Nickel binding enables isolation and reactivity of previously inaccessible 7-aza-2,3-indolynes.

N-Heteroaromatics are key elements of pharmaceuticals, agrochemicals, and materials. N-Heteroarynes provide a scaffold to build these essential molecules but are underused because five-membered N-heteroarynes have been largely inaccessible on account of the strain of a triple bond in that small of a ring. On the basis of principles of metal-ligand interactions that are foundational to organometallic chemistry, in this work we report the stabilization of five-membered N-heteroarynes in the nickel coordination sphere. A series of 1,2-bis(dicyclohexylphosphino)ethane nickel 7-azaindol-2,3-yne complexes were synthesized and characterized crystallographically and spectroscopically. Ambiphilic reactivity of the nickel 7-azaindol-2,3-yne complexes was observed with multiple nucleophilic, electrophilic, and enophilic coupling partners.

Ligand-Controlled Regioinduction in a PHOX-Ni Aryne Complex.

Phosphinooxazoline (PHOX) ligands have been used to control the regio- and enantioselectivity in a wide variety of metal-catalyzed reactions. Despite their widespread use, PHOX ligands have never been studied in metal-aryne complexes. Herein we report the first example of a PHOX-Ni aryne complex. As demonstrated in other systems, the differentiated P versus N donors and different steric environments of the unsymmetric ligand are able to induce regiocontrol. A 81:19 mixture of o-methoxy substituted aryne complexes is observed. Single-crystal X-ray crystallographic analysis, UV/vis spectroscopy, and cyclic voltammetry are used to gain further insight into the molecular and electronic structure of these complexes. Lastly, a methylation/deuteration sequence shows retention of the PHOX ligand-induced regiocontrol in the difunctionalized products and that the regiospecificity of these difunctionalizations is due to the trans influence of the P donor.

Redox-Neutral Decarboxylative and Desulfonylative C(sp3) Trifluoromethylation: Method Development and Mechanistic Inquiry.

Sodium triflinate (CF3SO2Na) is an inexpensive bench-stable radical CF3 source that is often activated by external oxidants such as peroxides. However, despite the commercial accessibility of CF3SO2Na, the salt has never been applied to decarboxylative trifluoromethylation due to challenges in controlled cross-radical coupling. We report a redox-neutral approach to decarboxylative C(sp3) trifluoromethylation of carboxylic acid derivatives. Mechanistic inquiry is performed to address the limitations in scope.

Redox Inversion: A Radical Analogue of Umpolung Reactivity for Base- and Metal-Free Catalytic C(sp3)-C(sp3) Coupling.

The construction of alkyl-alkyl bonds is a powerful tool in organic synthesis. Redox inversion, defined as switching the donor/acceptor profile of a functional group to its acceptor/donor profile, is used for C(sp3)-C(sp3) coupling. We report a photocatalytic coupling of carboxylic acids to form bibenzyls through a radical-radical coupling. Mechanistic insight is gained through control reactions. This unexplored redox-opposite relationship between a carboxylic acid and its redox-active ester is implemented in catalysis.

Radical-Polar Crossover Catalysis with a d0 Metal Enabled by a Redox-Active Ligand.

Radical-polar crossover mechanisms are invoked in numerous late transition metal and photocatalyzed reactions. To the best of our knowledge, reductive radical-polar crossover mechanisms are not invoked for group 3 early transition metals due to their propensity to exist in high oxidation states. Through use of a redox-active (tris)amido ligand we have accessed this mechanism for use with early transition metals. This mechanism is showcased through enabling product formation for a wide variety of elimination products from α-halo substituted benzylic bromides. The mechanism of this new type of reactivity with Sc is explored, and Hammett analysis reveals an anionic intermediate. The wide functional group tolerance of this reaction is also demonstrated.

Nickel(II/IV) Manifold Enables Room-Temperature C(sp3)-H Functionalization.

This Article demonstrates a mild oxidatively induced C(sp3)-H activation at a high-valent Ni center. In contrast with most C(sp3)-H activation reactions at NiII, the transformation proceeds at room temperature and generates an isolable NiIV σ-alkyl complex. Density functional theory studies show two plausible mechanisms for this C-H activation process involving triflate-assisted C-H cleavage at either a NiIV or a NiIII intermediate. The former pathway is modestly favored over the latter (by ∼3 kcal/mol). The NiIV σ-alkyl product of C-H cleavage reacts with a variety of nucleophiles to form C(sp3)-X bonds (X = halide, oxygen, nitrogen, sulfur, or carbon). These stoichiometric transformations can be coupled using N-fluoro-2,4,6-trimethylpyridinium triflate as a terminal oxidant in conjunction with chloride as a nucleophile to achieve a proof-of-principle NiII/IV-catalyzed C(sp3)-H functionalization reaction.

Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes.

Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp3 )-C and C(sp3 )-O bond-forming reactions at high-valent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral NiIV complex ligated by tris(pyrazolyl)borate and a cationic octahedral NiIII complex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1) C(sp3 )-C(sp2 ) bond-forming reductive elimination occurs from both centers, but the NiIII complex reacts up to 300-fold faster than the NiIV , depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2) Upon the addition of acetate (AcO- ), the NiIV complex exclusively undergoes C(sp3 )-OAc bond formation, while the NiIII analogue forms the C(sp3 )-C(sp2 ) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective M-C(sp3 ) bonds, and thus their relative reactivity towards outer-sphere SN 2-type bond-forming reactions.

Chiral Pincer Carbodicarbene Ligands for Enantioselective Rhodium-Catalyzed Hydroarylation of Terminal and Internal 1,3-Dienes with Indoles.

Catalytic enantioselective addition of N-heteroarenes to terminal and internal 1,3-dienes is reported. Reactions are promoted by 5 mol % of Rh catalyst supported by a new chiral pincer carbodicarbene ligand that delivers allylic substituted arenes in up to 95% yield and up to 98:2 er. Mechanistic and X-ray evidence is presented that supports that the reaction proceeds via a Rh(III)-η3-allyl.

Diastereoselective Synthesis of γ-Substituted 2-Butenolides via (CDC)-Rh-Catalyzed Intermolecular Hydroalkylation of Dienes with Silyloxyfurans.

Catalytic intermolecular hydroalkylation of dienes with silyloxyfuran nucleophiles is reported. Reactions are catalyzed by 5 mol % of a (CDC)-Rh complex and proceed in up to 87% yield and 6:1 dr (syn/anti) to provide allylic butenolides bearing vicinal stereocenters. Reactions proceed with terminal aryl and alkyl dienes and with modified silyl enol ether nucleophiles including a thiophenone variant. Utility of the products is demonstrated in the synthesis of a polypropionate anti,syn-stereotriad.

Lewis acid activation of carbodicarbene catalysts for Rh-catalyzed hydroarylation of dienes.

The activation of carbodicarbene (CDC)-Rh(I) pincer complexes by secondary binding of metal salts is reported for the catalytic site-selective hydro-heteroarylation of dienes (up to 98% yield and >98:2 γ:α). Reactions are promoted by 5 mol % of a readily available tridentate (CDC)-Rh complex in the presence of an inexpensive lithium salt. The reaction is compatible with a variety of terminal and internal dienes and tolerant of ester, alkyl halide, and boronate ester functional groups. X-ray data and mechanistic experiments provide support for the role of the metal salts on catalyst activation and shed light on the reaction mechanism. The increased efficiency (120 to 22 °C) made available by catalytic amounts of metal salts to catalysts containing C(0) donors is a significant aspect of the disclosed studies.

Intermolecular hydroamination of 1,3-dienes catalyzed by bis(phosphine)carbodicarbene-rhodium complexes.

A carbodicarbene (CDC)-based pincer ligand scaffold is reported, along with its application to site-selective Rh(I)-catalyzed intermolecular hydroamination of 1,3-dienes with aryl and alkyl amines. To the best of our knowledge, this is the first example of the use of a well-defined CDC complex as an efficient catalyst. Transformations proceed in the presence of 1.0-5.0 mol % Rh complex at 35-120 °C; allylic amines are obtained in up to 97% yield and with >98:2 site selectivity.

Batch reactor kinetic studies on the reductive dechlorination of chlorinated ethylenes by tetrakis-(4-sulfonatophenyl)porphyrin cobalt.

Tetrakis-(4-sulfonatophenyl)porphyrin cobalt was identified as a highly-active reductive dechlorination catalyst for chlorinated ethylenes. Through batch reactor kinetic studies, degradation of chlorinated ethylenes proceeded in a step-wise fashion with the sequential replacement of Cl by H. For perchloroethylene (PCE) and trichloroethylene (TCE), the dechlorination products were quantified and the C2 mass was accounted for. Degradation of the chlorinated ethylenes was found to be first-order in substrate. Dechlorination trials with increasing catalyst concentration showed a linearly increasing pseudo first-order rate constant which yielded rate laws for PCE and TCE degradation that are first-order in catalyst. The dechlorination activity of this catalyst was compared to that of another water-soluble cobalt porphyrin under the same reaction conditions and found to be comparable for PCE and TCE.