Enantioselective Synthesis of Primary Amines via Grignard Additions to Stereogenic N-(α-Phenyl-β-(benzyloxy)ethyl)nitrones

Article abstract of DOI:10.1021/jo00298a019

Addition of a wide range of Grignard to C-aryl- and C-alkyl-N-(α-phenyl-β-(benzyloxy)ethyl)nitrones (4-7) occurred with high diastereoselectivity (90:10 to 97:3 ratios) and good yields (56 - 97percent).Notable exceptions are allyl- and (o-methoxyphenyl)magnesium bromides (low selectivity but satisfactory yields) and isopropyl- and tert-butylmagnesium chlorides (high selectivity but 33 - 34percent 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 provenby 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-(α-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 CD2Cl2.Enantioselective syntheses of (S)-α-phenylethylamine (94percent ee) and (S)-2-heptylamine (82percent ee) were accomplished in five steps (33-39percent overall yields) from optically pure (S)-nitrones 4 and 7.