Influence of ring size on the reduction of vinylogous urethanes. Applications to the synthesis of lupinine and epilupinin

Joseph P Michael,Claudia San Fat,Gillian L Nattrass,Charles B De Koning,Christian V Stevens

doi:10.3998/ark.5550190.0003.908

Abstract

Short syntheses of the quinolizidine alkaloids lupinine and epilupinine via alkyl 3-(2-thioxo-1- piperdinyl)propanoates and the vinylogous urethanes prepared from them are reported. Alkyl piperidin-2-ylideneacetates were found to undergo reduction of the C=C bond with lithium aluminium hydride more readily than their pyrrolidin-2-ylideneacetate analogues, a finding that is in line with reports of the relative reactivities of double bonds exocyclic to five- and six- membered rings.

Highlights

The general approach to alkaloid and antibiotic synthesis explored in these laboratories over a number of years is based on the use of β-acylated enamines and related compounds as scaffolds upon which to build the more complex architectures found in a representative range of alkaloidal families.[1]
The vinylogous urethanes on which this study is based were prepared in two steps from pyrrolidine-2-thione12 7a or piperidine-2-thione12 7b, conjugate addition of which to esters of acrylic acid was readily achieved by stirring the reactants together in dry tetrahydrofuran at 40 °C in the presence of a catalytic quantity of sodium hydride[13] or sodium hydroxide (Scheme 2)
A critical feature of the previously reported synthesis of lupinine shown in Scheme 1 was the chemoselective reduction of the saturated ester group of intermediate 4 while leaving the vinylogous urethane untouched

Summary

Introduction

The general approach to alkaloid and antibiotic synthesis explored in these laboratories over a number of years is based on the use of β-acylated enamines (enaminones) and related compounds as scaffolds upon which to build the more complex architectures found in a representative range of alkaloidal families.[1].

Results

Conclusion