Synthesis of γ-azido-β-ureido ketones and their transformation into functionalized pyrrolines and pyrroles via staudinger/aza-wittig reaction

摘要

A simple two-step procedure yielding γ-azido-β-ureido ketones or/and their cyclic isomers, 6-(1-azidoalkyl)-4-hydroxyhexahydropyrimidin-2- ones, has been developed. The synthesis includes three-component condensation of acetals of 2-azidoaldehydes with urea or methylurea and p-toluenesulfinic acid in aqueous formic acid followed by reaction of the obtained N-[(2-azido-1-tosyl) alkyl]ureas with sodium enolates of α-functionalized ketones. The azido ketones or their cyclic isomers are transformed into ureido-substituted Δ~- or/and Δ~2-pyrrolines via Staudinger/aza-Wittig reaction promoted by PPh_3. The obtained pyrrolines are converted into 3-functionalized 1H-pyrroles via elimination of urea under acidic conditions. Convenient one-pot syntheses of 1H-pyrroles starting from N-[(2-azido-1-tosyl)alkyl]ureas or γ-azido-β-ureido ketones have been also developed.