Goldstein Elizabeth L, Takada Hirokazu, Sumii Yuji, Baba Katsuaki, Stoltz Brian M
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Tetrahedron. 2022 Sep 24;123. doi: 10.1016/j.tet.2022.132940. Epub 2022 Aug 6.
The synthesis of a variety of enantioenriched 2,2-disubstituted pyrrolidines is described. A stereogenic quaternary center is first formed utilizing an asymmetric allylic alkylation reaction of a benzyloxy imide, which can then be reduced to a chiral hydroxamic acid. This compound can then undergo a thermal "Spino" ring contraction to afford a carbamate protected 2,2-disubstituted pyrrolidine stereospecifically. These pyrrolidines can be further advanced to enantioenriched indolizidine compounds. This reaction sequence allows access to new molecules that could be useful in the development of pharmaceutical agents.
本文描述了多种对映体富集的2,2-二取代吡咯烷的合成方法。首先利用苄氧基酰亚胺的不对称烯丙基烷基化反应形成一个手性季碳中心，然后将其还原为手性异羟肟酸。该化合物随后可进行热“Spino”环收缩反应，立体专一性地得到氨基甲酸酯保护的2,2-二取代吡咯烷。这些吡咯烷可进一步转化为对映体富集的中氮茚化合物。该反应序列能够获得可用于药物研发的新分子。
