Construction of Fully Substituted Cyclobutanes by Tandem Reaction of 1,4-Diyn-3-ols and Anhydrides.

A concise and efficient synthesis of fully substituted cyclobutane derivatives from 1,4-diyn-3-ols and anhydrides was developed. Mechanistic studies indicated that a tandem esterification, isomerization to give allenyl ester, and homointermolecular [2+2] cycloaddition might be involved. The features of this protocol are its operational practicality, mild reaction conditions, and high regio- and stereoselectivity, and it is a readily accessible gram-scale synthesis.

Cu-Catalyzed Diarylthiolation of Ynones with Aryl Iodides and Elemental Sulfur: An Access to Tetrasubstituted (Z)-1,2-Bis(arylthio)alkenes and Benzo[b][1,4]dithiines.

A copper-catalyzed three-component reaction of ynones, aryl iodides, and elemental sulfur via a syn-addition process is established. The reaction features operational practicality, broad substrate scope, and readily accessible scale-up synthesis by affording a series of (Z)-1,2-bis(arylthio)alkenes in good to excellent yield. Moreover, benzo[b][1,4]dithiines can be also constructed efficiently by using 1,2-diiodobenzene as the coupling partner.

Construction of 3-Sulfonyl Naphthalenes via Tandem Reaction of 1,4-Diyn-3-yl Esters with Sodium Sulfinates.

Polysubstituted 3-sulfonyl naphthalenes were constructed in good to high yields by AlCl3-mediated tandem reaction of 1,4-diyn-3-yl esters and sodium sulfinates. This reaction proceeded under mild reaction conditions and tolerated a variety of functional groups. Moreover, the mechanistic studies indicated that the initial formation of allene under DBU from 1,4-diyn-3-yl ester and a sequence of nucleophilic addition of sodium sulfinate, the formation of allene, and intramolecular cyclization might be involved.

Acid-Controlled Access to ß-Sulfenyl Ketones and α,ß-Disulfonyl Ketones by Pummerer Reaction of ß-Keto Sulfones and Sulfoxides.

A convenient acid-mediated reaction of ß-keto sulfones with sulfoxides under metal-free conditions has been developed, thereby delivering the acid-controlled synthesis of ß-sulfenyl ketones and α,ß-disulfonyl ketones in good to excellent yields. The mechanism of the transformations has been studied carefully, which suggested the involvement of a radical process in the formation of α,ß-disulfonyl ketones.

Enantioselective Synthesis of C-N Axially Chiral N-Aryloxindoles by Asymmetric Rhodium-Catalyzed Dual C-H Activation.

The first enantioselective Satoh-Miura-type reaction is reported. A variety of C-N axially chiral N-aryloxindoles have been enantioselectively synthesized by an asymmetric rhodium-catalyzed dual C-H activation reaction of N-aryloxindoles and alkynes. High yields and enantioselectivities were obtained (up to 99 % yield and up to 99 % ee). To date, it is also the first example of the asymmetric synthesis of C-N axially chiral compounds by such a C-H activation strategy.

Cobalt-Catalyzed Cyclization of Aliphatic Amides and Terminal Alkynes with Silver-Cocatalyst.

A new method of cobalt-catalyzed synthesis of pyrrolidinones from aliphatic amides and terminal alkynes was discovered through a C-H bond functionalization process on unactivated sp(3) carbons with the silver cocatalyst using a bidentate auxiliary. For the first time, a broad range of easily accessible alkynes are exploited as the reaction partner in C(sp(3))-H bond activation to give the important 5-ethylidene-pyrrolidin-2-ones in a site-selective fashion. The reaction tolerates a wide variety of functional groups including -F, -Cl, -Br, -CF3, ether, cyclopropane, and thiophene. Both pyridine ligand and aromatic solvent play the important role for the promotion of reactivity. This cobalt-catalyzed cyclization reaction can be successfully extended to a variety of aromatic amides to afford a variety of isoindolinones. Attractive features of this catalytic system include its low cost, easy operation, and convenient access to a wide range of pyrrolidinones and isoindolinones.

Rh(III)-catalyzed selective C2 C-H acyloxylation of indoles.

Herein, we present the first highly regio- and chemoselective C2 C-H acyloxylation of indole under rhodium catalysis and an N-quinolinyl auxiliary. This strategy accommodates a wide range of indoles and structurally diverse carboxylic acids with good reaction efficiencies to yield functionalized indoles. The utility of this logic was demonstrated by the concise synthesis of the functionalized 2-oxindole derivatives. Preliminary mechanistic studies indicate that catalyst turnover of RhIII-RhIV/V-RhII/III-RhIII might be involved in this catalytic C-H transformation.

Electrochemical Rhodium-Catalyzed C-H Cyclodimerization of Alkynes to Access Diverse Functionalized Naphthalenes: Involvement of RhIV/V and RhI Dual Catalysis.

The first electrochemical rhodium-catalyzed C-H cyclodimerization of alkynes for the direct construction of functionalized naphthalenes was reported. The practicality and synthetic value of this strategy were demonstrated by the readily accessible scale-up synthesis and transformation of the products. Detailed mechanistic studies evidenced that electricity played an important role during the electrochemical disproportionation (ECD) process to generate and maintain the catalytically active RhIV/V and RhI species, which conducted the direct C-H activation.

Pd-Catalyzed Atroposelective C-H Acyloxylation Enabling Access to an Axially Chiral Biaryl Phenol Organocatalyst.

Herein, we present the Pd(II)-catalyzed atroposelective C-H acyloxylation strategy for the assembly of biaryl aldehyde atropoisomers using readily available amino acids as the catalytic auxiliary and chiral pool. This strategy exhibits a broad substrate scope with a good yield (≤90%) and excellent enantioselectivity (≤99%), furnishing functionalized aldehydes through direct asymmetric C-H oxidation. The application utility of this method was demonstrated by the concise synthesis of a kind of atropoisomeric amino-phenol organocatalyst, which enables good enantiocontrol in catalyzing asymmetric addition of diethylzinc to aldehydes.

Palladium-catalyzed interannular C-H amination of biaryl amines.

A palladium-catalyzed interannular C-H amination of biaryl amines with O-benzoylhydroxylamines is reported. This reaction undergoes smoothly with operational practicality and good tolerance of functional groups, thereby providing a concise synthesis of 2,2'-diaminobiaryls. Moreover, the readily accessible scale-up synthesis and the ability to transform the products into structurally diverse N-containing heterocycles demonstrate the synthetic potential of this catalytic protocol.

Expeditious synthesis of phenanthridines through a Pd/MnO2-mediated C-H arylation/oxidative annulation cascade from aldehydes, aryl iodides and amino acids.

The expeditious construction of phenanthridine scaffolds via a Pd/MnO2-mediated C-H arylation/oxidative annulation cascade involving aldehydes, aryl iodides and amino acids is disclosed. This reaction proceeds smoothly involving the formation of multiple chemical bonds with the tolerance of a wide range of functional groups. The control experiments suggest a radical mechanism for C-N bond formation via MnO2-promoted oxidative annulation of imine compounds. The synthetic utility of this transformation has been demonstrated via the straightforward access to bioactive natural alkaloid trisphaeridine and its analogue.

Construction of N-C Axial Chirality through Atroposelective C-H Olefination of N-Arylindoles by Palladium/Amino Acid Cooperative Catalysis.

Direct construction of N-C axial chirality via Pd-catalyzed atroposelective C-H olefination of N-arylindoles is reported. The crucial role of chiral amino acid as a cocatalyst in the regio- and stereocontrol has been disclosed. In this reaction, a wide range of arylindoles and functional alkenes could be well tolerated. Moreover, the practicality and synthetic value of this process were demonstrated by the divers and simple transformations of the products.

Selective C-H acylation of indoles with α-oxocarboxylic acids at the C4 position by palladium catalysis.

The first Pd-catalyzed direct C-H acylation of indoles at the C4 position with α-oxocarboxylic acids using a ketone directing group is described. This reaction exhibits high regioselectivity with the tolerance of a wide scope of functional groups to afford diverse acylated indoles in moderate-to-good yields. The control experiments evidence the generation of acyl radicals via K2S2O8 promoted decarboxylation of α-oxocarboxylic acids and the involvement of a PdII/PdIV catalytic cycle. Importantly, the synthetically useful selectivity observed might be applied to prepare indole derivatives with anti-tumor activity as tubulin inhibitors.

Metal-Free Synthesis of Functionalized Tetrasubstituted Alkenes by Three-Component Reaction of Alkynes, Iodine, and Sodium Sulfinates.

An operationally simple, efficient, and metal-/peroxide-free three-component reaction of alkynes, iodine, and sodium sulfinates has been developed for the construction of highly functionalized tetrasubstituted alkenes. Iodo- and sulfonyl-containing tetrasubstituted alkenes, such as vinyl ketones, allylic alcohols, and conjugated enynes, could be obtained regio- and stereoselectively in up to 96% yield.

Synthesis of Benzyl Esters via Functionalization of Multiple C-H Bonds by Palladium Catalysis.

A highly efficient, selective synthesis of benzyl esters by palladium catalysis is developed through the bidentate directing group assisted functionalization of multiple C(sp(3))-H bonds.

Copper-Mediated Aryloxylation and Vinyloxylation of ß-C(sp(3))-H Bond of Propionamides with Organosilanes.

A novel copper-mediated method for the aryloxylation and vinyloxylation of ß-C(sp(3))-H bonds of propioamides with organosilanes is described. The reaction proceeds with the assistance of an 8-aminoquinolyl auxiliary in a tandem way by the first oxidation of ß-C(sp(3))-H bonds and subsequent arylation/vinylation to give the aryloxylation/vinyloxylation products. This unusual aryloxy/vinyloxy forming reaction offers a new avenue for the functionalization of unactivated sp(3) C-H bonds in organic synthesis.