Work

Asymmetric formal [1 + 2 + 2]-cycloaddition of diazoamides with enamines and carbonyl compounds

Year: 2025

Type: article

Abstract: Cycloaddition reaction offers an ideal and powerful method for the construction of cyclic structures with molecular complexity and diversity. The exploration of versatile synthons, especially in situ formed species, for the assembly of poly-functionalized heterocycles in one-pot is an intriguing and challenging area in synthetic chemistry from the perspective of atom economy and bond formation efficiency. Herein, we report an asymmetric formal [1 + 2 + 2]-cycloaddition of readily accessible diazoamides with enamines and carbonyl compounds. This cascade reaction involves a 1,3-dipolar cycloaddition of ketones/aldehydes with the key zwitterionic intermediate that generated in situ through an intermolecular metal carbene transfer to nucleophilic enamines, which offers a direct access to spiro-tetrahydrofurans containing four consecutive stereocenters in high yields and excellent enantioselectivity through chiral copper complex or chiral dirhodium carboxylates catalysis. Cycloaddition reaction offers an ideal and powerful method for the construction of cyclic structures with molecular complexity and diversity. Herein, the authors report an asymmetric formal [1 + 2 + 2]-cycloaddition of diazoamides with enamines and carbonyl compounds, synthesizing spiro-tetrahydrofurans containing four consecutive stereocenters.

Source: Nature Communications

DOI: 10.1038/s41467-025-65612-3

Authors: Shanliang Dong, Minghan Yao, Yunzhe Wang, Xiongda Xie, Xinyu Jiang, Xinfang Xu

Institutions: Zhejiang Sci-Tech University, Sun Yat-sen University, Henan Normal University

Language: English

Topic: Cyclopropane Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: National Natural Science Foundation of China, Basic and Applied Basic Research Foundation of Guangdong Province