Mechanistic Studies and Identification of Catalyst Deactivation Pathways for Pyridine(diimine) Iron Catalyzed C(sp)-H Borylation.

The synthesis and application of aryl-substituted pyridine(diimine) iron complexes (PDI)FeCH to the catalytic borylation of heteroarenes under thermal conditions is described. Improvements in catalyst design and performance were guided by precatalyst activation studies, where investigations into stoichiometric reactivities of iron borohydride (4- Bu- PDI)Fe(HBPin) and iron furyl (4- Bu- PDI)Fe(2-methylfuryl) complexes revealed facile C(sp)-H activation and a slower and potentially turnover-limiting C(sp)-B formation step. Formation of the flyover dimer, [(4- Bu- PDI)Fe] was identified as a catalyst deactivation pathway and formally iron(0) complexes were found to be inactive for borylation.

Kinetic and thermodynamic control of C(sp)-H activation enables site-selective borylation.

Catalysts that distinguish between electronically distinct carbon-hydrogen (C-H) bonds without relying on steric effects or directing groups are challenging to design. In this work, cobalt precatalysts supported by -alkyl-imidazole-substituted pyridine dicarbene (ACNC) pincer ligands are described that enable undirected, remote borylation of fluoroaromatics and expansion of scope to include electron-rich arenes, pyridines, and tri- and difluoromethoxylated arenes, thereby addressing one of the major limitations of first-row transition metal C-H functionalization catalysts. Mechanistic studies established a kinetic preference for C-H bond activation at the -position despite cobalt-aryl complexes resulting from C-H activation being thermodynamically preferred.

Bimolecular Reductive Elimination of Ethane from Pyridine(diimine) Iron Methyl Complexes: Mechanism, Electronic Structure, and Entry into [2+2] Cycloaddition Catalysis.

The application of bimolecular reductive elimination to the activation of iron catalysts for alkene-diene cycloaddition is described. Key to this approach was the synthesis, characterization, electronic structure determination, and ultimately solution stability of a family of pyridine(diimine) iron methyl complexes with diverse steric properties and electronic ground states. Both the aryl-substituted, (PDI)FeCH and (PDI)FeCH (PDI = 2,6-(2,6-R-CHN═CMe)CHN), and the alkyl-substituted examples, (APDI)FeCH (APDI = 2,6-(CHN═CMe)CHN), have molecular structures significantly distorted from planarity and = 3/2 ground states.

Alcohol Synthesis by Cobalt-Catalyzed Visible-Light-Driven Reductive Hydroformylation.

A cobalt-catalyzed reductive hydroformylation of terminal and 1,1-disubstituted alkenes is described. One-carbon homologated alcohols were synthesized directly from CO and H, affording anti-Markovnikov products (34-87% yield) with exclusive regiocontrol (linear/branch >99:1) for minimally functionalized alkenes. Irradiation of the air-stable cobalt hydride, (dcype)Co(CO)H (dcype = dicyclohexylphosphinoethane) with blue light generated the active catalyst that mediates alkene hydroformylation and subsequent aldehyde hydrogenation.

C(sp)-H Activation with Bis(silylene)pyridine Cobalt(III) Complexes: Catalytic Hydrogen Isotope Exchange of Sterically-Hindered C-H Bonds.

The bis(silylene)pyridine cobalt(III) dihydride boryl, -[ SiNSi]Co(H)BPin (SiNSi = 2,6-[EtNSi(NBu)CAr] CHN, where Ar = CHCH, and Pin =pinacolato) has been used as a precatalyst for the hydrogen isotope exchange (HIE) of arenes and heteroarenes using benzene- as the deuterium source. Use of D as the source of the isotope produced modest levels of deuterium incorporation and stoichiometric studies established modification of the pincer ligand through irreversible addition of H across the silylene leading to catalyst deactivation. High levels of deuterium incorporation were observed with benzene- as the isotope source and enabled low (0.

Molybdenum-Catalyzed Asymmetric Hydrogenation of Fused Arenes and Heteroarenes.

The synthesis of enantioenriched molybdenum precatalysts for the asymmetric hydrogenation of substituted quinolines and naphthalenes is described. Three classes of pincer ligands with chiral substituents were evaluated as supporting ligands in the molybdenum-catalyzed hydrogenation reactions, where oxazoline imino(pyridine) chelates were identified as optimal. A series of 2,6-disubstituted quinolines was hydrogenated to enantioenriched decahydroquinolines with high diastereo- and enantioselectivities.

Development of Cobalt Catalysts for the -Selective C(sp)-H Borylation of Fluorinated Arenes.

Cobalt precatalysts for the -selective borylation of fluorinated arenes are described. Initial screening and stoichiometric reactivity studies culminated in the preparation of a cobalt alkyl precatalyst supported by the sterically protected terpyridine ( = 4'-(4--dimethylaminophenyl)-5,5″-dimethyl-2,2':6',2″-terpyridine). Under the optimized conditions, borylation with this precatalyst afforded up to 16 turnovers and near-exclusive regioselectivity with a range of substituted fluoroarenes in cyclopentyl methyl ether solvent at room temperature.

Visible-Light-Driven, Iridium-Catalyzed Hydrogen Atom Transfer: Mechanistic Studies, Identification of Intermediates, and Catalyst Improvements.

The harvesting of visible light is a powerful strategy for the synthesis of weak chemical bonds involving hydrogen that are below the thermodynamic threshold for spontaneous H evolution. Piano-stool iridium hydride complexes are effective for the blue-light-driven hydrogenation of organic substrates and contra-thermodynamic dearomative isomerization. In this work, a combination of spectroscopic measurements, isotopic labeling, structure-reactivity relationships, and computational studies has been used to explore the mechanism of these stoichiometric and catalytic reactions.

Effect of Pincer Methylation on the Selectivity and Activity in (PNP)Cobalt-Catalyzed C(sp)-H Borylation.

Cobalt complexes supported by a tetramethylated PNP pincer ligand (Me PNP = 2,6-(PrPCMe)(CHN)) have been synthesized and structurally characterized. Examples include cobalt(I)-choride, -methyl, -aryl and -benzofuranyl derivatives. The performance of these compounds was evaluated in the catalytic borylation of fluorinated arenes using BPin as the boron source.

Catalyst Design Principles Enabling Intermolecular Alkene-Diene [2+2] Cycloaddition and Depolymerization Reactions.

Aryl-substituted pyridine(diimine) iron complexes promote the catalytic [2 + 2] cycloadditions of alkenes and dienes to form vinylcyclobutanes as well as the oligomerization of butadiene to generate divinyl(oligocyclobutane), a microstructure of poly(butadiene) that is chemically recyclable. A systematic study on a series of iron butadiene complexes as well as their ruthenium congeners has provided insights into the essential features of the catalyst that promotes these cycloaddition reactions. Structural and computational studies on iron butadiene complexes identified that the structural rigidity of the tridentate pincer enables rare s-trans diene coordination.

A Tutorial on Selectivity Determination in C(sp)-H Oxidative Addition of Arenes by Transition Metal Complexes.

A Tutorial on factors that determine the selectivity in C(sp)-H activation and functionalization reactions involving two-electron oxidative addition processes with transition metals is presented. The interplay of the thermodynamics of C(sp)-H oxidative addition and kinetic influences upon regioselectivity are presented alongside pedagogically valuable experimental and computational results from the literature. Mechanisms and energetics of chelate-assisted C(sp)-H oxidative addition are examined, as are concepts related to chemoselectivity in the oxidative addition of C(sp)-H or C(sp)-X (X = F, Cl, Br, I) bonds with aryl halide substrates.

Mechanistic Origins of Regioselectivity in Cobalt-Catalyzed C(sp)-H Borylation of Benzoate Esters and Arylboronate Esters.

Synthetic and mechanistic investigations into the C(sp)-H borylation of various electronically diverse arenes catalyzed by bis(phosphine)pyridine (PNP) cobalt complexes are reported. Borylation of various benzoate esters and arylboronate esters gave remarkably high selectivities for the position to the functional group; in both cases, this regioselectivity was found to override the to fluorine regioselectivity previously reported for (PNP)Co borylation catalysts which arises from thermodynamic control of C(sp)-H oxidative addition. Mechanistic studies support two distinct pathways that result in -to-ester and -to-boronate ester regioselectivity by thermodynamic and kinetic control, respectively, of C(sp)-H oxidative addition.

C(sp)-H Borylation of Heterocycles by Well-Defined Bis(silylene)pyridine Cobalt(III) Precatalysts: Pincer Modification, C(sp)-H Activation and Catalytically Relevant Intermediates.

Well-defined bis(silylene)pyridine cobalt(III) precatalysts for C(sp)-H borylation have been synthesized and applied to the investigation of the mechanism of the catalytic borylation of furans and pyridines. Specifically, [( SiNSi)CoH]·NaHBEt ( SiNSi = 2,6-[EtNSi(NBu)CAr]CHN, = CH ( ), 4-MeCH ( )) and -[( SiNSi)Co(H)BPin] ( = CH ( ), 4-MeCH ( ), Pin = pinacolato) were prepared and employed as single component precatalysts for the C(sp)-H borylation of 2-methylfuran, benzofuran and 2,6-lutidine. The cobalt(III) precursors, and also promoted C(sp)-H activation of benzofuran, yielding [(SiNSi)CoH(Bf)] (Ar = 4-MeCH, , Bf = 2-benzofuranyl).

Synthesis and Reactivity of Organometallic Intermediates Relevant to Cobalt-Catalyzed Hydroformylation.

Intermediates relevant to cobalt-catalyzed alkene hydroformylation have been isolated and evaluated in fundamental organometallic transformations relevant to aldehyde formation. The 18-electron (R,R)-( DuPhos)Co(CO) H has been structurally characterized, and it promotes exclusive hydrogenation of styrene in the presence of 50 bar of H /CO gas (1:1) at 100 °C. Deuterium-labeling studies established reversible 2,1-insertion of styrene into the Co-D bond of (R,R)-( DuPhos)Co(CO) D.

A Boron Activating Effect Enables Cobalt-Catalyzed Asymmetric Hydrogenation of Sterically Hindered Alkenes.

Unsymmetric 1,1-diboryl alkenes bearing one -[BPin] (BPin = pinacolatoboryl) and one -[BDan] (BDan = 1,8-diaminonaphthalatoboryl) substituent each were hydrogenated in high yield and enantioselectivity using -symmetric pyridine(diimine) (PDI) cobalt complexes. High activities and stereoselectivities were observed with an array of 2-alkyl-, 2-aryl-, and 2-boryl-substituted 1,1-diboryl alkenes, giving rise to enantioenriched diborylalkane building blocks. Systematic study of substrate substituent effects identified competing steric and electronic demands in the key activating role of the boron substituents, whereby sterically unencumbered boronates such as -[BDan], -[BCat] (BCat = catecholatoboryl), and -[Beg] (Beg = ethylene glycolatoboryl) promote the hydrogenation of trisubstituted alkenes by enabling irreversible α-boron-directed insertion pathways to achieve otherwise challenging hydrogenations of trisubstituted alkenes.

Synthesis, Structure, and Hydrogenolysis of Pyridine Dicarbene Iron Dialkyl Complexes.

Two methods for the synthesis of bis(imidazol-2-ylidene)pyridine iron dialkyl complexes, (CNC)Fe(CHSiMe), have been developed. The first route consists of addition of two equivalents of LiCHSiMe to the iron dihalide complex, (CNC)FeBr, while the second relies on addition of the free CNC ligand to readily-prepared (py)Fe(CHSiMe) (py = pyridine). With aryl-substituted CNC ligands, octahedral complexes of the type ( CNC)Fe(CHSiMe)(N) ( CNC = bis(arylimidazol-2-ylidene)pyridine) were isolated, where the dinitrogen ligand occupies the site to the pyridine of the CNC-chelate.

Cobalt-Catalyzed Borylation of Fluorinated Arenes: Thermodynamic Control of C(sp)-H Oxidative Addition Results in -to-Fluorine Selectivity.

The mechanism of C(sp)-H borylation of fluorinated arenes with BPin (Pin = pinacolato) catalyzed by bis(phosphino)pyridine (PNP) cobalt complexes was studied to understand the origins of the uniquely high -to-fluorine regioselectivity observed in these reactions. Variable time normalization analysis (VTNA) of reaction time courses and deuterium kinetic isotope effect measurements established a kinetic regime wherein C(sp)-H oxidative addition is fast and reversible. Monitoring the reaction by in situ NMR spectroscopy revealed the intermediacy of a cobalt(I)-aryl complex that was generated with the same high -to-fluorine regioselectivity associated with the overall catalytic transformation.