Rerouting the Organocatalytic Benzoin Reaction toward Aldehyde Deuteration

Santosh C. Gadekar, Vasudevan Dhayalan, Ashim Nandi, Inbal L. Zak, Meital Shema Mizrachi, Sebastian Kozuch, Anat Milo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Reactive intermediates are key to halting and promoting chemical transformations; however, due to their elusive nature, they are not straightforwardly harnessed for reaction design. Herein, we describe studies aimed at stabilizing reactive intermediates in the N-heterocyclic carbene (NHC) catalytic cycle, which enabled the full shutdown of the known benzoin coupling pathway, while rerouting its intermediates toward deuteration. The reversible nature of NHC catalysis and the selective stabilization of reaction intermediates facilitated clean hydrogen-deuterium exchange reactions of aromatic aldehydes by D2O, even for challenging electron-withdrawing substrates. In several cases, the addition of catalytic amounts of phenyl boronic acid was used to further stabilize highly reactive intermediates and mitigate the formation of benzoin coupling byproducts. The mechanistic understanding at the foundation of this work resulted in unprecedented mild conditions with base and catalyst loadings as low as 0.1 mol %, and a scalable deuteration reaction applicable to a broad substrate scope with outstanding functional group tolerance. More importantly, adopting this approach enabled the construction of a guideline for identifying the appropriate catalyst and conditions for different substrates. Experimental studies combined with machine learning and computational methods shed light on the nontrivial mechanistic underpinnings of this reaction.

Original languageEnglish
Pages (from-to)14561-14569
Number of pages9
JournalACS Catalysis
Volume11
Issue number23
DOIs
StatePublished - 3 Dec 2021

Keywords

  • N-heterocyclic carbene
  • boronic acid
  • data science
  • deuteration
  • mechanism
  • organocatalysis
  • secondary sphere

Fingerprint

Dive into the research topics of 'Rerouting the Organocatalytic Benzoin Reaction toward Aldehyde Deuteration'. Together they form a unique fingerprint.

Cite this