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

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.