ENANTIOSELECTIVE SYNTHESIS OF PRIMARY AMINES VIA GRIGNARD ADDITIONS TO STEREOGENIC N-(ALPHA-PHENYL-BETA-(BENZYLOXY)ETHYL)NITRONES

Addition of a wide range of Grignard to C-aryl- and C-alkyl-N-(a-phenyl-|(β-(benzyloxy)ethyl)nitrones (47) occurred with high diastereoselectivity (90:10 to 97:3 ratios) and good yields (56-97%). Notable exceptions are allyl- and (o-methoxyphenyl)magnesium bromides (low selectivity but satisfactory yields) and isopropyl- and tert-butylmagnesium chlorides (high selectivity but 33-34% yields) with C-phenylnitrone 4. The relative stereochemistry of hydroxylamine adducts 8a,b (from reaction of 4 with CH3MgBr) and 19a,b (from C-pentylnitrone 7 with MeMgBr) was proven by various correlations and/or by degradation to enantiomerically enriched amines. The other stereochemical assignments are based upon 1H NMR spectral and polarity correlations and/or by analogy to the two proven cases. The configuration of the major product can be rationalized by assuming that the Grignard reagents attack the nitrone face opposite to the pseudoequatorial N-(a-phenyl) group in a six-membered magnesium chelate (27–28). 1H NMR spectral evidence indicates that a 1:1 complex of nitrone 4 and magnesium bromide exists in a chelated structure (29B) in CD2C12. Enantioselective syntheses of (S)-a-phenylethylamine (94% ee) and (S)-2-heptylamine (82% ee) were accomplished in five steps (33-39% overall yields) from optically pure (S)-nitrones 4 and 7. © 1990, American Chemical Society. All rights reserved.