Catalytic, Enantioselective β-Protonation through a Cooperative Activation Strategy

Michael H. Wang, David Barsoum, C. Benjamin Schwamb, Daniel T. Cohen, Brian C. Goess, Matthias Riedrich, Audrey Chan, Brooks E. Maki, Rama K Mishra, Karl A Scheidt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The NHC-catalyzed transformation of unsaturated aldehydes into saturated esters through an organocatalytic homoenolate process has been thoroughly studied. Leveraging a unique “Umpolung”-mediated β-protonation, this process has evolved from a test bed for homoenolate reactivity to a broader platform for asymmetric catalysis. Inspired by our success in using the β-protonation process to generate enals from ynals with good E/Z selectivity, our early studies found that an asymmetric variation of this reaction was not only feasible, but also adaptable to a kinetic resolution of secondary alcohols through NHC-catalyzed acylation. In-depth analysis of this process determined that careful catalyst and solvent pairing is critical for optimal yield and selectivity; proper choice of nonpolar solvent provided improved yield through suppression of an oxidative side reaction, while employment of a cooperative catalytic approach through inclusion of a hydrogen bond donor cocatalyst significantly improved enantioselectivity.

Original languageEnglish (US)
Pages (from-to)4689-4702
Number of pages14
JournalJournal of Organic Chemistry
Volume82
Issue number9
DOIs
StatePublished - May 5 2017

ASJC Scopus subject areas

  • Organic Chemistry

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