Harish K. Potukuchi

Mechanistic Insight into Direct Arylations with Ruthenium(II) Carboxylate Catalysts

Mechanistic studies revealed ruthenium-catalyzed direct arylations to proceed through reversible C-H bond activation and subsequent rate-limiting oxidative addition with aryl halides, which led to the development of widely applicable well-defined ruthenium(II) carboxylate catalysts.

Direct C–H bond arylations and alkenylations with phenol-derived fluorine-free electrophiles

Significant progress has been accomplished in direct C–H bond arylations of arenes and heteroarenes with readily accessible, inexpensive phenol derivatives. Thus, ruthenium biscarboxylate complexes and inexpensive cobalt compounds allowed for challenging C–H bond derivatizations of arenes. Further, palladium, nickel and cobalt catalysts set the stage for step-economical C–H/C–O bond functionalization with electron-rich as well as electron-deficient heteroarenes.

Well-Defined Ruthenium(II) Carboxylate as Catalyst for Direct C–H/C–O Bond Arylations with Phenols in Water

The ruthenium(II) carboxylate complex [Ru(O(2)CMes)(2)(p-cymene)] enabled efficient direct arylations of unactivated C-H bonds with easily available, inexpensive phenols. Extraordinary chemoselectivity of the well-defined ruthenium catalyst set the stage for challenging C-H/C-O bond functionalizations to occur under solvent-free conditions as well as in water, and allowed first direct C-H bond arylations with user-friendly diaryl sulfates as electrophiles.

Palladium-Catalyzed Dehydrogenative Direct Arylations of 1,2,3-Triazoles

Palladium-catalyzed intramolecular dehydrogenative direct arylations of 1,2,3-triazoles were accomplished under ambient pressure of air, which set the stage for a modular synthesis of annulated phenanthrenes through a reaction sequence comprising two distinct catalytic C-H bond functionalization reactions.

Kumada-Corriu cross-couplings with 2-pyridyl Grignard reagents.

Substituted heterobiaryls constitute privileged scaffolds of compounds with activities of relevance to various research areas, ranging from medicinal chemistry and catalysis to material sciences. Their regioselective syntheses rely strongly on transition-metal-catalyzed cross-coupling reactions, which have matured to being indispensable tools in modern organic syntheses. Since organomagnesium reagents are more readily available than are alternative organometallic nucleophiles, catalytic cross-couplings of Grignard reagents have proven particularly useful for streamlining heterobiaryl synthesis. Therefore, catalysts derived from various transition metals, such as nickel, palladium, iron, 12] cobalt, or manganese, were developed for Kumada–Corriu-type coupling reactions. 19] While this research significantly expanded the pool of viable electrophiles, cross-coupling reactions of electron-deficient N-heterocyclic nucleophiles continue to be challenging because of their reduced nucleophilicities. Hence, a generally applicable protocol for metal-catalyzed arylations of less nucleophilic 2-azine Grignard reagents has, to the best of our knowledge, proven elusive. As part of our program directed towards the use of air-stable secondary phosphine oxides (SPO) as preligands in transition-metal catalysis, we noted that efficient cross-couplings with 2-pyridyl organomagnesium compounds could be accomplished, provided that palladium catalysts derived from airand moisturestable SPOs were employed as preligands. Herein, we report on these findings, which highlight the unique reactivity profile of SPO preligands. At the outset of our studies, we probed various transitionmetal complexes and ligands in the cross-coupling of challenging 2-pyridyl Grignard 1 a with aryl bromide 2 a (Table 1). Unfortunately, monodentate phosphines 4 a–4 d provided unsatisfactory results (Table 1, entries 2–5), as did bidentate ligands 4 e–4 g or phosphite 5 (Table 1, entries 6– 9). Further, in situ generated (Table 1, entries 10 and 11) or preformed, well-defined palladium N-heterocyclic carbene complexes (Table 1, entries 12 and 13) did not deliver the desired product 3 a.

Tetra-ortho-Substituted Biaryls through Palladium-Catalyzed Suzuki−Miyaura Couplings with a Diaminochlorophosphine Ligand

A palladium complex derived from a sterically hindered diaminochlorophosphine allowed for Suzuki-Miyaura cross-couplings of chloroarenes with ample scope and provided access to tetra-ortho-substituted bi(hetero)aryls.

Copper-catalyzed CuAAC/intramolecular C-H arylation sequence: Synthesis of annulated 1,2,3-triazoles.

Summary Step-economical syntheses of annulated 1,2,3-triazoles were accomplished through copper-catalyzed intramolecular direct arylations in sustainable one-pot reactions. Thus, catalyzed cascade reactions involving [3 + 2]-azide–alkyne cycloadditions (CuAAC) and C–H bond functionalizations provided direct access to fully substituted 1,2,3-triazoles with excellent chemo- and regioselectivities. Likewise, the optimized catalytic system proved applicable to the direct preparation of 1,2-diarylated azoles through a one-pot C–H/N–H arylation reaction.