Bond Insertion Reaction Research Articles

Catalytic Asymmetric Carbene Insertion Reactions into B−H Bonds Using a Ru(II)‐Pheox Complex

AbstractThe Ru(II)‐Pheox catalyzed B−H bond insertion reactions of α‐methyl diazoesters with phosphine‐ and amine‐borane adducts were successfully developed. A unique α‐methyl diazoester (dinaphthylenyl diazopropionate) with triphenylphosphine‐borane afforded the highest enantioselectivity (up to 98 % ee). Moreover, a unique dinaphthylenyl diazophenylacetate was newly synthesized, leading to improved yield and enantioselectivity of the carbene transfer B−H insertion reaction.

Ruthenium-Catalyzed Chemoselective N-H Bond Insertion Reactions of 2-Pyridones/7-Azaindoles with Sulfoxonium Ylides.

A ruthenium-catalyzed highly chemoselective N-alkylation of 2-pyridones has been developed, affording N-alkylated 2-pyridone derivatives in good yields and excellent N-selectivity. The key to achieve this unprecedented N-H rather than O-H insertion reaction is the use of CpRu(PPh3)2Cl as the catalyst and sulfoxonium ylides as the alkylation reagents. Moreover, this protocol is also amenable to 7-azaindoles by slightly varying the reaction conditions. Furthermore, sulfonium ylides are also suitable alkylation reagents, providing the N-alkylated 2-pyridones in good selectivity.

Brønsted acid-catalyzed homogeneous O–H and S–H insertion reactions under metal- and ligand-free conditions

The economical and accessible CF3SO3H successfully catalyzed homogeneous O–H and S–H bond insertion reactions between hydroxyl compounds, thiols and diazo compounds under metal- and ligand-free conditions.

Copper-Catalyzed C—H Bond and N—H Bond Insertion Reaction Based on Azide-Ynamide Cyclization

Copper-Catalyzed C—H Bond and N—H Bond Insertion Reaction Based on Azide-Ynamide Cyclization

Visible‐Light‐Mediated S−H Bond Insertion Reactions of Diazoalkanes with Cysteine Residues in Batch and Flow

AbstractWe describe the application of S−H bond insertion reactions of aryl diazoacetates with cysteine residues that enabled metal‐free, S−H functionalization under visible‐light conditions. Moreover, this process could be intensified by a continuous‐flow photomicroreactor on the acceleration of the reaction (6.5 min residence time). The batch and flow protocols described were applied to obtain a wide range of functionalized cysteine derivatives and cysteine‐containing dipeptides, thus providing a straightforward and general platform for their functionalizations in mild conditions.magnified image

Transition-Metal-Catalyzed Synthesis of Organophosphorus Compounds Involving P–P Bond Cleavage

Organophosphorus compounds are used as drugs, pesticides, detergents, food additives, flame retardants, synthetic reagents, and catalysts, and their efficient synthesis is an important task in organic synthesis. To synthesize novel functional organophosphorus compounds, transition-metal-catalyzed methods have been developed, which were previously considered difficult because of the strong bonding that occurs between transition metals and phosphorus. Addition reactions of triphenylphosphine and sulfonic acids to unsaturated compounds in the presence of a rhodium or palladium catalyst lead to phosphonium salts, in direct contrast to the conventional synthesis involving substitution reactions of organohalogen compounds. Rhodium and palladium complexes catalyze the cleavage of P–P bonds in diphosphines and polyphosphines and can transfer organophosphorus groups to various organic compounds. Subsequent substitution and addition reactions proceed effectively, without using a base, to provide various novel organophosphorus compounds.1 Introduction2 Transition-Metal-Catalyzed Synthesis of Phosphonium Salts by Addition Reactions of Triphenylphosphine and Sulfonic Acids3 Rhodium-Catalyzed P–P Bond Cleavage and Exchange Reactions4 Transition-Metal-Catalyzed Substitution Reactions Using Diphosphines4.1 Reactions Involving Substitution of a Phosphorus Group by P–P Bond Cleavage4.2 Related Substitution Reactions of Organophosphorus Compounds4.3 Substitution Reactions of Acid Fluorides Involving P–P Bond Cleavage of Diphosphines5 Rhodium-Catalyzed P–P Bond Cleavage and Addition Reactions6 Rhodium-Catalyzed P–P Bond Cleavage and Insertion Reactions Using Polyphosphines7 Conclusions

P(OEt)3-Mediated Formal S–H Insertion: Reductive Couplings of Isatins with Thiols to Generate 3-Sulfenylated Oxindoles

A new P(OEt)3-mediated formal S–H bond-insertion reaction of isatins into thiols for the synthesis of valuable 3-sulfenylation oxindoles has been developed. This approach takes advantage of the unique reactivity of Kukhtin–Ramirez adducts to allow direct reductive S–H functionalization with commercially available and bench-stable starting materials.

Highly Enantioselective O-H Bond Insertion Reaction of α-Alkyl- and α-Alkenyl-α-diazoacetates with Water.

Catalytic asymmetric reactions in which water is a substrate are rare. Enantioselective transition-metal-catalyzed insertion of carbenes into the O-H bond of water can be used to incorporate water into the stereogenic center, but the reported chiral catalysts give good results only when α-aryl-α-diazoesters are used as the carbene precursors. Herein we report the first highly enantioselective O-H bond insertion reactions between water and α-alkyl- and α-alkenyl-α-diazoesters as carbene precursors, with catalysis by a combination of achiral dirhodium complexes and chiral phosphoric acids or chiral phosphoramides. Participation of the phosphoric acids or phosphoramides in the carbene transfer reaction markedly suppressed competing side reactions, such as β-H migration, carbene dimerization, and olefin isomerization, and thus ensured good yields of the desired products. Fine-tuning of the ester moiety facilitated enantiocontrol of the proton transfer reactions of the enol intermediates and resulted in excellent enantioselectivity. This protocol represents an efficient new method for preparation of multifunctionalized chiral α-alkyl and α-alkenyl hydroxyl esters, which readily undergo various transformations and can thus be used for the synthesis of bioactive compounds. Mechanistic studies revealed that the phosphoric acids and phosphoramides promoted highly enantioselective [1,2]- and [1,3]-proton transfer reactions of the enol intermediates. Maximization of molecular orbital overlap in the transition states of the proton transfer reactions was the original driving force to involve the proton shuttle catalysts in this process.

Highly Chemo-, Site-, and Enantioseletive para C-H Aminoalkylation of N-Monosubstituted Aniline Derivatives Affording 3-Amino-2-oxindoles.

In general, enantioselective C-H functionalization of N-monosubstituted anilines is a highly challenging task owing to the competitive chemoselective N-H bond insertion reactions. In this paper, we reported a direct highly chemo-, site-, and enantioselective para C-H aminoalkylation of N-monosubstituted aniline derivatives with isatin-derived ketimines in the presence of chiral phosphoric acids (CPAs) and offered a practical strategy for para asymmetric C-H functionalization of anilines containing N-H bonds.

Catalytic O–H bond insertion reactions using surface modified sewage sludge as a catalyst

More economically and greener surface modified sewage sludge for carbene insertion of diazo compounds into O–H bond of phenols with good yields and high functional group tolerance.

Iridium-catalyzed B-H insertion of sulfoxonium ylides and borane adducts: a versatile platform to α-boryl carbonyls.

Iridium-catalyzed boron-hydrogen bond insertion reactions of trimethylamine-borane and sulfoxonium ylides have been demonstrated, furnishing α-boryl ketones in moderate to excellent yields in most cases (51 examples; up to 84%). This practical and scalable insertion reaction showed broad substrate scope, high functional-group compatibility and could be applied in late-stage modification of structurally complex drug compounds. Further synthetic applications were also demonstrated.

Theoretical Study of the Mechanism of Catalytic Enanteoselective N-H and O-H Insertion Reactions.

Theoretical density functional theory (DFT) calculations were carried out to study bond insertion reactions using a copper(I)-Box-carbenoid as a bond activator. In order to understand the reaction mechanism where N-H and O-H bonds actively participate, the reaction force (RF) and activation strain model (ASM) were used. Results indicate that the first step of the reaction is barrierless for both bond insertions (N-H and O-H), and the second step of the insertion reaction in the phenol (O-H bond) is favored kinetically and thermodynamically with regard to the aniline substrate (N-H bond). The enantioselectivity is driven by the ligand of the catalyst by steric repulsion, favoring the formation of the R isomer. The analysis of the reaction force and ASM exhibited that the higher energy barrier in aniline is mainly due to a higher W2 contribution together with repulsive interactions, which hinders the insertion process.

Iridium-Catalyzed B-H Bond Insertion Reactions Using Sulfoxonium Ylides as Carbene Precursors toward α-Boryl Carbonyls.

An iridium-catalyzed B-H bond insertion reaction between borane adducts and sulfoxonium ylides to afford α-boryl carbonyls has been developed. The starting materials are safe and readily available. In addition, analogues of sulfoxonium ylides, such as sulfonium salts and sulfonium ylides could also be amenable to the reaction.

Rhodium-Catalyzed Si–H Bond Insertion Reactions Using Functionalized Alkynes as Carbene Precursors

Enantioselective transition-metal-catalyzed carbene insertion into Si–H bonds is a promising method for preparing chiral organosilicons; however, all the carbene precursors used to date in this rea...

Access to 1,1′‐Bifunctional Phosphane Iron(0) Complexes via P–N Bond‐Forming Reactions and Selective P‐Functionalizations

Reaction of Li/Cl phosphinidenoid Fe(CO)4 complex 2 with ammonia and different amines R1,R2NH yielded complexes 3–5 (3: R1 = R2 = H; 4a: R1 = H, R2 = Me; 4b: R1 = H, R2 = iPr; 4c: R1 = H, R2 = tBu; 4d: R1 = H, R2 = allyl; 4e: R1 = H, R2 = Ph; 5: R1 = Me, R2 = Me) having 1,1′‐bifunctional phosphane ligands via formal N–H bond insertion of the phosphorus center. Studies on deprotonation enabled access to the first structurally characterized K/N(H)R phosphinidenoid complex 6. The latter reacted with phosgene to provide selective access to the P‐chloro complex 7. Theoretical calculations provide insight into the mechanism of the formal N–H bond insertion reaction involving a nucleophilic displacement of chloride at phosphorus and a higher molecularity of a stepwise proton transfer mechanism.

Chiral 1,8-naphthyridine based ligands: Syntheses and characterization of Di- and tetranuclear copper (I) and silver (I) complexes

Oxazoline and camphor-pyrazole units are introduced on the 1,8-naphthyridine scaffold to access chiral ligands L1, L2 and L3. Metalation of these chiral ligands with Cu(I) and Ag(I) precursors afforded di- and tetranuclear complexes [Cu4I4(L1)2] (1), [Cu4I4(L2)2] (2), [Cu2I2(L3)] (3), [Cu2I(L2)2](OTf) (4), [Ag2(L1)2](OTf)2 (5) and [Ag4(L2)4Br](OTf)3 (6), containing [M4Xn] (n = 1,4 and X = Br, I) or [M2Xn] (n = 0, 1, 2 and X = I) core. All complexes are structurally characterized. Naphthyridine-derived ligands reveal bridge-chelate coordination motif and hold two metal centers in close proximity. The tetranuclear complexes are dimer of dinuclear complexes bridged by the halides. Electronic absorption and emission spectra of copper complexes are reported. Catalytic utility of all complexes are examined for asymmetric transformations but they showed poor activity probably due to limited solubility and coordinative saturation at the metal centers. The best results are obtained with [L3/Cu salt] combination for cyclopropanation of styrene, NH bond insertion and nitroaldol (Henry) reactions with very low enantioselectivity.

Iron-Catalyzed Enantioselective Si-H Bond Insertions.

The first iron-catalyzed enantioselective Si-H bond insertion reaction of α-diazoesters was developed. A new chiral spiro-bisoxazoline ligand has proven to be an optimal ligand for the asymmetric reaction to give versatile chiral α-silyl esters in good yields with high enantioselectivities. The mechanism and detailed stereochemical models for enantioselective induction were elucidated by DFT calculations, suggesting that the reaction proceeds via a concerted quintet transition state.

Selective C(sp3)–H Bond Insertion in Carbene/Alkyne Metathesis Reactions. Enantioselective Construction of Dihydroindoles

A general access to chiral dihydroindole derivatives in high yields is achieved by C–H functionalization in a highly site- and enantioselective cascade reaction of propargyl diazoacetates. Highly site-selective intramolecular C(sp3)–H bond insertions are realized by catalyst control. Sterically demanding dirhodium carboxylates, optimized with Rh2(S-BTPCP)4, favor C–H insertion into 1° C–H bonds with regioselectivities reaching >95:5 (1° > 2° benzylic) and >90% ee. With Rh2(S-TBPTTL)4, preferential 2° and 3° C–H bond insertion occurs due to the configuration of catalyst and electronic effects. The chiral dirhodium catalyst not only promotes carbene/alkyne metathesis (CAM) to generate the donor/donor carbene intermediate, but is also responsible for the observed asymmetric induction in the terminating C–H bond insertion reaction.

Rhodium-Catalyzed B-H Bond Insertion Reactions of Unstabilized Diazo Compounds Generated in Situ from Tosylhydrazones.

Although transition-metal-catalyzed B-H bond insertion of carbenes into stable borane adducts has emerged as a promising method for organoborane synthesis, all the diazo compounds used to date as carbene precursors have had an electron-withdrawing group to stabilize them. Herein, we report a protocol for rhodium-catalyzed B-H bond insertion reactions of unstabilized diazo compounds generated in situ from tosylhydrazones. In addition, by using chiral dirhodium catalysts, we also achieved an asymmetric version of the reaction with good to excellent enantioselectivities (up to 98:2 e.r.). This is the first enantioselective heteroatom-hydrogen bond insertion reaction to use unstabilized diazo compounds as carbene precursors. The protocol exhibited good functional group tolerance and could be carried out on a gram scale. It also enabled one-pot transformation of a carbonyl group to a boryl group enantioselectively. The B-H bond insertion products could be easily transformed into chiral alcohols and other widely used organoboron reagents with enantiomeric fidelity.

Gold‐Catalyzed Formal C−C Bond Insertion Reaction of 2‐Aryl‐2‐diazoesters with 1,3‐Diketones

The transition-metal-catalyzed formal C-C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3-diketones instead gives C-H bond insertion products. Herein, we report a protocol for a gold-catalyzed formal C-C bond insertion reaction of 2-aryl-2-diazoesters with 1,3-diketones, which provides efficient access to polycarbonyl compounds with an all-carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C-C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring-opening of the resulting donor-acceptor-type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis-acid-catalyzed C-C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.