Regio-, Stereo-, and Enantioselectivity in the Electrophilic Reactions of 2-Amino-4-phenyl-3-butenenitriles

Article abstract of DOI:10.1021/jo00059a027

The allylic anion generated from 2-(N-methylanilino)-4-phenyl-3-butenenitrile (1) reacted with iodomethane and 3-bromo-1-chloropropane in THF/HMPA to give γ-substituted products exclusively, predominantly in the 2Z-configuration.Substitution of the N-methylanilino group with the methyl ether of L-(-)-ephedrine resulted in the generation of chiral aminonitrile 2.Lithiated 2 reacted sluggishly in THF with allyl bromide and benzyl chloride in the absence of HMPA to give the γ-substituted products predominantly in the 2Z-configuration, with little diastereoselectivity.The aminonitrile 3 prepared from cinnamaldehyde, L-(-)-ephedrine, and KCN was lithiated with 2 equiv of LDA resulting in high facial selectivity (76 - 100 percent diastereomeric excess) in alkylations in the presence of HMPA and LiI.Lithiated 3 reacted with propionaldehyde, benzaldehyde, and p-bromobenzaldehyde at -78 deg C to give the γ-addition products, predominantly in the 4R-configuration (64 -78 percent de).The stereochemistry of the isomers of each product was determined by chemical correlation and spectral methods including analyses of the CD spectra and X-ray diffraction.A bicyclic transition state C wherein lithium is chelated by both amino and alkoxy groups is proposed to interpret the observed stereoselectivity.