Mechanism and Origins of Stereoselectivity in the Cinchona Thiourea- and Squaramide-Catalyzed Asymmetric Michael Addition of Nitroalkanes to Enones

Authors
Grayson, MN 

Change log
Abstract

We report density functional theory calculations that examine the mechanism and origins of stereoselectivity of Soós' landmark discovery from 2005 that cinchona thioureas catalyze the asymmetric Michael addition of nitroalkanes to enones. We show that the electrophile is activated by the catalyst's protonated amine and that the nucleophile binds to the thiourea moiety by hydrogen bonding. These results lead to the correction of published mechanistic work which did not consider this activation mode. We have also investigated the corresponding cinchona squaramide-catalyzed reaction and found that it proceeds by the same mechanism despite the differences in the geometry of the two catalysts' hydrogen-bond-donating groups, which demonstrates the generality of this mechanistic model.

Publication Date
2017-04-21
Online Publication Date
2017-03-20
Acceptance Date
2017-03-20
Keywords
0306 Physical Chemistry (incl. Structural)
Journal Title
The Journal of Organic Chemistry
Journal ISSN
0022-3263
1520-6904
Volume Title
82
Publisher
American Chemical Society
Sponsorship
M.N.G. thanks Girton College, Cambridge (Research Fellowship) for financial support. Part of this work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council.