Rhodium Catalyzed Regioselective C−H Allylation of Simple Arenes via C−C Bond Activation of Gem‐difluorinated Cyclopropanes

Abstract

Herein, we report a rhodium catalyzed directing‐group free regioselective C−H allylation of simple arenes. Readily available gem‐difluorinated cyclopropanes can be employed as highly reactive allyl surrogates via a sequence of C−C and C−F bond activation, providing allyl arene derivatives in good yields with high regioselectivity under mild conditions. The robust methodology enables facile late‐stage functionalization of complex bioactive molecules. The high efficiency of this reaction is also demonstrated by the high turnover number (TON, up to 1700) of the rhodium catalyst on gram‐scale experiments. Preliminary success on kinetic resolution of this transformation is achieved, providing a promising access to enantio‐enriched gem‐difluorinated cyclopropanes.

Rhodium-Catalyzed Enantio- and Regioselective Allylation of In-doles with gem-Difluorinated Cyclopropanes

“…The development of such enantioselective reaction faces a significant challenge, which is that nucleophiles, other than ambident nucleophiles, often favor linear-selectivity because of the preferential nucleophilic attack at the less hindered carbon atom of the allyl-metal intermediate. [7][8][9][10][11][12][13][14] Therefore, overcoming the innate reactivity would potentially lead to the development of asymmetric allylic coupling for constructing enantioenriched α-mono-fluoroalkenes. Our group has been continuously interested in the exploration of divergent reactivity of gem-DFCPs especially with rhodium catalysis.…”

“…8 Subsequently, the reaction scope has been extensively extended to access βmono-fluoroalkenes integrated with the formation of C−C, C−N, C−S and C−P bonds. [9][10][11] Importantly, Lv and Li developed an elegant strategy to switch the regioselectivity from linear to branched in Pd/NHC-catalyzed cross-coupling of gem-DFCPs via inner-sphere 3,3'-reductive elimination process (Scheme 1b). 12 The employment of π-conjugated ambident nucleophiles (including hydrazones, 12,13a ketones, 13b and allylboronates 13c,13d ) has been the key to the success, delivering a series of racemic α-mono-fluoroalkene compounds.…”

Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

“…246 The Xia group described a rhodium-catalyzed regioselective C−H allylation of arenes without any directing group. In this study, gem-difluorinated cyclopropanes were employed as 247 TADDOL-based derivatives have gained recognition as a significant source of chirality in chemical synthesis since Seebach's first study in 1987. 248,249 Transition metal complexes containing TADDOL-based phosphorus ligands have been highly effective in numerous enantioselective processes.…”

Rhodium-catalyzed asymmetric hydroamination of gem-difluoroallenes with anilines

“…It has been reported by Breit et al that allenes can provide completely atom-efficient path to allylmetal intermediates for asymmetric hydrofunctionalization reactions [42][43][44][45][46][47][48][49][50][51][52]. Notably, some recent research has paid attention to the formation of fluorinated allylmetal species from fluorinated molecules [53][54][55][56][57]. In this context, Hartwig and co-workers first described an iridium-catalyzed enantioselective allylic substitution of 3,3-difluoropropenes with carbon nucleophiles via monofluoro π-allyl species using F atom as a leaving group (Figure 1c) [58].…”