Nickel‐Catalyzed Enantioselective Direct Addition of 1,3‐Dienes to Aldehydes Enabled by Chiral Monodentate Diamidophosphite Ligands
Abstract
ABSTRACT Enantioenriched dienols are important structural motifs in numerous bioactive compounds and serve as valuable intermediates in organic synthesis. Although several synthetic routes have been developed, the most desirable approach is the direct addition of 1,3‐dienes to aldehydes, thereby avoiding the need for preformed alkenylmetal reagents. Herein, we report the first enantioselective direct addition of 1,3‐dienes to aldehydes, enabled by nickel(0) catalysis in combination with a newly developed class of chiral monodentate diamidophosphite ligands derived from chiral 1,2‐diamine scaffolds. This method affords chiral dienols in high yields and with excellent regio‐ and enantioselectivity under mild, redox‐neutral, and atom‐economical conditions. Comprehensive mechanistic studies—including both experimental investigations and DFT calculations—reveal a catalytic cycle involving oxo‐nickelacycle intermediates. The high selectivity arises from the chiral diamidophosphite ligands, which provide precise stereocontrol by stabilizing key intermediates through noncovalent CH···HC interactions.
Article Details
Authors (9)
Xiang‐Rui Liu
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China
Xiao‐Yuan Luo
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China
Yu‐Qing Wang
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China
Wen‐Jing Nan
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China
Mei‐Yu Liu
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China
Wei‐Guo Xiao
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China
Mengchun Ye
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry
Qi‐Lin Zhou
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry, Frontiers Science Center for New Organic Matter Nankai University Tianjin China
Li‐Jun Xiao
State Key Laboratory and Institute of Elemento‐Organic Chemistry College of Chemistry Frontiers Science Center For New Organic Matter Nankai University Tianjin China