High-Throughput Experimentation and Machine Learning-Assisted Optimization of Iridium-Catalyzed Cross-Dimerization of Sulfoxonium Ylides

Abstract

A novel and convenient approach that combines high-throughput experimentation (HTE) with machine learning (ML) technologies to achieve the first selective cross-dimerization of sulfoxonium ylides via iridium catalysis is presented. A variety of valuable amide-, ketone-, ester-, and N-heterocycle-substituted unsymmetrical E-alkenes are synthesized in good yields with high stereoselectivities. This mild method avoids the use of diazo compounds and is characterized by simple operation, high step-economy, and excellent chemoselectivity and functional group compatibility. The combined experimental and computational studies identify an amide-sulfoxonium ylide as a carbene precursor. Furthermore, a comprehensive exploration of the reaction space is also performed (600 reactions) and a machine learning model for reaction yield prediction has been constructed.

Keywords: Cross-Dimerization; High-Throughput Experimentation; Machine Learning; Sulfoxonium Ylides; Unsymmetrical Alkenes.