Gold-Catalyzed Tandem 1,3-Migration/Double Cyclopropanation of 1-Ene-4,n-diyne Esters to Tetracyclodecene and Tetracycloundecene Derivatives

Abstract

A synthetic method that relies on Au(I)-catalyzed tandem 1,3-acyloxy migration/double cyclopropanation of 1-ene-4,9-diyne and 1-ene-4,10-diyne esters to construct the respective architecturally challenging tetracyclodecene and tetracycloundecene derivatives is described. Achieved under mild reaction conditions, the transformation was shown to be robust with a wide variety of substitution patterns tolerated to give the two members of the carbocyclic family in good to excellent yields and as a single regio- and diastereomer.

Gold Catalyzed Cyclopropanation/[5+3] Cycloaddition of 1,4,9‐ and 1,4,10‐Allenenynes to Bicyclo[3.3.1]nonane Derivatives

“…In this regard, we became interested in the potential gold(I)‐catalyzed reaction chemistry of 1,4,9‐ and 1,4,10‐allenenynes (Scheme c). In the presence of the Group 11 complex, it was anticipated that the 1,4‐allenene motif of the starting material may likewise be prone to an initial cyclopropanation step . In doing so, we discovered that the bicyclo[3.1.0]hexene species I produced in this manner was susceptible to a stepwise [5+3] cycloaddition process to deliver the bicyclo[3.3.1]nonane ring system.…”

“…Homogeneous gold catalysis has become one of the most powerful synthetic tools to rapidly increase molecular complexity and diversity from readily accessible substrates in a single operation . In carbocyclic and heterocyclic synthesis, for instance, it has provided a number of elegant routes to a variety of targets of potential synthetic value from 1, n ‐allenenes, ‐allenynes and ‐enynes (Scheme a) .…”

“…Mechanistically, the reactions typically involve activation of the more electron‐rich and accessible of the two π ‐bonds and functionalization by a remaining pendant group and/or second starting material. For example, we recently reported a synthetic route to tetracyclodecenes and ‐undecenes that relied on an initial gold(I)‐mediated 1,3‐acyloxy migration/cyclopropanation of 1,4‐enyne esters containing an alkyne tether (Scheme b) . This is followed by a second cyclopropanation of the ensuing putative bicyclo[3.1.0]hexenylgold adduct I .…”

“…Homogeneous gold catalysis has become one of the most powerful synthetic tools to rapidly increase molecular complexity and diversity from readily accessible substrates in a single operation. [5][6][7][8][9][10][11] In carbocyclic and heterocyclic synthesis, for instance, it has provided a number of elegant routes to a variety of targets of potential synthetic value from 1,n-allenenes, -allenynes and -enynes (Scheme 1a). [6][7][8] Mechanistically, the reactions typically involve activation of the more electron-rich and accessible of the two π-bonds and functionalization by a remaining pendant group and/or second starting material.…”

“…For example, we recently reported a synthetic route to tetracyclodecenes and -undecenes that relied on an initial gold(I)mediated 1,3-acyloxy migration/cyclopropanation of 1,4-enyne esters containing an alkyne tether (Scheme 1b). [9] This is followed by a second cyclopropanation of the ensuing putative bicyclo [3.1.0] hexenylgold adduct I. In contrast, the analogous transformations of substrates containing a preformed alkene, alkyne and allene motif, thereby providing access to a potentially wider scope of cycloisomerization products, have not been explored.…”