Transition-Metal-Catalyzed Cyclization of1-(1-Alkynyl)Cyclopropyl Ketones and Oxime Ethers
|School||East China Normal University|
|Keywords||kinetic resolution cycloaddition reaction carbonylation tandemreaction transition-metal-catalyze|
Heterocyclic units are found the most important building blocks in many biological active natrural molecules and medicinal agents, for example, furans, pyrroles, oxazinanes and oxazepines, which are popular common skeltons in many important complex compounds. Transition-metal-catalyzed cycloaddition/cyclization/tandem reactions are unrivaled in their ability to provide rapid accesses to complex molecules from relatively simple starting materials. Therefore, it is important and significant to develop mild conditions and high atom-economy reactions in the catalysis of transition metal. Our study on the basis of the1-(1-alkynyl) cyclopropyl ketones and oxime ethers, achieved series of optically active heterocyclic compounds. The important aspects are as following:1. Cycloaddition reaction and kinetic resolution of1-(1-alkynyl)cyclopropyl ketonesWe achieved the distinct types of complex molecules from identical starting materials by subtly altering the choice of catalyst. The reaction of1-(1-alkynyl)-cycolpropyl ketones with nitrones, provided1,2-oxazines through [3+3] cycloaddition in modest to excellent yields and furo[3,4-d]-[1,2]oxazepines through [4+3] tandem double cyclization in excellent diastereoselectivity. At the same time, we also realized the rhodium-catalyzed carbonylation reaction of1-(1-alkynyl)cyclopropyl ketones through the insertion of carbon monoxide, affording3,4-fused bicyclic furans. As a consequence, series of optically active1-(1-alkynyl)cyclopropane ketones were obtained through the kinetic resulation of1-(1-alkynyl)cyclopropane ketones with nitrones in the catalysis of derived gold-complexes. After applied to the transformation of [4+3] cycloaddition and the carbonylation reaction, series of optically active furo[3,4-d]-[1,2]oxazepines and3,4-fused bicyclic furans were afforded, indicating that these reactions underwent via a SN2reaction pathway.1. Tadem/cycloclization reaction of1-(1-alkynyl)cyclopropane oxime ethersThe study on the basis of1-(1-alkynyl)cyclopropane oxime ethers in the catalysis of gold-complexes, achieved the [4+3] cycloaddition reaction with nitrones affording pyrrolo[3,4-d][1,2]oxazepines, and the tandem/cyclization reaction with nucleophiles affording highly substituted pyrroles. At the same time, optically active1-(1-alkynyl)-cyclopropane oxime ethers were synthesized from the corresponding optically active1-(1-alkynyl)cyclopropane ketones. After applied to the transformations, optically active pyrroles were afforded without loss of enantioenrichment, indicating that these reactions underwent via a SN2reaction pathway.