Pyrazolidinone-Aided Ru(II)-Catalyzed Regioselective C-H Annulation with Allenes.

Regioselective annulation of allenes via C-H activation represents an elegant synthetic approach toward the construction of valuable scaffolds. Considering the importance of allenes, herein we developed an unprecedented Ru(II)-catalyzed highly regioselective redox-neutral C-H activation/(4 + 1)-annulation of 1-arylpyrazolidinones employing allenyl acetates to access pyrazolo[1,2-a]indazol-1-one derivatives. Additionally, allenyl cyclic carbonates, which were never tested in C-H activation, were utilized to construct a similar class of heterocycles having a pendent alcohol functionality. Notably, double C-H functionalization was achieved by a simple modification of reaction conditions. The synthetic significance of this methodology is underscored by late-stage modification of natural products, broad substrate scope, gram-scale synthesis, and postfunctionalizations.

Rh(iii)-catalyzed sp3/sp2-C-H heteroarylations via cascade C-H activation and cyclization.

The development of an efficient strategy for facile access to quinoline-based bis-heterocycles holds paramount importance in medicinal chemistry. Herein, we describe a unified approach for accessing 8-(indol-3-yl)methyl-quinolines by integrating Cp*Rh(iii)-catalyzed C(sp3)-H bond activation of 8-methylquinolines followed by nucleophilic cyclization with o-ethynylaniline derivatives. Remarkably, methoxybiaryl ynones under similar catalytic conditions delivered quinoline tethered spiro[5.5]enone scaffolds via a dearomative 6-endo-dig C-cyclization. Moreover, leveraging this method for C8(sp2)-H bond activation of quinoline-N-oxide furnished biologically relevant oxindolyl-quinolines. This reaction proceeds via C(sp2)-H bond activation, regioselective alkyne insertion, oxygen-atom-transfer (OAT) and intramolecular nucleophilic cyclization in a cascade manner. One C-C, one C-N and one C[double bond, length as m-dash]O bond were created with concomitant formation of a quaternary center.

Pulsed electrolysis: enhancing primary benzylic C(sp3)-H nucleophilic fluorination.

Electrosynthesis is an efficient and powerful tool for the generation of elusive reactive intermediates. The application of alternative electrolysis waveforms provides a new level of control for dynamic redox environments. Herein, we demonstrate that pulsed electrolysis provides a favourable environment for the generation and fluorination of highly unstable primary benzylic cations from C(sp3)-H bonds. By introduction of a toff period, we propose this waveform modulates the electrical double layer to improve mass transport and limit over-oxidation.

Catalytic, Regioselective Hydrocarbofunctionalization of Unactivated Alkenes Triggered by trans-Acetoxypalladation of Alkynes.

Herein we demonstrate a Pd(II)-catalyzed regioselective hydrocarbofunctionalization of unactivated alkenes. The σ-vinyl-palladium(II) intermediate generated by the trans-acetoxypalladation of alkynes was added across carbon-carbon double bond to realize an efficient hydroalkenylation protocol. Bidentate auxiliary 8-aminoquinoline controls the regioselectivity of the carbopalladation step and thereby controls the regioselectivity of the hydroalkenylation. Additionally, when alkynes containing a hydroxy group at the three- or four-position were employed, the cascade sequence led to 1,6-dicarbonyl compounds via hydroalkenylation followed by intramolecular acyl migration.