Stereodivergent Synthesis through Catalytic Asymmetric Reversed Hydroboration

• Published in: Journal of the American Chemical Society Vol. 141; no. 11; pp. 4670 - 4677
• Main Authors: Gao, Tao-Tao, Zhang, Wen-Wen, Sun, Xin, Lu, Hou-Xiang, Li, Bi-Jie
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-03-2019
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.8b13520

The control of chemo-, regio-, diastereo-, and enantioselectivity is a central theme in organic synthesis. The capability to obtain the full set of stereoisomers of a molecule would significantly enhance the efficiency for the synthesis of natural product analogues and creation of chiral compound libraries for drug discovery. Despite the tremendous progress achieved in the field of asymmetric synthesis in the past decades, the precise control of both relative and absolute configurations in catalyst-controlled reactions that create multiple stereocenters remains a significant synthetic challenge. We report here the development of a catalyst-controlled hydroboration with hitherto unattainable selectivity. The Rh-catalyzed hydroboration of α, β-unsaturated carbonyl compounds with pinacolborane proceeds with high levels of regio-, diastereo-, and enantioselectivities to provide a hydroboration product with two vicinal stereocenters. Through the appropriate choice of substrate geometry (E or Z) and ligand enantiomer (S or R), all the possible diastereoisomers are readily accessible. The boron-containing products underwent many stereospecific transformations, thus providing a strategy for collective stereodivergent synthesis of diverse valuable chiral building blocks.