Highly regioselective palladium-catalyzed annulation reactions of heteroatom-substituted allenes for synthesis of condensed heterocycles

We have developed a highly regioselective synthesis of heterocycles via palladium-catalyzed annulation reaction of heteroatom-substituted allenes. Various aryl halides were reacted and one regioisomer was observed exclusively in all reactions. In addition, subsequent functionalizations of annulated products were carried out using alkyl metal reagents, and the introduction of alkyl moieties was accomplished.     

Transition-metal-catalyzed methods for synthesis of fluorenes

This report aims to summarize recent advances in syntheses of fluorenes and derivatives thereof by using methods based on catalytic or stoichiometric transformations of various aromatic compounds induced by transition metal compounds. These methods encompass various inter- and intramolecular processes such as cross-coupling reactions, carbonylations, CH activations, electrophilic aromatic substitutions, cycloaddition reactions of alkenes and alkynes.     

Novel 2,2-bipyridine ligand for palladium-catalyzed regioselective carbonylation

[reaction: see text] A palladium-catalyzed highly regioselective one-step carbonylation of 2,5-dibromo-3-methylpyridine is reported. A range of alkyl esters and amides can be prepared in good yield with better than 95:5 regioselectivity via this method. Key to the high regioselectivity for the formation aromatic amides is the introduction of a novel nonphosphine-based 2,2-bipyridine ligand. This novel reaction was scaled up smoothly in the plant to a 130-kg batch size and facilitated the delivery of bulk material for the clinical trials of Sch 66336, a candidate for oncologic treatments.     

A palladium-catalyzed one-pot procedure for the regioselective dimerization and cyanation of indoles

A one-pot method for the regioselective dimerization and cyanation of indoles has been developed. The reaction uses safe and nontoxic K₄[Fe(CN)₆]·3H₂O as the cyanating agent which introduces selectively a cyano group into the 3-position of biindoles with high efficiency.     

Diastereoselective synthesis of tetrahydroquinolines via a palladium-catalyzed Heck–Suzuki cascade reaction

A method for the diastereoselective synthesis of tetrahydroquinolines via a palladium-catalyzed Suzuki terminated Heck reaction is described. The reaction provides access to tetrahydroquinolines containing both quaternary and tertiary stereocenters. Ligand effects, a rationale for the high level of diastereoselectivity, and a mechanistic hypothesis are discussed.     

Tandem palladium-catalyzed urea arylation-intramolecular ester amidation: regioselective synthesis of 3-alkylated 2,4-quinazolinediones

o-Halo benzoates can be combined with monoalkyl ureas in a tandem palladium-catalyzed arylation-ester amidation sequence to deliver quinazolinedione products. The reactions are regioselective for formation of the 3-N-alkyl isomers. Significant variation of both coupling partners is possible, allowing the synthesis of a diverse array of substituted quinazolinediones, exemplified by the preparation of a simple unsymmetric-dialkylated natural product. [reaction: see text]     

Highly regioselective synthesis of 1,3-diiodonaphthalene derivatives via a sequential cascade iodocyclization

A novel and flexible sequentially cascade iodocyclization for the synthesis of highly substituted 1,3-diiodinated naphthalene derivatives in up to 99% yield under mild conditions is reported. The dihalogenated moiety can be readily introduced into the naphthalenes in a position that is usually not easily functionalized.     

Microwave-assisted palladium-catalyzed regioselective cyanothiolation of alkynes with thiocyanates

Applying microwave irradiation to palladium-catalyzed cyanothiolation of alkynes dramatically shortened the reaction time with good to excellent isolated yields.     

Convenient synthesis of 2,4-disubstituted pyrido[2,3-d]pyrimidines via regioselective palladium-catalyzed reactions

A novel and effective route for the synthesis of 2,4-disubstituted pyrido[2,3-d]pyrimidines III is reported starting from the corresponding 2,4-dichloropyridopyrimidine 1 through regioselective functionalization palladium-catalyzed C–C coupling reactions, by two successive palladium-catalyzed reactions involving an original regioselective chlorine discrimination. Alternatively, type III compounds were elaborated from 2 by C-2 chlorine further displacement of the C-4 isopropylsulfanyl group, which acted as a temporary C-4 protecting group. Further Suzuki–Miyaura cross-coupling reactions led to C-2 and C-4 disubstituted compounds.     

A highly regioselective palladium-catalyzed hydrophosphination of alkynes using a diphosphine-hydrosilane binary system

A novel transition-metal-catalyzed hydrophosphination of terminal alkynes using a diphosphine-hydrosilane binary system takes place regioselectively to provide vinylic phosphines, which undergo air oxidation during workup, affording the corresponding vinylphosphine oxides in good yields. In this hydrophosphination, hydrosilanes act as a useful hydrogen source, and furthermore, small amounts of oxygen is required to accomplish the reaction efficiently.     

Hydrogen bond directed highly regioselective palladium-catalyzed allylic substitution

The palladium-catalyzed allylic substitution of 5-vinyloxazolidinones and derivatives was investigated. Unusual and high regioselectivity for the branched product was observed. The regioselectivity was influenced by the type of substrate, the solvents, and the nucleophile. Imide-type nucleophiles were found to be directed to the internal carbon (branched:linear, 75:25 to >98:2), whereas sulfonamides, amines, and malonates added only to the terminal carbon of the allyl complex. Relatively nonpolar solvents such as toluene and THF favored the branched product (97:3 and 95:5, respectively). Acetonitrile and dichloromethane afforded lower regioselectivity (50:50 and 67:33, respectively), and the use of the protic solvent ethanol resulted in reversal of the regioselectivity (12:88). The directing group on the substrate was important. Amides afforded almost complete formation of the branched product, and carbamates gave a 50:50 mixture of regioisomers with phthalimide as the nucleophile. Evidence for direction of the nucleophile via hydrogen bonding was obtained by replacing the hydrogen of the amide with a methyl, resulting in the production of only the normal linear product.     

A first regioselective synthesis of 3-fluoroalkylated benzofurans via palladium-catalyzed annulation of fluorine-containing internal alkynes with variously substituted 2-iodophenol

The palladium-catalyzed annulation reaction of a variety of fluorine-containing internal alkynes with 2-iodophenol derivatives was investigated. The use of P(t-Bu)₃ as a ligand on palladium was found to be crucial in this annulation reaction, resulting in the exclusive formation of 3-fluoroalkylated benzofurans in high yields. ¹⁹F NMR analysis of the reaction mixture revealed that the addition of phenol to the fluoroalkylated alkynes was followed by intramolecular Heck reaction, giving to the corresponding 3-fluoroalkylated benzofurans.     

Palladium-catalyzed regioselective cascade reaction of carbon dioxide,amines and allenes for the synthesis of functionalized carbamates

A palladium-catalyzed regioselective three-component cascade reaction of carbon dioxide,amines and allenes has been developed,providing an expedient and practical method for the construction of a range of functionalized carbamates containing dihydrobenzofuran or indole moiety in moderate to excellent yields.The broad substrate scope,good functional group tolerance and excellent chemo-and regioselectivity are the features of the transformation.     

A new palladium-catalyzed synthesis of indoxyl derivatives

The reaction of iodoanilines with phenylacetylene and carbon monoxide catalyzedby a palladium(0) catalyst leads to indoxyl derivatives.