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

被引：24

作者：

Wu, Feng ^{[1
]}

Wu, Wen-Biao ^{[1
,2
]}

Xiao, Yuanjiu ^{[1
]}

Li, Zhenxing ^{[3
]}

Tang, Lei ^{[1
]}

He, Heng-Xian ^{[1
]}

Yang, Xue-Chun ^{[1
]}

Wang, Ji-Jie ^{[1
]}

Cai, Yuanlin ^{[1
]}

Xu, Tong-Tong ^{[1
]}

Tao, Jia-Hao ^{[1
]}

Wang, Guoqiang ^{[3
]}

Feng, Jian-Jun ^{[1
]}

机构：

[1] Hunan Univ, Coll Chem & Chem Engn, Adv Catalyt Engn Res Ctr, Minist Educ,State Key Lab Chemo Biosensing & Chemo, Changsha 410082, Hunan, Peoples R China

[2] Hunan First Normal Univ, Sch Phys & Chem, Changsha 410205, Peoples R China

[3] Nanjing Univ, Inst Theoret & Computat Chem, Sch Chem & Chem Engn, Nanjing 210093, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2024年 / 63卷 / 48期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

strained molecules; cycloadditions; asymmetric catalysis; bridged rings; atom-economy; 2-PI+2-SIGMA CYCLOADDITIONS; STRAIN-RELEASE; BASIS-SETS; CHEMISTRY; DESIGN; ACID; BIS(OXAZOLINE); COMPLEXITY; CHIRALITY;

D O I：

10.1002/anie.202406548

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 alpha-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94 % 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.

引用

页数：9

共 123 条

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