Regioselective Carbonylation of 2,2-Disubstituted Epoxides: An Alternative Route to Ketone-Based Aldol Products

Aran K. Hubbell, Anne M. Lapointe, Jessica R. Lamb, Geoffrey W. Coates

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We report the regioselective carbonylation of 2,2-disubstituted epoxides to β,β-disubstituted β-lactones. Mechanistic studies revealed epoxide ring-opening as the turnover limiting step, an insight that facilitated the development of improved reaction conditions using weakly donating, ethereal solvents. A wide range of epoxides can be carbonylated to β-lactones, which are subsequently ring-opened to produce ketone-based aldol adducts, providing an alternative to the Mukaiyama aldol reaction. Enantiopure epoxides were demonstrated to undergo the carbonylation/ring-opening process with retention of stereochemistry to form enantiopure β-hydroxy esters.

Original languageEnglish (US)
Pages (from-to)2474-2480
Number of pages7
JournalJournal of the American Chemical Society
Volume141
Issue number6
DOIs
StatePublished - Feb 13 2019
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Award DE-FG02-05ER15687, and ExxonMobil. A.K.H. acknowledges a training grant fellowship from the National Institute of General Medical Sciences (NIGMS T32-GM008500). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. J.R.L. acknowledges a graduate fellowship from the National Science Foundation (DGE-1144153). This work made use of the NMR Facility at Cornell University which is supported, in part, by the NSF under the Award CHE-1531632. We also owe a special thanks to Prof. Scott Denmark for helpful discussions.

Publisher Copyright:
© 2019 American Chemical Society.

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