Migratory Insertion Reactions Research Articles

Unveiling Mechanistic Complexity in Manganese-Catalyzed C-H Bond Functionalization Using IR Spectroscopy Over 16 Orders of Magnitude in Time.

ConspectusAn understanding of the mechanistic processes that underpin reactions catalyzed by 3d transition metals is vital for their development as potential replacements for scarce platinum group metals. However, this is a significant challenge because of the tendency of 3d metals to undergo mechanistically diverse pathways when compared with their heavier congeners, often as a consequence of one-electron transfer reactions and/or intrinsically weaker metal-ligand bonds. We have developed and implemented a new methodology to illuminate the pathways that underpin C-H bond functionalization pathways in reactions catalyzed by Mn-carbonyl compounds. By integrating measurements performed on catalytic reactions with in situ reaction monitoring and state-of-the-art ultrafast spectroscopic methods, unique insight into the mode of action and fate of the catalyst have been obtained.Using a combination of time-resolved spectroscopy and in situ low-temperature NMR studies, we have shown that photolysis of manganese-carbonyl precatalysts results in rapid (<5 ps) CO dissociation─the same process that occurs under thermal catalytic conditions. This enabled the detection of the key states relevant to catalysis, including solvent and alkyne complexes and their resulting transformation into manganacycles, which results from a migratory insertion reaction into the Mn-C bond. By systematic variation of the substrates (many of which are real-world structurally diverse substrates and not simple benchmark systems) and quantification of the resulting rate constants for the insertion step, a universal model for this migratory insertion process has been developed. The time-resolved spectroscopic method gave insight into fundamental mechanistic pathways underpinning other aspects of modern synthetic chemistry. The most notable was the first direct experimental observation of the concerted metalation deprotonation (CMD) mechanism through which carboxylate groups are able to mediate C-H bond activation at a metal center. This step underpins a host of important synthetic applications. This study demonstrated how the time-resolved multiple probe spectroscopy (TRMPS) method enables the observation of mechanistic process occurring on time scales from several picoseconds through to μs in a single experiment, thereby allowing the sequential observation of solvation, ligand substitution, migratory insertion, and ultimate protonation of a Mn-C bond.These studies have been complemented by an investigation of the "in reaction flask" catalyst behavior, which has provided additional insight into new pathways for precatalyst activation, including evidence that alkyne C-H bond activation may occur before heterocycle activation. Crucial insight into the fate of the catalyst species showed that excess water played a key role in deactivation to give higher-order hydroxyl-bridged manganese carbonyl clusters, which were independently found to be inactive. Traditional in situ IR and NMR spectroscopic analysis on the second time scale bridges the gap to the analysis of real catalytic reaction systems. As a whole, this work has provided unprecedented insight into the processes underpinning manganese-catalyzed reactions spanning 16 orders of magnitude in time.

Heavier Group 14 Congeners of Metalla‐isobenzenes: Access to Metalla‐isosilabenzene and Metalla‐isogermabenzene by One‐Pot Reactions

Comprehensive SummaryMetalla‐isosilabenzenes and metalla‐isogermabenzenes have been successfully synthesized by the formal [5+1]‐cycloaddition of diethynylsilane or diethynylgermane with simple metal complexes. This is the first example of a heavier Group 14 metalla‐isobenzene isomer bearing a cumulative double bond motif within a metallacycle. These novel complexes were fully characterized by NMR spectroscopy and single‐crystal X‐ray diffraction analysis. The stabilization of the cyclic metal‐vinylidene complexes has been analyzed using density functional theory (DFT) calculations. When the metalla‐isosilabenzenes bearing Si—H bond were treated with the trityl salt as a hydride scavenger, the formation of silylium cation was observed spectroscopically. Both of metalla‐isosilabenzenes and metalla‐isogermabenzenes can readily undergo migratory insertion reactions to furnish siloles or germoles.

A concise synthesis of marine natural product (−)-15-oxopuupehenol from (+)-sclarelide

A step-economical synthesis of (−)-15-oxopuupehenol from cheap and readily available (+)-sclarelide is achieved with 20.3% overall yield in 9 steps. The key features of this synthetic mythology include a palladium catalyzed tandem carbine migratory insertion reaction to construct the key skeleton, a DDQ-mediated isomerization/oxidation of allyl alcohol to afford α, β-unsaturated ketone, and a NaOH-induced intramolecular Michael addition followed by acetonide deprotection to give (−)-15-oxopuupehenol.

Transition-Metal-Catalyzed C-H Bond Functionalization of Arenes/Heteroarenes via Tandem C-H Activation and Subsequent Carbene Migratory Insertion Strategy.

The past decade has witnessed tremendous developments in transition-metal-catalyzed C-H bond activation and subsequent carbene migratory insertion reactions, thus assisting in the construction of diverse arene/heteroarene scaffolds. Various transition-metal catalysts serve this purpose and provide efficient pathways for an easy access to substituted heterocycles. A brief introduction to metal-carbenes has been provided along with key mechanistic pathways underlying the coupling reactions. The purpose of this review is to provide a concise knowledge about diverse directing group-assisted coupling of varied arenes/heteroarenes and acceptor-acceptor/donor-acceptor diazo compounds. The review also highlights the synthesis of various carbocycles and fused heterocycles through diazo insertion pathways, via C-C, C-N and C-O bond forming reactions. The mechanism usually involves a C-H activation process, followed by diazo insertion leading to subsequent coupling.

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions.

A combined experimental–computational approach has been used to study the cyclopropanation reaction of N-hydroxyphthalimide diazoacetate (NHPI-DA) with various olefins, catalyzed by a ruthenium-phenyloxazoline (Ru-Pheox) complex. Kinetic studies show that the better selectivity of the employed redox-active NHPI diazoacetate is a result of a much slower dimerization reaction compared to aliphatic diazoacetates. Density functional theory calculations reveal that several reactions can take place with similar energy barriers, namely, dimerization of the NHPI diazoacetate, cyclopropanation (inner-sphere and outer-sphere), and a previously unrecognized migratory insertion of the carbene into the phenyloxazoline ligand. The calculations show that the migratory insertion reaction yields an unconsidered ruthenium complex that is catalytically competent for both the dimerization and cyclopropanation, and its relevance is assessed experimentally. The stereoselectivity of the reaction is argued to stem from an intricate balance between the various mechanistic scenarios.

Synthesis and structural determination of [Rh(opo)(CO)(PR3)] complexes (opo− = 2-oxopyridin-1-olate) and in situ isomeric behavior from preliminary kinetic study of iodomethane oxidative addition

A range of complexes, [Rh(opo)(CO)(PR3)], with opo− = 2-oxopyridin-1-olate, and [Rh(opo)(CO)2] (1), [Rh(opo)(CO)(PPh3)] (2AI/BI ), [Rh(opo)(CO)(PPh2Cy)] (3AI/BI ), [Rh(opo)(CO)(PPhCy2)] (4AI/BI ), [Rh(opo) (CO)(PCy3)] (5AI/BI ), [Rh(opo)(CO)(P(o-Tol)3)] (6AI/BI ), [Rh(opo)(CO) (P(m-Tol)3)] (7AI/BI ), [Rh(opo)(CO)(P(p-Tol)3)] (8AI/BI ), and cis-[Rh(opo)(CO)(CH3)(I)(PPh3)] (2AII ), were synthesized and characterized by IR and NMR spectroscopy. Two isomers (A = major, MaI; B = minor, MiI) were observed in ca. 2:1 ratios for complexes 2–8 due to the similar characteristics of the chelating O-donors, yet non-symmetric within the bidentate ligand. Single crystal X-ray diffraction yielded the solid-state structures of the major isomers of 4AI , 5AI , 6AI , and 2AII . Metallophilic interactions were observed between neighboring Rh(I) centers in [Rh(opo)(CO)2] (1) with an intermolecular Rh···Rh distance of 3.5780(5) Å. These interactions do not occur in the crystal structures of 4AI , 5AI , 6AI , and 2AII , attributed to the steric bulk of the phosphine ligands and the interactions observed in the crystal lattice of these structures. Preliminary iodomethane oxidative addition (OA) to the rhodium(I) complexes [Rh(opo)(CO)(PR3)] was investigated by IR, NMR, and UV-Vis spectroscopy, yielding corresponding alkyl intermediate species (nAII /BII ) or acyl products (nAIII /BIII ), respectively, for n = 2–8 and PR3 = PPh3 (2), PPh2Cy (3), PPhCy2 (4), PCy3 (5), P(o-Tol)3 (6), P(m-Tol)3 (7), P(p-Tol)3 (8). The rates of OA and assumed subsequent migratory carbonyl insertion (CI) reactions were identical within standard deviations, suggesting the CI to be fast relative to the OA. Moreover, the interconversion between the two isomers A and B seemed to be a slower process, governed by the relative steric strain induced by the tertiary phosphine ligands and not by the rates.

Group 4 Organometallics Supported by Sterically Hindered β‐Diketonates

The synthesis, characterization, and reactivity of group 4 organometallics supported by β‐diketonates is reported. Sterically hindered β‐diketonates, such as 2,6‐dimesitylbenzoyl pinacolone (L1) and 2,6‐dimesitylbenzoyl acetylmesitylene (L2), preclude the formation of tetrakis‐ and tris‐chelates, halting at cis‐octahedrally coordinated M(Ln)2Cl2 (M = Ti, Zr, Hf; Ln = L1, L2). Metathesis with benzylmagnesium chloride affords M(Ln)2Bn2 (M = Zr, Hf) and the reduced Ti(L1)2Bn(THF) species. These are the first structurally‐characterized metal alkyl complexes exclusively supported by β‐diketonates among the group 4 metals. Thermolysis of Zr(Ln)2Bn2 complexes results in unimolecular migratory insertion reaction, forming an enone by‐product and ZrO2. Combined Eyring analyses and computational investigations suggest the bond rearrangements are initiated by an initial benzyl migration reaction to the less hindered carbonyl group on the ligand. Activation of M(Ln)2Bn2 (M = Zr, Hf) in the presence of olefins resulted in similar oxygen abstraction. Implications and prospects for β‐diketonate‐supported catalysis are discussed.

Facile insertion of ethylene into a group 14 element-carbon bond: effects of the HOMO-LUMO energy gap on reactivity.

The diarylstannylenes, Sn(AriPr4)2 and Sn(AriPr6)2, (AriPr4 = C6H3-2,6-(C6H3-2,6-iPr2)2, AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2), undergo a facile migratory insertion reaction with ethylene at 60 °C to afford the alkyl aryl stannylenes AriPr4SnCH2CH2AriPr4 and AriPr6SnCH2CH2AriPr6 which were characterized via1H, 13C and 119Sn NMR, UV-vis and IR spectroscopy, as well as by X-ray crystallography. Quantum mechanical calculations were performed, and two potential mechanisms were identified, with a migratory insertion reaction pathyway being energetically preferred.

Efficient and stereodivergent synthesis of unsaturated acyclic fragments bearing contiguous stereogenic elements.

Synthetic organic strategies that enable the catalytic and rapid assembly of a large array of organic compounds possessing multiple stereocenters in acyclic systems are somewhat rare, especially when it comes to reaching today’s high standards of efficiency and selectivity. In particular, the catalytic preparation of a three-dimensional molecular layout of a simple acyclic hydrocarbon skeleton possessing several stereocenters from simple and readily available reagents still represents a vastly uncharted domain. Here, we report a rapid, modular, stereodivergent and diversity-oriented unified strategy to construct acyclic molecular frameworks bearing up to four contiguous and congested stereogenic elements, with remarkably high levels of stereocontrol and in only three catalytic steps from commercially available alkynes. A regio- and diastereoselective catalytic Heck migratory insertion reaction of alkenylcyclopropyl carbinols merging selective C–C bond cleavage of a cyclopropane represents the key step.

Reactions of Metal-Carbon Bonds within Six-Membered Metallaaromatic Rings.

Metallaaromatics represent a distinct and attractive class of heterocycles, which have greatly expanded the library of known aromatics. They have garnered extensive research interest on account of their unique properties, organometallic reactivity, and aromaticity. The metal-carbon bonds have been regarded as the most active reaction sites of metallaaromatics and a variety of related reactions have been demonstrated in the literature. This Minireview summarized recent findings on the reactivity of the metal-carbon bonds, mainly relevant to the representative metallaaromatics with six-membered ring scaffolds. A series of reactions occurred on the metal-carbon bonds, including the nucleophilic addition reactions, nucleophilic aromatic substitution reactions, electrophilic addition reactions, reactions with unsaturated compounds, and migratory insertion reactions, have been classified. These reactions demonstrate that the metal-carbon bonds of metallaaromatics can undergo typical reactions for both aromatic species and metal carbene/carbyne complexes. Meanwhile, the reactivity trends of the metal-carbon bonds are strongly affected by the metal centers and the effect of the corresponding substituents of metallacycles.

Reactivity of a trans-[H–MoMo–H] unit towards alkenes and alkynes: bimetallic migratory insertion, H-elimination and other reactions

A full house of elementary reactions across a quadruple MoMo bond.

Low-Valent Ate Complexes Formed in Cobalt-Catalyzed Cross-Coupling Reactions with 1,3-Dienes as Additives.

The combination of CoCl2 and 1,3-dienes is known to catalyze challenging alkyl-alkyl cross-coupling reactions between Grignard reagents and alkyl halides, but the mechanism of these valuable transformations remains speculative. Herein, electrospray-ionization mass spectrometry is used to identify and characterize the elusive intermediates of these and related reactions. The vast majority of detected species contain low-valent cobalt(I) centers and diene molecules. Charge tagging, deuterium labeling, and gas-phase fragmentation experiments elucidate the likely origin of these species and show that the diene not only binds to Co as a π ligand, but also undergoes migratory insertion reactions into Co-H and Co-R bonds. The resulting species have a strong tendency to form anionic cobalt(I) ate complexes, the superior nucleophilicity of which should render them highly reactive toward electrophilic substrates and, thus, presumably is the key to the high catalytic efficiency of the system under investigation. Upon the reaction of the in situ formed cobalt(I) ate complexes with organyl halides, only the final cross-coupling product could be detected, but no cobalt(III) species. This finding implies that this reaction step proceeds in a direct manner without any intermediate or, alternatively, that it involves an intermediate with a very short lifetime.

Activation of Small Molecules by the Metal-Amido Bond of Rhodium(III) and Iridium(III) (η5-C5Me5)M-Aminopyridinate Complexes.

We report the synthesis and structural characterization of five-coordinate complexes of rhodium and iridium of the type [(η5-C5Me5)M(N^N)]+ (3-M+), where N^N represents the aminopyridinate ligand derived from 2-NH(Ph)-6-(Xyl)C5H3N (Xyl = 2,6-Me2C6H3). The two complexes were isolated as salts of the BArF anion (BArF = B[3,5-(CF3)2C6H3]4). The M-Namido bond of complexes 3-M+ readily activated CO, C2H4, and H2. Thus, compounds 3-M+ reacted with CO under ambient conditions, but whereas for 3-Rh+, CO migratory insertion was fast, yielding a carbamoyl carbonyl species, 4-Rh+, the stronger Ir-Namido bond of complex 3-Ir+ caused the reaction to stop at the CO coordination stage. In contrast, 3-Ir+ reacted reversibly with C2H4, forming adduct 5-Ir+, which subsequently rearranged irreversibly to [Ir](H)(═C(Me)N(Ph)-) complex 6-Ir+, which contains an N-stabilized carbene ligand. Computational studies supported a migratory insertion mechanism, giving first a β-stabilized linear alkyl unit, [Ir]CH2CH2N(Ph)-, followed by a multistep rearrangement that led to the final product 6-Ir+. Both β- and α-H eliminations, as well as their microscopic reverse migratory insertion reactions, were implicated in the alkyl-to-hydride-carbene reorganization. The analogous reaction of 3-Rh+ with C2H4 originated a complex mixture of products from which only a branched alkyl [Rh]C(H)(Me)N(Ph)- (5-Rh+) could be isolated, featuring a β-agostic methyl interaction. Reactions of 3-M+ with H2 promoted a catalytic isomerization of the Ap ligand from classical κ2-N,N' binding to κ-N plus η3-pseudoallyl coordination mode.

Iron Pincer Complexes Incorporating Bipyridine: A Strategy for Stabilization of Reactive Species

Treatment of FeCl2(thf)1.5 with the pincer ligand bis(dicyclohexylphosphinomethyl)pyrrolide (CyPNP) in the presence of 2,2′-bipyridine (bipy) affords the six-coordinate complex [FeCl(bipy)(CyPNP)]. The chloride complex exhibits spin-crossover behavior and serves as a starting point for a series of bipy-coordinated iron(II) pincer compounds, including the hydride species [FeH(bipy)(CyPNP)]. Chemical reduction of [FeCl(bipy)(CyPNP)] generates the new complex [Fe(bipy)(CyPNP)], which is found to be consistent with a structure featuring iron(I) as opposed to a bipy radical anion. Reactivity studies with the bipy complexes demonstrate that they are more prone to migratory insertion and β-hydrogen elimination reactions than the corresponding dicarbonyl analogues and that in certain instances the bipy ligand can be sequestered by treatment with a Lewis acid. These observations demonstrate that coordination of bipyridine to pincer-ligated iron(II) species provides a means of stabilizing otherwise unstable compoun...

Palladium-Catalyzed [3+3] Annulation of Vinyl Chromium(0) Carbene Complexes through Carbene Migratory Insertion/Tsuji-Trost Reaction.

Vinyl chromium(0) Fischer carbene complexes were employed as the source of π-allylic palladium species for catalytic [3+3] annulation under palladium catalysis. Mechanistically, this transformation is proposed to involve carbene migratory insertion and intramolecular Tsuji-Trost reaction as the key steps. Substituted six-membered heterocyclic flavonones and quinolines are obtained, depending on the nucleophilic functional group on the coupling partners.

Fundamental organometallic chemistry under bimetallic influence: driving β-hydride elimination and diverting migratory insertion at Cu and Ni.

Bimetallic effects on stoichiometric β-hydride elimination and migratory insertion reactions were examined. Bimetallic reaction conditions drove β-hydride elimination at Cu, while bimetallic C-B elimination occurred in the absence of β-hydrogens. The inherent migratory insertion chemistry of alkynes at Ni was diverted under bimetallic reaction conditions to favor C-H deprotonation.

ChemInform Abstract: Enantioselective Palladium‐Catalyzed C—H Functionalization of Indoles Using an Axially Chiral 2,2′‐Bipyridine Ligand.

AbstractThese transformations represent the first successful application of bipyridine ligands with axial chirality in palladium‐catalyzed carbene migratory insertion reactions.

Enantioselective Palladium‐Catalyzed CH Functionalization of Indoles Using an Axially Chiral 2,2′‐Bipyridine Ligand

A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.

Enantioselective Palladium‐Catalyzed CH Functionalization of Indoles Using an Axially Chiral 2,2′‐Bipyridine Ligand

AbstractA palladium‐catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2′‐bipyridine ligand, thus providing the desired indol‐3‐acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α‐aryl‐α‐diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium‐catalyzed carbene migratory insertion reactions.

Rearrangement of Metallabenzynes to Chlorocyclopentadienyl Complexes

Treatment of the osmabenzyne complex Os{≡C-C(SiMe3)═C(CH3)-C(SiMe3)═CH−}Cl2(PPh3)2 with Mo(CO)6 in refluxing benzene produced the η5-chlorocyclopentadienyl complex Os{η5-C5HCl(CH3)(SiMe3)2}Cl(CO)(PPh3) and Mo(CO)5(PPh3). A computational study suggests that the chlorocyclopentadienyl complex is most likely produced via the carbene intermediate Os{═C(C(SiMe3)═C(CH3)-C(SiMe3)═CH−)}Cl2(CO)(PPh3) formed by a migratory insertion reaction of the osmabenzyne complex Os{≡C-C(SiMe3)═C(CH3)-C(SiMe3)═CH}Cl2(CO)(PPh3). DFT calculations show that the relative thermal stability of metallabenzynes Os(≡C-CH═CHCH═CH)Cl2(L)2 and the corresponding isomeric carbene complexes Os{═C(−CH═CHCH═CH−)}Cl2(L)2 as well as the chlorocyclopentadienyl complexes Os(η5-C5ClH4)Cl(L)2 (L = CO, phosphine, pyridine, amine) is strongly dependent on ligand L.