Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
Angew Chem Int Ed Engl. 2017 May 15;56(21):5834-5838. doi: 10.1002/anie.201612048. Epub 2017 Apr 21.
A silver(I) and amine co-catalyzed desymmetrization of 4-propargylamino cyclohexanones for the direct enantioselective synthesis of 2-azabicyclo[3.3.1]nonanes is described. Exploiting reactivity arising from dual activation of the pendant terminal alkyne by silver(I) and the ketone moiety through transient enamine formation, this synthetically relevant transformation is easy to perform, efficient and broad in scope. High enantioselectivity (up to 96 % ee) was achieved by exploiting a significant matching effect between the chirality of a cinchona alkaloid-derived aminophosphine ligand for the silver(I) salt and the 2-bis(aryl)methylpyrrolidine catalyst which was rationalized by DFT calculations. This allowed for the preparation of both enantiomers of the bicyclic product with near-identical stereocontrol.
描述了一种银（I）和胺共同催化的 4-炔丙基氨基环己酮的去对称化反应，用于直接对映选择性合成 2-氮杂双环[3.3.1]壬烷。利用银（I）和通过瞬态烯胺形成酮部分对末端炔烃的双重活化产生的反应性，这种与合成相关的转化易于进行、高效且具有广泛的范围。通过利用手性金鸡纳生物碱衍生的氨基膦配体与银（I）盐之间的显著匹配效应，以及通过 DFT 计算合理化的 2-双（芳基）甲基吡咯烷催化剂之间的匹配效应，实现了高对映选择性（高达 96%ee）。这允许用近乎相同的立体控制制备两种非对映异构体的双环产物。
