Gold(â… )-catalyzed Cyclization Of Conjugated Enyne Keto Oxime Ethers:a Facile Access To Highly Substituted Pyrroles

Heterocyclic structures are widely present in most natural products and man-made molecules, such as furans, pyrroles, oxazinanes and azepines. These heterocyclic compounds may have potential physiological or pharmacological activity. Thus the development of simple, efficient methods to synthetize these compounds is be of importance and attracts much interest of chemists. This study focused on the gold(I)-catalyzed cyclization and cycloaddition of the2-(1-alkynyl)-alk-2-en-1-one oxime ethers leading to a series of heterocyclic or polycyclic fused compounds.Substituted oxime ethers compounds can be easily and efficiently prepared from the conjugated enyne ketone with O-alkyl hydroxyamines. We proposed that gold(I) would mediate the cyclization of oxime ether compounds to afford a pyrrolyl gold carbocation intermediate. This intermediate would be captured by several kinds of reagents.Firstly, this intermediate would react with nucleophile to afford2,3,5-tri-substituted N-methoxyl pyrroles after protonation. Moderate enantioselectivity can be obtained by the use of (R)-C2-tunePhos derived gold complexes as chiral catalyst.Secondly, the gold(Ⅰ)-catalyzed asymmetric [3+3] cycloaddition of2-(1-alkynyl)-alk-2-en-l-one oxime ethers with nitrones was investigated, which provided pyrrlo[3,4-d][1,2]oxazinanes in modest to excellent yield and highly diastereo-and enantioselectivity. It is noteworthy that no loss of the efficiency and selectivity was observed during the scale up operation.At the end, this intermediate could react with α,β-unsaturated imines to afford fused heterobicyclic pyrrlo[3,4-c]azepines by unusual [4+3] cycloaddition consisting of1,2-alkyl migration. When Tadddol derived chiral phosphramidite ligands were applied to this reaction, good enantioselectivity was achieved.