Zinc-Catalyzed Enantioselective Formal (3+2) Cycloadditions of Bicyclobutanes with Imines: Catalytic Asymmetric Synthesis of Azabicyclo[2.1.1]hexanes.

Autor: Wu F; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Wu WB; Hunan University, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, P. R. China, 410082, Changsha, CHINA., Xiao Y; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Li Z; Nanjing University, School of Chemistry and Chemical Engineering, CHINA., Tang L; Hunan University, College of Chemistry and Chemical Engineering, CHINA., He HX; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Yang XC; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Wang JJ; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Cai Y; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Xu TT; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Tao JH; Hunan University, College of Chemistry and Chemical Engineering, CHINA., Wang G; Nanjing University, School of Chemistry and Chemical Engineering, CHINA., Feng JJ; Hunan University, College of Chemistry and Chemical Engineering, Lushan Road(s), Yuelu District, Changsha, 410082, Changsha, CHINA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Sep 01, pp. e202406548. Date of Electronic Publication: 2024 Sep 01.
DOI: 10.1002/anie.202406548
Abstrakt: The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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