jo061032t_si_004.pdf (914.51 kB)
General Strategy for the Syntheses of Corynanthe, Tacaman, and Oxindole Alkaloids
journal contribution
posted on 2006-08-18, 00:00 authored by Alexander Deiters, Martin Pettersson, Stephen F. MartinWe report herein the total synthesis of the corynanthe alkaloid dihydrocorynantheol and the formal
syntheses of the indole alkaloids tacamonine, rhynchophylline, and hirsutine. The strategies for assembling
the corynanthe and tacaman skeletal frameworks comprised of both the classical ABD → ABCD and
ABC → ABCD approaches wherein the variously substituted piperidinone D-rings were formed via ring-closing metathesis (RCM) followed by a 1,4-addition to introduce the requisite side chain at C(15). Since
1,4-additions to α,β-unsaturated lactams represent an underdeveloped field, we conducted a series of
studies with two unsaturated lactams employing organocuprates and metal enolates as the nucleophiles.
These studies revealed that organocuprates derived from Grignard reagents and either stoichiometric
amounts of CuCN or catalytic amounts of CuBr·DMS complex are excellent nucleophiles for such
additions; TMSCl was a crucial additive for optimizing these reactions. The anion derived from ethyl
1,3-dithiolane-2-carboxylate was also an excellent nucleophile in these 1,4-additions, although the
stereochemistry of such 1,4-additions to carboline-derived, unsaturated lactams was sensitive to substitution
on the indole nitrogen atom. The ABD → ABCD approach to these alkaloids featured a novel one-pot
sequence of an RCM reaction and a zirconocene-catalyzed carbomagnesation followed by a second RCM
to generate the D-ring.