Pd/C-mediated coupling of aryl halides with terminal alkynes in water

2-Aminoethanol facilitated the alkynylation of aryl halides (Sonogashira reaction) under palladium/charcoal-copper catalysis in water affording a mild and practical method for the synthesis of arylalkynes. A variety of terminal alkynes were coupled with aryl iodides and bromides possessing no hydrophilic functional groups to give the coupled products in good to excellent yields.     

A highly effective synthesis of 2-alkynyl-7-azaindoles: Pd/C-mediated alkynylation of heteroaryl halides in water

The reaction of 4-chloro-2-iodo-7-azaindole with terminal alkynes was investigated using 10% Pd/C-PPh₃-CuI as a catalyst system in water. This study afforded a new, mild and selective process for the preparation of 2-alkynyl-4-chloro-7-azaindole in good yields via C-C bond forming reaction. The resulting chloro derivative can be functionalized further via another Pd-mediated C-C bond forming reaction with arylboronic acid.     

Sequential catalytic isomerization and allylic substitution. Conversion of racemic branched allylic carbonates to enantioenriched allylic substitution products

A catalytic protocol for the conversion of readily accessible racemic, branched aromatic allylic esters to branched allylic amines, ethers, and alkyls has been developed. Palladium-catalyzed isomerization of branched allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave the branched allylic products in good yield with high regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor branched allylic esters gave products in >90% ee. High enantiomeric excesses were also observed for the products from the reactions of 2-thienyl acetates and dienyl carbonates.     

Structure determination of a key intermediate of the enantioselective Pd complex catalyzed allylic substitution reaction

The structure of a catalytic intermediate with important implications for the interpretation of the stereochemical outcome of the palladium complex catalyzed allylic substitution with phosphino-oxazoline (PHOX) ligands is determined by liquid state NMR. The complex displays a novel structure that is highly distorted compared with other palladium eta2-olefin complexes known so far. The structure has been determined from nuclear overhauser data (NOE), scalar coupling constants, and long range projection angle restraints derived from dipole dipole cross-correlated relaxation of multiple quantum coherence. The latter restraints have been implemented into a distance geometry protocol. The projection angle restraints yield a higher precision in the determination of the relative orientation of the two molecular moieties and are essential to provide an exact structural definition of the olefinic part of the catalytic intermediate with respect to the ligand.     

Phosphoramidite ligands in iridium-catalyzed allylic substitution

A new phosphoramidite ligand was used in the iridium-catalyzed allylic substitution reaction. This permitted high regio- and enantioselectivities on a wide variety of substrates and nucleophiles. Because of the stereospecificity of the reaction obtained by using branched substrates, a kinetic resolution reaction was attempted. The origin of the impressive efficiency of this ligand in terms of kinetics was explored in detail, as was the role of the substituent in the ortho-position of the amine moiety.     

Intra/intermolecular direct allylic alkylation via Pd(II)-catalyzed allylic C-H activation

The first catalytic direct alkylation of allylic C-H bonds via Pd(II)-catalysis is described in the absence of base. Polysubstituted cyclic compounds can also be constructed by the intramolecular direct allylic alkylation.     

Practical procedure for copper(I)-catalyzed allylic boryl substitution with stoichiometric alkoxide base

We have developed a useful procedure for borylation using catalytic CuCl/Xantphos and stoichiometric K(O-t-Bu): the highly versatile method is suitable for the synthesis of allylboronates including those with terminal and internal allylic systems, cyclic structures, and functional groups. Optically active allylboronates were synthesized from prochiral substrates with a chiral diphosphine ligand using this procedure. The reaction rate is generally higher than the original Cu(O-t-Bu)/ligand catalyst system, which we previously reported.     

Aziridine-derived iminophosphine ligands in palladium-catalyzed allylic substitution

New iminophosphines have been synthesized from (R,R)-1-amino-2-diphenylphosphino cyclohexane (R.R)-1 in good to excellent yields. The catalysts obtained from iminophosphines 3a-g and [Pd(C₃H₅)Cl]₂ promote the enantioselective allylic substitution of 1,3-diphenyl-2-propenyl acetate (6) with diethyl malonate with good enantioselectivity. The air-stable complex PdCl₂[κ²-P,N-(R,R)-2-Ph₂PC₆H₁₀NCHPh] (4) has been prepared and structurally characterized by X-ray crystallography.     

Palladium-catalyzed deracemization of allylic carbonates in water with formation of allylic alcohols: hydrogen carbonate ion as nucleophile in the palladium-catalyzed allylic substitution and kinetic resolution

The palladium-catalyzed deracemization of racemic cyclic and acyclic allylic methyl carbonates in water in the presence of N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphophino)benzamide] proceeds with high enantioselectivities to give the corresponding allylic alcohols in high yields. This deracemization involves a palladium-catalyzed allylic substitution with the in-situ-formed hydrogen carbonate ion and an irreversible decomposition of the intermediate allylic hydrogen carbonates, with formation of the corresponding allylic alcohols. The palladium-catalyzed reaction of racemic cyclic allylic acetates with potassium hydrogen carbonate in water in the presence of the chiral bisphosphane proceeds with a highly selective kinetic resolution to give the corresponding allylic alcohols and allylic acetates.     

Highly modular P-OP ligands in asymmetric allylic substitution

A library of highly modular P-OP ligands have been evaluated in Pd-catalysed allylic substitutions with C- and N-nucleophiles. Catalyst optimisation via a variation of the phosphino and phosphite substituents led to a ‘lead’ catalyst, which efficiently mediated the allylic substitutions when various combinations of substrates and nucleophiles were tested. Ground-state calculations were carried out and these allowed a clearer understanding of the stereochemical outcome of the reaction.     

Synthesis of isocoumarins via Pd/C-mediated reactions of o-iodobenzoic acid with terminal alkynes

The coupling reaction of o-iodobenzoic acid with terminal alkynes by using a catalyst system of 10% Pd/C-Et3N-CuI-PPh3 has been studied in a variety of solvents. 3-Substituted isocoumarins were formed in good yields and with good regioselectivity when the reaction was performed in EtOH.     

Copper catalyzed enantioselective allylic substitution by MeMgX

Methyl Grignard undergoes highly regio (>90/10) and enantioselective (ee 91-96%) copper catalyzed allylic substitution on cinnamyl-type chlorides. CuBr (3%) and 3.3% of a chiral phosphoramidite ligand are sufficient for a complete reaction. The synthesis of a precursor of (+)-Naproxen is described. The reaction can be extended to alkyl substituted allylic chlorides (ee 72%).     

Practical and efficient entry to isoflavones by Pd(0)/C-mediated Suzuki-Miyaura reaction. Total synthesis of geranylated isoflavones

A scalable synthesis of isoflavones taking advantage of the Suzuki-Miyaura reaction catalyzed by Pd(0)/C is described. The approach developed has been extended to the total synthesis of 7-O-geranylformononetin, griffonianone D, and conrauinone D, which did not display cytotoxicity against human HeLa carcinoma cells. In addition, this study established unambiguously the absolute configuration of natural griffonianone D.     

On the key role of water in the allylic activation catalysed by Pd (II) bis phosphinite complexes

Palladium and platinum complexes of bisphosphinites and bisphosphines derived from mandelic acid have been prepared and characterized. Their ability to catalyze allylation of imines with allyltributylstannane has been studied. Bisphophinite complexes of Pd (II) are shown to be ideal and they work best in the presence of one equivalent of water. The near neutral conditions employed make the catalysts suitable for a wide variety of substrates.     

Palladium-catalyzed enantioselective allylic substitution by chiral p,n-heterodonor ligands

Summary Chiral P,N-heterodonor ligands are effective in the enantioselective allylic substitution of 1,2-diphenyl-2-propenyl acetate with dimethylmalonate. The reactions are conveniently carried out at ambient temperature. The excellent levels of enantiomeric excess up to 98% were obtained in good conversion.     

Chiral thiazoline ligands: application in Pd-catalysed allylic substitution

A series of thiazoline ligands, analogues of well-known oxazolines, easily prepared from chiral aminoalcohols and appropriate dithioesters, was tested in the Pd-catalysed allylic substitution. A systematic comparison with the corresponding oxazolines (using literature data or our own tests) has been made for each case. Some important differences (between their catalytic activity and enantioselectivity) were noted for the two types of ligands, especially in the case of bis(thiazolines) and bis(oxazolines).     

Imidazolium-tagged ferrocenyl diphosphanes in allylic substitution with heteroatom nucleophiles

Imidazolium-tagged ferrocenyl diphosphanes are useful ligands in palladium-catalyzed allylic substitutions with heteroatom nucleophiles. Substitution with phthalimide proceeds with high enantioselectivity (up to 92% ee) in various ionic liquids. Reaction with p-cresol as nucleophile affords allylation product in up to 62% ee, while using tolylsulfinate as a nucleophile gives a product with very little or no enantioselectivity. Under these reaction conditions, catalyst recyclability is challenging, and decrease in activity as well as enantioselectivity was observed.     

Hydroxylamines as oxygen atom nucleophiles in transition-metal-catalyzed allylic substitution

[reaction: see text] The viability of hydroxylamines as nucleophiles in transition-metal-catalyzed allylic substitutions was examined. We have found that the oxygen atom of hydroxylamines having an N-electron-withdrawing substituent (also known as hydroxamic acids) acts as a reactive nucleophile. The palladium-catalyzed O-allylic substitution of hydroxylamines with allylic carbonate afforded the linear hydroxylamines. The selective formation of the branched hydroxylamines was observed in iridium-catalyzed reaction. Regio- and enantioselective allylic substitution of the unsymmetrical phosphates with hydroxylamines was studied by using the iridium complex of chiral pybox ligand. The aqueous-medium reaction with hydroxylamines proceeded smoothly in the presence of Ba(OH)(2).H(2)O to give the branched products with good enantioselectivities.