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

Abstract

a b s t r a c tIn the presence of the N-heterocyclic carbene gold catalyst (IPrAuNCPhSbF 6 , 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.

Gold(I)‐Catalyzed Allene–Diene–Alkyne Coupling Reaction to Polycycles

“…oligomerization) is not taken into account. [ 13 ] However, gold has been rarely used in CADA reactions compared to other transition metals. [ 14–17 ] An example of gold‐catalyzed dearomatization involving one alkyne unit was shown by Bandini et al [ 18 ] They converted naphthyl propargyl ethers 1 to naphthalene‐2‐one derivatives 2 (Scheme 1a).…”

“…oligomerization) is not taken into account. [13] [JohnPhosAu(NCMe)]SbF 6 (5 mol-%) [35] RT, 2 h, CDCl 3 47 -100 2…”

Au-Catalyzed [2 + 3] Annulation of Enamides with Propargyl Esters: Total Synthesis of Cephalotaxine and Cephalezomine H

“…Synthetically, a diversity-oriented assembly of such a functionalized azaspirocyclic nucleus is of major importance in the expeditious synthesis of related natural products and their analogues. Focusing on the construction of the 1-azaspiro[4.4]­nonane ring system driven by the synthesis of cephalotaxine-type alkaloids, we have recently explored a novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl esters (Scheme ). To our knowledge, this [2 + 3] annulation has not been thoroughly explored in the enamide chemistry and the gold-catalyzed propargyl chemistry. − Herein we wish to present our preliminary results on this annulation reaction as well as its application in the total synthesis of cephalotaxine and its congener cephalezomine H.…”