Au-Catalyzed Intermolecular [2+2] Cycloadditions between Chloroalkynes and Unactivated Alkenes

Abstract

The [2+2] cycloaddition is a versatile strategy for the synthesis of strained cyclobutenes of high synthetic value. In this study, two efficient intermolecular [2+2] cycloadditions between two different types of chloroalkynes and unactivated alkene are realized with gold catalysis. Of significance is that the reaction works with challenging monosubstituted unactivated alkenes, which is unprecedented in gold catalysis and scarcely documented in other metal-catalyzed/promoted reactions; moreover, the reaction exhibits excellent regioselectivities, which are much better than those reported in literature. With 1,2-disubstituted unactivated alkenes, the reaction is largely stereospecific. The cyclobutene products can be prepared in nearly gram scale and readily undergo further reactions including various cross-coupling reactions using the C(sp)-Cl and/or C(sp)-SPh bond, which in turn substantially broaden the scope of accessible cyclobutenes and enhance the synthetic utility of this bimolecular reaction.

Gold(I)‐Catalyzed Haloalkynylation of Aryl Alkynes: Two Pathways, One Goal

“…This reaction principle can also be extended to bromoacetylenes 4 and 1,2‐disubstituted alkenes ( 5 ; Scheme b) and represents one of the few examples for gold(I)‐catalyzed reactions where the triple bond remains after the reaction . In the case of the gold(I)‐catalyzed haloalkynylation of cyclic alkenes, a side reaction, namely the already known gold(I)‐catalyzed [2+2] cycloaddition, takes place (Scheme b) . The bromoalkynylation of cyclic alkenes proceeds via a trans addition and can also be accomplished enantioselectively by the use of chiral gold(I) catalysts …”

Recent Progress in N-Heterocyclic Carbene Gold-Catalyzed Reactions of Alkynes Involving Oxidation/Amination/Cycloaddition

“…Very recently, Zhang and coworkers described a new mode of NHC gold-catalyzed [2+2] cycloaddition reaction of alkynes with alkene, allowing the facile synthesis of various valuable cyclobutenes [113]. Of note, achieving this cycloaddition reaction was highly challenging due to the fact that alkenes involved in such a tandem sequence were all electronically inactivated.…”

AuI‐Catalyzed Haloalkynylation of Alkenes

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The formal insertiono fa lkenes into aromatic chloro-a nd bromoalkynes takes place under cationic gold catalysis. Very recently, the group of Zhang showed that chloroalkynes are also suitable substrates in such [2+ +2] cycloadditions, leading in this case to valuable chlorocyclobutenes [3] (Scheme 1B). [1] In 2010, Echavarren and co-workers discoveredt he intermolecular [2+ +2] cycloadditiono fa lkenes and alkynes, one of the most fundamental transformations in this field and av aluablet ool for the synthesiso fc yclobutenes [2] (Scheme 1A).

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