Cobalt alkyl complexes bearing readily available and redox-active 2,2′:6′,2″-terpyridine and α-diimine ligands have been synthesized, and their electronic structures have been elucidated. In each case, the supporting chelate is reduced to the monoanionic, radical form that is engaged in antiferromagnetic coupling with the cobalt­(II) center. Both classes of cobalt alkyls proved to be effective for the isomerization–hydroboration of sterically hindered alkenes. An α-diimine-substituted cobalt allyl complex proved exceptionally active for the reduction of hindered tri-, tetra-, and geminally substituted alkenes, representing one of the most active homogeneous catalysts known for hydroboration. With limonene, formation of an η3-allyl complex with a C–H agostic interaction was identified and accounts for the sluggish reactivity observed with diene substrates. For the terpyridine derivative, unique Markovnikov selectivity with styrene was also observed with HBPin.

Cobalt dialkyl and bis(carboxylate) complexes bearing α-diimine ligands have been synthesized and demonstrated as active for the C(sp(3))-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(sp(3))-H bonds.

A highly diastereoselective carbon–carbon bond-forming reaction involving the tandem coupling of benzyltriboronates, enoates, and alkyl halides is described. This method was enabled by the discovery of α-diimine nickel catalysts that promote the chemoselective triborylation of benzylic C(sp3)–H bonds using B2Pin2 (Pin = pinacolate). The C–H functionalization method is effective with methylarenes and for the diborylation of secondary benzylic C–H bonds, providing direct access to polyboron building blocks from readily available hydrocarbons. Combination of the benzylic perborylation with a new deborylative conjugate addition–alkylation method enables a one-pot procedure in which multiple simple precursors are combined to generate diastereopure products containing quaternary stereocenters.

Cobalt dialkyl complexes bearing α-diimine ligands proved to be active precatalysts for the nondirected, C(sp3)−H selective hydrogen isotope exchange (HIE) of alkylarenes using D2 gas as the deuterium source. Alkylarenes with a variety of substitution patterns and heteroatom substituents on the arene ring were successfully labeled, enabling high levels of incorporation into primary, secondary, and tertiary benzylic C(sp3)−H bonds. In some cases, the HIE proceeded with high diastereoselectivity and application of the cobalt-catalyzed method to enantioenriched substrates with benzylic stereocenters provided enantioretentive hydrogen isotope exchange at tertiary carbons.

A nickel-catalyzed method for the site-selective hydrogen isotope exchange (HIE) of C­(sp2)–H bonds in nitrogen heteroarenes is described and applied to the tritiation of pharmaceuticals. The α-diimine nickel hydride complex [(iPrDI)­Ni­(μ2–H)]2 (iPrDI = N,N′-bis­(2,6-diisopropylphenyl)-2,3-butanediimine) mediates efficient HIE when employed as a single component precatalyst or generated in situ from readily available and air-stable metal and ligand precursors (iPrDI, [(NEt3)­Ni­(OPiv)2]2 (Piv = pivaloyl) and (EtO)3SiH). The nickel catalyst offers distinct advantages over existing methods, including: (i) high HIE activity at low D2 or T2 pressure; (ii) tolerance of functional groups, including aryl chlorides, alcohols, secondary amides, and sulfones; (iii) activity with nitrogen-rich molecules such as the chemotherapeutic imatinib; and (iv) the ability to promote HIE in sterically hindered positions generally inaccessible with other transition metal catalysts. Representative active pharmaceutical ingredients were tritiated with specific activities in excess of the thresholds required for drug absorption, distribution, metabolism, and excretion studies (1 Ci/mmol) and for protein receptor–ligand binding assays (15 Ci/mmol). The activity and selectivity of the nickel-catalyzed method are demonstrated by comparison with the current state-of-the-art single-site (iridium and iron) and heterogeneous (Raney nickel and rhodium black) catalysts. A pathway involving C­(sp2)–H activation by a α-diimine nickel hydride monomer is consistent with the experimentally measured relative rate constants for HIE with electronically disparate pyridines, the pressure-dependence of activity, positional selectivity preferences, and kinetic isotope effects.