Construction of Alkaloid-Type Bis Carbazoles via Pd(II)-Catalyzed C-H Functionalization.

We report the construction of unsymmetrical dimeric carbazoles and π-extended bis carbazoles (having an aryl ring spacer) via the C-H functionalization route. Generally, oxidative coupling and traditional cross-coupling reactions have been used to construct bis- and π-extended carbazoles. Natural bis carbazole alkaloids and synthetic dimeric carbazoles are important molecules in medicinal, materials chemistry research.

Synthesis of biaryl-based carbazoles C-H functionalization and exploration of their anticancer activities.

The synthesis of a library of new biaryl-based carbazoles bidentate directing group-assisted C-H functionalization and preliminary screening of the anticancer properties of biaryl-based carbazoles is reported. While various classes of modified carbazoles are known for their applications in materials and medicinal chemistry, to our knowledge, the biological activities of designed biaryl-based carbazoles have been rarely known. Given the prominence of carbazoles in research in medicinal chemistry, we envisioned the scope for new scaffolds of carbazole-based biaryl structures.

Surface Acidic Species-Driven Reductive Amination of Furfural with Ru/T-ZrO.

Catalyst development for upgrading bio-based chemicals towards primary amines has increasingly attracted owing to their applications in the pharmaceutical and polymer industries. The surface acidic sites in metal oxide-based catalysts play a key role in the reductive amination of aldehydes/ketones involving H and NH; however, the crucial role of the type of surface acidic species and their strength remains unclear. Herein, this study exhibits the catalytic reductive amination of furfural (FUR) to furfurylamine (FUA) with Ru supported on tetragonal (Ru/T-ZrO) and monoclinic (Ru/M-ZrO) ZrO.

Picolinamide-assisted -C-H functionalization of pyrenylglycine derivatives using aryl iodides.

Chemical transformations involving the pyrenylglycine motif (an unnatural amino acid) and practical methods toward it are seldom known. This work aimed at developing a method for synthesizing novel pyrenylglycine (pyrene-based glycine) unnatural amino acid derivatives. To realize this, initially, a new pyrenylglycine substrate possessing the picolinamide moiety was assembled the Ugi multicomponent reaction.

Pd(II)-catalyzed coupling of C-H bonds of carboxamides with iodoazobenzenes toward modified azobenzenes.

In this paper, we report a synthetic protocol for the construction of biaryl motif-based or π-extended azobenzene and alkylated azobenzene derivatives the Pd(II)-catalyzed bidentate directing group (DG)-aided C-H activation and functionalization strategy. In the past, the synthesis of biaryl motif-based azobenzenes was accomplished through the traditional cross-coupling reaction involving organometallic reagents and aryl halides or equivalent coupling partners. We have shown the direct coupling of C-H bonds of aromatic/aliphatic carboxamides (possessing a DG) with iodoazobenzenes as the coupling partners through the Pd(II)-catalyzed bidentate DG-aided, site-selective C-H functionalization method.

Pd(II)-catalyzed selective β-C-H functionalization of azobenzene carboxamides.

We report a Pd(II)-catalyzed bidentate directing group 8-aminoquinoline-aided, site-selective β-C-H functionalization protocol for assembling modified azobenzene carboxamides. Considering the importance of azobenzenes in chemical sciences, this paper reports a new route for enriching the library of modified azobenzene motifs.

Azobenzene-based unnatural amino acid scaffolds a Pd(II)-catalyzed C(sp)-H arylation strategy.

Azobenzene-based unnatural amino acid motifs were synthesized Pd(II)-catalyzed diastereoselective C(sp)-H arylation of amino acid carboxamides with iodoacetanilides and Mills azo coupling.

Construction of carbazole-based unnatural amino acid scaffolds Pd(II)-catalyzed C(sp)-H functionalization.

We report the synthesis of carbazole-based unnatural α-amino acid and non-α-amino acid derivatives a Pd(II)-catalyzed bidentate directing group 8-aminoquinoline-aided β-C(sp)-H activation/functionalization method. Various -phthaloyl, DL-, L- and D-carboxamides derived from their corresponding α-amino acids, non-α-amino acids and aliphatic carboxamides were subjected to the β-C(sp)-H functionalization with 3-iodocarbazoles in the presence of a Pd(II) catalyst to afford the corresponding carbazole moiety installed unnatural amino acid derivatives and aliphatic carboxamides. Carbazole motif-containing racemic (DL) and enantiopure (L and D) amino acid derivatives including phenylalanine, norvaline, leucine, norleucine and 2-aminooctanoic acid with -stereochemistry and various non-α-amino acid derivatives including GABA have been synthesized.

Advances in the Catalytic Reductive Amination of Furfural to Furfural Amine: The Momentous Role of Active Metal Sites.

One-pot synthesis of sustainable primary amines by catalytic reductive amination of bio-based carbonyl compounds with NH and H is emerging as a promising and robust approach. The primary amines, especially furfuryl amine (FUA) derived from furfural (FUR), with a wide range of applications from pharmaceuticals to agrochemicals, have attracted much attention due to their versatility. This Review is majorly comprised of two segments on the reductive amination of FUR to FUA, one with precious (Ru, Pd, Rh) and the other with non-precious (Co, Ni) metals on different supports and in various solvent systems in the presence of NH and H .

Diastereoselective palladium-catalyzed functionalization of prochiral C(sp)-H bonds of aliphatic and alicyclic compounds.

We highlight the reported developments of the palladium-catalyzed C-H activation and functionalization of the inactive/unreactive prochiral C(sp)-H bonds of aliphatic and alicyclic compounds. There exist numerous classical methods for generating contiguous stereogenic centers in a compound with a high degree of stereocontrol. Along similar lines, the Pd(II)-catalyzed, directing group-aided functionalization of inactive prochiral/diastereotopic C(sp)-H bonds have been exploited to accomplish the stereoselective construction of stereo-arrays in organic compounds.

Pd(II)-Catalyzed Arylation and Intramolecular Amidation of γ-C(sp)-H Bonds: En Route to Arylheteroarylmethane and Pyrrolidone Ring Annulated Furan/Thiophene Scaffolds.

We report the Pd(II)-catalyzed, bidentate directing group (BDG)-assisted arylation and successive arylation/intramolecular amidation of γ-C(sp)-H bonds. The Pd(II)-catalyzed BDG-assisted C-H activation and functionalization of the β-C(sp)-H bonds of carboxylic acids are well documented, but only a few reports are available that deal with the BDG-directed functionalization of the γ-C(sp)-H bonds. Various 3-methylthiophene/furan-2-carboxamides (1a-e) were derived from their corresponding carboxylic acids and bidentate directing groups.

Pd(II)-Catalyzed, Picolinamide-Assisted, Z-Selective γ-Arylation of Allylamines To Construct Z-Cinnamylamines.

Investigations of Pd(II)-catalyzed, picolinamide-assisted, γ-C(sp)-H activation and Z-selective arylation of allylamines are reported. The reactions of N-allylpicolinamides with various aryl iodides in the presence of the catalyst Pd(OAc) and additive AgOAc have led to the selective γ-arylation of allylamines to construct various cinnamylamines with moderate to good yields and good to high E/Z ratios. To obtain good E/Z ratios, the Pd(II)-catalyzed arylation reaction of N-allylpicolinamides was probed using different additives, directing groups, and reaction conditions.

Pd(II)-Catalyzed Bidentate Directing Group-Aided Chemoselective Acetoxylation of Remote ε-C(sp)-H Bonds in Heteroaryl-Aryl-Based Biaryl Systems.

In this Article, we report our successful attempt on the Pd(II)-catalyzed, bidentate directing group-aided, chemoselective acetoxylation/substitution of remote ε-C(sp)-H bonds using heteroaryl-aryl-based biaryl systems. While the bidentate directing group (BDG)-aided, C-H activation, and functionalization/acetoxylation of the β-, γ-, and δ-C-H bonds of the appropriate carboxamide systems were well documented, there exist only rare reports dealing with the C-H activation and functionalization of remote ε-C-H bonds of appropriate substrates. Especially, the BDG-aided chemoselective acetoxylation of the remote ε-C(sp)-H bond over cyclization has not been explored well.

4-Amino-2,1,3-benzothiadiazole as a Removable Bidentate Directing Group for the Pd(II)-Catalyzed Arylation/Oxygenation of sp/sp β-C-H Bonds of Carboxamides.

In this paper, we report 4-amino-2,1,3-benzothiadiazole (ABTD) as a new bidentate directing group for the Pd(II)-catalyzed sp/sp C-H activation/functionalization of various aliphatic/alicyclic/aromatic carboxamide systems. The Pd(II)-catalyzed, ABTD-directed sp C-H arylation/acetoxylation of aliphatic- and alicyclic carboxamides afforded the corresponding β-C-H arylated/acetoxylated carboxamides. The Pd(II)-catalyzed, ABTD-directed sp C-H arylation of cyclobutanecarboxamide with different aryl iodides afforded the corresponding bis β-C-H arylated cyclobutanecarboxamides having all-cis stereochemistry with a high degree of stereocontrol.

Diastereoselective Pd(II)-Catalyzed sp C-H Arylation Followed by Ring Opening of Cyclopropanecarboxamides: Construction of anti β-Acyloxy Carboxamide Derivatives.

The diastereoselective Pd(OAc)-catalyzed, bidentate ligand-directed sp C-H activation/arylation followed by ring opening of cyclopropanecarboxamides, which were assembled from cyclopropanecarbonyl chlorides and bidentate ligands (e.g., 8-aminoquinoline and 2-(methylthio)aniline), has been investigated.

Pd(OAc)2-Catalyzed, AgOAc-Promoted Z Selective Directed β-Arylation of Acrylamide Systems and Stereoselective Construction of Z-Cinnamamide Scaffolds.

A Pd(OAc)2-catalyzed, AgOAc-promoted and bidentate ligand-directed Z selective C-H activation, followed by the β-arylation of the C(sp(2))-H bond of N-(quinolin-8-yl)acrylamide systems with aryl- and heteroaryl iodides, and a contemporary method for the construction of various Z-cinnamamides and β,β-diarylated acrylamides are reported. A plausible reaction mechanism comprising the bidentate ligand-aided, chelation-based C-H functionalization was proposed for the observed Z selective β-arylation of N-(quinolin-8-yl)acrylamide systems.

Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3) C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.

An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities.

Direct bis-arylation of cyclobutanecarboxamide via double C-H activation: an auxiliary-aided diastereoselective Pd-catalyzed access to trisubstituted cyclobutane scaffolds having three contiguous stereocenters and an all-cis stereochemistry.

An auxiliary-aided Pd-catalyzed highly diastereoselective double C-H activation and direct bis-arylation of methylene C(sp(3))-H bonds of cyclobutanecarboxamides and the syntheses of several novel trisubstituted cyclobutanecarboxamide scaffolds having an all-cis stereochemistry are reported. Extensive screening of various auxiliaries and reaction conditions was performed to firmly establish the optimized reaction conditions required for effecting the mono- or double C-H arylation of cyclobutanecarboxamides. The auxiliary-attached cyclobutanecarboxamides 15a, 15g, and 15h, prepared from the auxiliaries such as, 8-aminoquinoline, 2-(methylthio)aniline, and N',N'-dimethylethane-1,2-diamine were found to undergo an efficient direct bis-arylation.

Auxiliary-enabled Pd-catalyzed direct arylation of methylene C(sp3)-H bond of cyclopropanes: highly diastereoselective assembling of di- and trisubstituted cyclopropanecarboxamides.

An auxiliary-enabled and Pd(OAc)2-catalyzed direct arylation of C(sp(3))-H bonds of cyclopropanes and production of di- and trisubstituted cyclopropanecarboxamides having contiguous stereocenters are reported. The installation of aryl groups on cyclopropanecarboxamides led to the assembling of novel mono- and di- aryl-N-(quinolin-8-yl)cyclopropanecarboxamide scaffolds and mono- and di- aryl-N-(2-(methylthio)phenyl)cyclopropanecarboxamides. The stereochemistry of products was unequivocally assigned from the X-ray structures of key compounds.

Esters as acylating reagent in a Friedel-Crafts reaction: indium tribromide catalyzed acylation of arenes using dimethylchlorosilane.

The Friedel-Crafts acylation of arenes with esters by dimethylchlorosilane and 10 mol % of indium tribromide has been achieved. The key intermediate RCOOSi(Cl)Me(2) is generated from alkoxy esters with the evolution of the corresponding alkanes. The scope of the alkoxy ester moiety was wide: tert-butyl, benzyl, allyl, and isopropyl esters were successful.

Diastereoselective production of homoallylic alcohols bearing quaternary centers from gamma-substituted allylic indiums and ketones.

Highly stereoselective In-employed addition of gamma-substituted allylic halides (cyclohexenyl halides, cinnamyl halides, and ethyl 4-bromocrotonate) to ketones is established to produce homoallyl alcohols bearing quaternary centers. The reactivity patterns and relative stability of allylic indiums were studied. The addition of water characteristically affected the reactions.

In(III)-mediated chemoselective dehydrogenative interaction of ClMe(2)SiH with carboxylic acids: direct chemo- and regioselective Friedel-Crafts acylation of aromatic ethers.

[reaction: see text] Chemoselective dehydrogenative interaction of ClMe(2)SiH with a carboxylic acid group in the presence of InX3 is reported. 13C NMR investigation revealed the formation of PhCOOSi(Cl)Me(2) as the major transient intermediate. Chemo- and regioselective Friedel-Crafts acylation of aromatic ethers directly from carboxylic acids was established.

Anomalous reaction of Rh2(OAc)4-generated transient carbonyl ylides: chemoselective synthesis of epoxy-bridged tetrahydropyranone, oxepanone, oxocinone, and oxoninone ring systems.

A series of symmetrical and unsymmetrical alpha,beta-unsaturated ketones such as arylmethylidenecycloalkanones (16, 19), bis(arylmethylidene)cycloalkanones (21, 23, 27), bisdiphenylnonatetraenones (30), and bis(phenylpropenylidene)cycloalkanones (33, 38, 42) were synthesized and subjected to the rhodium(II)-catalyzed tandem cyclization-cycloaddition reactions with various alpha-diazo ketones. These reactions afforded spiro epoxy-bridged tetrahydropyranone, spiro epoxy-bridged oxepanone (41, 43), epoxyoxocin-4(5H)-one (35, 37), and epoxyoxonin-5(6H)-one (40) frameworks starting from relatively simple precursors. The regio- and stereochemistry and solid-state architecture arrangements of several products were characterized by single-crystal X-ray structure analysis.

High chelation control of three contiguous stereogenic centers in the Reformatsky reactions of indium enolates with alpha-hydroxy ketones: unexpected stereochemistry of lactone formation.

[reaction: see text] A boat-type of chelated bicyclic transition state involving highly diastereoselective construction of three contiguous stereogenic centers in the Reformatsky reaction of indium enolates with alpha-alkoxy/hydroxy ketones is proposed. alpha-Hydroxy ketones with indium enolates furnished highly diastereoselective lactones, while alpha-alkoxy ketones gave acyclic esters in moderate selectivities. X-ray structure analyses of key products unequivocally revealed the unexpected stereochemistry of products and the reaction pathway.