Unexpected copper-catalyzed aerobic oxidative cleavage of C(sp3)-C(sp3) bond of glycol ethers

An unexpected Cu-catalyzed oxidative cleavage of the C(sp(3))-C(sp(3)) bond in glycol ethers by using air or molecular oxygen as the terminal stoichiometric oxidant is demonstrated. As a result, the corresponding α-acyloxy ethers and formates of 1,2-ethanediol are formed by direct coupling of carboxylic acids and aldehydes with glycol ethers under the reaction conditions. This method represents the first example of Cu-catalyzed aerobic cleavage of saturated C-C bond in ethers.     

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.     

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.     

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.     

Palladium-catalyzed synthesis of benzosilolo[2,3-b]indoles via cleavage of a C(sp3)-Si bond and consequent intramolecular C(sp2)-Si coupling

An efficient process involving Pd-catalyzed selective cleavage of a C(sp(3))-Si bond and consequent intramolecular C(sp(2))-Si coupling has been developed, affording benzosilolo[2,3-b]indoles as a new type of silicon-bridged polyheteroarene in excellent yields. Aldehyde was found for the first time to be able to promote the efficiency of the catalytic process remarkably.     

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.     

Sequential protocol for C(sp3)-H carboxylation with CO2: transition-metal-catalyzed benzylic C-H silylation and fluoride-mediated carboxylation

One of the most challenging transformations in current organic chemistry is the catalytic carboxylation of a C(sp(3))-H bond using CO(2) gas, an inexpensive and ubiquitous C1 source. A sequential protocol for C(sp(3))-H carboxylation by employing a nitrogen-directed, metal-assisted, C-H activation/catalytic silylation reaction in conjunction with fluoride-mediated carboxylation with CO(2) was established. The carboxylation proceeded only at the benzylic C(sp(3))-Si bond, not at the aromatic C(sp(2))-Si, which is advantageous for further manipulations of the products.     

Synthesis of dibenzofurans directly from aryl halides and ortho-bromophenols via one-pot consecutive SNAr and intramolecular palladium-catalyzed aryl-aryl coupling reactions

A series of dibenzofurans were efficiently and conveniently synthesized via one-pot consecutive C(sp(2))-O bond formation reaction (SNAr) in the presence of anhydrous K(2)CO(3), followed by C(sp(2))-C(sp(2)) bond formation reaction (intramolecular palladium-catalyzed aryl-aryl coupling reaction) between aryl halides and ortho-bromophenols. The desired dibenzofurans were obtained in 32-99% isolated yields.     

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.     

Rational Design of a Palladium-Catalyzed C(sp) -C(sp) Cross-Coupling Reaction Inspired by Kinetic Studies

Less is More: A highly selective Pd-catalyzed C(sp) -C(sp) cross-coupling reaction between terminal alkynes and 1-bromoacetylenes has been developed. Catalyst loading is low (only 0.0001-0.01?mol?% of Pd is required) and provides products with high selectivities and good to excellent yields under mild conditions. TBAB=tetrabutylammonium bromide, TON=turnover number.     

Synthesis of cyclic thioethers through tandem C(sp3)-S and C(sp2)-S bond formations from alpha,beta'-dichloro vinyl ketones

The synthesis of 5- to 8-memebered cyclic thioethers 4 has been achieved through a simple two-step sequence. The present methodology utilizes the facile Friedel-Crafts acylation of terminal alkynes 1 with acid chlorides 2 followed by tandem C(sp(3))-S and C(sp(2))-S bond formations with NaSH.xH(2)O.     

Zinc(II)-catalyzed redox cross-dehydrogenative coupling of propargylic amines and terminal alkynes for synthesis of N-tethered 1,6-enynes

The zinc(II)-catalyzed redox cross-dehydrogenative coupling (CDC) of propargylic amines and terminal alkynes proceeds to afford N-tethered 1,6-enynes. In the current CDC reaction, a C(sp)-C(sp(3)) bond is formed between the carbon adjacent to the nitrogen atom in the propargylic amine and the terminal carbon of the alkyne with reduction of the C-C triple bond of the propargylic amine, which acts as an internal oxidant.     

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.     

C(arenium)-C(alkyl) bond making and breaking: key process in the platinum-mediated C(aryl)-C(alkyl) bond formation. Analogies to organic electrophilic aromatic substitution

The reaction of cationic platinum aqua complexes 2 [Pt(C(6)H(2)[CH(2)NMe(2)](2)-E-4)(OH(2))](X') (X' = SO(3)CF(3), BF(4)) with alkyl halides RX gave various air-stable arenium complexes 3-5 containing a new C-C bond (R = Me, 3; Et, 4; Bn, 5). Electron-releasing oxo-substituents on the aromatic ligand (E = e.g., OH, b; OMe, c) enhance the reactivity of the aqua complex 2 and were essential for arenium formation from alkyl halides different from MeX. This process is initiated by oxidative addition of alkyl halides to the platinum(II) center of 2, which affords (alkyl)(aryl) platinum(IV) complexes (e.g., 9, alkyl = benzyl) as intermediates. Spectroscopic analyses provided direct evidence for a subsequent reversible 1,2-sigmatropic shift of the alkyl group along the Pt-C(aryl) bond, which is identical to repetitive C(arenium)-C(alkyl) bond making and breaking and concerted metal reduction and oxidation. Temperature-dependent NMR spectroscopy revealed DeltaH degrees = -1.3 (+/- 0.1) kJ mol(-1), DeltaS degrees = +3.8 (+/- 0.2) J mol(-1) K(-1), and DeltaG degrees (298) = -2.4 (+/- 0.1) kJ mol(-1) for the formation of the arenium complex 5b from 9 involving the migration of a benzyl group. The arenium complexes were transformed to cyclohexadiene-type addition products 7 or to demetalated alkyl-substituted arenes, 8, thus completing the platinum-mediated formation of a sp(2)-sp(3) C-C bond which is analogous to the aromatic substitution of a [PtX](+) unit by an alkyl cation R(+). The formation of related trimethylsilyl arenium complexes 6 suggests arenium complexes as key intermediates, not only in (metal-mediated) sp(2)-sp(3) C-C bond making and breaking but also in silyl-directed cyclometalation.     

Pd-catalyzed cross-coupling reactions of alkyl halides

Cross-coupling reactions have become indispensable tools for creating carbon-carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on C(sp(3))-C(sp(3)), C(sp(3))-C(sp(2)) and C(sp(3))-C(sp) bond formation as complementary methods to conventional C(sp(2))-C(sp(2)), C(sp(2))-C(sp) and C(sp)-C(sp) coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.     

Phenyliodine bis(trifluoroacetate)-mediated oxidative C-C bond formation: synthesis of 3-hydroxy-2-oxindoles and spirooxindoles from anilides

The reaction of phenyliodine bis(trifluoroacetate) (PIFA) with a series of anilides 1 (E = CO(2)Et) in CF(3)CH(2)OH was found to give 3-hydroxy-2-oxindole derivatives 2, while that with various anilides 1' (E = CON(R(4))Ar) afforded the C(2)-symmetric or unsymmetric spirooxindoles 3. These processes feature a metal-free oxidative C(sp(2))-C(sp(3)) bond formation, followed by oxidative hydroxylation or spirocyclization.     

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.     

Total synthesis of scytophycin C. 2. Coupling reaction of the C(1)-C(18) segment and the C(19)-C(31) segment, a key macrolactonization, and the crucial terminal amidation reaction

[reaction: see text] Stereoselective syntheses of the C(1)-C(18) segment (segment A) and the C(19)-C(31) segment (segment B) are described in the preceding paper. This paper reports the key coupling reaction of both segments, 22-membered lactonization, and the crucial terminal amidation reaction culminating in the total synthesis of scytophycin C.     

Synthesis of the C6-C21 segment of amphidinolide E

[reaction: see text] A convergent approach to a C6-C21 segment of the polyketide amphidinolide E has been developed through combination of three subunits by allenylindium bromide-aldehyde addition and Suzuki sp2-sp3 coupling.     

Palladium-catalyzed amidation by chemoselective C(sp3)-H activation: concise route to oxindoles using a carbamoyl chloride precursor

Quite select: a new strategy was developed for the synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad(2)PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp(3))-H activation proceeded in the presence of a C(sp(2))-H bond. Ad=adamantyl.