Transition metal-catalyzed asymmetric three-component dicarbofunctionalization of unactivated alkenes

Enantioselective Directed Nickel-Catalyzed Three-Component Reductive Arylalkylation of Alkenes via the Carbometalation/Radical Cross-Coupling Sequence

“…To showcase the versatility of this robust enantioselective arylalkylation, we further applied it to the functionalizations of natural products and druglike molecule derivatives. Notably, both alkyl-and aryl iodides derivatized from L-menthol (55), diacetone-D-glucose (56), diacetone-Dgalactopyranose ( 57), (S)-naproxen (58,59), bezafibrate (60), isoxepac (61), and mecarbinate (62), efficiently underwent the alkene arylalkylation to produce the corresponding products with high levels of stereocontrol. Unfortunately, other Csp 2and Csp-coupling partners, such as alkenyl and alkynyl bromides, were employed but could not proceed in good yields under standard conditions (see Supporting Information for more details).…”

“…As a continuation of our interest in this area, we herein disclose the first enantioselective nickel-catalyzed reductive three-component arylalkylation between terminal or internal alkenes, aryl halides, and alkyl halides through carbonickelation/Csp 3 –Csp 3 cross-coupling sequence (Figure d). This reductive asymmetric arylalkylation of alkenes makes it reasonable to proceed with the chiral aryl–[Ni] complex in situ catalytically generated from aryl halides performing stereoselective carbonickelation of alkene ,,,− to afford the chiral α-branched Csp 3 –Ni intermediate with opposite regioselectivity to those radical relay strategies. − A coordinating-group-based chelation strategy is employed to stabilize the enantiomerically enriched Csp 3 –Ni intermediate as a transient nickelacycle followed by radical cross-coupling with alkyl halides to deliver aryl/alkyl difunctionalized products with exquisite control of regio-, chemo-, and enantioselectivity. Additionally, this reaction, devoid of the need for preprepared and sensitive organometallic reagents, is compatible with a broad range of electrophilic aryl and alkyl sources possessing various reactive functional groups.…”

Auxiliary-controlled regiodivergent NiH-catalyzed gem-difluoroallylation of alkenyl amines via defluorinative olefin cross-coupling

“…In recent years, the directing group strategy has emerged as a powerful and attractive toolkit for executing functionalization of unactivated alkenes, and the auxiliaries could dictate the regioselectivity by stabilization of different sizes of metallacycles. 7 As part of our continuous interest in Ni-catalyzed functionalization of alkenyl amine compounds, 8 we speculated that the judicious selection of auxiliaries would provide regiodivergent access to structurally diverse branched amines via Ni migration 9 or non-migration. Herein, we report our discovery that auxiliary-controlled switchable site-selectivity 10 can be achieved in Ni-catalyzed gem -difluoroallylation of alkenyl amines with aryl and alkyl trifluoromethyl alkenes.…”

Palladium-catalyzed carbomonofluoromethylation of unactivated alkenes: rapid access to γ-monofluoromethyl carboxylic acid derivatives

“…During the past few years, transition-metal-catalyzed difunctionalization of unactivated alkenes has attracted tremendous attention because it enables rapid build-up of complex molecules from easily available chemicals. 6 Among them, Engle's group has established a series of pioneering works on the β,γ-vicinal difunctionalization of unactivated alkenes, which provides a powerful tool for constructing functionalized carboxylic acid derivatives. 7 In light of the potential utility of monofluoromethyl carboxylic acid derivatives, we questioned whether a carbomonofluoromethylation of unactivated alkenes could be achieved using a nucleophilic fluoromethylating agent.…”