Dipolarophile‐Steered Formal Stereodivergent Synthesis of 2,5‐cis/trans‐Pyrrolidines Based on Asymmetric 1,3‐Dipolar Cycloaddition of Imino Lactones

• Published in: Chemistry : a European journal Vol. 29; no. 66; pp. e202302609 - n/a
• Main Authors: Furuya, Shohei, Muroi, Kenji, Kanemoto, Kazuya, Fukuzawa, Shin‐ichi
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 24.11.2023; Wiley Subscription Services, Inc
• Subjects: 1,3-dipolar cycloaddition; Alkenes; Asymmetric synthesis; Asymmetry; azomethine ylides; Chemistry; Chemistry, Multidisciplinary; Cycloaddition; Decarboxylation; Lactones; Physical Sciences; Science & Technology; silver catalyst; stereodivergent; Synthesis; azomethine ylides; ESTER; asymmetric synthesis; ISOXAZOL-5-ONES; silver catalyst; CONSTRUCTION; ENONES; SELECTIVE 3+2 CYCLOADDITION; stereodivergent; EXO; 1,3-dipolar cycloaddition
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202302609

The stereodivergent asymmetric synthesis of 2,5‐trans/cis pyrrolidines by 1,3‐dipolar cycloaddition using two different types of activated alkenes is described. When ylidene‐isoxazolones were employed as dipolarophiles, the Ag/(S,Sp)‐iPr‐FcPHOX‐catalyzed asymmetric [3+2] cycloaddition of imino lactones proceeded with 2,5‐trans selectivity. Subsequent decarboxylation of the isoxazolone rings produced pyrrolidines with 2,5‐trans stereoretention. In the reaction using acyclic enones as activated alkenes, the Ag/(R,Sp)‐ThioClickFerrophos complex‐catalyzed asymmetric [3+2] cycloaddition afforded 2,5‐cis substituted pyrrolidines in high yields and enantioselectivities. Therefore, these methods can be considered as a formal stereodivergent synthesis of 2,5‐cis/trans pyrrolidines. The formal diastereodivergent asymmetric synthesis of 2,5‐cis/trans pyrrolidines was achieved by using a different type of activated alkenes. The silver complex‐catalyzed asymmetric 1,3‐dipolar cycloaddition of imino lactones with ylidene‐isoxazolones, and subsequent transformation afforded chiral pyrrolidines with 2,5‐trans diastereoselectivity. In contrast, 2,5‐cis substituted pyrrolidines were obtained by the reaction of imino lactones with acyclic enones.