Tuning the Acceptors in Catalyzed Cyclizations Initiated by Allenes. Silylstannylation/Cyclization of Allene-Aldehydes for Synthesis of Polyalkylated Indolizidines Including 223A Congeners

Starting from succinamide and 1,2-heptadiene-4-ol, a racemic allene-aldehyde substrate, 20, suitable
for R3SiSnR‘3-mediated cyclization was synthesized in six steps and in 21% yield. Stereoselective
cyclization (relative cis configuration at the new stereogenic centers of the homoallyl alcohol
generated) proceeded smoothly, giving a mixture of indolizidinols bearing five contiguous stereocenters in a combined yield of 80%. Relative configurations of each of the products were
unequivocally established by a combination of 2D NMR experiments and single-crystal X-ray
analysis. The major indolizidinol obtained in 32% yield was elaborated into indolizidine 5,8-epi-indolizidine 223A via a five-step reaction sequence in 32% overall yield. The second major component
(24%) of the key cyclization yielded, in four steps, indolizidine 6,8-epi-223 in 14% yield. Even though
revision of the initially postulated structure foiled our original synthetic plans for the natural
product, indolizidine 223A, the new stereoselective cyclization strategy and several selective
transformations of the indolizidine derivatives reported here may find further applications for the
synthesis of highly alkylated indolizidine and other related alkaloids.