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

• Published in: Angewandte Chemie International Edition Vol. 62; no. 48; pp. e202313638 - n/a
• Main Authors: Xu, Yougen, Gao, Yadong, Su, Lebin, Wu, Haiting, Tian, Hao, Zeng, Majian, Xu, Chunqiu, Zhu, Xinwei, Liao, Kuangbiao
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 27.11.2023; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkenes; Catalysis; Chemistry; Chemistry, Multidisciplinary; Cross-Dimerization; Dimerization; Experimentation; Functional groups; High-Throughput Experimentation; Iridium; Ketones; Learning algorithms; Machine Learning; Optimization; Physical Sciences; Science & Technology; Sulfoxonium Ylides; Unsymmetrical Alkenes; FUNCTIONALIZATION; INSERTION; Cross-Dimerization; Unsymmetrical Alkenes; H BOND; REACTIVITY; Sulfoxonium Ylides; High-Throughput Experimentation; Machine Learning; PREDICTION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202313638

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. By combining high‐throughput experimentation and machine learning technologies, we developed the first iridium‐catalyzed cross‐dimerization of two sulfoxonium ylides, leading to various unsymmetrical E‐alkenes. Excellent chemoselectivity and functional group compatibility under mild conditions enable this protocol to be of practical significance. A machine learning model for yield prediction further demonstrated its utilities and generalities.