Visible-Light-Induced para-Difluoroalkylation of Aniline Derivatives.

Visible-light-induced, iridium catalyzed, para-selective C-H difluoroalkylation of aniline derivatives under mild reaction conditions is reported. Various substrates and bioactive compounds, such as precursors of vorinostat and chlorpropham, were all well tolerated. This protocol features a wide substrate scope, high regioselectivity, low catalyst usage, and operational simplicity.

Direct para-Selective C-H Amination of Iodobenzenes: Highly Efficient Approach for the Synthesis of Diarylamines.

Iodine(III)-mediated synthesis of 4-iodo-N-phenylaniline from iodobenzene has been achieved, and the reaction can proceed under mild conditions. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. The remaining iodine group provides an effective platform for converting the products into several valuable asymmetric diphenylamines. Most importantly, this reaction can be easily scaled up to the ten-gram scale, highlighting its synthetic utility. The mechanistic study revealed that the in situ generated aryl hypervalent iodine intermediate is the key factor to realize this para-selective C-H amination reaction.

Palladium-Catalyzed Isoquinoline Synthesis by Tandem C-H Allylation and Oxidative Cyclization of Benzylamines with Allyl Acetate.

A novel approach to synthesize 3-methylisoquinolines via a one-pot, two-step, palladium(II)-catalyzed tandem C-H allylation/intermolecular amination and aromatization is reported. A wide series of 3-methylisoquinoline derivatives were obtained directly using this method in moderate to good yields, and we highlight the synthetic importance of this new transformation.

Direct ortho-Selective C-H Functionalization of Carboxybenzyl-Protected Arylalkylamines via Ir(III)-Catalyzed C-H Activation.

A convenient and practical approach to synthesize ortho-alkynylated arylalkylamines through ortho-selective C-H functionalization has been developed using Cbz-amide as the directing group and Ir(III) as the catalyst. Various substrates were well tolerated, affording the corresponding products in moderate to good yields. Moreover, preliminary mechanistic study revealed the role of the amide as the coordination center to cooperate with the Ir(III) complex during C-H activation. Development of this Cbz-amide-promoted CAr-H functionalization offers a practical approach with potential applications in organic synthesis.

Microwave-Assisted Regioselective Synthesis of 3-Functionalized Indole Derivatives via Three-Component Domino Reaction.

A microwave-assisted regioselective synthesis of 3-functionalized indole derivatives via a three-component domino reaction of anilines, arylglyoxal monohydrates, and cyclic 1,3-dicarbonyl compounds is described. The main advantages of this protocol are short reaction times, practical simplicity, its metal-free nature, the availability of starting materials, green solvents, and high regioselectivity.

Ruthenium-Catalyzed Carbonylation of Oxalyl Amide-Protected Benzylamines with Isocyanate as the Carbonyl Source.

An efficient synthesis of isoindolin-1-ones from oxalyl amide-protected benzylamines, through ruthenium-catalyzed intramolecular C(sp2)-H carbonylation, has been developed. Variously substituted benzylamines could be well tolerated in this new protocol, affording the corresponding products in moderate to excellent yields. This approach constitutes the first example of Ru(II)-catalyzed C(sp2)-H carbonylation with isocyanate as a novel commercially available carbonyl source.

Pd-Catalyzed regioselective sequential meta-, ortho-C-H functionalization of arenes: a predictable approach to the synthesis of polysubstituted ß-arylethylamines.

With the assistance of the same bidentate directing group, the first example of sequential, controllable C-H functionalization of ß-arylethylamines at different positions for the construction of polysubstituted arenes is reported. Pd-Catalyzed highly regioselective ortho-C-H functionalization reactions of meta-aryl substituted arylethylamines are performed, including alkynylation, iodination, acetoxylation and amination, which led to a concise approach to the synthesis of polysubstituted ß-arylethylamine derivatives.

An efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives under catalyst-free conditions.

A concise, efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives via a three-component reaction of 4-oxo-4H-chromene-3-carbaldehydes, malononitrile or cyanoacetates, and aromatic amines under catalyst-free conditions in an environmentally friendly medium (ethanol-water, 3:1 v/v) is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.

Rhodium(III)-Catalyzed Oxidative C-H/C-H Cross-Coupling of Heteroarenes and Masked Benzylamines.

The first example of oxidative C-H/C-H cross-coupling of oxalyl amide-protected benzylamines and various heteroarenes in the presence of a rhodium(III) catalyst has been developed. The route provides a means of synthesizing ortho-heteroarylated benzylamines. The methodology presents broad substrate scope, great functional group tolerance, and good to excellent yields in the synthesis of substituted benzylamines. The study also reveals that the thienoisoquinoline derivatives can be accessed through the intramolecular amination of thiophenyl-substituted benzylamines with palladium(II).

Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.

Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives.

Highly regioselective meta arylation of oxalyl amide-protected ß-arylethylamine via the Catellani reaction.

The first bidentate directing group assisted highly selective meta arylation of ß-arylethylamine derivatives via palladium/norbornene catalysis is reported, and the range of aryl iodides for the oxalyl amide assisted meta-selective arylation reactions is broadest yet reported. This meta arylation also proceeds well with thiophene derivatives, giving the corresponding products in satisfactory yields. And three-step functionalization of arylethyloxalamide with three different functional groups is successfully performed.

Palladium-Catalyzed Oxalyl Amide-Directed γ-Arylation of Aliphatic Amines.

A method for palladium-catalyzed oxalyl amide-directed arylation of α-unsubstituted aliphatic amines with aryl iodides has been developed. A wide variety of aryl iodides are tolerated in this transformation, affording various γ-arylpropylamine derivatives. Heterocyclic iodides can also be competent reagents in this γ-C(sp(3))-H bonds transformation.

Multicomponent Strategy to Pyrazolo[3,4-e]indolizine Derivatives under Microwave Irradiation.

A simple and efficient one-pot construction of pyrazolo[3,4-e]indolizine derivatives via a diethylamine-catalyzed three-component domino reaction of arylglyoxals, cyclic 1,3-diones, and 5-aminopyrazoles under microwave irradiation is described. In this one-pot transformation, seven bonds and two new rings are efficiently formed. This synthesis was confirmed to follow the group-assisted-purification (GAP) chemistry process, which can avoid traditional recrystallization or chromatography purification methods.

Palladium-Catalyzed ortho-Olefination of Phenyl Acetic and Phenyl Propylacetic Esters via C-H Bond Activation.

A highly regioselective palladium-catalyzed ester-directed ortho-olefination of phenyl acetic and propionic esters with olefins via C-H bond activation has been developed. A wide variety of phenyl acetic and propionic esters were tolerated in this transformation, affording the corresponding olefinated aromatic compounds. The ortho-olefination of heterocyclic acetic and propionic esters also took place smoothly giving the products in good yields, thus proving the potential utility of this protocol in synthetic chemistry.

Efficient synthesis and evaluation of antitumor activities of novel functionalized 1,8-naphthyridine derivatives.

An efficient synthesis of novel functionalized 1,8-naphthyridine and chromeno[2,3-b]quinoline derivatives via cascade reaction of 2-chloroquinoline-3-carbaldehyde and enaminones or cyclic 1,3-dicarbonyl compounds was developed. All of the 1,8-naphthyridine derivatives synthesized were evaluated for their antiproliferative properties in vitro against cancer cells and several compounds were found to have high activities.

Multicomponent strategy to indeno[2,1-c]pyridine and hydroisoquinoline derivatives through cleavage of carbon­carbon bond.

A concise and efficient three-component domino reaction has been developed for the synthesis of polyfunctionalized indenopyridine and hydroisoquinoline derivatives via the cleavage of a C­C bond under transition-metal-free conditions. This reaction provides facile access to complex nitrogen-containing heterocycles by simply mixing three common starting materials in EtOH in the presence of 20 mol % NaOH under microwave irradiation conditions.

Highly selective synthesis of functionalized polyhydroisoquinoline derivatives via a three-component domino reaction.

Two series of novel functionalized polyhydroisoquinoline derivatives have been synthesized via the three-component domino reaction of glutaraldehyde and malononitrile with a series of ß-ketoamides under microwave irradiation conditions in the presence of a catalytic amount of Et3N (10 mol%). This reaction represents the first reported process for the facile conversion of a ß-ketoamide to a hydroisoquinoline via a C-N bond cleavage reaction without the need for a multistep reaction process.

An efficient three-component synthesis of highly functionalized tetrahydroacenaphtho[1,2-b]indolone derivatives catalyzed by L-proline.

An efficient and diastereoselective synthetic procedure for highly functionalized tetrahydroacenaphtho[1,2-b]indolone derivatives was successfully developed by the three-component reaction of acenaphthequinone, enaminones, and barbituric acid in the presence of a catalytic amount of L-proline. This method has the advantages of convenient operation, excellent yields, mild reaction conditions, and environmental friendliness.

Selective synthesis of polyfunctionalized pyrido[2,3-b]indoles by multicomponent domino reactions.

A series of novel polyfunctionalized pyrido[2,3-b]indoles were synthesized by three- or four-component domino reactions under microwave irradiation. This protocol has the advantages of readily available starting materials, short reaction times, high yields, easy workup, and high chemo- and regioselectivities.

Efficient synthesis of functionalized benzo[b][1,8]naphthyridine derivatives via three-component reaction catalyzed by L-proline.

A facile and efficient one-pot procedure for the preparation of functionalized benzo[b][1,8]naphthyridine derivatives by three-component reaction of 2-chloroquinoline-3-carbaldehyde, 1,3-dicarbonyl compounds, and enaminones catalyzed by l-proline is described. This new protocol has the advantages of environmental friendliness, good yields, and convenient operation.