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.     

Palladium-Catalyzed Cascade Process Consisting of Isocyanide Insertion and Benzylic C(sp(3))-H Activation: Concise Synthesis of Indole Derivatives

Synthesis of the indole skeleton was achieved using a Pd-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp(3))-H activation. It was found that slow addition of isocyanide is effective for reducing the amount of catalyst needed and Ad(2)P(n)Bu is a good ligand for C(sp(3))-H activation. The construction of the tetracyclic carbazole skeleton was also achieved by a Pd-catalyzed domino reaction incorporating alkyne insertion.     

Mechanism of cooperative catalysis in a lewis Acid promoted nickel-catalyzed dual C-h activation reaction

The mechanism of cooperativity offered by AlMe(3) in a Ni-catalyzed dehydrogenative cycloaddition between substituted formamides and an alkyne is investigated by using DFT(SMD(toluene)/M06/6-31G**) methods. The preferred pathway is identified to involve dual C-H activation, with first a higher barrier formyl C(sp(2))-H oxidative insertion followed by benzylic methyl C(sp(3))-H activation. The cooperativity is traced to be of kinetic origin as evidenced by stabilized transition states when AlMe(3) is bound to the formyl group, particularly in the oxidative insertion step.     

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.     

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.     

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.     

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.     

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.     

Double C-H activation: the palladium-catalyzed direct C-arylation of xanthines with arenes

The novel Pd-catalyzed C(sp(2))-H/C(sp(2))-H cross-coupling of unactivated xanthines with unactivated arenes utilizing a combination of Ag(I) and O(2) as oxidants exclusively yields C-8 arylated xanthines in a single synthetic operation.     

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.     

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.     

Carbon-based leaving group in substitution reactions: functionalization of sp3-hybridized quaternary and tertiary benzylic carbon centers

Lewis acid promoted substitution reactions employing Meldrum's acid and 5-methyl Meldrum's acid as carbon-based leaving groups are described which transform unstrained quaternary and tertiary benzylic C(sp(3))-C(sp(3)) bonds into C(sp(3))-X bonds (X = C, H, N). Importantly, this reaction has a broad scope in terms of both suitable substrates and nucleophiles with good to excellent yields obtained (typically >90%).     

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.     

Iron-facilitated direct oxidative C-H transformation of allylarenes or alkenes to alkenyl nitriles

This paper describes the first direct approach to alkenyl nitriles from allylarenes or alkenes facilitated by an inexpensive homogeneous iron catalyst. Three C-H bond cleavages occur under the mild conditions during this process. Mechanistic studies indicate that the cleavage of the allyl C(sp(3))-H bond is involved in the rate-determining step. This observation may provide an opportunity to achieve C(sp(3))-H functionalization catalyzed by an iron catalyst.     

Dehydrogenative [4 + 2] cycloaddition of formamides with alkynes through double C-H activation

Formamides having 1-arylalkyl groups on nitrogen undergo an unprecedented dehydrogenative [4 + 2] cycloaddition reaction with alkynes via nickel/AlMe(3) cooperative catalysis to give highly substituted dihydropyridone derivatives in good yields. Notably, the transformation proceeds through double functionalization of C(sp(2))-H and C(sp(3))-H bonds in the formamides.     

Synthesis of tricyclic nitrogen heterocycles by a sequence of palladium-catalyzed N-H and C(sp3)-H arylations

A range of tricyclic nitrogen heterocycles were synthesized in a straightforward and efficient manner via a sequence involving palladium-catalyzed N-arylation and C(sp(3))-H arylation as the key steps. Whereas the C(sp(3))-H arylation furnished fused 6,5,6-membered ring systems efficiently, the formation of the more strained 6,5,5-membered systems proved to be more challenging and required a subtle adjustment of the reaction conditions.     

Photochemically induced radical transformation of C(sp3)-H bonds to C(sp3)-CN bonds

A general protocol for direct transformation of unreactive C(sp(3))-H bonds to C(sp(3))-CN bonds has been developed. The C-H activation was effected by photoexcited benzophenone, and the generated carbon radical was subsequently trapped with tosyl cyanide to afford the corresponding nitrile in a highly efficient manner. The present methodology is widely applicable to versatile starting materials and, thus, serves as a powerful tool for selective one-carbon elongation for construction of architecturally complex molecules.     

Palladium-Catalyzed C(sp(3))-H Arylation of Diarylmethanes at Room Temperature: Synthesis of Triarylmethanes via Deprotonative-Cross-Coupling Processes

Although metal-catalyzed direct arylation reactions of non- or weakly acidic C-H bonds have recently received much attention, chemists have relied heavily on substrates with appropriately placed directing groups to steer reactivity. To date, examples of intermolecular arylation of unactivated C(sp(3))-H bonds in the absence of a directing group remain scarce. We report herein the first general, high-yielding, and scalable method for palladium-catalyzed C(sp(3))-H arylation of simple diarylmethane derivatives with aryl bromides at room temperature. This method facilitates access to a variety of sterically and electronically diverse hetero- and nonheteroaryl-containing triarylmethanes, a class of compounds with various applications and interesting biological activity. Key to the success of this approach is an in situ metalation of the substrate via C-H deprotonation under catalytic cross-coupling conditions, which is referred to as a deprotonative-cross-coupling process (DCCP). Base and catalyst identification were performed by high-throughput experimentation (HTE) and led to a unique base/catalyst combination [KN(SiMe(3))(2)/Pd-NiXantphos] that proved to efficiently promote the room-temperature DCCP of diarylmethanes. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of substrates that are known to undergo O-, N-, enolate-, and C(sp(2))-H arylation.     

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.     

Formation of a tetra-sigma-bonded intermediate in acetylethyne binding on Si(100)-2 x 1

The covalent binding of acetylethyne on Si(100)-2 x 1 has been investigated using high-resolution electron energy loss spectroscopy (HREELS) and X-ray photoelectron spectroscopy (XPS). The HREELS spectra of chemisorbed monolayers show the absence of the C=O, C[triple bond]C, and C(sp)-H stretching modes coupled with the appearance of C=C (at 1580 cm(-1)) and C(sp2)-H (at 3067 cm(-1)) stretching modes. This demonstrates that both of the C=O and CC groups of acetylethyne directly participate in binding with silicon surfaces to form C-O and C=C bonds, respectively, which is further confirmed by the XPS studies. A tetra-sigma-binding configuration through two [2 + 2]-like cycloaddition reactions in acetylethyne binding on Si(100) is proposed to account for the experimental observation. The cycloadduct containing a C=C double bond may be employed as an intermediate for further in situ chemical syntheses of multilayer organic thin films or surface functionalization.