Mitchell T Andrew, Zhao Cunxiang, Romo Daniel
Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, USA.
J Org Chem. 2008 Dec 19;73(24):9544-51. doi: 10.1021/jo801604k.
A full account of studies leading to the development of a cascade sequence that generates as many as two C-C bonds, one C-O bond, and three new stereocenters providing substituted tetrahydrofurans (THFs) from simple gamma-ketoaldehydes and thiopyridyl ketene acetals is described. The process involves a tandem Mukaiyama aldol-lactonization (TMAL) and accumulated evidence suggests the intermediacy of a silylated beta-lactone that is intercepted by the pendant ketone. Formation of a cyclic oxocarbenium is followed by reduction with silicon-based nucleophiles leading to a highly diastereoselective synthesis of tetrahydrofurans. This cascade process has now been extended to the synthesis of tetrahydropyrans from simple delta-ketoaldehydes. The stereochemical outcome of the cascade processes described was determined by NOE correlations, coupling constant analysis, and X-ray crystallography of the derived oxygen heterocycles and is in accord with established and recently proposed models for nucleophilic additions to cyclic 5- and 6-membered oxocarbenium ions. The utility of this process was demonstrated by the synthesis of the tetrahydrofuran fragment of colopsinol B.
本文描述了一系列研究，这些研究促成了一种级联反应序列的开发，该序列可从简单的γ-酮醛和硫代吡啶基乙烯酮缩醛生成多达两个C-C键、一个C-O键和三个新的立体中心，从而提供取代的四氢呋喃（THF）。该过程涉及串联的Mukaiyama羟醛-内酯化反应（TMAL），并且积累的证据表明，一种被侧链酮截获的硅烷基化β-内酯是反应中间体。环状氧鎓离子形成后，会被硅基亲核试剂还原，从而实现四氢呋喃的高非对映选择性合成。现在，这种级联过程已扩展到从简单的δ-酮醛合成四氢吡喃。所描述的级联过程的立体化学结果通过NOE相关、耦合常数分析以及衍生的含氧杂环的X射线晶体学确定，并且与已确立的以及最近提出的亲核加成到环状5元和6元氧鎓离子的模型一致。通过合成colopsinol B的四氢呋喃片段证明了该过程的实用性。
