Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, SK, S7N 5C9, Canada.
Angew Chem Int Ed Engl. 2021 Dec 13;60(51):26777-26782. doi: 10.1002/anie.202111895. Epub 2021 Nov 10.
Total synthesis of the noncontiguous polypropionate dolabriferol C was achieved by retro-Claisen fragmentation of its putative contiguous precursor under mild conditions, thus establishing the former as a plausible isolation artifact. The precursor was prepared by a novel one-pot three-component bisaldol coupling of a meso (Z,Z)-bisenolate (generated in situ from a 3,7-diketone) with two enantioenriched aldehydes to set the absolute configuration of seven stereocenters in one step. The first aldol reaction proceeded with enantioselective desymmetrization of the bisenolate to produce an enantiomerically pure enolate-aldolate. Quenching at this stage enabled a streamlined synthesis of dolabriferol. Addition of a racemic aldehyde to the enolate-aldolate resulted in aldol coupling with kinetic resolution of the "matched" aldehyde; overall, a sequential enantiotopic-group-selective (SEGS) bisaldol reaction. Because the desired adduct results from the "mismatched" aldol reaction, use of enantioenriched aldehyde was required.
非连续聚丙酯 dolabriferol C 的全合成是通过其假定的连续前体在温和条件下的反-Claisen 断裂来实现的，从而证明前者是一种合理的分离假象。前体是通过新颖的一锅三组分双醛缩合反应制备的，其中 meso（Z，Z）-双烯醇盐（由 3,7-二酮原位生成）与两个对映体富集的醛反应，一步构建七个立体中心的绝对构型。第一个醛醇反应通过双烯醇盐的对映选择性去对称化进行，生成对映体纯的烯醇-烯醇缩醛。在此阶段进行淬灭，可以简化 dolabriferol 的合成。向烯醇-烯醇缩醛中添加外消旋醛，导致与“匹配”醛的醛醇偶联，具有动力学拆分；总体上是顺序对映选择性基团选择性（SEGS）双醛缩合反应。由于所需的加合物是由“不匹配”的醛醇反应产生的，因此需要使用对映体富集的醛。
