Periodicals

nature synthesis

Authors

Yuanbiao An,Yifei Zhu ,Xingxing Ma ,Peiyu Zhang* (AI Chemistry Group, Future Chemistry Department, XtalPi Inc) ,Qiuling Song 

Abstract

Allylamines are used for diverse applications in organic synthesis, drug discovery, agrochemicals and functional materials. Despite their importance, allylamine synthesis still relies largely on specific amine partners, prefunctionalized C=C frameworks or noble metal catalysts, limiting their structural diversity. In addition, stereoselective construction of chiral allylamines featuring well-defined C=C bonds remains a persistent challenge in this field. Here we report a general and modular platform for the assembly of stereodefined allylamines through masked alkenyl anion intermediates. The intermediates are generated in situ via a 1,2-metallate shift of alkynyl tetracoordinate boron compounds that engage in a metal-free cascade reaction with diverse amines and aldehydes in the presence of a common Brønsted acid. This reaction exhibits precise regioselectivity at the C=C bond, along with a self-regulated sequence, involving imine formation followed by stereodefined alkenylation, ensuring exclusive chemo- and regioselectivity with exceptional Z/E ratios (exclusive Z-isomer formation). The reaction demonstrates broad substrate generality, accommodating various primary and secondary amines (both aromatic and aliphatic), enamines, and ammonia equivalents (tert-butyloxycarbonyl-NH₂), drugs, as well as chiral amines and amino acids or esters. Notably, the latter chiral compounds enable efficient construction of stereodefined allylamine architectures with excellent diastereomeric ratios (>20:1). The protocol also exhibits broad aldehyde compatibility, efficiently accommodating substrates ranging from formaldehyde to aliphatic, (hetero)aromatic, α,β-unsaturated aldehydes and formyl formates.