Selenium-induced Cyclofunctionalisation of Allylic 0

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452

J . CHEM. SOC., CHEM. COMMUN.,

1989

Selenium-induced Cyclofunctionalisation of Allylic 0-Methyl Isoureas: Synthesis of lmidazolines (4,5-Dihydroimidazoles) and 5,6-Di hydro-I,3-oxazines Raimundo Freire, Elisa 1. Leon, Jose A. Salazar," and Ernest0 Suarez lnstituto de Productos Naturales Organicos, C.S.I.C., La Laguna, Tenerife, Spain lmidazolines are prepared by treatment of allylic 0-methyl isoureas with phenylselenenyl chloride in the presence of silica gel; when the organoselenium-mediated cyclisation is performed with phenylselenenyl trifluoromethanesulphonate and trifluoromethanesulphonic acid 5,6-dihydro-I ,3-oxazines are obtained.

In the preceding communication1 we described the syntheses of 2-oxazolines by reaction of allylic ureas with phenylselenenyl chloride , and by sequential treatment of (3-phenylseleno ureas with trimethyloxonium tetrafluoroborate and di-isopropylethylamine. Our attempts to modify the regioselectivity or to carry out this selenium-induced cyclisation by formation of a carbon-nitrogen bond were unsuccessful. In the present paper we report that these goals can be accomplished when 0-methyl isoureas are used as starting materials. As shown in Scheme 1 and Table 1, depending on the method of cyclofunctionalisation used, imidazolines or 5,6-dihydro-l,3-oxazines can be obtained by 5-exo-N-cyclisation or 6-endo-O-cyclisation, respectively, of the 0-methyl isoureas. These reactions, together with the afore-mentioned, compose an interesting approach to the stereoselective syntheses of 1,2- and 1,3-arninoalcohols, and vicinal diamines. Thus, treatment (method A) of the 0-methyl isourea (3) (1 mmol in 50 ml of CHC13), in the dark, under argon, with phenylselenenyl chloride (2 mmol) in the presence of recently oven-dried silica gel (Merck, 0.063-0.2 mm, 4 g) at 25 "C for 6 h gives the imidazoline (4)f as a single stereoisomer (68% yield), and starting material (3) (26% yield).* The stereochemical course of the reaction contrasts with that observed in the selenium-mediated cyclisation of the related allylic urea (1) in which both stereoisomers (trans : cis

t (4): 1.r. (CHC13) 3500, 3405, 1670 cm-1; 'H n.m.r. (C6D6) 6 3.14, 3.56 (2H, ABX,J 12.8,6.0,7.5Hz), 3.53 (3H, s), 4.31 ( l H , dq,J4.0, 6.0, 7.5 Hz), 4.74 ( l H , brd, J 4.0 Hz), 6.9-7.4 (10H); 13C n.m.r. (C6D6) 6 32.8 (CH,), 53.47 (CH, CH,), 67.42 (CH); m/r 344.0586, 346.0583 ( M + ) .

2 : 1) are formed. This behaviour could be explained by the existence of an equilibrium between the 0-methyl isourea and the imidazolines that leads to the exclusive isolation of the most stable trans-cycloadduct . The reaction temperature proved to be critical and must be carefully adjusted for each compound, as shown in Table 1; when this is diminished the undesired (3-hydroxyselenides may be the sole products obtained (compare entries 2 and 3). But when the reaction temperature is increased the initially formed imidazoline is mainly transformed into the starting O-methyl isourea. In a typical procedure for the preparation of 5,6-dihydro1,3-oxazines (method B), phenylselenenyl chloride (1.5 mmol) was added dropwise, at O"C, in the dark and under argon, for 15 min, to a well stirred suspension of silver

SePh

I

NH

NH2

Scheme 1. Tf = S0,CF3.

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1989

453

Table 1. Cyclofunctionalisation of allylic O-methyl isoureas.

Isourea

Methoda A

Temp./"C 25

Time/h 6

2 3

A Ab

25 50

16 10

4 5 6

A B B

30 30 45

18 1 3

7 8

B C

25 45

2 7


Entry 1

(3)

a The reactions were carried out in the dark and under argon. Method A : isourea (1 mmol), CHCI, (50 ml), silica gel (4 g), PhSeCl (2 mmol). Method B: isourea (1 mmol), 1,2-dichloroethane (50 ml), silica ge1/1&20% water (4 g), PhSeCl(l.5 mmol), CF3S03Ag (1.5 mmol), CF3S03H (1 mmol). Method C: isourea (1 mmol), 1,2-dichIoroethane (50 ml), silica ge1/10-20% water (4 g), N-phenylselenophthalimide(2 mmol), CF3S0,H (1.5 mmol), HBF4 (1 mmol). 1,2-Dichloroethane was used as solvent. c Ratio erythro: threo 3 : 2.

(11 1

NH

CBH,,

I phseq II

Meo-!&

MeO-C-YH

Method 6

H' 0

A

PhS e H

w '

A

(8)

(12)

(9)

*

.

KOH

aq or A 1 0 PhSe"

(16)

NH

Scheme 2. Tf = S02CF3.

II

NH-C-OM

U

SePh (10)

(11)

trifluoromethanesulphonate (1.5 mmol) in 1,2-dichloroethane (25 ml) and the mixture was allowed to warm to room temperature (15 min). Then, the 0-methyl isourea (3) (1 mmol) in 1,2-dichloroethane (25 ml), trifluoromethanesulphonic acid (1 mmol), and silica ge1/20% water (4 g) were sequentially added, and the mixture was stirred at 30°C for 1 h. Usual workup and aluminium oxide (neutral, activity 11-111) column chromatography gave ( 5 ) as a 3 : 2 mixture of stereoisomers.$ The silver salt reagent can be avoided using

Prn-fB"n NH- C- OMe

P h S e O * k N

II

NH

(12)

(13) SePh

Prn*hn

O Y N NH2

(14 1

$ The highly electrophilic phenylselenenyl trifluoromethanesulphonate has been successfully used in selenium-induced cyclisations of unsaturated carboxylic acid derivatives.3 ( 5 ) : Unresolved mixture of stereoisomers; i.r. (CHCI,) 3500, 3390, 1660 cm-I; mlz 330.0367, 332.0355 ( M + ) .t r u ~ ( 5 )IH : n.m.r. (CDC13) 6 4.55 ( l H , d, JS.OHz), 4 . 4 - 4 . 1 (4H, both stereoisomers), 3.40 ( l H , m); 13C n.rn.r. (CDC13) 6 154.29 (C), 67.50 (CH,), 58.95 (CH), 41.73 (CH). cis-(5):IH n.m.r. (CDC1,) 6 4.98 ( l H , d , J 5.0 Hz), 4.4 4.1 (4H, both stereoisomers), 3.74 ( l H , m); I3C n.m.r. (CDC13) 6 154.61 (C), 66.11 (CH,), 56.33 (CH), 40.35 (CH).

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454 method C, as indicated in entry 8. However, longer reaction times and higher temperatures are required. Specially noteworthy is the observed endo cyclisation of the monosubstituted alkene (3), an electronically unfavourable process. Two intermediates (15) and (16) (Scheme 2) were isolated in the cyclofunctionalisation of (11). The presence of the trifluoromethanesulphonyl group in (16) is inferred from i.r. (Y,, 1280, 1020 cm-1) and 13C n.m.r. (6 120.23, 9). We have no reasons to explain the exclusive 6-endo cyclisation noted under these conditions, but it must be related to the steric hindrance in (A) (Scheme 2). This work was supported by the Investigation Programme No. PB0406 of the Dlreccion General de Investigacih

J. CHEM. SOC., CHEM. COMMUN.,

1989

Cientifica y TCcnica. E. I. L. thanks the Ministerio de Educaci6n y Ciencia for a fellowship.

Received, 3rd October 1988; Corn. 81039391

References 1 C. Betancor, E. I. Leon, T. Prange, J. A. Salazar, and E. SuBrez, preceding communication. 2 For a bromo-based method see: H. Kohn and S. H. Jung, J . Am. Chem. SOC.,1983, 105,4106. 3 S. Murata and T. Suzuki, Chem. Lett., 1987, 849.