Direct Regioselective Hydro(hetero)arylation/Cyclocondensation Reactions of β-(2-Aminophenyl)-α,β-ynones by Means of Transition-Metal Catalysis/Brønsted Acid Synergism: Experimental Results and Computational Insights.

Experimental results and computational insights explain the key role of transition-metal catalysis/Brønsted acid synergism in the achievement of the sequential regioselective direct heteroarylation/cyclocondensation reactions of β-(2-aminophenyl)-α,β-ynones with a variety of electron-rich aromatic heterocyclic/arenes to afford quinoline-(hetero)aromatic hybrids. The first approach to the synthesis of 4-(1-pyrrol-2-yl)quinolines is described. The effectiveness of various transition metals is compared.

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1()-ones.

Cascade cyclocarbopalladation of the readily available aryl/alkyl-substituted propargylic amides containing an aryl iodide moiety, followed by Suzuki-Miyaura coupling with arylboronic acids, allowed an efficient regio- and stereoselective synthesis of tetrasubstituted 4-methylene-3,4-dihydroisoquinolin-1(2)-ones. Moreover, cascade cyclocarbopalladation, followed by the reaction with 2-alkynyltrifluoroacetanilides, accomplished a double cyclization to afford challenging 4-methylene-3,4-dihydroisoquinolin-1(2)-ones bearing a 3-indolyl substituent through aminopalladation/reductive elimination.

Experimental results and computational insight into sequential reactions of β-(2-aminophenyl)-α,β-ynones with aryl isocyanates/benzoyl isothiocyanate.

The investigation on tandem addition/cyclization reactions of β-(2-aminophenyl)-α,β-ynones with aryl isocyanates/benzoyl isothiocyanate is reported. Experimental results show the suitable conditions to selectively direct the reaction outcome towards the product of 6-exo-dig N-, O-, or S-annulation of the in situ generated alkynyl urea/thiourea intermediate. The reaction of a variety of β-(2-aminophenyl)-α,β-ynones with aryl isocyanates/benzoyl isothiocyanate led to the selective formation of quinazoline or benzoxazine/benzothiazine derivatives, respectively.

Synthesis of indolo[1,2-]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with ,-dimethylformamide dimethyl acetal.

An efficient strategy for the synthesis of 6-unsubstituted indolo[1,2-]quinazolines is described. The Pd-catalyzed reaction of -(-aminophenylethynyl) trifluoroacetanilides with Ar-B(OH) afforded 2-(-aminophenyl)-3-arylindoles, that were converted to 12-arylindolo[1,2-]quinazolines by adding dimethylformamide dimethyl acetal (DMFDMA) to the reaction mixture after extractive work-up. This reaction outcome is different from the previously reported Pd-catalyzed sequential reaction of the same substrates with Ar-I, Ar-Br and ArNBF, that afforded 12-arylindolo[1,2-]quinazolin-6(5)-ones.

Gold-Catalyzed Cascade Reaction of β-(2-Aminophenyl)-α,β-ynones with Ynamides: A Sequential Route to Polysubstituted 2-Aminoquinolines.

A novel, efficient, and mild synthetic route for the preparation of 2-aminoquinolines via a gold-catalyzed cascade reaction of β-(2-aminophenyl)-α,β-ynones with ynamides has been developed. This process tolerates a wide range of functionalities such as halogen, alkyl, aryl, and heteroaryl groups, leading to original heterocycles in fair to very good yields.

Pd- and Rh-Catalyzed Hydroarylation of γ-(2-Methoxycarbonylphenyl)propargylic Alcohols: Approaches to 4- or 5-Substituted Seven-Membered Benzolactones and 3,3-Disubstituted Phthalides.

A study of the palladium-catalyzed hydroarylation/hydrovinylation reaction of γ-(2-methoxycarbonylphenyl)propargylic alcohols with aryl iodides/vinyl triflates and of the rhodium-catalyzed one with organoboron derivatives is described. The opposite regiochemical outcome of the two processes allows an easy selective approach to 5- or 4-substituted benzoxepin-1(3H)-ones by combining the hydroarylative/hydrovinylative step with cyclocondensation between -OH and -COOMe groups in the intermediate γ,γ-disubstituted or β,γ-disubstituted allylic alcohols. A one-flask procedure to give benzo[c]oxepin-1(3H)-ones directly from the starting alkyne has been also developed.

Brønsted acid catalyzed cascade reactions of 2-[(2-aminophenyl)ethynyl]phenylamine derivatives with aldehydes: a new approach to the synthesis of 2,2'-disubstituted 1H,1'H-3,3'-biindoles.

An unusual Brønsted acid catalyzed cascade reaction of 2-[(2-aminophenyl)ethynyl]phenylamine derivatives with aryl(heteroaryl)aldehydes to afford an efficient alternative entry into 2,2'-disubstituted-1H,1'H-3,3'-biindoles under metal-free conditions is reported.

Palladium-catalyzed cascade reactions of 1-(3-arylprop-2-ynyloxy)-2-bromo benzene derivatives with organoboron compounds.

Applications of the cascade cyclocarbopalladation reaction followed by Suzuki-Miyaura coupling reactions of the readily available aryl-substituted propargylic aryl ethers with arylboronic acid and potassium trans-β-styryltrifluoroborate accomplish a new versatile entry in the synthesis of benzofuran derivatives. Notably, a new approach to the challenging synthesis of C3 functionalized 2-unsubstituted benzofurans has been developed by a cyclocarbopalladation/cross-coupling/aromatization process.

2-Substituted 3-arylindoles through palladium-catalyzed arylative cyclization of 2-alkynyltrifluoroacetanilides with arylboronic acids under oxidative conditions.

Free NH 2-substituted 3-arylindoles have been prepared usually in good to high yields through the palladium-catalyzed reaction of readily available 2-alkynyltrifluoroacetanilides with arylboronic acids under oxidative conditions. The reaction tolerates a variety of useful functional groups both in the arylboronic acid and in the alkyne, including chloro, formyl, and ester groups.

Gold versus silver catalyzed intramolecular hydroarylation reactions of [(3-arylprop-2-ynyl)oxy]benzene derivatives.

The scope and the generality of gold versus silver catalyzed intramolecular hydroarylation reactions of 3-[(3-arylprop-2-ynyl)oxy]benzene derivatives in terms of rings substitution were investigated. Only products deriving from 6-endo cyclization were exclusively formed. The features of substituents had a considerable effect on the reaction outcome in the presence of silver catalysis, whereas gold catalysis revealed a unique blend of reactivity and selectivity and represented the only choice for the intramolecular hydroarylation reaction of the starting substrates bearing electron deficient arenes.

An alternative one-pot gold-catalyzed approach to the assembly of 11H-indolo[3,2-c]quinolines.

A new one-pot approach was developed to construct the 11H-indolo[3,2-c]quinoline scaffold through a gold-catalysed reaction of 2-[(2-aminophenyl)ethynyl]phenylamine derivatives with aldehydes. The broad scope and the high regioselectivity of this new protocol as well as the mild and neutral reaction conditions make it a viable alternative to the previously reported procedures.

Sequential rhodium-catalyzed stereo- and regioselective addition of organoboron derivatives to the alkyl 4-hydroxy-2-alkynoates/lactonizaction reaction.

The sequential rhodium-catalyzed addition/lactonization reaction of organoboron derivatives to alkyl 4-hydroxy-2-alkynoates would constitute a novel methodology for the synthesis of 4-aryl/heteroaryl/vinyl-2(5H)-furanones with an excellent control of the regio- and chemoselectivity. The role played by rhodium precatalyst, ligands, reaction medium, and the feature of organoboron derivatives has been explored.

Palladium-catalyzed reaction of o-alkynyltrifluoroacetanilides with 1-bromoalkynes. An approach to 2-substituted 3-alkynylindoles and 2-substituted 3-acylindoles.

The palladium-catalyzed reaction of o-alkynyltrifluoroacetanilides with 1-bromoalkynes affords free N-H 2-substituted 3-alkynylindoles in satisfactory to high yield. 2-Substituted 3-alkynylindoles revealed useful intermediates for the regioselective synthesis of 2-substituted 3-acylindoles. The latter can be prepared from o-alkynyltrifluoroacetanilides and 1-bromoalkynes via a one-pot cyclization-hydration protocol, omitting the isolation of 2-substituted 3-alkynylindoles.

Gold-catalyzed reactions of 2-alkynyl-phenylamines with alpha,beta-enones.

[reaction: see text] The gold-catalyzed reaction of 2-alkynyl-phenylamines with alpha,beta-enones represents a new general one-pot entry into C-3-alkyl-indoles by sequential reactions. Gold-catalyzed sequential cyclization/alkylation, N-alkylation/cyclization, or N-alkylation/cyclization/alkylation reactions leading to different indoles can be directed by changing the 2-alkynyl-phenylamine 1/alpha,beta-enone 3 ratio and the reaction temperature. Unusual gold-catalyzed rearrangement reaction of indoles are observed at 140 degrees C.

Sequential amination/annulation/aromatization reaction of carbonyl compounds and propargylamine: a new one-pot approach to functionalized pyridines.

A general one-pot synthesis of pyridines 4a-t from the reaction of dialkyl acyclic/cyclic ketones 1a-i, methyl, aryl/heteroaryl ketones 1m-r, and aldehydes bearing alpha-hydrogens 1s,t with propargylamine 2 is described. Gold and copper salts are efficient catalysts for the reaction of ketones with 2. The formation of the pyridines 4 is suggested to proceed through the sequential amination of carbonyl compounds followed by regioselective 6-endo-dig cyclization of the N-propargylenamine (N-propargyldienamine) intermediate 3(5) and aromatization reaction.

Electrophilic cyclization of o-acetoxy- and o-benzyloxyalkynylpyridines: an easy entry into 2,3-disubstituted furopyridines.

[reaction: see text] 2,3-Disubstituted furo[3,2-b]pyridines, 2,3-disubstituted furo[2,3-b]pyridines, and 2,3-disubstituted furo[2,3-c]pyridines are readily prepared under mild conditions via the palladium-catalyzed cross-coupling of 1-alkynes with o-iodoacetoxy- or o-iodobenzyloxypyridines, followed by electrophilic cyclization by I(2) or by PdCl(2) under a balloon of carbon monoxide.

12-Acylindolo[1,2-c]quinazolines by palladium-catalyzed cyclocarbonylation of o-alkynyltrifluoroacetanilides.

6-Trifluoromethyl-12-acylindolo[1,2-c]quinazolines are prepared in high yield through the palladium-catalyzed reaction of bis(o-trifluoroacetamidophenyl)acetylene with aryl or vinyl halides and triflates. The reaction, which tolerates a variety of important functional groups, probably involves the formation of a 3-acyl-2-(o-trifluoroacetamidophenyl)indole intermediate, followed by its cyclization to the indoloquinazoline product. [reaction: see text]