Trinuclear Gold‐Catalyzed 1,2‐Difunctionalization of Alkenes

Abstract

Activated alkyl halides have been extensively explored to generate alkyl radicals with Ru‐ and Ir‐ photocatalysts for 1,2‐difunctionalization of alkenes, but unactivated alkyl bromides remain challenging substrates due to their strong reduction potential. Here we report a three‐component 1,2‐difunctionalization reaction of alkenes, unactivated alkyl bromides and nucleophiles (e.g., amines and indoles) using a trinuclear gold catalyst [Au3(tppm)2](OTf)3. It can achieve the 1,2‐aminoalkylation and 1,2‐alkylarylation readily. This protocol has a broad reaction scope and excellent functional group compatibility (>100 examples with up to 96 % yield). It also affords a robust formal [2+2+1] cyclization strategy for the concise construction of pyrrolidine skeletons under mild reaction conditions. Mechanistic studies support an inner‐sphere single electron transfer pathway for the successful cleavage of inert C−Br bonds.

Inner‐Sphere Single Electron Transfer in Polynuclear Gold Photocatalysis

“…As a prototype example of the dinuclear gold(I) photocatalysts, [Au 2 (μ-dppm) 2 ] 2 + (dppm =bis(diphenylphosphino)methane) has been extensively utilized to achieve various photo-induced transformation, such as CÀ X bond cleavage, CÀ C, CÀ N crossing-coupling and formal radical-radical coupling. [7,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Detailed reviews of most of these results can be found elsewhere, [6][7][8]29] and thus, will not be reiterated here. This concept focuses on contributions toward the understanding of the ISET mechanism in polynuclear gold photoredox reactions.…”

“…By expanding the concept of ISET of polynuclear gold complexes, Xie and coworkers recently reported a three-component 1,2-difunctionalization reaction of alkenes, unactivated alkyl bromides and nucleophiles (such as amines and indoles), using trinuclear gold catalyst [Au 3 (tppm) 2 ](OTf) 3 (Scheme 6). [28] The approach exhibits broad substrate applicability and can activate inert primary, secondary, and tertiary bromides to generate alkyl radicals. In-depth investigations into the reaction mechanism were also conducted.…”

Visible-Light-Induced Regioselective Cascade Radical Cyclization of α-Bromocarbonyls: Access to Benzazepine Derivatives

“…Radical cascade reactions have proven to be an important and effective tool in modern organic synthesis in the past decades . In recent years, visible-light photoredox catalysis as an attractive strategy to assemble diverse carbocyclic and heterocyclic skeletons has become one of the most exciting developments in the field of organic synthesis .…”

Electrocatalytic conversion of ω-azido carboxylic acids to 1-pyrrolines via a combined process of oxidative decarboxylation and intramolecular Schmidt rearrangement

“…1). 7–10 Therefore, many strategies for the synthesis of 1-pyrrolines have been developed by synthetic chemists, and the common methods include the intramolecular cyclization of bifunctional compounds and intermolecular multicomponent cycloaddition 11–14 and [3 + 2] cycloaddition of 1,3-dipoles and alkenes or cyclopropanes (the Huisgen cycloaddition reaction). 15–19 The intramolecular Schmidt rearrangement of alkyl azides provides an alternative route to 1-pyrrolines, 20 although only moderate yields were observed in early studies.…”