-NMR (400 MHz, DMSO-d6):

δ = 8.12 (dt, J = 8.90, J = 1.91, 2H, Ar-H), 7.22 (dt, J = 8.90, J = 1.91, 2H, Ar-H), 3.38 (s, 1H, CH3(Ar-)C-(O)-CHCOO), 1.66 (s, 3H, CH3(Ar-)C-(O)-CHCOO).

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Synthesis of 2-(4-nitrophenyl)propanal

Me

Me O O

O2N

O Na

O

HCl, H2O ∆, -CO2

O2N

13.65 g of rac-sodium 3-methyl-3-(4-nitrophenyl)oxirane-2-carboxylate (0.557 mol, 1 eq.) is dissolved in 250 ml water under heating, until formation of a clear solution. The solution is heated to 70 °C under reflux condenser, equipped with a bubbler. 3.37 ml of conc. HCl (0.067, 1.2 eq.) is added dropwise to the solution. The reaction is over, when no more bubbles formed at the bubble counter (4-5 hours). The solution is then extracted three times with diethyl ether. The organic phase is dried over sodium sulfate. The solvent is removed. The product is isolated by column chromatography (eluent: mixture of cyclohexane / ethyl acetate). The reaction should not be heated so long. The product decomposes during distillation or heating. Yield: 8% (1 g isolated, the product was decomposed during distillation or heating).

Me O O2 N 1

H-NMR (400 MHz, CDCl3):

δ = 9.72 (d, J = 1.19, 1H, -CHO), 8.24 (dt, J = 8.84, J = 1.78, 2H, Ar-H), 7.39 (dt, J = 8.48, J = 1.65, 2H, Ar-H), 3.78 (q, J = 6.95, 1H, ArCH(CH3)CHO), 1.52 (d, J = 7.17, 3H, ArCH(CH3)CHO).

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Entry 7 Me

Me O MeO

PhIO/HBF4 OEt2 mol. sieve 4Å, r.t.

O MeO

Method A2 In 50 ml flask, 164 mg of 2-(4-methoxyphenyl)propanal (1 mmol, 1 eq.) and 50 µl of nheptane (0.360 mmol, d = 0.865 g/ml) (internal standard) are solved in 5 ml 1,4-dioxane (abs.) under argon atmosphere. 220 mg of iodosobenzene (1 mmol, 1 eq.) is added to the solution. Ca. 5 g of molecular sieve 4 Å is added to the suspension. 193 µl of tetrafluoroboric acid etherat complex (1.1 mmol, 1.1 eq. 50-55% ether), diluted to the total volume of 5 ml in 1,4dioxane, is added dropwise within 10 minutes to the suspension. The reaction is stirred for another 10 days at room temperature. A few of samples are taken during the reaction. The samples are analyzed by GC. Preparation of the samples: 700 µl of the sample is first diluted to 2 ml in diethyether, and then washed with saturated sodium thiosulfate solution. The aqueous solution is removed. The organic phase is washed then with saturated sodium 16

bicarbonate solution. The aqueous phase is removed. The organic phase is dried with little sodium sulfate and filtered. At the end of the reaction is worked up analogously to the procedure of the samples. The product is isolated by column chromatography (eluent = cyclohexane/ethyl acetate = 10:1).

Yield: 42% (GC-yield) Conversion: 47 %

Me O MeO 1

H-NMR (400 MHz, CDCl3):

δ = 7.93 (dt, J = 8.88, J = 2.07, 2H, Ar-H), 6.93 (dt, J = 8.93, J = 2.10, 2H, Ar-H), 3.86 (s, 3H, ArOCH3), 2.55 (s, 3H, ArCOCH3).

17

Synthesis of 2-(4-methoxyphenyl)propanal

Me Me MeO

O

Ag2O, I2 1,4-dioxane / Wasser: 5 / 1

MeO

2.96 g of trans-anethol (20 mmol, 1 eq.) is dissolved in 120 mL mixture of 1,4-dioxane-water (5:1). 7.23 g of silver oxide (31 mmol, 1.55 eq.) is added in one portion. To the vigorously stirred suspension, 7.87 g (31 mmol, 1.55 eq.) iodine is added in portionwise within 5 min. The first purple and then red-colored solution is stirred for an hour at room temperature. The suspension is then filtered. The clear red solution is washed with saturated sodium thiosulfate, and the red color disappears. The mixture is then extracted three times with diethyl ether. The organic phase is dried over sodium sulfate, and filtered. The solvent is removed. The residue is distilled under high vacuum (bp.0.36 mbar = 65 °C). Yield: 83 % (2.73 g)

Me O MeO 1

H-NMR (400 MHz, CDCl3):

δ = 9.64 (d, J = 1.47, 1H, -CHO), 7,13 (dt, J = 8.72, J = 2.07, 2H, Ar-H), 6.91 (dt, J = 8.72, J = 2.18, 2H, Ar-H), 3.80 (s, 3H, -OCH3), 3.58 (qd, J = 6.94, J = 1.37, 1H, -CHCHO), 1.41 (d, J = 7.15, 3H, CH3CH(Ar)CHO).

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Entry 8 O

O

PhIO/BF3 OEt2 Ph

Me

CH2Cl2, molsieve 4Å, 0°C

r.t.

Ph

Me

Method C1 In a two-necked flask equipped with two bubble counters, which are connected and filled with the CO2 detection reagent (barium hydroxide) and with the CO detection reagent (PdCl2/HCl in water), respectively, 804 mg of 2-phenylpropanal (6 mmol, 1 equiv.) is solved in 30 ml of abs. CH2Cl2. 1.32 g (6 mmol, 1 eq.) iodosylbenzene and ca. 5 g of mol. sieve 4Å are added to the solution. Under stirring, 1.740 ml of BF3·OEt2 (48% solution in ether) (6.6 mmol, 1.1 eq), diluted to 30 ml with CH2Cl2 (abs.), is added dropwise using a syringe pump with a drop rate of 5 ml/h over four hours to the suspension under ice bath. Gas is formed and in bubble counter; and later a precipitate of Pd metal is observed. The reaction mixture is then stirred for 44 hours at room temperature. The reaction mixture is washed with saturated sodium thiosulfate, and extracted twice with ether. The organic phase is washed with saturated 19

sodium bicarbonate solution, separated, dried over sodium sulfate, and filtered. The solvent is evaporated to 4-5 ml, and the product was isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1).

Yield: 40% Conversion: 82%

O Ph 1

Me

H-NMR (300 MHz, CDCl3):

δ = 7.96 (d, 2H, Ar-H), 7.56 (tt, J = 7.43, J = 1.29, 1H, Ar-H), 7.46 (t, 2H, Ar-H), 2.61 (s, 3H, -COCH3).

GC/MS-Ei m/z (%): 121.1(2), 120.0(34), 106.1(5), 105.0(92), 91.1(2), 89.0(1), 78.2(7), 77.0(100), 75.2(3), 74.1(5), 73.0(1), 65.1(2), 63.2(3), 62.2(2), 61.2(1), 52.4(4), 51.2(40), 50.3(19), 49.3(3), 44.3(6), 43.4(20).

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Entry 9

O

PhIO/HBF4 (48% in water)

O

1,4-dioxane/water = 1:1, r.t.

Method B3 136 mg of 2-(4-methoxyphenyl)acetaldehyde (1 mmol, 1 eq.) is dissolved in 20 ml 1,4dioxane under Argon. 330 mg of iodosylbenzene (1.5 mmol, 1.5 equiv.) is added to the solution. 220 µl of HBF4 (1.7 mmol, 1.7 eq. 48% in water) is added to the suspension. The suspension is stirred for 4.5 days at room temperature. The reaction mixture will be clearer with the time. After 4.5 days, the reaction mixture is washed with saturated sodium thiosulfate solution, and extracted twice with ether. The organic phase dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1).

Yield: 59 % Conversion: 74%

O 1

H-NMR (300 MHz, CDCl3):

δ = 7.96 (d, J = 7.2 Hz, 2H, Ar-H), 7.59-7.52 (t, J = 7.2 Hz, 1H, Ar-H), 7.49-7.42 (t, J = 7.2 Hz, 2H, Ar-H), 3.05-2.96 (q, J = 7.3 Hz, 2H, PhCOCH2CH3), 1.23 (t, J = 7.3, 3H, PhCOCH2CH3).

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Synthesis of 2-phenylbutanal

AcO OAc OAc I O OH

O

O

CH2Cl2

To a solution of 1.0 g of 2-phenylbutan-1-ol (6.67 mmol, 1 eq.) in 25 ml of dichloromethane is added 22.12 ml of Dess-Martin reagent (7.00 mmol, 1.05 eq., 15% solution in dichloromethane) dropwise at 0°C. The yellowish reaction mixture is then allowed to warm slowly to room temperature. It is observed with the time a precipitate. The reaction is stirred for one hour more at room temperature (TLC control). The reaction mixture is washed with saturated sodium thiosulfate, with 1 M NaOH and then with brine. The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product is then isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1).

22

Yield: 62% (613 mg) O

1

H-NMR (400 MHz, CDCl3):

δ = 9.68 (d, J = 2.04, 1H, -CHO), 7.41-7.24 (m, 3H, Ar-H), 7.22-7.16 (m, 2H, Ar-H), 3.40 (td, J = 7.47, J = 1.92, 1H, -CHCHO), 2,20-2.03 (m, 1H, -CH2CHCHO), 1.85-1.68 (m, 1H, CH2CHCHO), 0.91 (t, J = 7.46, 3H, CH3CH2CH(Ar)CHO).

23

Entry 10

O

O

O PhIO / BF3 Et2O

OH

+

CH2Cl2, mol. sieve 4Å, 2h

In a 25 ml two-necked flask, 101 mg of 2-cyclohexyl-2-phenylacetaldehyde (0.5 mmol, 1 eq.) is dissolved in 5 ml dichloromethane (abs.) under argon atmosphere. The solution is mixed with 110 mg (0.5 mmol, 1 eq.) iodosylbenzene. The suspension is stirred for 5 minutes at room temperature. Then 145 µl (0.55 mmol, 1.1 eq. 48% ether) BF3·OEt2 complex, which is diluted to 5 ml with dichloromethane, are injected within 10 minutes into the suspension. The reaction is stirred for 2 hours at room temperature, and then extracted with saturated sodium thiosulfate and with 20 ml diethyl ether. Sat. sodium thiosulfate was added and extracted with diethyl ether. The organic phase is shaken with saturated sodium hydrogen carbonate, and separated. The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate: 10 / 1). Cyclohexylphenylmethanone: yield: 57%, 2-Cyclohexyl-2-phenylacetic acid: yield: 9% (GC-yield) 2-Cyclohexyl-2-phenylacetic acid was detected by GC/MS-Ei analysis as a sideproduct.

O

Cyclohexylphenylmethanone: 1

H-NMR (400 MHz, CDCl3):

δ = 7.93-7.91 (m, 2H, Ar-H), 7.54-7.50 (m, 3H, Ar-H), 3.24 (tt, J = 11.2, J = 3.6, 1H, CHCHO), 1.89-1.20 (m, 10H, (-CH2-)5CH(Ph-)CHO).

24

GC/MS-Ei m/z (%): 189.2(4), 188.1(49), 186.9(2), 170.1(1), 147.0(1), 146.0(1), 133.1(12), 120.0(6), 107.1(2), 106.0(6), 105.0(100), 78.2(1), 77.1(13), 67.3(1), 55.3(4), 51.3(1).

O

OH

2-Cyclohexyl-2-phenylacetic acid GC/MS-EI m/z(%): 218.1(3), 137.1(4), 136.0(63), 133.1(4), 113.1(31), 112.1(26), 111.1(50), 107.0(40), 106.0(33), 105.0(81), 96.1(5), 95.1(100), 83.1(24), 79.1(8), 78.1(3), 77.1(30), 69.2(4), 67.2(7), 58.0(3), 55.2(13).

25

Synthesis of 2-cyclohexyl-2-phenylacetaldehyde

1) LiAlH4 N

O

2) Ethanol

To a suspension of 380 mg of LiAlH4 (10 mmol) in 10 ml diethyl ether (abs.) at 0 °C under argon, 1.38 g of ethanol (abs.) (1.74 ml, 30 mmol) is added dropwise: Hydrogen gas development is observed. 1.99 g of 2-cyclohexyl-2-phenylacetonitril (10 mmol) in 10 ml diethyl ether is added dropwise to the suspension. The gray suspension is stirred for an hour at r.t. (after an hour, TLC-controls). After end of the reaction, ice-water is added dropwise the reaction mixture under ice-bath, until end of gas formation. 5% of sulfuric acid is then added so long to the formed precipitate, until dissolution of the precipitate. The mixture is extracted three times with diethyl ether. The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1).

Yield: 25%

O

1

H-NMR (400 MHz, CDCl3):

δ = 9.70 (d, J = 3.51, 1H, -CHO), 7.42-7.14 (m, 5H, Ar-H), 3.24 (dd, J = 3.32, J = 9.60, CHCHO),

2.18-2.03

(m,

1H,

-CH2CH(CH2-)CHCHO),

1.89-0.77

(m, 10H, (-CH2-

)5CHCH(Ar)CHO).

26

Entry 11 O

O PhIO / HBF4 (48% in water) 1,4-dioxane-water: 1:1

Method B2 250 mg of 1,2,3,4-tetrahydronaphthalene-1-carbaldehyde (1.5 mmol, 1 eq.) is dissolved in 20 ml of 1,4-dioxane-water mixture (1:1). 515 mg of iodosylbenzene (2.25 mmol, 1.5 eq.) is added. 336 µL of aqueous tetrafluoroboric acid (2.57 mmol, 1.7 eq., d = 1.4 g / mL, 48%) is added dropwise within 10 minutes to the suspension. The suspension is stirred for three days at room temperature, the solution will be clearer. After three days, the reaction mixture is washed with saturated sodium thiosulfate solution and extracted twice with diethyl ether. The organic phase is washed with saturated sodium bicarbonate solution. The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 20 / 1 → 10 / 1).

27

Yield: 39%

O

1

H-NMR (300 MHz, CDCl3):

δ = 8.03 (dd, J = 7.86, J = 0.86 Hz, 1H, Ar-H), 7.46 (td, J = 7.50 Hz, J = 1.28 Hz, 1H, Ar-H), 7.34-7.22 (m, 2H, Ar-H), 2.97 (t, J = 6.11 Hz, 2H, -CH2COAr), 2.66 (t, J = 6.89 Hz, 2H, ArCH2CH2CH2COAr), 2.14 (q, J = 6,63 Hz, 2H, ArCH2CH2CH2COAr).

28

Synthesis of 1,2,3,4-tetrahydro-1-(methoxymethylene)naphthalene

MeO

O 1) n-BuLi, PhLi 2) Ph3PCH2OCH3Cl

6.2 ml n-BuLi (1.6 M in hexane) and then 14 ml of PhLi (1.8 M in ether) are added dropwise under inert gas to a suspension of 10.3 g of methoxymethylphosphoniumchlorid (30 mmol, 1.5 eq.) in 40 ml diethyl ether at -78 ° C. The ethanol/dry ice bath is removed. The yellow suspension is then stirred at 0 °C for another hour. The suspension will be brown. The suspension is again cooled to -78 °C. 2.92 g of α-tetralone (20 mmol) in 15 ml ether solution is added to the suspension. The mixture is stirred another two hours at r. t. The suspension will be orange. The mixture is poured into saturated ice-cold Ammonium chloride solution, and extracted three times with ethyl acetate. The organic phase is washed once with water and once with brine. The organic phase is dried over magnesium sulfate, and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 5:1). From three fractions, the second fraction is the product.

Yield: 55% (1.92 g)

MeO

1

H-NMR (400 MHz, CDCl3):

δ = 7.05 (m, 4H, Ar-H), 6.62 (t, J = 1,70, 1H, -C=CH(OMe)), 3.73 (s, 3H, -OCH3), 2.73 (t, J = 6.3, 2H, -CH2C=CH(OMe)), 2.51 (t, J = 6.6, 2H, ArCH2CH2CH2C=CH(OMe)), 1.83-1.73 (m, 2H, ArCH2CH2CH2C=CH(OMe)).

29

Synthesis of 1,2,3,4-tetrahydronaphthalene-1-carbaldehyde

MeO

O HCOOH

A mixture of 1.92 g (10.34 mmol) 1,2,3,4-tetrahydro-1-(methoxymethylene)naphthalene and 12 ml of formic acid are stirred at room temperature for 16 hours. The result solution is brown. After 16 hours stirring, the pH value of the reaction mixture is increased with saturated NaHCO3 solution to pH = 8.2, and extracted three times with ethyl acetate. The organic phase is washed once with water and once with brine. The organic phase is dried over magnesium sulfate, and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 50:1). From five fractions, the first fraction is the product.

Yield: 29% (475 mg) 30

O

1

H-NMR (300 MHz, CDCl3):

δ = 9.66 (d, J = 2.26 Hz, -CHO), 7.21-7.10 (m, 4H, Ar-H), 3.57 (m, 1H, -CHCHO), 2.76 (t, J = 6.47 Hz, 2H, -CH2CHCHO), 2.27-2.09 (m, 2H, ArCH2CH2CH2CHCHO), 1.84-1.72 (m, 2H, ArCH2CH2CH2CHCHO).

Entry 12 Me

O O

PhIO / HBF4 (48% in water)

Me

1,4-dioxane-water: 1:1

184 mg of 2-(naphthalen-3-yl)propanal (1 mmol, 1 eq.) is dissolved in 20 ml of 1,4-dioxanewater mixture (1:1). 330 mg of iodosylbenzene (1.5 mmol, 1.3 eq.) is added to the solution. 31

220 µl of HBF4 (311 mg, 1.7 eq., 48% in water) is added dropwise to the solution. The resulting suspension is stirred for five days at room temperature. The reaction mixture is washed with saturated sodium thiosulfate solution, and extracted twice with 50 ml diethyl ether. The organic phase is washed this time with saturated sodium bicarbonate solution, and separated. The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1). Yield: 42% O Me

1-(naphthalene-6yl)ethanone 1

H-NMR (400 MHz, CDCl3):

δ = 8.47 (s, 1H, Ar-H), 8.07-7.85 (m, 4H, Ar-H), 7.64-7.52 (m, 2H, Ar-H), 2.73 (s, 3H, ArCOCH3).

32

Synthesis of 2-(1-methoxyprop-1-en-2-yl)naphthalene

Me

Me O

Ph3PCH2OCH3Cl

OMe

t-BuOK, toluene, r.t.

6 g of 1-(naphthalen-6-yl)ethanone (35.25 mmol, 1eq.) is dissolved in 120 ml toluene under argon atmosphere. 18.1 g of methoxymethyltriphenylphosphoniumchloride (52.87 mmol, 1.5 equiv.) is added at room temperature. 6.5 g of potassium t-butoxide (58.16 mmol, 1.6 eq.) is added in four portions every 15 minutes to the suspension. The orange suspension is stirred until the mixture is deep red and clear. This takes three hours (TLC control). The solution is added dropwise to 300 ml water. The mixture is stirred for 10 min. and extracted three times with ethyl acetate. The organic layer is dried over magnesium sulfate. The solvent is removed. The product is isolated by the column chromatography (eluent: cyclohexane / ethyl acetate = 4:1). The product is a white solid.

Yield: 80 % (7.3 g)

Me OMe

1

H-NMR (300 MHz, CDCl3):

δ = 7.98-7.66 (m, 4H, Ar-H), 7.57-7.36 (m, 2H, Ar-H), 7.31-7.12 (dt, 1H, Ar-H), 6.60-6.22 (two “s”, J = 115 Hz, -C=CHOCH3), 3.75 (d, J = 14 Hz, 3H, -OCH3), 2.09 (d, J = 20 Hz, ArCH3C=CHOCH3).

33

Synthesis of 2-(naphthalen-6-yl)propanal

Me

Me OMe

1N HCl, EtOH/THF

O

7.2 g of 2-(1-methoxyprop-1-en-2-yl)naphthalene (36.36 mmol) is dissolved in 200 ml of THF. Under ice cooling, 1N HCl solution is added dropwise 200 ml every 10 min. in 4 portions to solution. Finally, 130 ml of ethanol (technical) is added to the solution. The solution is heated to 50 °C under reflux condenser for 6 hours. After cooling to room temperature, solid sodium bicarbonate is added to the colorless solution (CO2 development), until the pH value is neutral. The aqueous solution is extracted three times with ethyl acetate. The organic phase is washed once with water. The organic phase is dried over magnesium sulfate. The solvent is then removed. The product is then isolated by column chromatography

34

(eluent: cyclohexane / ethyl acetate = 4:1). Three fractions are obtained; the second fraction is the product.

Yield: 52% (3.44 g)

Me O

1

H-NMR (300 MHz, CDCl3):

δ = 9.77 (d, J = 1.35 Hz, 1H, Ar-CH3CHCHO), 7.89-7.79 (m, 4H, Ar-H), 7.68 (s, 1H, Ar-H), 7.52-7.46 (m, 2H, Ar-H), 7.32 (dd, J = 8.48 Hz, J = 1.76 Hz, 1H, Ar-H), 3.80 (q, J = 7.32, J = 6.95, 1H, -CH3CHCHO), 1.54 (d, J = 7.15, 3H, Ar-CH3CHCHO).

35

Entry 13

Ph

O

O

PhIO / HBF4 OEt2 (50% in ether)

Ph

CH2Cl2, r.t.

Ph

Ph

O + Ph

Ph

+

Ph

O OH

In a two-necked flask equipped with two bubble counters, which are connected and filled with the CO2 detection reagent (barium hydroxide) and with the CO detection reagent (PdCl2/HCl in water), respectively, 400 mg of 2,2-diphenylacetaldeyde (2.042 mmol, 1 eq.) is solved in 10 ml CH2Cl2 (abs.) under argon. 895 mg of iodosylbenzene (4.332 mmol 2.12 eq.) added to the solution. Undern stirring, 755 µl of tetrafluoroboric etherate complex (4.2 mmol, 2.10 eq., 50-55% in ether), diluted to th total volume of 10 ml in abs. CH2Cl2 is added dropwise using a syringe pump with a drop rate 4 ml/h to the suspension. First Gas development and then BaCO3 precipitate and Pd metal are observed in bubble counters. After two and half hours, the solution is washed with saturated sodium bicarbonate solution, and seperated. The organic phase is dried over sodium sulfate and filtered. The solvent is removed. The product is isolated by column chromatography (cyclohexane / ethyl acetate = 10:1).

Benzophenone yield: 85%, 2,2-Diphenylacetic acid yield : 5% and benzaldehyd yield: 6% (detected by GC/MS-Ei analysis as byproducts).

O Ph 1

Ph

H-NMR (400 MHz, CDCl3):

δ = 7.81 (d, J = 7.92, 4H), 7.59 (tt, J = 7.40, J = 1.37, 2H), 7.48 (tt, J = 7.12, J = 1.30, 4H).

36

GC/MS-Ei m/z(%): 183.1(12), 182.1(>89), 181.0(22), 154.1(3), 153.1(4), 152.1(6), 151.1(2), 150.1(1), 126.0(1), 106.1(8), 105.0(>100), 91.1(1), 87.1(1), 78.2(11), 77.1(>96), 76.1(23), 75.2(8), 74.1(9), 73.0(1), 64.2(1), 63.2(4), 62.2(2), 53.3(1), 52.3(4), 51.3(>67).

Diphenylacetic acid: GC/MS-Ei m/z(%): 213.2(2), 212.2(14), 184.2(2), 167.2(4), 166.2(100), 165.2(51), 164.2(2), 163.2(1), 152.2(4), 139.2(1), 115.2(1), 83.2(3), 82.2(4).

Benzaldehyde: GC/MS-Ei m/z(%): 107.2(7), 106.2(100), 105.2(89), 78.3(8), 77.2(52), 76.2(2), 75.2(1), 74.2(4), 63.3(1), 52.4(1).

37

Entries 14,15 O

O PhIO / HBF4 OEt2 CH2Cl2, r.t.

Method A1 In a two-necked flask equipped with two bubble counters, which are connected and filled with the CO2 detection reagent (barium hydroxide) and with the CO detection reagent (PdCl2/HCl in water), respectively, 388 mg of 9-formylfluorene (2 mmol, 1 eq.) is dissolved in 10 ml of CH2Cl2 (abs.) under argon. 440 mg of iodosylbenzene (2 mmol, 1 eq.) is than added to the solution. Under stirring, 404 µl of tetrafluoroboric etherate complex (2.3 mmol, 1.15 eq. 5055% ether), diluted previously to the total volume of 10 ml in CH2Cl2 (abs.), is added dropwise within three minutes to the suspension. BaCO3 precipitate and Pd metal are observed in bubble counters. The reaction mixture is washed with saturated sodium bicarbonate solution. The solution is filtered, and GC/MS-Ei is measured. The solvent is removed and the product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1). Two fractions are obtained. The second fraction is the product.

Yield: 70% (255 mg)

O

1

H-NMR (300 MHz, CDCl3):

δ = 7.58 (d, J = 7.6 Hz, 2H, Ar-H), 7.47-7.36 (m, 4H, Ar-H), 7.29-7.21 (m, 2H, Ar-H).

38

GC/MS-Ei m/z(%): 181.0(13), 180.0(100), 153.0(3), 152.0(36), 151.0(16), 150.0(12), 126.0(3)

Method B1 In a two-necked flask equipped with two bubble counters, which are connected and filled with the CO2 detection reagent (barium hydroxide) and with the CO detection reagent (PdCl2/HCl in water), respectively, 388 mg of 9-formylfluorene (2 mmol, 1 eq.) is dissolved in 10 ml CH2Cl2 (abs.). 440 mg of iodosylbenzene (2 mmol, 1 eq.) is added to the solution. Under stirring, 404 µl of tetrafluoroboric acid (3.1 mmol, 1.15 eq., 48% in water) is added in three minutes to the suspension. The reaction mixture is stirred 24 hours at r.t. vigorously. BaCO3 precipitate and Pd metal are observed in bubblers. The solution is washed with saturated sodium bicarbonate solution and seperated. The organic phase is dried over sodium sulfate and filtered. A sample is taken for GC/MS analysis. The solvent is removed under reduced pressure. The product is isolated by column chromatography (eluent: mixture of cyclohexane / ethyl acetate = 10:1). Two fractions are obtained. The second fraction is the product.

Yield: 87 % (313 mg). 39

Synthesis of (9H-fluorene-9-yliden)methanol

O 1) potassium ethanolate 2) ethyl formate

First of all, potassium ethanolate salt is prepared. 12 g of potassium is cuted in cyclohexane bad, and this was added portionswise under inert gas and reflux condenser to enough of ethanol in 250 ml two-necked flask so that the solvent boiling continuously, until all potassium reacts (ca. 20 ml ethanol abs.). The solvent are then removed under high vacuum. Under inert gas, diethyl ether (75 ml) and than 15 g of fluorene (0.09 mol, 1 eq.) is added to the freshly prepared pottasium ethanolate.. 20 g of ethyl formate (0.27 mol, 3 eq.) dissolved in 50 ml ether, is added dropwise over two hours to strongly red-colored solution, the whole solution stirred 4 hours at room temperature (TLC control).The reaction mixture is hydrolyzed slowly with 75 ml water, and extracted three times with ether. The organic phase is dried over sodium sulfate, filtered and the solvent removed. The dark red oil is distilled under high vacuum (The product is very unstable and polymerized with the time. It must be stored at -20 °C).

Yield: 80%

O

1

H-NMR (400 MHz, CDCl3):

δ = 9.2 (d, 1H, Ar-CHO), 7.85 (d, 2H, Ar-H), 7.6 (d, 2H, Ar-H), 7.5 (t, 2H, Ar-H), 7.39 (t, 2H, Ar-H), 4.75 (d, 1H, (Ar)2-CH-CHO).

40

GC/MS-Ei m/z(%): 195.0(3), 194.0(22), 167.0(7), 166.0(67), 165.0(100), 163.9(12), 162.9(15), 161.9(1), 138.9(4).

Entries 16,17 O

O PhIO / HBF4 OEt2

O

O

Method A1 500 mg of 9,10-dihydroanthracen-9,10-dicarbaldehyde (2.12 mmol, 1 eq.) is dissolved in 10 ml dichloromethane (abs.). 933 mg of PhIO (4.24 mmol, 2 eq.) is added. 745 µL of tetrafluoroboric acid etherat complex (4.24 mmol, 2 eq., 50-55% ether) is diluted to 10 ml of dichloromethane. This is added dropwise to the suspension. The reaction mixture is stirred for two hours at room temperature (TLC control). The solution is washed with saturated sodium bicarbonate and extracted three times with each 10 ml of dichloromethane. The organic phase is dried over sodium sulfate, filtered, and concentrated. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate = 10:1).

41

O

O

Yield: 93 % (410 mg) 1

H-NMR (300 MHz, CDCl3):

δ = 8.32 (dd, J = 3.3 Hz, J = 5.7 Hz, 4H, Ar-H), 7.81 (dd, J = 3.3 Hz, J = 5.7 Hz, 4H, Ar-H).

GC/MS-Ei m/z(%): 209.2(3), 208.2(26), 207.1(2), 181.2(12), 180.1(100), 179.1(4), 153.2(8), 152.1(75), 151.1(36), 150.1(19), 126.1(6), 125.1(2), 103.9(1), 102.1(2), 99.1(1), 98.1(1), 90.1(6), 87.1(1), 77.2(4), 76.2(23), 75.2(7), 74.1(3), 63.2(5).

Method B 1 500 mg of 9,10-dihydroanthracen-9,10-dicarbaldehyde (2.12 mmol, 1 eq.) is dissolved in 10 ml dichloromethane. 933 mg of PhIO (4.24 mmol, 2 eq.) is added. 854 µL (4.24 mmol, 2 eq., 48% solution in water) HBF4, diluted previously to the total volume of 10 ml in 42

dichloromethane, is added dropwise to the suspension. The reaction mixture is stirred for 2 hours at room temperature (TLC control). The solution is washed with saturated Sodium bicarbonate and extracted three times with each 10 ml of dichloromethane. The organic phase is dried over sodium sulfate, filtered, and concentrated. The product is isolated by column chromatography (eluent: cyclohexane / ethyl acetate: 10 / 1).

Yield: 91 % (400 mg)

Synthesis of 9,10-dihydroanthracen-9,10-vinylencarbonate

O

O

O +

O O

O ∆, 8 h

A mixture of 3.1 ml of vinylene carbonate (0.05 mol, 5 eq., d = 1.36 g/mL) and 1.78 g (0.01 mol, 1 eq.) of anthracene are heated for 8 hours under argon. Black solution is formed. When the solution-temperature reaches to 50 °C, the solution is diluted with 30 ml of methanol (abs.), whereby the non reacted vinylene carbonate is solved in methanol. The solution is allowed to cool to room temperature. The product is crystallized. The crystals are filtered, and are washed with cold methanol, and the product is dried under high vacuum.

Yield: 90 % (2.36 g)

Melting Point: 259-260°C

O

O

O

1

H-NMR (300 MHz, CDCl3):

δ = 7.39 (m, 4H, Ar-H), 7.26 (m, 4H, Ar-H), 4.89 (bs, 2H, (-CH-CH-COCOCO), 4.70 (bs, 2H, Ar2-CH2(CH(O)CH(O)CO)).

43

Synthesis of 9,10-Dihydroanthracen-9,10-ethylendiol

O O

OH

O

KOH

OH

2.36 g of anthracene cyclic carbonate (8.94 mmol, 1 eq.), 2.06 g (mmol, 4.16 eq.) potassium hydroxide are heated at 70-75°C in 2.7 ml water and in 22 ml ethanol for two hours. The suspension is filtered hot, and 6 ml of water is added to the solution, and then cooled to 0°C, whereby the product crystallizes. The crystals are filtrated, and washed with water.

Yield: 80% (1.69 g)

Melting Point: 202-204°C

44

OH OH

1

H-NMR (300 MHz, CDCl3):

δ = 7.37 (dd, J = 3.2 Hz, J = 5.4 Hz, 2H, Ar-H), 7.31 (dd, J = 3.2 Hz, J = 5.4 Hz, 2H, Ar-H), 7.20 (dd, J = 3.2 Hz, J = 5.4 Hz, 2H, Ar-H), 7.15 (q, 2H, Ar-H), 4.41 (s, 2H -(-CHCOH)2), 4.05 (s, 2H -(-CH(CHCOH)2)2), 2.21 (s, 2H, -(COH)2).

45

Synthesis of 9,10-Dihydroanthracen-9,10-dicarbaldehyde

OH OH

O Pd(OAc)4 CH3COOH O

To a solution of 1.69 g of cyclic diol (7.09 mmol, 1 eq.) in 28 ml of acetic acid is added 3.46 g (7.81 mmol, 1.1 eq.) Pb(OAc)4 in portions. After 20 min. stirring at room temperature, the solution is colored from colorless to yellow. The consumption of palladium acetate can be detected with iodine-starch test paper. The whole solution is added to dichloromethane, it is washed with dilute sodium hydroxide solution until the pH-paper shows neutral. The organic phase is separated, dried over sodium sulfate, filtered and the solvent is removed.

Yield: 90% (1.52 g)

Melting Point: 144-146°C O

O 1

H-NMR (300 MHz, CDCl3):

δ = 9.45 (d, 2H, J = 2.3 Hz, (-CHO)2), 8.75 (dd, J = 3.2 Hz, J = 6.9 Hz, 4H, Ar-H), 7.70 (dd, J = 3.2 Hz, J = 6.9 Hz, 4H, Ar-H), 4.96 (d, J = 2.3 Hz, 2H, (ArCHCHO)2).

46

Preparation of substrates was carried out according to the following literatures:

(a) Lodge, E. P.; Heathcock C. H. J. Am. Chem. Soc. 1987, 109, 3353. (b) Roda, G.; Danieli B. Tetrahedron Asymm. 1999, 10, 3939. (c) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277. (d) Yamazaki, J.; Watanabe, T.; Tanaka, K. Tetrahedron Asymm. 2001, 12, 669. (e) Garnier, J. M.; Robin, S.; Rousseau, G. Eur. J. Org. Chem. 2007, 20, 3281. (f) Hoffmann, S.; Nicoletti, M.; List B. J. Am. Chem. Soc. 2006, 128, 13074. (g) Ellingboe, J. W.; Lombarto, L. J.; Alessi, T. R.; Nguyen, T. T.; Guzzo, F. J. Med. Chem. 1993, 36, 2485. (h) Wenkert, E.; Mueller, R. A.; Reardon, Jr. E. J.; Sathe, S. S.; Scharf, D. J.; Tosi, G. J. Am. Chem. Soc. 1970, 92, 7428. (i) Hurst, J. R.; Wilson, S. L.; Schuster, G. B.; Tetrahedron 1985, 41, 2191. (j) Ahlbrecht, H.; Funk, W.; Reiner M. Th. Tetrahedron 1976, 32, 479. (k) Murdock, K. C.; Child, R. G.; Lin, Y-i.; Warren, J. D.; Fabio, P. F. J. Med. Chem. 1982, 25, 505. (l) Kikuchi, H.; Kogure, K.; Toyoda, M. Chem. Lett. 1984, 341. (m) Wislicenus, W.; Waldmueller, M. Chem. Ber. 1909, 42, 789. 47