Asymmetric Reductive and Alkynylative Heck Bicyclization of Enynes to Access Conformationally Restricted Aza[3.1.0]bicycles

Xiaolei Huang; Minh Hieu Nguyen; Maoping Pu; Luoqiang Zhang; Yonggui Robin Chi; Yun-Dong Wu; Jianrong Steve Zhou

doi:10.1002/anie.202000859

Asymmetric Reductive and Alkynylative Heck Bicyclization of Enynes to Access Conformationally Restricted Aza[3.1.0]bicycles

Angew Chem Int Ed Engl. 2020 Jun 26;59(27):10814-10818. doi: 10.1002/anie.202000859. Epub 2020 Apr 30.

Authors

Xiaolei Huang¹, Minh Hieu Nguyen¹, Maoping Pu², Luoqiang Zhang³, Yonggui Robin Chi¹, Yun-Dong Wu⁴, Jianrong Steve Zhou³

Affiliations

¹ Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.
² Shenzhen Bay Laboratory, Shenzhen, 518055, China.
³ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, 2199 Lishui Road, Room F312, Nanshan District, Shenzhen, 518055, China.
⁴ Lab of Computational Chemistry and Drug Design, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen Bay Laboratory, Shenzhen, 518055, China.

PMID: 32219962
DOI: 10.1002/anie.202000859

Abstract

Conformationally restricted azabicycles are becoming increasingly important in medicinal research. Asymmetric Heck bicyclization of enynes proceeds to give medicinally useful aza[3.1.0] and aza[4.1.0] bicycles with excellent enantioselectivity. The key organopalladium species after bicyclization can be trapped by silanes and terminal alkynes.

Keywords: alkynylation; azabicycles; palladium; reductive Heck reaction; strained rings.

Publication types

Research Support, Non-U.S. Gov't