Chiral 1, 2, 3‐Triazolium Salt Catalyzed Asymmetric Mono‐ and Dialkylation of 2, 5‐Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers. Issue 9 (19th January 2022)

• Record Type: Journal Article
• Authors: Yang, Ju‐Song; Lu, Ka; Li, Chen‐Xiao; Zhao, Zu‐Hang; Zhang, Xiao‐Ming; Zhang, Fu‐Min; Tu, Yong‐Qiang
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-19
• Subjects: 1, 2, 3-Triazolium Salts -- 2, 5-Diketopiperazines -- Asymmetric Catalysis -- Dialkylation -- Phase-Transfer Catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202114129
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Novel asymmetric mono‐ and dialkylation reactions of α‐substituted 2, 5‐diketopiperazines catalyzed by new chiral spirocyclic‐amide‐derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2, 5‐diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis ‐diastereo‐ and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2, 5‐diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations. Abstract : Chiral spirocyclic‐amide‐derived triazolium salts were used as new phase‐transfer organocatalysts for asymmetric alkylation to construct 2, 5‐diketopiperazine motifs containing one or two tetrasubstituted carbon centers in high yields with excellent cis ‐diastereoselectivity and enantioselectivity. Control experiments and DFT calculations revealed the possible reaction mechanism and the origins of the exceptional diastereo‐ and enantioselectivity.