An efficient and practical Rh­(III)-catalyzed redox-neutral [4 + 1] annulation of N-phenoxy amides with α,α-difluoromethylene alkynes has been realized to give direct access to the Z-configured monofluoroalkenyl dihydrobenzo­[d]­isoxazole framework with broad substrate compatibility and good functional group tolerance, which was further enhanced by the late-stage C–H modification of complex bioactive compounds. Subsequent density functional theory calculations revealed that the stereoselective β–F elimination involving an allene species played a decisive role in determining the reaction outcome and such Z-selectivity.

Cp*Rh(III)-catalyzed [4 + 3] annulation of N-methoxy amides for the direct assembly of seven-numbered 2H-azepin-2-one frameworks has been realized with gem-difluorocyclopropenes acting as innovative β-monofluorinated three sp 2 carbon sources. Either annular arylamides or linear acrylamides with the embedment of various functional groups, including DNA-tagged substrates, were found to be compatible with the established [4 + 3] reaction mode. A redox-neutral Rh(III)−Rh(V)−Rh(III) catalytic cycle, specifically via HOAc-assisted tandem site-/regioselective oxidative addition/reductive elimination/ C−F bond cleavage-enabled ring-scission involving the unprecedented olefinic C(sp 2 )−C(sp 2 ) bond cleavage, has been deduced based on experimental and computational mechanistic studies. Taken together, our findings not only identified gem-difluorocyclopropenes as potent and efficient coupling partners for C−H activation development but also provided a sound basis for the organic integration of transition-metal-catalyzed C−H functionalization with cyclopropene and fluorine chemistries.

By virtue of an efficient rhodium(III)‐catalyzed redox‐neutral C−H activation/ring‐opening of a strained ring/[4+2] annulation cascade of N‐methoxybenzamides with propargyl cycloalkanols, diverse 3‐acyl isoquinolin‐1(2H)‐ones were directly obtained in good yields and with excellent functional group compatibility. Additionally, their antitumor activities against various human cancer cells including HepG2, A549, MCF‐7 and SH‐SY5Y were evaluated and the action mechanism of the selected compound was also investigated in vitro. The results revealed that these products possessed a potent efficacy, by inhibiting proliferation and inducing apoptosis in a time‐dependent and dose‐dependent manner, suggesting that such compounds can serve as promising candidates for anti lung cancer drug discovery.