An application of the intramolecular Heck reaction: A new strategy in the synthesis of Hasubanan alkaloids. Preparation of unsymmetrical biaryls via the Stille cross-coupling reaction: Synthesis of highly functional intermediates towards the synthesis of vindoline.

摘要

The intramolecular Heck reaction was used to construct the core structure of the hasubanan alkaloids. The application of the Heck reaction constitutes a new synthetic pathway to the hasubanan alkaloid skeleton and is the first example of the formation of two adjacent quaternary carbon centers via a 6-exo cyclization process. Other highlights of this synthesis are (a) the asymmetric Birch reduction-alkylation of a L-prolinol derived 5-methoxy-2-[2-(4-methoxyphenoxy)ethyl benzamide 113 with 2-[5-benzyloxy-2-iodo-4-methoxyphenyl]-iodoethane 199 to give 1,4-cyclohexadiene 200, (b) enol ether hydrolysis of 200 to give cis and trans hydroxyl amides 202 and (c) a chemoselective Hofmann-like rearrangement to afford carbamate 206.; The Stille cross-coupling reaction was employed in the synthesis of a highly functional biaryl intermediate. The Stille cross-coupling reaction of 2-methoxy-5-(tributyl-stannanyl)-benzoic acid methyl ester 259 and 2-bromo-5-methoxy-phenyl carbamic acid methyl ester 236 gave 235b in excellent yields. The highly functional intermediate 235b contains a protected amine functionality that would be used in the formation of the indole ring present in the alkaloid vindoline.