A Highly Effective One-Pot Bicycloannulation Methodology for the Synthesis of Berban and Yohimban Systems Based on Organotin-Mediated Three-Component Coupling (N-Acylative Pentadienylation of C=N Bonds)

Article abstract of DOI:10.1021/jo00057a028

A highly effective bicycloannulation methodology for the synthesis of berban and yohimban alkaloid systems is described.Three-component coupling reactions of 2,4-pentadienyltin reagents with C=N bonds and α,β-unsaturated acyl chlorides furnish bicycloannulated products in a one-pot operation.For example, the reactions of 2,4-pentadienyltributyltin(1) with isoquinoline derivatives activated by acryloyl chloride afford the tetracyclic (+/-)-allo-berban systems stereoselectively.Similarly, the reaction of 1 with 3,4-dihydro-β-carboline (11) gives the pentacyclic (+/-)-allo-yohimban system.The reaction is not affected by the stereochemistry of the 2,4-pentadienyltin reagent.A new substituted 2,4-pentadienyltin reagent, 3-(hydroxymethyl)-2,4-pentadienyltrimethyltin (19), is prepared via 3-(hydroxymethyl)pentadienyl dianion.The three-component coupling reaction of 19 with 11 and acryloyl chloride affords the (+/-)-allo-16-(hydroxymethyl)yohimban system, from which (+/-)nitraraine is readily synthesized.In addition, 1,3-asymmetric induction leads to the high diastereoselectivity realized in bicycloannulation (up to 94percent de) when (S)-3-<(tert-butyldimethylsiloxy)methyl>-3,4-dihydroisoquinoline (27), which is readily derived from L-phenylalanine, is used in the three-component coupling reaction.