Gold catalysis: up to six new bonds by a domino [3+2]/[2+1]/[2+1] cycloaddition

Abstract

In the presence of the N-heterocyclic carbene gold catalyst (IPrAuNCPhSbF6, 2), propargyl ester 1 undergoes a formal [3+2] cycloaddition reaction with vinyl ethers at room temperature. If the reaction was allowed to continue with excess propargyl ester, one or two sequential cyclopropanations occur on the enolate double bond of the [3+2] reaction product. The one-pot domino cycloaddition reactions created cyclopropanation products with multiple rings, formed multiple new sigma bonds, and new stereocenters. When 2-methoxypropene was allowed to react with excess propargyl ester 1 in the presence of the Au(I) catalyst 2, two tandem cyclopropanations occurred on the initial [3+2] cycloaddition product, which yields a product with a tricyclic carbon frame, six new sigma bonds, and eight new stereocenters. Hence the observation sets a new record for gold-catalyzed domino reactions. The assignment of the product stereochemistry was performed by NMR spectroscopy and confirmed by an X-ray structure analysis.