Dipole-Stabilized Carbanions: The α' Lithiation of Piperidides

Article abstract of DOI:10.1021/ja00316a033

The α' lithiations and subsequent electrophilic substitutions of two series of piperidides are reported.In the cases of 2,4,6-triisopropylbenzopiperidide (5) and 4-tert-butyl-2,4,6-triisopropylbenzopiperidide (6) lithiations and electrophilic substitutions give α'-substituted products, as shown in Table I, which cannot be cleaved. 2,2-Diethylbutanopiperidide (19), 4-phenyl-2,2-diethylbutanopiperidide (20), and N,N-diethyl-2,2-diethylbutanamide (18) undergo α' lithiation and electrophilic substitution as shown in Table II to give products that can be cleaved to the substituted amines.This sequence thus provides the (α-lithioalkyl)alkylamine synthetic equivalent from secondary amines.The addition of the α'-lithiated piperidides from 20 to aldehydes is shown to provide equatorial substitution with erythro and threo isomers of the amido alcohol 31 produced in a 1:1 ratio.Exclusive conversion to an equatorial threo amino ester 36t is observed on treatment with strong acid.All four possible equatorial-axial and erythro-threo isomers of the amino alcohol 34 can be obtained by appropriate manipulations.The formation of the equatorially substituted products from 6 and 20 and of syn products from N,N-diethyl-2,4,6-triisopropylbenzamide (4) is noted to be consistent with oxygen-lithium complexation and dipole stabilization as important factors in α' lithiation.