Rhodium(III)-Catalyzed Asymmetric 1,2-Carboamidation of Alkenes Enables Access to Chiral 2,3-Dihydro-3-benzofuranmethanamides

Abstract

Through the initial screening and further rational design of chiral cyclopentadienyl ligands, a chiral rhodium-catalyzed enantioselective 1,2-carboamidation of aromatic tethered alkenes was developed, enabling the asymmetric preparation of various chiral 2,3-dihydro-3-benzofuranmethanamides with an enantioenriched all-carbon quaternary center at the β position of amide. This robust transformation has a broad functional group tolerance, excellent enantioselectivities (up to 98.5:1.5 er), and a mild reaction conditions, releasing CO2 as the single byproduct.

RhodiumIII-catalyzed remote difunctionalization of arenes assisted by a relay directing group

“…On the basis of our above studies and previously related reports, 7,10,18 a plausible mechanism is proposed to account for the present catalytic tandem reaction (Scheme 9). The reaction catalytic cycle starts from coordination of the directing group of 1a to the Rh( iii ) catalyst species.…”

“… 17 Intriguingly, analogous intramolecular annulations have been realized by using meta -olefin-tethered arenes via chelation-assisted C–H activation ( Scheme 2b ). 18 However, this reaction system is limited to the arenes with an olefin unit tethered at the meta - or ortho -position. Herein, we report Rh III -catalyzed C–H activation, insertion of an unsaturated coupling partner (relay directing group), second C–H activation, and intramolecular alkene insertion cascade, leading to efficient synthesis of 2,3-dihydrobenzofuran compounds with a quaternary carbon center ( Scheme 2c ).…”

Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review

“…In the same year, another rhodium-catalyzed approach for the asymmetric synthesis of dihydrobenzofuran derivatives 51 was put forward by Yu 51 et al In their methodology, aryl-joined alkenes 49 and substituted dioxazolone 37 were subjected to chiral rhodium-promoted carboamidation, using copper acetate as an additive in the presence of AgSbF 6 and dichloroethane to attain the enantioselective synthesis of dihydrobenzofurans 51 in 44–83% yield with up to 98.5 : 1.5 enantiomeric ratio. The reaction mechanism was proposed to undergo C–H activation and migratory insertion, followed by oxidative addition to generate intermediate 50 .…”

Rhodium-Catalyzed Asymmetric C–H Functionalization Reactions

“…165 Recently, Yang, Zhou, and co-workers reported a tandem intramolecular C−H alkylation/intermolecular amidation with Cp x Rh complex Rh-2h bearing bulky substituents at 3,3′-position, affording the chiral dihydrobenzofurans 215 in up to 83% yield and 97% ee with Weinreb amide as the directing group (Scheme 33c). 166 In 2017, Ellman and co-workers described a Cp x Rh complex Rh-2p catalyzed asymmetric hydroarylation of nitroalkenes 217 (up to 73% yield, 82% ee, Scheme 34a). 167 Later in 2021, a new catalytic system involving [SCpRh] Rh-5c was reported by You and co-workers, which could enhance both yield and enantioselectivity of the reaction (up to 92% yield, 92% ee, Scheme 34b).…”

“…In 2020, a Cp x Rh complex Rh-8 with planar chiral ferrocene-fused cyclopentadiene ligand was synthesized by Wang and co-workers, which enabled the formation of chiral isoquinolones 212 in good yields, albeit with moderate enantiomeric excesses (up to >99% yield, 75% ee, Scheme b) . Recently, Yang, Zhou, and co-workers reported a tandem intramolecular C–H alkylation/intermolecular amidation with Cp x Rh complex Rh-2h bearing bulky substituents at 3,3′-position, affording the chiral dihydro-benzofurans 215 in up to 83% yield and 97% ee with Weinreb amide as the directing group (Scheme c) …”