Dimethyl(methylene)ammonium salts: Mannich reagents

Abstract

(A) Trimethylsilyl enol ethers derived from ketones and aldehydes add to salts 1-3 and the reaction proceeds via a silyloxonium ion which hydrolyzes on aqueous workup. This method has been used for the synthesis of the two regioselective Mannich bases of 2-methylcyclohexanone.8 (B) Enolates generated by the decomposition of α-diazo ketones in the presence of trialkylborane provide Mannich bases in excellent regioselectivity from simple unsymmetrical ketones.9 (C) Salts 1-3 serve as excellent one-carbon equivalents for an α-methylene group. The dimethylamino group can be easily eliminated by quaternization with iodomethane followed by treatment with base or direct purification on silica-gel chromatography. This method was successfully applied to an elegant synthetic approach toward Xestocyclamine A.10 (D) Electron-rich aromatic and heteroaromatic compounds have been shown to undergo condensation reactions with salts 1-3 with excellent regiocontrol. Monosubstituted phenols, which usually afford mixtures of ortho, para and diaminomethylated products under conventional methods, react with 1 or 2 to afford the orthoproduct in excellent yield, presumably because of ion pair interaction between the phenoxide anion and the iminium salt.11 (E) Aryl and heteroaryl stannanes react with salt 1 to afford an ipso-substitution product of the stannyl group. The directing effect of tin allows for the preparation of Mannich bases with an ipso substitution pattern which is not ordinarily obtained under traditional procedures.12 (F) Analogous to the enolate additions, organometallic reagents such as Grignards,13 cuprates14 and lithium reagents15 add to salt 2 to produce N,N-dimethylamine. Similarly, the salts have been added to hydrazines 16 and oximes.17.