Intramolecular C-H insertion in ring-expanded N-heterocyclic carbenes

Mild heating of the ring-expanded N-heterocyclic carbenes 7-Mes and 6-Mes results in intramolecular insertion of the carbene into an ortho-methyl C-H bond. In the presence of traces of acid, the resulting products ring-open to afford N-alkyl indoles.     

Metal-free N-iodosuccinimide-catalyzed mild oxidative C-H bond amination of benzoxazoles

A facile, efficient, and mild protocol for the synthesis of aminobenzoxazoles has been developed using direct oxidative C-H bond amination of benzoxazoles with secondary or primary amines. The reaction was performed using catalytic amount of N-iodosuccinimide and aqueous hydrogen peroxide as a green oxidant and in the absence of transition metals. Reaction proceeds smoothly at ambient temperature and requires shorter reaction time to furnish excellent yield of the desired products. Various cyclic, acyclic, and functionalized aliphatic amines were well tolerated under optimized reaction conditions and provided good to excellent yield of the respective aminobenzoxazoles.     

Rhodium catalyzed synthesis of isoindolinones via C-H activation of N-benzoylsulfonamides

An efficient approach to a wide range of isoindolinones, including 3-monosubstituted and 3,3-disubstituted isoindolinones, from the annulation of N-benzoylsulfonamides with olefins and diazoacetate has been developed. The transformation is broadly compatible with both terminal and internal olefins. Moreover, diazoacetate is for the first time incorporated into an amide-directed C-H functionalization reaction. Specifically, the rhodium complex [{RhCl₂Cp*}₂] enables the in situ dimerization of diazoacetate in addition to its role in catalyzing C-H functionalization/cross-coupling.     

Intramolecular gamma-hydroxylations of nonactivated C-H bonds with copper complexes and molecular oxygen

Copper(I) complexes incorporating the isomeric bidentate ligands IMPY (iminomethyl-2-pyridines) or AMPY (aminomethylene-2-pyridines) are quite unusual in their ability to bind and activate molecular oxygen. Using these complexes, hydroxylations of nonactivated CH, CH2, or CH3 groups in the gamma-position in relation to the imino-nitrogen atom, and with a specific orientation of one H atom with respect to the binuclear Cu-O species, can be achieved in synthetically useful yields. Through mechanistic studies employing conformationally well-defined molecules (for example, cyclic isoprenoids), coupled with solid-state X-ray structure analyses and force-field calculations, we postulate a seven-membered transition state for this reaction in which six atoms lie approximately in a plane. This plane is defined by the positions of the lone pairs on the nitrogen atoms, as well as the copper and the oxygen atoms. For a successful hydroxylation, one hydrogen atom should be located close to this plane. Prediction of the stereochemical course of these reactions is possible based on a simple geometrical criterion. The convenient introduction of IMPY and AMPY groups as auxiliaries into oxo and primary amino compounds and the simple hydrolysis after the hydroxylation procedure has allowed the synthesis of 3-hydroxy-1-oxo and 3-hydroxy-1-amino compounds. If desired, the 3-hydroxy-1-IMPY and -1-AMPY compounds can be reduced with NaBH4 to obtain 3-hydroxy-1-aminomethylpyridines. For a successful hydroxylation procedure, the method employed for the synthesis of the CuI complexes is very important. Starting either from CuI salts or from CuII salts with a subsequent reduction with benzoin/triethylamine may turn out to be the better way, depending on the ligand and the molecular structure.     

A tandem C-H insertion—acetal cleavage sequence: stereocontrolled synthesis of substituted tetrahydrofurans

A short sequence involving Rh(II) mediated carbene insertion followed by Lewis acid promoted reductive acetal cleavage with Et₃SiH provides a stereoselective method for the construction of 2,3,5-trisubstituted tetrahydrofuran rings.     

Regioselective access to substituted oxindoles via rhodium-catalyzed carbene C-H insertion

Rhodium-catalyzed decomposition of diazoamides followed by insertion of the resulting carbenes into an aromatic C-H bond gives access to substituted oxindoles. The reaction takes place with aromatic rings substituted by either electron-donating or -withdrawing groups at ortho, meta or para positions and the regioselectivity can be controlled by a substitution α to the diazo functionality. In the presence of an ester, the reaction leads to the formation of 2-silyloxyindole-3-carboxylates in 40-85% yields and regioselectivities up to 80% are observed in the case of meta-substituted substrates. This selectivity mainly relies on steric factors and use of a more bulky N,N-diethylamide then affords 2-silyloxyindole-3-carboxamides in 42-91% yields with complete regioselectivity.     

Efficient iodine catalyzed chemoselective synthesis of aminals—an access to N,N-acetals by the addition of lactams to N-acyl imines

A highly efficient protocol has been developed for the synthesis of aminals from γ-butyrolactam and benzaldehyde using iodine as Lewis acid catalyst. The attack of γ-butyrolactam nucleophile to intermediate N-acyliminium ion was more favorable, when aryl aldehyde bears the electron donating group (EDG). Iodine plays a key role in these reaction transformations. This current mild protocol is environmentally benign and cost-effective method for the synthesis of industrially and pharmaceutically useful scaffolds.     

Carbene adduct of cyclopalladated ferrocenylimine as an efficient catalyst for the amination of aryl chlorides

A novel air- and moisture-stable carbene adduct of cyclopalladated ferrocenylimine has been synthesized and characterized. The structure of this compound was determined by X-ray crystal structure analysis. This adduct has been applied as an efficient catalyst for the amination of aryl chlorides.     

On the efficiency of two-coordinate palladium(0) N-heterocyclic carbene complexes in amination and Suzuki-Miyaura reactions of aryl chlorides

The catalytic activity of novel two-coordinate palladium N-heterocyclic carbene complexes that differ in their steric and electronic properties is compared in catalytic amination and Suzuki-Miyaura cross-couplings.     

Toward a general method for CCC N-heterocyclic carbene pincer synthesis: Metallation and transmetallation strategies for concurrent activation of three C-H bonds

A general solution to the preparation of pincer complexes that require the formation of two N-heterocyclic carbenes (NHC’s) and the activation of an aryl C-H bond is reported. The reaction of a phenylene-bridged bis(imidazolium) salt with Zr(NMe₂)₄ generated the requisite CCC-NHC Zr pincer complex, which has been characterized by X-ray crystallography. Subsequent manipulation of the Zr coordination sphere by reaction with MeI demonstrated the robustness of the ligand geometry at Zr and led to the isolation and structural characterization of a CCC-NHC Zr triiodide pincer complex. A variation of the methodology has been applied to a saturated NHC analog to produce the corresponding CCC-NHC Zr pincer complex. Importantly, it has been found that CCC-NHC Zr pincer complexes can be generated in situ and transmetallated with an appropriate Rh source to generate CCC-NHC Rh pincer structures. These two methodologies, metallation of CCC-NHC precursors with transition metal amido complexes combined with transmetallation, hold great promise for opening general synthetic pathways to a wide variety of transition metal CCC-NHC pincer complexes.     

Synthesis of two-coordinate iron aryloxides and their reactions with organic azide: Intramolecular C-H bond amination

The synthesis and reaction of homoleptic iron(II) complexes with 2,6-di-adamantyl-substituted aryloxides [OC₆H₂-2,6-Ad-4-R]⁻ ([OAr^AdR]⁻, Ad = adamantyl, R = Me, ⁱPr) are described. Monomeric two-coordinate iron aryloxides Fe(OAr^AdR)₂ (R = Me, 1; ⁱPr, 2) were synthesized by the reaction of Fe[N(SiMe₃)₂]₂ with 2 equiv of HOAr^AdR. Treatment of 1 and 2 with 1-azidoadamantane resulted in intramolecular insertion of an adamantyl nitrene into a methylene C-H bond of the aryloxide adamantyl substituent, yielding the corresponding amine-aryloxide complexes Fe(OAr^AdR)(OAr^AdR-NHAd) (R = Me, 3; ⁱPr, 4). Molecular structures of all these complexes are reported.     

Microwave assisted solvent free amination of halo-(pyridine or pyrimidine) without transition metal catalyst

A solvent free direct amination of halo-(pyridine or pyrimidine) has been developed in good to high yields under computer-controlled microwave irradiation without transition metal catalyst. This reaction is a solvent and metal free, useful method for coupling of halo-(pyridine or pyrimidine) with pyrrolidine and piperidine derivatives by nucleophilic aromatic substitution (S_NAr).     

Synthesis of indoles via palladium-catalyzed C-H activation of N-aryl amides followed by coupling with alkynes

A convenient and efficient method for the construction of indole skeleton was developed via Pd-catalyzed C-H activation of N-aryl amides and subsequent coupling with alkynes. Both stoichiometric and catalytic versions have been successfully achieved.     

Synthesis and characterization of bidentate NHC-Pd complexes and their role in amination reactions

The new well-defined and air-stable ortho-xylyl-linked N-heterocyclic carbene (NHC) Pd complexes (2a-d) have been synthesized and characterized by elemental analysis, ¹H NMR, ¹³C NMR, IR spectroscopy, and single crystal X-ray diffraction studies. The palladium atom in the complex 2a lies on a crystallographic mirror plane and can be described as having a square-planar coordination environment with the carbene atoms of the benzimidazole rings of the ligand occupying two coordination sites in cis positions. Two further coordination sites are occupied by chloride ligands. The benzimidazole rings are connected to each other by an ortho-xylyl bridge. The catalytic activity of these palladium complexes has been tested in the coupling reactions of various N-containing substrates with bromobenzene. A preliminary catalytic study shows that the bis(NHC)-Pd complexes are highly active in the Buchwald-Hartwig amination reaction.     

Catalytic amination reactions mediated by Co(II) Schiff base complexes

Co(acacen), 1, (acacen = 2,11-dihydroxy-4,9-dimethyl-5,8-diaza-2,4,8,10-dodecatetraene dianion) was found to be a highly efficient catalyst for the allylic amination of non activated alkenes, using N-(p-toluensulfonyl)iminophenyliodinane (PhINTs) as nitrene precursor. This reactivity has been extended to the less reactive C-H bond of toluene. The effect of reaction times and of added cosolvent on yields and selectivities was investigated. Under the best conditions, allylic amines were obtained in a 40-70% isolated yield. A complex derived from the stoichiometric reaction of Co(acacen), 1, with PhINTs has been isolated and spectroscopically characterized. Such a complex, although not able to transfer its NTs moiety to alkenes, is still active in catalyzing allylic amination of cyclohexene.     

Selective palladium-catalyzed amination of the heterocyclic core of variolins

A new and selective palladium-catalyzed amination of the pyrido[3′,3′:4,5]pyrrolo[1,2-c]pyrimidine nucleus, the heterocyclic core of the variolin alkaloids, is described. The method allows the introduction of amino and aryl- and alkylamino substituents on the C9 position in advanced precursors of variolin B and deoxyvariolin.     

Highly stereoselective addition of organozinc reagents to pentopyranose derived glycals: effect of protecting group and assignment of C-glycoside stereochemistry

The nucleophilic addition of ethyl 3-propionylzinc iodide to a variety of differently protected pentopyranose derived d-glycals 6a-g proceeds with good to high levels of diastereoselectivity to provide the corresponding β-C-glycosides 7. The stereochemistry of the para-nitrobenzoate derivative 7d has been confirmed by X-ray crystallography, and the stereochemistry of the other β-C-glycoside products has been correlated to 7d. The stereochemical outcome observed supports the earlier suggestion by Isobe that through-space effects are important in stabilising and controlling the reactivity of the intermediate oxonium species represented by 11.