Cyclobutene vs 1,3-Diene Formation in the Gold-Catalyzed Reaction of Alkynes with Alkenes: The Complete Mechanistic Picture

Abstract

The intermolecular gold(I)-catalyzed reaction between arylalkynes and alkenes leads to cyclobutenes by a [2 + 2] cycloaddition, which takes place stepwise, first by formation of cyclopropyl gold(I) carbenes, followed by a ring expansion. However, 1,3-butadienes are also formed in the case of ortho-substituted arylalkynes by a metathesis-type process. The corresponding reaction of alkenes with aryl-1,3-butadiynes, ethynylogous to arylalkynes, leads exclusively to cyclobutenes. A comprehensive mechanism for the gold(I)-catalyzed reaction of alkynes with alkenes is proposed on the basis of density functional theory calculations, which shows that the two pathways leading to cyclobutenes or dienes are very close in energy. The key intermediates are cyclopropyl gold(I) carbenes, which have been independently generated by retro-Buchner reaction from stereodefined 1a,7b-dihydro-1H-cyclopropa[a]naphthalenes.

Diastereospecific Gold(I)‐Catalyzed Cyclization Cascade for the Controlled Preparation of N‐ and N,O‐Heterocycles

“…We also investigated the possibility of the cyclopropyl gold carbene isomerization that leads to the inversion of the fully substituted carbon center . Although transition states TS iso ( I E7M ‐ I Z7M ) and TS iso ( I E6M ‐ I Z6M ) connecting I E7M / I Z7M and I E6M / I Z6M , respectively, were indeed located, the calculated activation barriers (Δ G ≠ =17.5 and 14.1 kcal mol −1 ; respectively) were found to be incomparable with the O‐ or N‐nucleophilic attack (Δ G ≠ =2.4–5.8 kcal mol −1 , Schemes and ), suggesting this process is irrelevant for this particular reaction system.…”

Broadening the Scope of the Gold‐Catalyzed [2+2] Cycloaddition Reaction: Synthesis of Vinylcyclobutenes and Further Transformations

“…Recently, we found that the [2+2] cycloaddition reaction can be applied to aryl‐ and alkyl‐substituted 1,3‐diynes, in which only the terminal alkyne is activated by gold(I) to give rise to 1‐alkynyl cyclobutenes . However, other types of products could be formed as a result of the intramolecular reaction of the cyclopropyl gold(I) carbenes with other functional groups.…”

“…Our group developed a gold(I)‐catalyzed intermolecular [2+2] cycloaddition reaction of aryl‐ and cyclopropyl‐substituted terminal alkynes with alkenes to give rise to cyclobutenes regioselectively (Scheme a) . The reaction proceeds satisfactorily in the presence of bulky phosphine gold(I) catalysts, such as A and B .…”

“…Catalyst B with the softer counterion BAr 4 F – provided cyclobutenes in better yields than catalyst A with SbF 6 – as the anion, by slowing down the formation of σ,π‐(alkyne)digold(I) complexes, which are unproductive intermediates in this catalytic process . Our mechanistic studies showed that the key intermediates in this reaction are cyclopropyl gold(I) carbenes, which undergo ring expansion to yield the cyclobutenes (Scheme a) …”

“…a) Gold(I)‐catalyzed [2+2] cycloaddition reaction to form cyclobutenes . b) Formal [2+2+2] cycloaddition reaction of alkynes with ketoalkenes .…”