Intramolecular Diels-Alder Reaction of Cyclopropenyl Vinylarenes: Access to Benzonorcarane Derivatives.

Intramolecular Diels-Alder vinylarene reaction (IMDAV) is a [4 + 2] cycloaddition that employs styrene derivatives as conjugated dienes, whose poor reactivity arises from the required loss of aromaticity, which is recovered by a subsequent [1,3]-H shift. Herein, we describe the use of cyclopropene as a dienophile, harnessing its strain energy to drive the IMDAV reaction. Benzonorcarane scaffolds form in good yields, excellent stereoselectivity, and broad functional tolerance. Theoretical calculations and NMR studies have revealed significant mechanistic insights.

C-H Fluoromethoxylation of Arenes by Photoredox Catalysis.

Redox-active N-(fluoromethoxy)benzotriazoles were made accessible from fluoroacetic acid and hydroxybenzotriazoles via electrodecarboxylative coupling. After alkylation, they become effective monofluoromethoxylation reagents, enabling the photocatalytic C-H functionalization of arenes. Thus, irradiation of 1-(OCH2 F)-3-Me-6-(CF3 )benzotriazolium triflate with blue LED light in the presence of [Ru(bpy)3 (PF6 )2 ] promotes the synthesis of diversely functionalized aryl monofluoromethyl ethers. This method allows the late-stage functionalization of biologically relevant structures without relying on ecologically problematic halofluorocarbons.

Taking electrodecarboxylative etherification beyond Hofer-Moest using a radical C-O coupling strategy.

Established electrodecarboxylative etherification protocols are based on Hofer-Moest-type reaction pathways. An oxidative decarboxylation gives rise to radicals, which are further oxidised to carbocations. This is possible only for benzylic or otherwise stabilised substrates. Here, we report the electrodecarboxylative radical-radical coupling of lithium alkylcarboxylates with 1-hydroxybenzotriazole at platinum electrodes in methanol/pyridine to afford alkyl benzotriazole ethers. The substrate scope of this electrochemical radical coupling extends to primary and secondary alkylcarboxylates. The benzotriazole products easily undergo reductive cleavage to the alcohols. They can also serve as synthetic hubs to access a wide variety of functional groups. This reaction prototype demonstrates that electrodecarboxylative C-O bond formation can be taken beyond the intrinsic substrate limitations of Hofer-Moest mechanisms.

Rhodium-Catalyzed Copper-Assisted Intermolecular Domino C-H Annulation of 1,3-Diynes with Picolinamides: Access to Pentacyclic π-Extended Systems.

A new mode of reactivity of 1,3-diynes in rhodium-catalyzed oxidative annulation reactions has enabled the rapid assembly of extended π systems from readily available picolinamide derivatives. The process involves a double C-H bond activation and the iterative annulation of two 1,3-diyne units, with each alkyne moiety engaged in an orchestrated insertion sequence with high regiocontrol, leading to the formation of five new C-C bonds and the construction of four fused rings in a single operation. Either isoquinoline-1-carboxamides or fused polycyclic systems can be accessed by a switch in the regioselectivity of the second diyne insertion depending on the reaction conditions. DFT theoretical calculations have elucidated that the cooperative participation of both rhodium and copper in substrate activation, favored in the presence of excess of the copper(II) salt, is key to such a reversal of regioselectivity and subsequent multiple cyclization leading to fused polycyclic products. The role of copper was found to be essential in assisting both multiple insertion and rhodium-walking sequences, with the implication of intermediates with a Rh-Cu bond (2.60 Å).

Cobalt-Catalyzed ortho-C-H Functionalization/Alkyne Annulation of Benzylamine Derivatives: Access to Dihydroisoquinolines.

A practical picolinamide-directed C-H functionalization/alkyne annulation of benzylamine derivatives enabling access to the previously elusive 1,4-dihydroisoquinoline skeleton was developed using molecular O2 as the sole oxidant and Co(OAc)2 as precatalyst. The method is compatible with both internal and terminal alkynes and shows high versatility and functional-group tolerance. Furthermore, full preservation of enantiopurity is observed when using non-racemic α-substituted benzylamine derivatives. Kinetic analysis of the reagents and catalyst, labeling experiments, and the isolation and identification of catalytically competent Co-complexes revealed important insights about the mechanism.

RhI/RhIII catalyst-controlled divergent aryl/heteroaryl C-H bond functionalization of picolinamides with alkynes.

The ability to establish switchable site-selectivity through catalyst control in the direct functionalization of molecules that contain distinct C-H bonds remains a demanding challenge that would enable the construction of diverse scaffolds from the same starting materials. Herein we describe the realization of this goal, namely a divergent heteroaryl/aryl C-H functionalization of aromatic picolinamide derivatives, targeting two distinct C-H sites, either at the pyridine ring or at the arene unit, to afford isoquinoline or ortho-olefinated benzylamine (or phenethylamine) derivatives. This complementary reactivity has been achieved on the basis of a RhIII/RhI switch in the catalyst, resulting in different mechanistic outcomes. Notably, a series of experimental and DFT mechanistic studies revealed important insights about the mechanism of the reaction and reasons behind the divergent regiochemical outcome.

Synthesis of alkylidene pyrrolo[3,4-b]pyridin-7-one derivatives via Rh(III)-catalyzed cascade oxidative alkenylation/annulation of picolinamides.

A practical Rh(III)-catalyzed cascade olefination/annulation of picolinamides leading to pyrrolo[3,4-b]pyridines has been developed. The reaction shows wide scope, complete regiocontrol and excellent stereoselectivity.

Copper-catalyzed ortho-C-H amination of protected anilines with secondary amines.

A practical Cu-catalyzed picolinamide-directed o-amination of anilines showing excellent mono-substitution selectivity and high functional group tolerance has been developed.

Copper-catalyzed ortho-halogenation of protected anilines.

A practical Cu-catalyzed direct ortho-halogenation of anilines under aerobic conditions has been developed. The reaction shows typically excellent mono-substitution selectivity, high ortho-regiocontrol and large functional group tolerance.