Highly regioselective carbonylation of unactivated C(sp3)-H bonds by ruthenium carbonyl

The regioselective carbonylation of unactivated C(sp(3))-H bonds of aliphatic amides was achieved using Ru(3)(CO)(12) as a catalyst. The presence of a 2-pyridinylmethylamine moiety in the amide is crucial for a successful reaction. The reaction shows a preference for C-H bonds of methyl groups as opposed to methylene C-H bonds and tolerates a variety of functional groups. The stoichiometric reaction of an amide with Ru(3)(CO)(12) gave a dinuclear ruthenium complex in which the 2-pyridinylmethylamino moiety was coordinated to the ruthenium center in an N,N manner.     

Conversion of a (sp3)C-F bond of alkyl fluorides to (sp3)C-X (X = Cl, C, H, O, S, Se, Te, N) bonds using organoaluminium reagents

A simple method for the conversion of (sp(3))C-F bonds of alkyl fluorides to (sp(3))C-X (X = Cl, C, H, O, S, Se, Te, N) bonds has been achieved by the use of a hexane solution of organoaluminum reagents having Al-X bonds.     

Organocatalytic deprotonative functionalization of C(sp(2))-H and C(sp(3))-H bonds using in situ generated onium amide bases

Onium amides, generated in situ from the combination of aminosilanes and onium fluorides (R(4)PF, R(4)NF), are employed for the first time as bases for catalytic deprotonative functionalization of C(sp(2))-H and activated C(sp(3))-H bonds under mild conditions.     

Efficient alkyl ether synthesis via palladium-catalyzed, picolinamide-directed alkoxylation of unactivated C(sp3)-H and C(sp2)-H bonds at remote positions

We report the efficient synthesis of alkyl ethers by the functionalization of unactivated sp(3)- and sp(2)-hybridized C-H bonds. In the Pd(OAc)(2)-catalyzed, PhI(OAc)(2)-mediated reaction system, picolinamide-protected amine substrates undergo facile alkoxylation at the γ or δ positions with a range of alcohols, including t-BuOH, to give alkoxylated products. This method features a relatively broad substrate scope for amines and alcohols, inexpensive reagents, and convenient operating conditions. This method highlights the emerging value of unactivated C-H bonds, particularly the C(sp(3))-H bond of methyl groups, as functional groups in organic synthesis.     

Palladium-catalyzed direct ethynylation of C(sp3)-H bonds in aliphatic carboxylic acid derivatives

The first catalytic alkynylation of unactivated C(sp(3))-H bonds has been accomplished. The method allows for the straightforward introduction of an ethynyl group into aliphatic acid derivatives under palladium catalysis. This new reaction can be applied to the rapid elaboration of complex aliphatic acids, for example, via azide/alkyne cycloaddition.     

Palladium-catalyzed oxidative carbonylation of benzylic C-H bonds via nondirected C(sp3)-H activation

A new strategy for generating benzylpalladium reactive species from toluenes via nondirected C(sp(3))-H activation has been developed. This led to construction of an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives from inexpensive, commercially available starting materials.     

Access to C(sp3)-C(sp2) and C(sp2)-C(sp2) bond formation via sequential intermolecular carbopalladation of multiple carbon-carbon bonds

A synthetic strategy of 4-benzyl-substituted 1,3-butadiene derivatives through Pd-catalyzed three-component coupling reaction of benzyl chlorides, alkynes, and monosubstituted alkenes is described. This tandem coupling reaction forms a C(sp(3))-C(sp(2)) bond and a C(sp(2))-C(sp(2)) bond sequentially in a single-step operation.     

C(sp)-C(sp3) bond formation through Cu-catalyzed cross-coupling of N-tosylhydrazones and trialkylsilylethynes

Copper-catalyzed cross-coupling of N-tosylhydrazones with trialkylsilylethynes leads to the formation of C(sp)-C(sp(3)) bonds. Cu carbene migratory insertion is proposed to play the key role in this transformation.     

Room-temperature catalytic hydrodefluorination of C(sp3)-F bonds

Room-temperature catalytic hydrodefluorination of the strong C(sp3)-F bonds in benzotrifluorides and fluoropentane is catalyzed by Et3Si[B(C6F5)4] and uses Et3SiH as the source of H. Ar-CF3 compounds are converted to Ar-CH3 and fluropentane to pentane. The reaction is thought to proceed via abstraction of F- by Et3Si[B(C6F5)4], and the substituent effects are consistent with this hypothesis.     

Palladium-catalyzed silyl C(sp3)-H bond activation

The first transition-metal-catalyzed activation of silyl C(sp(3))-H bond was realized and synthetically applied. A variety of organic skeletons substituted with SiMe(3) groups could undergo the Pd-catalyzed intramolecular coupling reaction, resulting in an unprecedented synthetic method for yielding six-membered silacycles. It was found that the adjacent Si atom played an essential role for the activation of the C(sp(3))-H bond of the SiMe(3) group; no activation reaction of the C(sp(3))-H bond of the CMe(3) group took place under the same reaction conditions.     

Regioselective ring expansion of 2,4-diiminoazetidines via cleavage of C-N and C(sp3)-H bonds: efficient construction of 2,3-dihydropyrimidinesulfonamides

A highly regioselective base-mediated ring expansion of 2,4-diiminoazetidines via cleavage of C-N and C(sp(3))-H bonds is achieved for the first time to afford efficiently 2,3-dihydropyrimidinesulfonamides. The mechanism of the ring expansion via tandem 4π electrocyclic ring-opening/1,5-H shift/6π electrocyclic ring-closing is well confirmed by the trapping experiments of two key intermediates and deuterium labeling studies.     

Metal catalyzed C(sp(3))-H bond amination of 2-alkyl azaarenes with diethyl azodicarboxylate

Metal-catalyzed direct C(sp(3))-H bond amination of 2-alkyl azaarenes with N[double bond, length as m-dash]N double bonds has been developed, which expands the scope of C(sp(3))-H bond activation reactions and provides a new access to medicinally important azaarene derivatives.     

Diastereo- and enantioselective intramolecular C(sp3)-H arylation for the synthesis of fused cyclopentanes

All C-H bonds are not equal: The intramolecular arylation of unactivated C(sp(3))-H bonds in the presence of a chiral Pd/binepine catalyst allows the synthesis of fused cyclopentanes efficiently and in an diastereo- and enantioselective manner (see scheme).     

Efficient protiodesilylation of unactivated C(sp3)-SiMe2Ph bonds using tetrabutylammonium fluoride

[reaction: see text] The protiodesilylation of unactivated C(sp3)-SiMe2Ph bonds proceeds efficiently by treatment with tetrabutylammonium fluoride in wet DMF or THF via isolable dimethylsilanol intermediates.     

Aza-oxindole synthesis by oxidative coupling of C(sp2)-H and C(sp3)-H centers

A Cu(II) mediated oxidative C(sp(2))-H and C(sp(3))-H coupling protocol gives access to aza-oxindoles in good to excellent yield in the presence of NaOtBu as base and toluene as solvent.     

Rhodium-catalyzed activation of C(sp3)-X (X = Cl, Br) bond: an intermolecular halogen exchange case

A RhCl(PPh(3))(3)-catalyzed halogen-exchange reaction between allyl and alkyl halides with β-H atoms was observed. The possible mechanism of the reaction involves oxidative addition and reductive elimination of the C(sp(3))-X bonds, which is not common in organometallic chemistry.     

Original palladium pincer complexes deriving from 1,3-bis(thiophosphinoyl)indene proligands: C(sp3)-H versus C(sp2)-H bond activation

A series of original 2-indenylidene palladium pincer complexes {PdL[Ind(Ph(2)P==S)(2)]} (L = HNCy(2), PPh(3), Cl(-)) have been prepared by double C-H activation of a 1,3-bis(thiophosphinoyl)indene proligand. Crystallographic analyses and DFT calculations indicate that the bonding situation of the {Pd[Ind(Ph(2)P==S)(2)]} fragment is essentially governed by the conjugated and rigid nature of the dianionic pincer ligand, the nature of the coligand having little influence. The formation of the 2-indenylidene complexes involves either a 2-indenyl pincer or a four-membered cyclometalated complex as an intermediate, suggesting that C(sp(2))-H or C(sp(3))-H bond activation takes place. However, deuterium labelling experiences show that in all cases, C(sp(3))-H bond activation occurs followed eventually by a Pd/H exchange. Nevertheless, evidence for direct C(sp(2))-H bond activation under mild conditions is obtained when a methyl group is introduced at the indene proligand to prevent C(sp(3))-H bond activation. The ensuing dissymmetrical 2-indenyl palladium pincer complex has been fully characterized.     

Copper-catalyzed decarboxylative C(sp2)-C(sp3) coupling reactions via radical mechanism

We have successfully developed an example of copper-catalyzed decarboxylative C(sp(2))-C(sp(3)) coupling reactions via C-H functionalization for the first time. It is noteworthy that our catalytic system is very stable, low-cost, palladium-free, ligand-free, and easily accessible.     

Rhodium(I)‐Catalyzed Sequential C(sp)C(sp3) and C(sp3)C(sp3) Bond Formation through Migratory Carbene Insertion

A Rh^I‐catalyzed three‐component reaction of tert‐propargyl alcohol, diazoester, and alkyl halide has been developed. This reaction can be considered as a carbene‐involving sequential alkyl and alkynyl coupling, in which C(sp)? C(sp³) and C(sp³)? C(sp³) bonds are built successively on the carbenic carbon atom. The Rh^I‐carbene migratory insertion of an alkynyl moiety and subsequent alkylation are proposed to account for the two separate C? C bond formations. This reaction provides an efficient and tunable method for the construction of all‐carbon quaternary center.     

Synthesis of polycyclic molecules by double C(sp2)-H/C(sp3)-H arylations with a single palladium catalyst

Polycyclic molecules were obtained in good yields by double C(sp(2))-H/C(sp(3))-H arylations mediated by a single palladium/phosphine catalyst. Both double intermolecular/intramolecular and intramolecular/intramolecular C-C couplings were performed successfully, which indicates that this concept has a broad applicability for the rapid construction of molecular complexity.