Gold(I)-Catalyzed Intramolecular [4+2] Cycloadditions of Arylalkynes or 1,3-Enynes with Alkenes:  Scope and Mechanism

Abstract

The cyclizations of enynes substituted at the alkyne gives products of formal [4+2] cyclization with Au(I) catalysts. 1,8-Dien-3-ynes cyclize by a 5-exo-dig pathway to form hydrindanes. 1,6-Enynes with an aryl ring at the alkyne give 2,3,9,9a-tetrahydro-1H-cyclopenta[b]naphthalenes by a 5-exo-dig cyclization followed by a Friedel-Crafts-type ring expansion. A 6-endo-dig cyclization is also observed in some cases as a minor process, although in a few cases, this is the major cyclization pathway. In addition to cationic gold complexes bearing bulky biphenyl phosphines, a gold complex with tris(2,6-di-tert-butylphenyl)phosphite is exceptionally reactive as a catalyst for this reaction. This cyclization can also be carried out very efficiently with heating under microwave irradiation. DFT calculations support a stepwise mechanism for the cycloaddition by the initial formation of an anti-cyclopropyl gold(I)-carbene, followed by its opening to form a carbocation stabilized by a pi interaction with the aryl ring, which undergoes a Friedel-Crafts-type reaction.

A porphyrin complex of Gold(I): (Phosphine)gold(I) azides as cation precursors

“…These are the catalytic agents in a broad range of transformations at unsaturated carbon centers, primarily alkynes and allenes. Oftentimes a (phosphine)-or (N-heterocyclic carbene)gold(I) cation is formed in situ by halide abstraction with silver(I) reagents (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). An immediate complication is the fate of silver, which itself has a notorious affinity for unsaturated carbon.…”

Methodology for the Construction of the Bicyclo[4.3.0]nonane Core

“…Cyclohexenyl system 166 forms hydrindone 167 when exposed to triphenylphosphinegold triflate in modest yield [98]. Dienyne 168 has been shown on three accounts to form substituted hydrindadiene 169 in good yields utilizing gold catalysts [86,87,91]. Cyclopentane system 170 under the action of Grubbs I allowed for hydrindane 171 to be formed [97].…”

“…Enyne metathesis has found an increasing interest in the synthesis of natural products (see Scheme 24) [80][81][82][83][84]. It has found significant use in the synthesis of larger ring systems [85][86][87][88][89] and hetereocyclic systems [90][91][92][93][94][95], but only occasionally in the synthesis of hydrindanes [96][97][98][99]. Palladium, platinum, gold, and ruthenium have been found to be the catalysts of choice for this class of reactions.…”

Expanding the frontier of gold-catalyzed cyclizations and rational ligand design.

“…41,284,285 For example, the cationic gold complex Au-1, developed by Echavarren and co-workers, exhibited excellent stability and catalytic activity in the cycloisomerization of enynes due to its bulky and electron-rich phosphine ligand. 176,215,303,304 Accordingly, we first employed Au-1 as the catalyst in the reaction of 2-phenylethynyl benzaldehyde with ethyl vinyl ether. To our delight, along with…”

“…Based on previous experimental and computational studies of Au-catalyzed rearrangements of enynes, 176 in which the formation of cyclopropyl Au-carbenes have been invoked, we also considered the possibility of the [2+2] mechanism proceeding via an epoxy Au-carbene as shown in Figure 6. In this mechanism we envisaged that an initial 6-exo cyclization via TS-9 to form H could then form epoxide I. Fragmentation of this epoxide could then lead to the formal [2+2] addition bicyclic J that upon ringopening forms the enone product.…”