Data-driven design of new chiral carboxylic acid for construction of indoles with C-central and C–N axial chirality via cobalt catalysis

• Published in: Nature communications Vol. 14; no. 1; pp. 3149 - 9
• Main Authors: Zhang, Zi-Jing, Li, Shu-Wen, Oliveira, João C. A., Li, Yanjun, Chen, Xinran, Zhang, Shuo-Qing, Xu, Li-Cheng, Rogge, Torben, Hong, Xin, Ackermann, Lutz
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 140/131; 140/58; 639/638/549/933; 639/638/77/883; Alkylation; Carboxylic acids; Catalysis; Catalysts; Chirality; Cobalt; Design; Enantiomers; Humanities and Social Sciences; Indoles; Knowledge management; Learning algorithms; Machine learning; multidisciplinary; Science; Science (multidisciplinary); Statistics; Stereoselectivity; Workflow
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-38872-0

Challenging enantio- and diastereoselective cobalt-catalyzed C–H alkylation has been realized by an innovative data-driven knowledge transfer strategy. Harnessing the statistics of a related transformation as the knowledge source, the designed machine learning (ML) model took advantage of delta learning and enabled accurate and extrapolative enantioselectivity predictions. Powered by the knowledge transfer model, the virtual screening of a broad scope of 360 chiral carboxylic acids led to the discovery of a new catalyst featuring an intriguing furyl moiety. Further experiments verified that the predicted chiral carboxylic acid can achieve excellent stereochemical control for the target C–H alkylation, which supported the expedient synthesis for a large library of substituted indoles with C -central and C–N axial chirality. The reported machine learning approach provides a powerful data engine to accelerate the discovery of molecular catalysis by harnessing the hidden value of the available structure-performance statistics. The design of efficient and selective catalysts is a formidable challenge in chemical science. Here the authors design a data-driven workflow to achieve the digitalized knowledge transfer between the synthetically relevant transformations, which was demonstrated in the prediction of chiral carboxylic acid co-catalyst for the cobalt-catalyzed asymmetric C–H alkylation of indoles.