The importance of understanding (pre)catalyst activation in versatile C-H bond functionalisations catalysed by [Mn2(CO)10].

Mn-catalysed reactions offer great potential in synthetic organic and organometallic chemistry and the success of Mn carbonyl complexes as (pre)catalysts hinges on their stabilisation by strong field ligands enabling Mn(i)-based, redox neutral, catalytic cycles. The mechanistic processes underpinning the activation of the ubiquitous Mn(0) (pre)catalyst [Mn2(CO)10] in C-H bond functionalisation reactions is now reported for the first time. By combining time-resolved infra-red (TRIR) spectroscopy on a ps-ms timescale and in operando studies using in situ infra-red spectroscopy, insight into the microscopic bond activation processes which lead to the catalytic activity of [Mn2(CO)10] has been gained. Using an exemplar system, based on the annulation between an imine, 1, and Ph2C2, 2, TRIR spectroscopy enabled the key intermediate [Mn2(CO)9(1)], formed by CO loss from [Mn2(CO)10], to be identified. In operando studies demonstrate that [Mn2(CO)9(1)] is also formed from [Mn2(CO)10] under the catalytic conditions and is converted into a mononuclear manganacycle, [Mn(CO)4(C^N)] (C^N = cyclometallated imine), a second molecule of 1 acts as the oxidant which is, in turn, reduced to an amine. As [Mn(CO)4(C^N)] complexes are catalytically competent, a direct route from [Mn2(CO)10] into the Mn(i) catalytic reaction coordinate has been determined. Critically, the mechanistic differences between [Mn2(CO)10] and Mn(i) (pre)catalysts have been delineated, informing future catalyst screening studies.

Gold(I)-Catalyzed Intermolecular Aryloxyvinylation with Acetylene Gas.

Acetylene gas is an important feedstock for chemical production, although it is underutilized in organic synthesis. We have developed an intermolecular gold(I)-catalyzed alkyne/alkene reaction of o-allylphenols with acetylene gas that gives rise to chromanes by a stereospecific aryloxycyclization through the nucleophilic regioselective opening of cyclopropyl gold(I)-carbene intermediates. The synthetic application of this method was demonstrated in the late-stage functionalization of the natural product lapachol.

Understanding Precatalyst Activation and Speciation in Manganese-Catalyzed C-H Bond Functionalization Reactions.

An investigation into species formed following precatalyst activation in Mn-catalyzed C-H bond functionalization reactions is reported. Time-resolved infrared spectroscopy demonstrates that light-induced CO dissociation from precatalysts [Mn(C^N)(CO)4] (C^N = cyclometalated 2-phenylpyridine (1a), cyclometalated 1,1-bis(4-methoxyphenyl)methanimine (1b)) in a toluene solution of 2-phenylpyridine (2a) or 1,1-bis(4-methoxyphenyl)methanimine (2b) results in the initial formation of solvent complexes fac-[Mn(C^N)(CO)3(toluene)]. Subsequent solvent substitution on a nanosecond time scale then yields fac-[Mn(C^N)(CO)3(κ1-(N)-2a)] and fac-[Mn(C^N)(CO)3(κ1-(N)-2b)], respectively. When the experiments are performed in the presence of phenylacetylene, the initial formation of fac-[Mn(C^N)(CO)3(toluene)] is followed by a competitive substitution reaction to give fac-[Mn(C^N)(CO)3(2)] and fac-[Mn(C^N)(CO)3(η2-PhC2H)]. The fate of the reaction mixture depends on the nature of the nitrogen-containing substrate used. In the case of 2-phenylpyridine, migratory insertion of the alkyne into the Mn-C bond occurs, and fac-[Mn(C^N)(CO)3(κ1-(N)-2a)] remains unchanged. In contrast, when 2b is used, substitution of the η2-bound phenylacetylene by 2b occurs on a microsecond time scale, and fac-[Mn(C^N)(CO)3(κ1-(N)-2b)] is the sole product from the reaction. Calculations with density functional theory indicate that this difference in behavior may be correlated with the different affinities of 2a and 2b for the manganese. This study therefore demonstrates that speciation immediately following precatalyst activation is a kinetically controlled event. The most dominant species in the reaction mixture (the solvent) initially binds to the metal. The subsequent substitution of the metal-bound solvent is also kinetically controlled (on a ns time scale) prior to the thermodynamic distribution of products being obtained.

A comprehensive understanding of carbon-carbon bond formation by alkyne migratory insertion into manganacycles.

Migratory insertion (MI) is one of the most important processes underpinning the transition metal-catalysed formation of C-C and C-X bonds. In this work, a comprehensive model of MI is presented, based on the direct observation of the states involved in the coupling of alkynes with cyclometallated ligands, augmented with insight from computational chemistry. Time-resolved spectroscopy demonstrates that photolysis of complexes [Mn(C^N)(CO)4] (C^N = cyclometalated ligand) results in ultra-fast dissociation of a CO ligand. Performing the experiment in a toluene solution of an alkyne results in the initial formation of a solvent complex fac-[Mn(C^N)(toluene)(CO)3]. Solvent substitution gives an η2-alkyne complex fac-[Mn(C^N)(η2-R1C2R2)(CO)3] which undergoes MI of the unsaturated ligand into the Mn-C bond. These data allowed for the dependence of second order rate constants for solvent substitution and first order rate constants for C-C bond formation to be determined. A systematic investigation into the influence of the alkyne and C^N ligand on this process is reported. The experimental data enabled the development of a computational model for the MI reaction which demonstrated that a synergic interaction between the metal and the nascent C-C bond controls both the rate and regiochemical outcome of the reaction. The time-resolved spectroscopic method enabled the observation of a multi-step reaction occurring over 8 orders of magnitude in time, including the formation of solvent complexes, ligand substitution and two sequential C-C bond formation steps.

Direct Observation of the Microscopic Reverse of the Ubiquitous Concerted Metalation Deprotonation Step in C-H Bond Activation Catalysis.

The ability of carboxylate groups to promote the direct functionalization of C-H bonds in organic compounds is unquestionably one of the most important discoveries in modern chemical synthesis. Extensive computational studies have indicated that this process proceeds through the deprotonation of a metal-coordinated C-H bond by the basic carboxylate, yet experimental validation of these predicted mechanistic pathways is limited and fraught with difficulty, mainly as rapid proton transfer is frequently obscured in ensemble measures in multistep reactions (i.e., a catalytic cycle consisting of several steps). In this paper, we describe a strategy to experimentally observe the microscopic reverse of the key C-H bond activation step underpinning functionalization processes (viz. M-C bond protonation). This has been achieved by utilizing photochemical activation of the thermally robust precursor [Mn(ppy)(CO)4] (ppy = metalated 2-phenylpyridine) in neat acetic acid. Time-resolved infrared spectroscopy on the picosecond-millisecond time scale allows direct observation of the states involved in the proton transfer from the acetic acid to the cyclometalated ligand, providing direct experimental evidence for the computationally predicted reaction pathways. The power of this approach to probe the mechanistic pathways in transition-metal-catalyzed reactions is demonstrated through experiments performed in toluene solution in the presence of PhC2H and HOAc. These allowed for the observation of sequential displacement of the metal-bound solvent by the alkyne, C-C bond formation though insertion in the Mn-C bond, and a slower protonation step by HOAc to generate the product of a Mn(I)-catalyzed C-H bond functionalization reaction.

Light- and Manganese-Initiated Borylation of Aryl Diazonium Salts: Mechanistic Insight on the Ultrafast Time-Scale Revealed by Time-Resolved Spectroscopic Analysis.

Manganese-mediated borylation of aryl/heteroaryl diazonium salts emerges as a general and versatile synthetic methodology for the synthesis of the corresponding boronate esters. The reaction proved an ideal testing ground for delineating the Mn species responsible for the photochemical reaction processes, that is, involving either Mn radical or Mn cationic species, which is dependent on the presence of a suitably strong oxidant. Our findings are important for a plethora of processes employing Mn-containing carbonyl species as initiators and/or catalysts, which have considerable potential in synthetic applications.

Correction: Time-resolved infra-red spectroscopy reveals competitive water and dinitrogen coordination to a manganese(i) carbonyl complex.

Correction for 'Time-resolved infra-red spectroscopy reveals competitive water and dinitrogen coordination to a manganese(i) carbonyl complex' by Jonathan B. Eastwood et al., Dalton Trans., 2020, DOI: .

Time-resolved infra-red spectroscopy reveals competitive water and dinitrogen coordination to a manganese(i) carbonyl complex.

Time-resolved infra-red (TRIR) spectroscopy has been used to demonstrate that photolysis of [Mn(C^N)(CO)4] (C^N = bis-(4-methoxyphenyl)methanimine) in heptane solution results in ultra-fast CO dissociation and ultimate formation of a rare Mn-containing dinitrogen complex fac-[Mn(C^N)(CO)3(N2)] with a diagnostic stretching mode for a terminal-bound N[triple bond, length as m-dash]N ligand at 2249 cm-1. An isotopic shift to 2174 cm-1 was observed when the reaction was performed under 15N2 and the band was not present when the experiment was undertaken under an atmosphere of argon, reinforcing this assignment. An intermediate solvent complex fac-[Mn(C^N)(CO)3(heptane)] was identified which is formed in less than 2 ps, indicating that CO-release occurs on an ultra-fast timescale. The heptane ligand is labile and is readily displaced by both N2 and water to give fac-[Mn(C^N)(CO)3(N2)] and fac-[Mn(C^N)(CO)3(OH2)] respectively. The fac-[Mn(C^N)(CO)3(heptane)] framework showed a significant affinity for N2, as performing the reaction under air produced significant amounts of fac-[Mn(C^N)(CO)3(N2)]. Kinetic analysis reveals that the substitution of heptane by N2 (k = (1.028 ± 0.004) × 109 mol-1 dm3 s-1), and H2O is competitive on fast (<1 µs) time scales. The binding of water is reversible and, under an atmosphere of N2, some fac-[Mn(C^N)(CO)3(OH2)] converts to fac-[Mn(C^N)(CO)3(N2)].

Delineating the critical role of acid additives in Mn-catalysed C-H bond functionalisation processes.

Addition of co-catalytic Cy2NH to Mn-catalysed C-H bond activation reactions suggests that the conjugate acid, Cy2NH2X, influences catalysis. Here, acids are shown to positively influence C-H bond alkenylation catalysis involving alkynes. For certain types of alkynes an acid additive is critical to catalysis. In stark contrast, acids retard catalysis involving acrylates. [Cy2NH2]X salts also play a key role in thwarting catalyst degradation to manganese clusters. Our findings enable unreactive substrates to be alkenylated.

Mechanistic Insight into Catalytic Redox-Neutral C-H Bond Activation Involving Manganese(I) Carbonyls: Catalyst Activation, Turnover, and Deactivation Pathways Reveal an Intricate Network of Steps.

Manganese(I) carbonyl-catalyzed C-H bond functionalization of 2-phenylpyridine and related compounds containing suitable metal directing groups has recently emerged as a potentially useful synthetic methodology for the introduction of various groups to the ortho position of a benzene ring. Preliminary mechanistic studies have highlighted that these reactions could proceed via numerous different species and steps and, moreover, potentially different catalytic cycles. The primary requirement for typically 10 mol % catalyst, oftentimes the ubiquitous precursor catalyst, BrMn(CO)5, has not yet been questioned nor significantly improved upon, suggesting catalytic deactivation may be a serious issue to be understood and resolved. Several critical questions are further raised by the species responsible for providing a source of protons in the protonation of vinyl-manganese(I) carbonyl intermediates. In this study, using a combination of experimental and theoretical methods, we provide comprehensive answers to the key mechanistic questions concerning the Mn(I) carbonyl-catalyzed C-H bond functionalization of 2-phenylpyridine and related compounds. Our results enable the explanation of alkyne substrate dependencies, i.e., internal versus terminal alkynes. We found that there are different catalyst activation pathways for BrMn(CO)5, e.g., terminal alkynes lead to the generation of MnI-acetylide species, whose formation is reminiscent of CuI-acetylide species proposed to be of critical importance in Sonogashira cross-coupling processes. We have unequivocally established that alkyne, 2-phenylpyridine, and water can facilitate hydrogen transfer in the protonation step, leading to the liberation of protonated alkene products.

Mild and Regioselective Pd(OAc)2-Catalyzed C-H Arylation of Tryptophans by [ArN2]X, Promoted by Tosic Acid.

A regioselective Pd-mediated C-H bond arylation methodology for tryptophans, utilizing stable aryldiazonium salts, affords C2-arylated tryptophan derivatives, in several cases quantitatively. The reactions proceed in air, without base, and at room temperature in EtOAc. The synthetic methodology has been evaluated and compared against other tryptophan derivative arylation methods using the CHEM21 green chemistry toolkit. The behavior of the Pd catalyst species has been probed in preliminary mechanistic studies, which indicate that the reaction is operating homogeneously, although Pd nanoparticles are formed during substrate turnover. The effects of these higher order Pd species on catalysis, under the reaction conditions examined, appear to be minimal: e.g., acting as a Pd reservoir in the latter stages of substrate turnover or as a moribund form (derived from catalyst deactivation). We have determined that TsOH shortens the induction period observed when [ArN2]BF4 salts are employed with Pd(OAc)2. Pd(OTs)2(MeCN)2 was found to be a superior precatalyst (confirmed by kinetic studies) in comparison to Pd(OAc)2.

Manganese(I)-Catalyzed C-H Activation: The Key Role of a 7-Membered Manganacycle in H-Transfer and Reductive Elimination.

Manganese-catalyzed C-H bond activation chemistry is emerging as a powerful and complementary method for molecular functionalization. A highly reactive seven-membered Mn(I) intermediate is detected and characterized that is effective for H-transfer or reductive elimination to deliver alkenylated or pyridinium products, respectively. The two pathways are determined at Mn(I) by judicious choice of an electron-deficient 2-pyrone substrate containing a 2-pyridyl directing group, which undergoes regioselective C-H bond activation, serving as a valuable system for probing the mechanistic features of Mn C-H bond activation chemistry.