Copper‐Catalyzed Defluorinative Hydroarylation of Alkenes with Polyfluoroarenes

Abstract

A catalytic defluorinative hydroarylation of alkenes with polyfluoroarenes in the presence of dppbz-ligated Cu catalyst and silanes was developed. This method provides a straightforward and alternative avenue to synthetic important polyfluorinated arenes with readily available and bench-stable alkenes as latent nucleophiles, and therefore avoids conventional reliance on stoichiometric quantities of organometallic reagents. This reaction proceeds under very mild conditions and exhibits good functional group compatibility and high level of regioselectivity. The synthetic potential of this method was further demonstrated by a gram-scale synthesis, and an array of experimental studies were also carried out to elaborate the probable mechanism.

Palladium‐Catalyzed C(sp2/sp3)−H Arylation of Aryl Glycinamide Derivatives Using Picolinamide as Directing Group

“… [11] Finally, to demonstrate the synthetic versatility of the protocol, we subjected the mono ‐arylated compound 20 m to Suzuki‐Miyaura cross‐coupling reaction with phenylboronic acid 29 , affording p ‐terphenyl derivative 30 in 82 % yield (C, Scheme 8). [31] The structure of compounds 26 a , 27 a , 27 h , and 28 was unequivocally determined by single‐crystal X‐ray diffraction data (for details, see Supporting Information) [19]…”

“…[11] Finally, to demonstrate the synthetic versatility of the protocol, we subjected the mono-arylated compound 20 m to Suzuki-Miyaura cross-coupling reaction with phenylboronic acid 29, affording p-terphenyl derivative 30 in 82 % yield (C, Scheme 8). [31] The structure of compounds 26 a, 27 a, 27 h, and 28 was unequivocally determined by single-crystal X-ray diffraction data (for details, see Supporting Information). [19] Computational results for the Pd(II)-mediated double C(sp 2 / sp 3 )À H bond activation Similar to the case of the C(sp 2 )À H activation reaction, a simple model consisting of a complexation-activation mechanism of the Ugi adduct 26 a has been used, resulting in the cleavage of either, the C(sp 2 )À H bond (A, Scheme 9) or the C(sp 3 )À H bond (B, Scheme 9).…”

Transition-Metal-Catalyzed Alkylation of Polyfluoroarenes through C–F Bond Cleavage

“…18 On the basis of these research results, we envisioned that the in-situ-generated catalytic loading of organocuprates, originating from the insertion of CuH catalyst into unsaturated C-C bonds, might act as the preformed organometallics in coupling with polyfluoroarenes, and hence should provide an alternative access to the desired alkylated polyfluoroarenes. 19 After screening a series of conditions, we were delighted to find that the expected cross-coupling of styrene (1a) with polyfluoroarene 2a indeed occurred in a site-specific C-F bond-cleavage fashion in the presence of 1,2bis(diphenylphosphino)benzene (dppbz)-ligated copper bis(2-ethylhexanoate) as the catalyst and dimethoxy(methyl)silane (DMMS) as the hydride source, providing the expected product 3a in a nearly quantitative yield. Encour-aged by this promising result, we then evaluated a wide range of alkenes and polyfluoroarenes for their general applicability in this reaction.…”

Decarboxylative Polyfluoroarylation of Alkylcarboxylic Acids

“…Derivatization by defluorinative alkylation with organometallic reagents is challenging for complex small molecules because their conversion to organometallics can be difficult as a consequence of the presence of diverse functional groups. To avoid the use of stoichiometric alkylmetallic reagents, catalytic in situ generation of alkyl‐cuprates from alkenes was reported [10] but despite great advances, only styrenes and activated alkenes were demonstrated to successfully participate in this reaction. The Weaver group reported the addition of perfluorinated (het)arene‐derived radicals to π systems, including alkenes, alkynes, and arenes, [11] with radicals being generated through photocatalytic single‐electron reductive C−F fragmentation [11d, 12] .…”