Enantioselective Allenation of Terminal Alkynes Catalyzed by Copper Halides of Mixed Oxidation States and Its Application to the Total Synthesis of Scorodonin. Issue 4 (15th December 2021)

• Record Type: Journal Article
• Authors: Wu, Guolin; Yao, Yuan; Li, Gen; Zhang, Xue; Qian, Hui; Ma, Shengming
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-15
• Subjects: alkynes -- allenes -- copper -- enantioselectivity -- regioselectivity; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202112427
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Naturally occurring conjugated allenynes are of general interest owing to their potent and various biological activities. The 1, 5‐H transfer of alka‐1, 4‐diyn‐3‐yl amines would be one of the most straightforward yet challenging approaches to such compounds since, in principle, two regioisomers may be formed involving two C−C triple bonds. Herein, a catalytic recipe of copper halides with mixed oxidation states, i.e., CuCl/CuBr2, has been identified to address the issues of the side reaction of conjugate addition and the selectivity of 1, 5‐H transfer of alka‐1, 4‐diyn‐3‐yl amines in EATA (enantioselective allenation of terminal alkynes) reaction involving 2‐alkynals. This method provided various allenynes with excellent enantioselectivities, and was also applied to the first highly enantioselective total synthesis of natural product scorodonin. Mechanistic studies and DFT calculations elucidated the regioselectivity for the observed 1, 5‐H transfer. Abstract : An efficient CuCl/CuBr2 co‐catalyzed enantioselective allenation of 2‐alkynals involving the highly regio‐ and stereoselective 1, 5‐H transfer of 1, 4‐diyn‐3‐yl amine intermediates has been developed. Various allenynes were obtained with excellent enantioselectivities. This reaction was applied to the first highly enantioselective total synthesis of natural product (−)‐scorodonin and its enantiomer.