Antonella Goggiamani

2,3-disubstituted indoles via palladium-catalyzed reaction of 2-alkynyltrifluoroacetanilides with arenediazonium tetrafluoroborates

A novel palladium-catalyzed synthesis of free N-H 2,3-disubstituted indoles from arenediazonium tetrafluoroborates and 2-alkynyltrifluoroacetanilides is presented. The reaction tolerates a variety of useful substituents both in the starting alkyne and the arenediazonium salt, including bromo and chloro substituents, nitro, cyano, keto, ester, and ether groups, as well as ortho substituents such as methoxy and methyl groups.

Sonogashira cross-coupling of arenediazonium salts.

Arenediazonium salts represent an attractive alternative to aryl halides or triflates because of their higher reactivity, their tolerance of milder conditions, their availability from inexpensive anilines, and because additional base is not required in several applications. Arenediazonium salts have been used in a variety of palladium-catalyzed reactions, including Mizoroki–Heck reactions, Suzuki–Miyaura and Stille crosscoupling reactions, and carbonylation reactions, in the synthesis of sulfinic acids and boronic esters; their use in hydroarylation reactions has also been described. Nevertheless, the alkynylation of arenediazonium salts continues to represent a challenge. After the seminal works of Sonogashira et al. , Heck and Dieck, and Cassar on the alkynylation of aryl iodides and bromides, a great deal of work has been done to extend the scope of the reaction to include an even wider range of reactants; however, the extension of the reaction to arenediazonium salts remains unresolved. To the best of our knowledge, the sole attempt to involve arenediazonium salts in the formation of arylacetylenes was made by GenÞt and co-workers, who obtained only small amounts of the desired cross-coupling derivative by palladium-catalyzed reaction of potassium 1-hexenyltrifluoroborate with para-toluenediazonium tetrafluoroborate. We investigated the reaction using phenylacetylene (1a) and 4-methoxybenzenediazonium tetrafluoroborate (2a) as the model system. No evidence of the formation of cross-coupling product 3a was found using [Pd2(dba)3] (dba = dibenzylideneacetone) or Pd(OAc)2 with a variety of phosphine (PPh3, Xphos, HP(tBu)3BF4) or carbene ligands, generated from 1,3bis(2,6-diisopropylphenyl)imidazolium chloride in the presence of base; a screen of different solvents (MeOH, THF, DME, DMF), in the presence or absence of base (iPr2NEt, K2CO3, Bu4NOAc) and CuI at temperatures ranging from room temperature to 60 8C also afforded no cross-coupled product. In all cases, complex reaction mixtures were obtained, and anisole and 1,4-diphenyl-1,3-diyne were frequently the main by-products. To overcome this limit of the palladium-based chemistry of arenediazonium salts, we reasoned that a strategy in which arylacetylenes are formed by an iododediazoniation reaction, followed by a Sonogashira cross-coupling might be successful. Iododediazoniation is a well-established reaction, and recently remarkable advances have been reported in this area. Nevertheless, no examples of its utilization in a sequential process with a palladium-catalyzed reaction have yet been described. Herein, we show that such a sequential process is indeed possible and report the first utilization of arenediazonium salts in Sonogashira cross-coupling reactions. An initial screen using [PdCl2(PPh3)2], CuI, and Et2NH in MeCN at room temperature showed that 3a could be isolated in 48 % yield in the presence of nBu4NI (1.5 equiv) or NaI (2 equiv; Table 1, entries 1 and 2). Optimization studies were then performed by changing the nature and number of equivalents of the base.

One-pot gold-catalyzed synthesis of azepino[1,2-a]indoles.

Indoles from scratch: A gold(I)/N-heterocyclic carbene complex (IPr=1,3-di(isopropylphenyl)imidazol-2-ylidene) was found to be particularly effective as a catalyst, enabling the one-pot synthesis of tricyclic azepinoindoles by an unprecedented cascade reaction. Readily available substrates, high chemoselectivity, good yields, and water as the only stoichiometric by-product are some of the main advantages of this method.

Arenediazonium tetrafluoroborates in palladium-catalyzed C–P bond-forming reactions. Synthesis of arylphosphonates, -phosphine oxides, and -phosphines

A novel palladium-catalyzed synthesis of arylphosphonates from arenediazonium tetrafluoroborates and triethylphosphite or diethylphosphite is presented. The reaction tolerates useful substituents including bromo, chloro, nitro, ether, cyano, keto, and ester groups, can be performed as a one-pot process from anilines omitting the isolation of arenediazonium salts, and can be extended to the preparation of arylphosphine oxides and arylphosphines.

Suzuki-Miyaura cross-coupling of arenediazonium salts catalyzed by alginate/gellan-stabilized palladium nanoparticles under aerobic conditions in water

The use of palladium nanoparticles stabilized by natural beads made of an alginate/gellan mixture in the Suzuki-Miyaura cross-coupling reaction of arenediazonium tetrafluoroborates with potassium aryltrifluoroborates (1 : 1 molar ratio) with loading as low as 0.01–0.002 mol% under aerobic, phosphine-, and base-free conditions in water is described. The catalyst system can be reused several times without significant loss of activity.

4-Aryl-2-quinolones from 3,3-Diarylacrylamides through Intramolecular Copper-Catalyzed C–H Functionalization/C–N Bond Formation

Free NH 3,3-diarylacrylamides are cyclized to substituted 2-quinolones in the presence of CuI, PPh(3), and KO-t-Bu in o-xylene at 100 °C. The reaction proceeds through a C-H functionalization/C-N bond formation process. With unsymmetrical 3,3-diarylacrylamides, high selectivity is observed using substrates where the aromatic ring trans to the amide group bears o-methyl, -chloro, or -bromo substituents.

Heck reaction of arenediazonium salts with N,N-diprotected allylamines. Synthesis of cinnamylamines and indoles.

Novel palladium-catalyzed reactions of arenediazonium tetrafluoroborates with N,N-diprotected allylamines are presented. The reaction of arenediazonium tetrafluoroborates with N,N-(Boc)(2) allylamine allows for an easy approach to cinnamylamines whereas using 2-alkynyl-N-(allyl)trifluoroacetanilides and 2-iodo-N-(allyl)trifluoroacetanilide the reaction provides a useful tool for appending indole rings to aniline fragments.

The [(E,E,E)-1,6,11-tris(p-toluenesulfonyl)-1,6,11-triazacyclopentadeca-3,8, 13-triene]Pd(0) complex in the hydroarylation of alkynes in ionic liquids. An approach to quinolines

Abstract The hydroarylation of alkynes can be successfully conducted in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF 4 ) in the presence of the [( E , E , E )-1,6,11-tris( p -toluenesulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triene]Pd(0) complex. The catalytic ionic solution can be recycled for reuse in subsequent reaction runs. The procedure has been applied to the preparation of 3-arylquinolines through a domino hydroarylation/cyclization process.

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.

Multisubstituted benzo[b]furans through a copper- and/or palladium-catalyzed assembly and functionalization process

Full details as well as the study of the scope, limitations, and further elaboration of a straightforward approach to the synthesis of 2,5,7-trisubstituted benzo[b]furans from 2-bromo- and 2-chloro-6-iodo-4-substituted phenols through a consecutive copper- and/or palladium-catalyzed assembly and functionalization process is described. Functionalization at the C(7) position is carried out by Suzuki–Miyaura cross-coupling, alkynylation, alkenylation, and C–N bond forming reactions. A one-pot protocol for the synthesis of 2,5,7-trisubstituted benzo[b]furans is also reported.