Regioselective Alkylpolyfluoroarylation of Styrenes by Copper-Catalyzed C(sp³)–H and C(sp²)–H Double Activation

Abstract

A novel dehydrogenative dicarbofunctionalization of vinyl arenes with polyfluoroarenes and unactivated alkanes enabled by copper catalysis has been accomplished under mild conditions. This transformation provides a regioselective route to highly functionalized polyfluoroaryl compounds that occur as structural scaffolds in a variety of pharmaceuticals and materials. Preliminary mechanistic studies indicate that the carbon-based radical and copper intermediate are involved in the reaction, and the reaction pathway is dominated by the bond dissociation energy (BDE) of C(sp 3 )−H bonds. Letter pubs.acs.org/OrgLett

Copper-catalyzed functionalization/transformation of styrenes with polyhaloalkanes and arenes enables the synthesis of heteroarene-containing gem-dihaloalkenes

“…A plausible mechanism has been proposed based on the above experimental results and literature reports (Scheme 2). 3–10,12 Firstly, bromotrichloromethane ( 2a ) interacts with the copper( i ) catalyst to produce trichloromethyl radical A via single electron transfer (SET). Subsequently, radical A attacks the carbon–carbon double bond of alkene ( 1a ) to produce benzyl radical B , which is oxidized by the copper( ii ) catalyst to give benzyl carbocation intermediate C , while regenerating the copper( i ) catalyst.…”

“…1 A well-known process for alkene functionalization, namely atom transfer radical addition (ATRA), was well established by Kharasch to functionalize olefins with polyhaloalkyl groups and halogens through a radical-mediated addition (Scheme 1a, top). 2 The radical-mediated functionalization of olefins using polyhaloalkyl radicals, a highly reactive intermediate, in the presence of a transition metal catalyst, peroxide or photoredox catalyst also provides a particularly efficient and convenient tool for the construction of polyhaloalkyl-containing complex molecules, such as ethers, 3 amines, 4 heterocycles, 5 and azides 6 (Scheme 1a, bottom). Despite considerable achievements, the radical-mediated poylalkylarylation of alkenes involving C–H functionalization is still limited to a two-component intramolecular cyclization only, while further transformation of the polyhaloalkyl groups in a single step has rarely been reported.…”

Visible-Light-Mediated NHC and Tertiary Amine Catalysis Enabling α-H Acylation of Alkenes

“…It is worth highlighting that the catalytic system is compatible with 3i or 3j , indicating that the HAT process can be ignored . Notably, the presence of a highly electron deficient group (−F, −Cl, −Br, −CF 3 ) ( 3d – 3g ) on the phenyl ring was tolerated in this reaction, which not only provides the possibility for further conversion but also manifests that a benzylic-cation-involved mechanism could be excluded . Moreover, the functional groups at the ortho - and meta- positions of the styrene were well tolerated, affording the corresponding products in good yields ( 3l – 3p ).…”

“…17 Notably, the presence of a highly electron deficient group (−F, −Cl, −Br, −CF 3 ) (3d−3g) on the phenyl ring was tolerated in this reaction, which not only provides the possibility for further conversion but also manifests that a benzylic-cation-involved mechanism could be excluded. 18 Moreover, the functional groups at the ortho-and metapositions of the styrene were well tolerated, affording the corresponding products in good yields (3l−3p). More importantly, good yields can be obtained with di-or trisubstituted styrene (3q, 3r) as substrates for model reactions, suggesting that this catalytic system has no pronounced effect on the steric hindrance for the aromatic core.…”