ALPHA-AMINO CARBANION EQUIVALENTS. METALATION AND ALKYLATION OF TRISUBSTITUTED FORMAMIDINES

N'-tert-Butyl and cyclohexyl formamidines were prepared either from imidic esters of tertiary formamides or by transamination of N,N-dimethyl trisubstituted formamidines. Amidines derived from dialkyl amines, N-methyl aniline, 1,2,3,4-tetrahydroisoquinoline, indoline, 1,2,3,4-tetrahydroquinoline, and 1,2,3,4-tetrahydro-(beta)-carboline were studied. All were deprotonated adjacent to the amino nitrogen with organolithium reagents (usually either sec- or tert-butyllithium). Use of a methoxymethyl blocking group on the indole nitrogen of (beta)-carboline enabled deprotonation in the 1-position of this system. Reactions of the intermediate carbanions with aldehydes, alkyl and benzyl halides, and other miscellaneous electrophiles occurred efficiently. The (alpha)-substituted amidine products were converted to amines by either hydrolysis, reduction, or hydrazinolysis. The applicability of the overall process for elaborated alkaloid synthesis was demonstrated by several of the investigated systems.