Premium
Enantioselective Silver and Amine Co‐catalyzed Desymmetrizing Cycloisomerization of Alkyne‐Linked Cyclohexanones
Author(s) -
Manzano Rubén,
Datta Swarup,
Paton Robert S.,
Dixon Darren J.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201612048
Subject(s) - enantioselective synthesis , chemistry , cycloisomerization , alkyne , desymmetrization , moiety , ketone , combinatorial chemistry , bicyclic molecule , enamine , stereochemistry , enantiomer , catalysis , organic chemistry
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.