Recent advances in asymmetric [2+1] cycloaddition with α-cyano diazo compounds

Abstract

The asymmetric [2 + 1] cycloaddition of α-cyano diazo compounds has emerged as an efficient and versatile strategy for synthesizing cyano-substituted cyclopropanes, which are valuable scaffolds in medicinal chemistry, materials science, and natural product synthesis. The unique electrophilicity and planar conjugation of cyano-substituted carbenes have enabled highly selective [2 + 1] cycloaddition reactions with a wide range of substrates, including alkenes, alkynes, allenes, and aromatic compounds. Recent advancements in catalyst design, particularly the use of dirhodium(II) complexes, cobalt(II) porphyrins, and biocatalysts like engineered myoglobin, have achieved remarkable levels of enantioselectivity and diastereoselectivity. These methodologies have not only expanded the synthetic scope but also revealed mechanistic insights into carbene transfer reactions, such as the influence of π–π stacking and hydrogen bonding on stereoselectivity. Despite these successes, challenges remain in addressing substrate limitations, enhancing reaction efficiency under mild and sustainable conditions, and exploring new applications in drug discovery and beyond. This review highlights the latest developments in this field, providing a foundation for future research into the design of novel catalytic systems and the broader utilization of α-cyano diazo compounds in synthetic organic chemistry.