Activation and discovery of earth-abundant metal catalysts using sodium tert-butoxide

First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such, iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions. However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved, covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2π+2π] alkene cycloaddition. This activation method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a generic platform for the discovery and application of non-precious metal catalysis

Highly Selective Bis(imino)pyridine Iron-Catalyzed Alkene Hydroboration

Bis(imino)pyridine iron dinitrogen complexes have been shown to promote the anti-Markovnikov catalytic hydroboration of terminal, internal, and geminal alkenes with high activity and selectivity. The isolated iron dinitrogen compounds offer distinct advantages in substrate scope and overall performance over known precious metal catalysts and previously reported in situ generated iron species

Bis(imino)pyridine Cobalt-Catalyzed Alkene Isomerization–Hydroboration: A Strategy for Remote Hydrofunctionalization with Terminal Selectivity

Bis­(imino)­pyridine cobalt methyl complexes are active for the catalytic hydroboration of terminal, geminal, disubstituted internal, tri- and tetrasubstituted alkenes using pinacolborane (HBPin). The most active cobalt catalyst was obtained by introducing a pyrrolidinyl substituent into the 4-position of the bis­(imino)­pyridine chelate, enabling the facile hydroboration of sterically hindered substrates such as 1-methylcyclohexene, α-pinene, and 2,3-dimethyl-2-butene. Notably, these hydroboration reactions proceed with high activity and anti-Markovnikov selectivity in neat substrates at 23 °C. With internal olefins, the cobalt catalyst places the boron substituent exclusively at the terminal positions of an alkyl chain, providing a convenient method for hydrofunctionalization of remote C–H bonds

Mechanistic Studies of Cobalt-Catalyzed C(sp²)–H Borylation of Five-Membered Heteroarenes with Pinacolborane

Studies into the mechanism of cobalt-catalyzed C­(sp²)–H borylation of five-membered heteroarenes with pinacolborane (HBPin) as the boron source established the catalyst resting state as the <i>trans</i>-cobalt­(III) dihydride boryl, <b>(</b>^<b>iPr</b><b>PNP)­Co­(H)</b>_<b>2</b><b>(BPin)</b> (^iPrPNP = 2,6-(ⁱPr₂PCH₂)₂(C₅H₃N)), at both low and high substrate conversions. The overall first-order rate law and observation of a normal deuterium kinetic isotope effect on the borylation of benzofuran versus benzofuran-2-<i>d</i>₁ support H₂ reductive elimination from the cobalt­(III) dihydride boryl as the turnover-limiting step. These findings stand in contrast to that established previously for the borylation of 2,6-lutidine with the same cobalt precatalyst, where borylation of the 4-position of the pincer occurred faster than the substrate turnover and arene C–H activation by a cobalt­(I) boryl is turnover-limiting. Evaluation of the catalytic activity of different cobalt precursors in the C–H borylation of benzofuran with HBPin established that the ligand design principles for C–H borylation depend on the identities of both the arene and the boron reagent used: electron-donating groups improve catalytic activity of the borylation of pyridines and arenes with B₂Pin₂, whereas electron-withdrawing groups improve catalytic activity of the borylation of five-membered heteroarenes with HBPin. Catalyst deactivation by P–C bond cleavage from a cobalt­(I) hydride was observed in the C–H borylation of arene substrates with C–H bonds that are less acidic than those of five-membered heteroarenes using HBPin and explains the requirement of B₂Pin₂ to achieve synthetically useful yields with these arene substrates

Bis(imino)pyridine Cobalt-Catalyzed Alkene Isomerization–Hydroboration: A Strategy for Remote Hydrofunctionalization with Terminal Selectivity

Bis­(imino)­pyridine cobalt methyl complexes are active for the catalytic hydroboration of terminal, geminal, disubstituted internal, tri- and tetrasubstituted alkenes using pinacolborane (HBPin). The most active cobalt catalyst was obtained by introducing a pyrrolidinyl substituent into the 4-position of the bis­(imino)­pyridine chelate, enabling the facile hydroboration of sterically hindered substrates such as 1-methylcyclohexene, α-pinene, and 2,3-dimethyl-2-butene. Notably, these hydroboration reactions proceed with high activity and anti-Markovnikov selectivity in neat substrates at 23 °C. With internal olefins, the cobalt catalyst places the boron substituent exclusively at the terminal positions of an alkyl chain, providing a convenient method for hydrofunctionalization of remote C–H bonds

C(sp²)–H Borylation of Fluorinated Arenes Using an Air-Stable Cobalt Precatalyst: Electronically Enhanced Site Selectivity Enables Synthetic Opportunities

Cobalt catalysts with electronically enhanced site selectivity have been developed, as evidenced by the high <i>ortho</i>-to-fluorine selectivity observed in the C­(sp²)–H borylation of fluorinated arenes. Both the air-sensitive cobalt­(III) dihydride boryl 4-Me-(^iPrPNP)­Co­(H)₂BPin (<b>1</b>) and the air-stable cobalt­(II) bis­(pivalate) 4-Me-(^iPrPNP)­Co­(O₂C^tBu)₂ (<b>2</b>) compounds were effective and exhibited broad functional group tolerance across a wide range of fluoroarenes containing electronically diverse functional groups, regardless of the substitution pattern on the arene. The electronically enhanced <i>ortho</i>-to-fluorine selectivity observed with the cobalt catalysts was maintained in the presence of a benzylic dimethylamine and hydrosilanes, overriding the established directing-group effects observed with precious-metal catalysts. The synthetically useful selectivity observed with cobalt was applied to an efficient synthesis of the anti-inflammatory drug flurbiprofen

Cobalt-Catalyzed C–H Borylation

A family of pincer-ligated cobalt complexes has been synthesized and are active for the catalytic C−H borylation of heterocycles and arenes. The cobalt catalysts operate with high activity and under mild conditions and do not require excess borane reagents. Up to 5000 turnovers for methyl furan-2-carboxylate have been observed at ambient temperature with 0.02 mol % catalyst loadings. A catalytic cycle that relies on a cobalt­(I)–(III) redox couple is proposed

Cobalt-Catalyzed C–H Borylation

A family of pincer-ligated cobalt complexes has been synthesized and are active for the catalytic C−H borylation of heterocycles and arenes. The cobalt catalysts operate with high activity and under mild conditions and do not require excess borane reagents. Up to 5000 turnovers for methyl furan-2-carboxylate have been observed at ambient temperature with 0.02 mol % catalyst loadings. A catalytic cycle that relies on a cobalt­(I)–(III) redox couple is proposed

Cobalt-Catalyzed C(sp²)‑H Borylation: Mechanistic Insights Inspire Catalyst Design

A comprehensive study into the mechanism of bis­(phosphino)­pyridine (PNP) cobalt-catalyzed C–H borylation of 2,6-lutidine using B₂Pin₂ (Pin = pinacolate) has been conducted. The experimentally observed rate law, deuterium kinetic isotope effects, and identification of the catalyst resting state support turnover limiting C–H activation from a fully characterized cobalt­(I) boryl intermediate. Monitoring the catalytic reaction as a function of time revealed that borylation of the 4-position of the pincer in the cobalt catalyst was faster than arene borylation. Cyclic voltammetry established the electron withdrawing influence of 4-BPin, which slows the rate of C–H oxidative addition and hence overall catalytic turnover. This mechanistic insight inspired the next generation of 4-substituted PNP cobalt catalysts with electron donating and sterically blocking methyl and pyrrolidinyl substituents that exhibited increased activity for the C–H borylation of unactivated arenes. The rationally designed catalysts promote effective turnover with stoichiometric quantities of arene substrate and B₂Pin₂. Kinetic studies on the improved catalyst, <b>4-(H)</b>_<b>2</b><b>BPin</b>, established a change in turnover limiting step from C–H oxidative addition to C–B reductive elimination. The iridium congener of the optimized cobalt catalyst, <b>6-(H)</b>_<b>2</b><b>BPin</b>, was prepared and crystallographically characterized and proved inactive for C–H borylation, a result of the high kinetic barrier for reductive elimination from octahedral Ir­(III) complexes

Cobalt-Catalyzed Benzylic Borylation: Enabling Polyborylation and Functionalization of Remote, Unactivated C(sp³)–H Bonds

Cobalt dialkyl and bis­(carboxylate) complexes bearing α-diimine ligands have been synthesized and demonstrated as active for the C­(sp³)-H borylation of a range of substituted alkyl arenes using B₂Pin₂ (Pin = pinacolate) as the boron source. At longer reaction times, rare examples of polyborylation were observed, and in the case of toluene, all three benzylic C-H positions were functionalized. Coupling benzylic C-H activation with alkyl isomerization enabled a base-metal-catalyzed method for the borylation of remote, unactivated C­(sp³)-H bonds