Palladium-catalyzed double arylations of terminal olefins in acetic acid

A palladium-catalyzed Heck diarylation of terminal olefins under ligand-free conditions in acetic acid is described. This procedure allows double arylation of terminal olefins affording trisubstituted olefins in good to excellent yields. The methodology is applicable to the coupling of both electron-deficient and electron-rich aryl iodides leading to symmetrical and unsymmetrical β,β-diarylated alkenes.     

Palladium-catalyzed Heck reaction of in-situ generated benzylic iodides and styrenes

A palladium-catalyzed Heck reaction of in-situ generated benzylic iodides and styrenes has been achieved. The reaction proceeds in a one-pot manner through 1) addition perfluoroalkyl iodides to styrenes to give benzylic iodides, 2) followed by a palladium-catalyzed Heck coupling of the resulting benzylic iodides with the same alkenes in high regio- and stereoselectivity. A variety of perfluoroalkylated alkenes were obtained in moderate to excellent yields.     

Sequential assembly strategy for tetrasubstituted olefin synthesis using vinyl 2-pyrimidyl sulfide as a platform

We have developed a programmable and diversity-oriented synthetic scheme for tetrasubstituted olefins through a site-selective and sequential assembly of pi-components onto a C=C core of vinyl 2-pyrimidyl sulfide. Noteworthy features are that (i) all components assembled stem from readily available organic halides or their Grignard reagents, (ii) the installation at the desired position can be achieved by the addition of the components in the appropriate order, and (iii) simple alteration of addition order in the sequence results in the production of all possible regio- and stereoisomers of multisubstituted olefins.     

Diversity-oriented synthesis of tamoxifen-type tetrasubstituted olefins

A general synthetic scheme for tamoxifen-type tetrasubstituted olefins based on the novel Cu-catalyzed carbomagnesation across alkynyl(2-pyridyl)silane has been developed. A wide array of electronically and structurally diverse tetrasubstituted olefins can be prepared in a regiocontrolled, stereocontrolled, and diversity-oriented manner. Noteworthy features are that (i) the three aryl groups, which are believed to be important (essential) for anti-estrogenic activity, can be varied at will because they all stem from readily available aryl iodides, and (ii) any stereo- and regioisomers can, in principle, be prepared by simply changing the applying order of aryl iodides into the sequence.     

Pd-mBDPP-catalyzed regioselective internal arylation of electron-rich olefins by aryl halides

meso-2,4-Bis(diphenylphosphino)pentane (mBDPP) has proved to be an effective regiocontrolling ligand for palladium-catalyzed internal arylation by aryl bromides of electron-rich olefins in a common solvent DMSO with no need for any halide scavengers. The arylation of the benchmark electron-rich olefin butyl vinyl ether took place smoothly to afford exclusively alpha-arylated product with high isolated yields. The better performance of mBDPP, compared with that of the commonly used DPPP [1,3-bis(diphenylphosphino)propane], highlights the important but subtle effect of ligand on the regioselectivity of the Heck arylation reactions.     

Selective synthesis of 3-methyleneindolin-2-ones by one-pot multicatalytic processes

A novel one-pot multicatalytic route for the synthesis of 3-methyleneindolin-2-ones has been developed involving sequential copper-catalyzed amination and palladium-catalyzed C-H functionalization processes. In the presence of CuI and Pd(OAc)₂, a variety of propiolamides underwent the reaction with iodides to afford the corresponding 3-methyleneindolin-2-ones in moderate yields.     

A one-pot synthesis of (E)-disubstituted alkenes by a bimetallic [Rh-Pd]-catalyzed hydrosilylation/hiyama cross-coupling sequence

A bimetallic [Rh-Pd] catalyst was prepared by soaking into an iodide ionic gel an equimolar solution of [RhCl(PPh(3))(3)] and Pd(OAc)(2) in CH(2)Cl(2). Its catalytic activity was evaluated by rhodium-catalyzed hydrosilylation (H), palladium-catalyzed Hiyama coupling (C), and in the one-pot hydrosilylation/Hiyama coupling sequence (H/C). It was found that the homogeneous combination [RhCl(PPh(3))(3)]/NaI was a superior system compared to the polyionic mono- and bimetallic rhodium catalysts in the hydrosilylation of terminal alkynes. Interestingly, the most effective catalyst in terms of stereo- and chemoselectivities was observed to be the bimetallic ionic gel [Rh-Pd] in the one-pot process leading to (E)-alkenes with good yields. The remarkable stereocontrol is ascribed to a beneficial Pd-catalyzed isomerization from the mixture of stereoisomeric vinylsilanes obtained in the initial hydrosilylation step into the more stable (E)-adduct. The [Rh-Pd] heterogeneous catalyst also showed a higher chemoselectivity than the homogeneous catalytic combination, and no detrimental formation of Sonogashira side product was observed due to an ionic-gel-mediated kinetic modulation. To illustrate its scope and limitations, the described one-pot bimetallic catalytic sequence was extended to functionalized terminal alkynes and various iodide substrates. Conjugated systems, such as hydroxycinnamaldehyde, dienes, and trienes, were synthesized in good overall yields. To avoid deactivation of the Rh species, N-heterocyclic iodides had to be added sequentially after completion of hydrosilylation.     

Palladium-catalyzed regiocontrolled internal heteroarylation of electron-rich olefins with heteroaryl halides

A highly efficient palladium-catalyzed Heck coupling reaction of heteroaryl halides with electron-rich vinyl ether and hydroxyalkyl vinyl ethers is described. It was found that the choice of solvent, ligand, and reaction temperature had a fundamental influence on the regioselectivity and reactivity of the reaction, and the combination of Pd(OAc)₂ and DPPF in ethylene glycol led to the most effective catalytic system. Under these conditions, a variety of heteroaryl halides reacted very quickly with electron-rich olefins to afford exclusively the branched products in good to excellent yields without employing triflates, halide scavengers, or ionic liquids.     

Enantiomerically pure alpha-amino acid synthesis via hydroboration-suzuki cross-coupling

The Garner aldehyde-derived methylene alkene 5 and the corresponding benzyloxycarbonyl compound 25 undergo hydroboration with 9-BBN-H followed by palladium-catalyzed Suzuki coupling reactions with aryl and vinyl halides. After one-pot hydrolysis-oxidation, a range of known and novel nonproteinogenic amino acids were isolated as their N-protected derivatives. These novel organoborane homoalanine anion equivalents are generated and transformed under mild conditions and with wide functional group tolerance: electron-rich and -poor aromatic iodides and bromides (and a vinyl bromide) all undergo efficient Suzuki coupling. The extension of this methodology to prepare meso-DAP, R,R-DAP, and R,R-DAS is also described.     

CuI/Dabco as a highly active catalytic system for the Heck-type reaction

An efficient catalytic system using CuI/Dabco (triethylenediamine) for the Heck-type cross-coupling reaction was developed. In the presence of 10 mol % of CuI and 20 mol % of Dabco, the coupling of various aromatic iodides and 1-((Z)-2-bromovinyl)benzene with olefins was carried out efficiently and selectively to afford the corresponding internal olefins in moderate to good yields.     

Vinyliodonium salts : their stereospecific synthesis and reactions as the activated vinyl halides

Vinyliodonium salts $\text{2}$ were synthesized from vinylsilanes $\text{1}$ by the reaction with iodosylbenzene and triethyloxonium tetrafluoroborate. The reaction occurs stereospecifically with retention of configuration. Vinyliodonium salts $\text{2}$ are highly effective as the activated species of vinyl iodides. Thus, a variety of substituted olefins including α-cyano and α-nitro olefins, vinyl sulfides, vinyl halides, and α,β-unsaturated esters, were prepared from $\text{2}$ under mild reaction conditions.     

Stereoselective synthesis of multisubstituted butadienes through directed Mizoroki-Heck reaction and homocoupling reaction of vinyl(2-pyridyl)silane

[reaction: see text] We have developed the homocoupling reaction of alkenyl(2-pyridyl)silanes mediated by CuI and CsF, in which the strong directing effect of the 2-pyridyl group was observed. The homocoupling reaction was successfully integrated with the Mizoroki-Heck reaction of vinyl(2-pyridyl)silane with aryl halides, enabling a rapid and stereoselective synthesis of multisubstituted butadienes. From a relatively small compound library, it was possible to detect a number of fluorescent butadienes with a wide range of fluorescence color variations (blue to reddish-orange).     

Palladium-catalyzed carbonylative coupling reactions of aryl iodides with hexamethyldisilane (HMDS) to benzoyl silanes

A novel procedure for the palladium-catalyzed carbonylative synthesis of acyl silanes has been developed. Starting from aryl iodides and hexamethyldisilane (HMDS) various benzoyl silanes are produced in moderate to good yields.     

Acyl iodides in organic synthesis: IX. Cleavage of the Si-O-C and Si-O-Si moieties

Reactions of acyl iodides RCOI (R = Me, Ph) with organosilicon compounds involve cleavage of the Si-O-C and Si-O-Si fragments. Acetyl iodide reacts with alkyl(alkoxy)silanes with evolution of heat, and cleavage of the Si-O bond results in the formation of oligo-or polysiloxanes, alkyl iodides, and alkyl acetates. 1,3-Diacetoxytetramethyldisiloxane is formed in the reaction of acetyl iodide with dimethoxy(dimethyl)silane. Acyl iodides readily react with 1-ethoxysilatrane to give 1-acyloxysilatranes as a result of cleavage of the C-O bond. The reaction of acetyl iodide with hexaethyldisiloxane yields triethylsilyl acetate and triethyliodosilane, while in the reaction with octamethyltrisiloxane iodo(trimethyl)silane and dimethyl(trimethylsiloxy)silyl acetate are obtained.     

Chiral (R)- and (S)-allylic alcohols via a one-pot chemoenzymatic synthesis

Chiral (R)- and (S)-allylic alcohols with an enantiomeric excess exceeding 99% have been prepared in good to high overall isolated yields through a two-step one-pot chemoenzymatic process based on the palladium-catalyzed Heck reaction of aryl iodides with butenone followed by an enzymatic reduction of the resultant vinylic substitution products. Alcohol dehydrogenases from Lactobacillus brevis and Thermoanaerobacter species were used to attain (R)- and (S)-stereoselectivity, respectively.     

Palladium/Imidazolium salt as a versatile catalyst for sequential coupling reactions of aryl dihalides to unsymmetrically substituted arenes

A simple method for one-pot sequential Heck/Suzuki coupling reactions of a range of substituted aryl dihalides has been described. The Pd(OAc)₂/imidazolium system catalyzed double coupling reactions proceed without isolation of the intermediates giving unsymmetrically polysubstituted biphenyls in good to excellent yields. Further couplings of the resultant products bearing additional C-Cl bonds with substituted arylboronic acids or amines lead to unsymmetrical terphenyls and aminobiphenyl derivatives.     

2,2′-Diamino-6,6′-dimethylbiphenyl as an efficient ligand in the palladium-catalyzed Suzuki–Miyaura and Mizoroki–Heck reactions

2,2′-Diamino-6,6′-dimethylbiphenyl was found to be an efficient ligand in the palladium-catalyzed Suzuki–Miyaura coupling reactions of aryl iodides, bromides, and chlorides and Mizoroki–Heck reactions of aryl iodides and bromides. Under appropriate conditions, all reactions gave the desired products in moderate to excellent yields. The ligand is inexpensive, air-stable and easy to available.     

Heck-type arylation of 2-cycloalken-1-ones with arylpalladium intermediates formed by decarboxylative palladation and by aryl iodide insertion

[reaction: see text] A palladium-catalyzed decarboxylative arylation reaction was shown to produce Heck-type coupling products using a number of different arene carboxylic acid and 2-cycloalken-1-one substrates. The more conventional Heck coupling of an aryl iodide and a 2-cycloalken-1-one reactant was also briefly explored for comparison, where it was found that phosphine-free (Jeffery) conditions afforded the highest yield of product.     

Pd-catalyzed efficient one-pot sequential cross-coupling reactions of aryl dihalides

The palladium complex containing N-heterocyclic carbene ligands catalyzes one-pot sequential Heck/Suzuki, Heck/Heck, and Heck/Sonogashira coupling reactions of aryl dihalides to afford unsymmetrically substituted arenes in excellent yields.     

Additions of allenyl/propargyl organometallic reagents to 4-oxoazetidine-2-carbaldehydes: novel palladium-catalyzed domino reactions in allenynes

Metal-mediated carbonyl allenylation and propargylation of 4-oxoazetidine-2-carbaldehydes were investigated in aqueous environment. Different propargyl bromide and metal promoters showed varied regio- and stereoselectivities on product formation. In addition, an unprecedented one-pot stereoselective synthesis of beta-chlorinated allylic alcohols, which can also be considered as functionalized allylsilanes, has been developed, which involves tin(IV) chloride-mediated reaction of propargyltrimethylsilane and 4-oxoazetidine-2-carbaldehydes. Some of the resulting coupling products were submitted to transition metal catalyzed reactions, such as the allenic Pauson-Khand and palladium-catalyzed reactions, leading to novel fused or bridged tricyclic beta-lactams. Remarkably, a novel domino process, namely the allene cyclization/intramolecular Heck reaction was found. A likely mechanism for the cascade reaction should involve an intramolecular cyclization on a (pi-allyl)palladium complex and a Heck-type reaction.