The Mills Laboratory is tackling real-world synthetic problems with Earth-abundant transition metal catalysts

The formation of manganese–oxo catalysts involved in C(sp³)–H bond oxidation was explored in the targeted synthesis of (salen/salophen)manganese complexes that varied axial ligand identity and varied oxidation state of the manganese center. Isolated compounds included dinuclear (salen/salophen)manganese(III)–μ-hydroxo and trinuclear (salen)manganese(IV/III/IV)–μ-oxo, the latter of which formed by oxidation with catalytically relevant oxidant iodosylbenzene. The X-ray structure of trinuclear complex (salen)manganese(IV/III/IV)–μ-oxo indicated a Mn(IV)–O–Mn(III)–O–Mn(IV) motif, with nearly linear Mn–O–Mn angles of 166.19(12)° and 172.47(15)°, Mn(IV)–O bond lengths of 1.948(2) and 1.998(2) Å, and Mn(III)–O bond lengths of 2.102(2) and 2.118(2) Å. All well-defined (salen/salophen)manganese hydroxo and oxo compounds served as precatalysts for oxidation of C(sp³)–H substrates 9,10-dihydroanthracene (>99% conversion), fluorene (52–70% conversion), and phenylcyclohexane (with lower 18–23% conversion), albeit with lower rate of activity for the isolated trinuclear μ-oxo compound, allowing its assignment as an off-cycle catalyst aggregate. These data supported the proposal of a manganese(III/V) cycle for C(sp³)–H oxidation, which involved monomerization of the dinuclear (salen)manganese(III)-μ-hydroxo catalyst prior to rate-determining C(sp³)–H activation.

A cobalt(II) catalyst supported by the ligand 2-(diphenylphosphino)phenol (P,O) was developed for the C(sp²)–C(sp³) Negishi arylation of alkyl(pyridyl)sulfones, which are bench-stable, nonorganohalide C(sp³)–S electrophiles. Employing the catalyst generated in situ from 5 mol % P,O ligand and 5 mol % cobalt(II) bromide, a variety of (hetero)aryl C(sp²)–C(sp³) products were synthesized derived from primary and secondary alkyl sulfones, including difluoromethylation using 2-((difluoromethyl)sulfonyl)pyridine, and cross-coupling of sulfone derived from the thiol-containing ACE inhibitor captopril. Freeze-quench X-band EPR spectroscopy of a catalytic reaction established the catalyst resting state as low-spin (S = 1/2), square-pyramidal (P,O)cobalt(II)–aryl, a rare example of a cobalt(II)–aryl complex detected during a cross-coupling reaction. These data informed the cobalt(II/III/I/0) catalytic cycle involving alkyl radical capture at the (P,O)cobalt(II)–aryl catalyst resting state, enabling selective formation of the C(sp²)–C(sp³) product.

To explore arylboron transmetalation at manganese(I), reactions of 4-fluorophenylborates with pentacarbonylmanganese(I) hexafluorophosphate cation (CO)₅Mn(MeCN)(PF₆) were evaluated for the formation of 4-fluorophenylmanganese(I) pentacarbonyl (CO)₅Mn(4-F–C₆H₄). The optimal reagent was neopentylglycol 4-fluorophenylboronic ester activated with n-butyllithium, which reacted with (CO)₅Mn(MeCN)(PF₆) to give (CO)₅Mn(4-F–C₆H₄) in 58% yield. These conditions were extrapolated to reactions involving other neopentylglycol esters to yield a scope of seven (CO)₅Mn(I)–aryls with varied substitutions on the aryl ring. The bench-stable, diamagnetic (CO)₅Mn(I)–aryl compounds were purified by flash column chromatography on silica and were characterized by IR spectroscopy and by ¹H, ¹³C, ¹⁹F, and ⁵⁵Mn NMR spectroscopies, with solid-state molecular structures verified by X-ray crystallography. Finally, (CO)₅Mn(4-F–C₆H₄) was explored as a synthetic arylating reagent in reactions with various electrophiles and nucleophiles, with organic products including those from aryl C(sp²)–X and aroyl C(sp²)CO–X bond formation.