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.

以丁二酰胺（succinamide）与1,2-庚二烯-4-醇（1,2-heptadiene-4-ol）为起始原料，经6步反应以21%的总收率合成了适用于三烷基硅基三烷基锡（R3SiSnR'3）介导环化反应的外消旋联烯醛底物20。该底物经立体选择性环化反应顺利进行，所生成的高烯丙醇（homoallyl alcohol）的新手性中心呈现相对顺式构型，最终得到含5个连续手性中心的吲哚里西啶醇（indolizidinols）混合物，总收率达80%。通过二维核磁共振（2D NMR）实验与单晶X射线衍射分析（single-crystal X-ray analysis）联用的方法，明确确定了所有产物的相对构型。以32%收率分离得到的主要吲哚里西啶醇组分，经5步反应序列以32%的总收率衍生得到5,8-表吲哚里西啶223A。关键环化产物中的第二主要组分（占总收率24%）经4步反应，以14%的总收率得到6,8-表-223吲哚里西啶。尽管最初提出的结构修正打乱了我们针对天然产物吲哚里西啶223A的原始合成计划，但本文所报道的新型立体选择性环化策略以及吲哚里西啶衍生物的若干选择性转化反应，有望在高烷基化吲哚里西啶及其他相关生物碱（alkaloids）的合成中获得进一步应用。