Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies

Soumitra V. Athavale, Adam Simon, Kendall N. Houk, Scott E. Denmark

Research output: Contribution to journalArticle

Abstract

The Soai reaction has profoundly impacted chemists’ perspective of autocatalysis, chiral symmetry breaking, absolute asymmetric synthesis and its role in the origin of biological homochirality. Here we describe the unprecedented observation of asymmetry-amplifying autocatalysis in the alkylation of 5-(trimethylsilylethynyl)pyridine-3-carbaldehyde using diisopropylzinc. Kinetic studies with a surrogate substrate and spectroscopic analysis of a series of zinc alkoxides that incorporate specific structural mutations reveal a ‘pyridine-assisted cube escape’. The new tetrameric cluster functions as a catalyst that activates the substrate through a two-point binding mode and poises a coordinated diisopropylzinc moiety for alkyl group transfer. Transition-state models leading to both the homochiral and heterochiral products were validated by density functional theory calculations. Moreover, experimental and computational analysis of the heterochiral complex provides a definitive explanation for the nonlinear behaviour of this system. Our deconstruction of the Soai system reveals the structural logic for autocatalyst evolution, function and substrate compatibility—a central mechanistic aspect of this iconic transformation. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)412-423
Number of pages12
JournalNature Chemistry
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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