Stereoselective Suzuki-Miyaura cross-coupling reactions of potassium alkenyltrifluoroborates with alkenyl bromides

[reaction: see text] The stereoselective synthesis of conjugated dienes using air-stable potassium alkenyltrifluoroborates as coupling partners is described. The palladium-catalyzed cross-coupling reaction of potassium (E)- and (Z)-alkenyltrifluoroborates with either (E)- or (Z)-alkenyl bromides proceeds readily with moderate to excellent yields to give the corresponding (E,E)-, (E,Z)-, (Z,E)-, or (Z,Z)-conjugated dienes stereospecifically. The cross-coupling can generally be effected using 5 mol % of Pd(OAc)2, 10 mol % of PPh3, and 3 equiv of Cs2CO3 in THF-H2O (10:1). A variety of functional groups are tolerated in both coupling partners.     

Palladium-catalyzed cross-coupling of stereospecific potassium cyclopropyl trifluoroborates with aryl bromides

[reaction: see text] Stereospecific cyclopropanation of alkenylboronic esters of pinacol followed by in situ treatment with excess KHF(2) afforded the corresponding potassium cyclopropyl trifluoroborates in high yields, which then underwent Suzuki-Miyaura cross-coupling reactions with aryl bromides to give cyclopropyl-substituted arenes in good yields with retention of configuration. This promises to be a useful method for the synthesis of enantiomerically pure cyclopropanes.     

B-alkyl suzuki-miyaura cross-coupling reactions with air-stable potassium alkyltrifluoroborates

The palladium-catalyzed cross-coupling reaction of substituted potassium alkyltrifluoroborates with aryl halides and aryl triflates proceeds readily with moderate to good yields. The potassium alkyltrifluoroborates 1, 2, and 3a-e were easily synthesized and obtained as air-stable crystalline solids that can be stored for long periods of time. All of the cross-couplings proceed under the same reaction conditions using PdCl(2)(dppf).CH(2)Cl(2) as catalyst in THF-H(2)O in the presence of 3 equiv of Cs(2)CO(3) as base.     

Palladium-catalyzed cross-coupling reaction: Direct allylation of aryl bromides with allyl acetate

Various aryl bromides underwent a palladium-catalyzed cross-coupling reaction with allyl acetate in the presence of hexa-n-butylditin to give the allylated products in very high yields.     

Palladium(0)-catalyzed suzuki-miyaura cross-coupling reactions of potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides

Efficient palladium(0)-catalyzed Suzuki-Miyaura cross-couplings are described. The reactions involving potassium aryl- and heteroaryltrifluoroborates with alkenyl bromides can generally be carried out using < or =2 mol % of palladium catalyst and 3 equiv of base in toluene/H2O. When stereodefined alkenyl bromides are employed, the resulting styrene derivatives are accessed stereospecifically. A variety of functional groups are tolerated in both coupling partners.     

Palladium-catalyzed cross-coupling reactions of amines with alkenyl bromides: a new method for the synthesis of enamines and imines

The palladium-catalyzed cross-coupling reaction of alkenyl bromides with secondary and primary amines gives rise to enamines and imines, respectively. This new transformation expands the applicability of palladium-catalyzed C-N bond forming reactions (the Buchwald-Hartwig amination), which have mostly been applied to aryl halides. After screening of different ligands, bases, and solvents, the catalytic combination [Pd(2)(dba)(3)]/BINAP in the presence of NaOtBu in toluene gave the best results in the cross-coupling of secondary amines with 1-bromostyrene (dba=dibenzylideneacetone, BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl). The corresponding enamines are obtained cleanly and in nearly quantitative yields. However, steric hindrance seems to be a limitation of the reaction, as amines carrying large substituents are not well converted. The same methodology can be applied to the coupling of secondary amines with 2-bromostyrene. Moreover, the reaction with substituted 2-bromopropenes allows regioselective synthesis of isomerizable terminal enamines without isomerization of the double bond. The best catalytic conditions for the cross-coupling of 1-bromostyrene with primary amines include again the use of the Pd(0)/BINAP/NaOtBu system. The reaction gives rise to the expected imines in very short times and with low catalyst loadings. A set of structurally diverse imines can be prepared by this methodology through variations in the structure of both coupling partners. However, 2-bromostyrene failed to give good results in this coupling reaction, probably due to product inhibition of the catalytic cycle. Competition experiments of vinyl versus aryl amination reveal that the reaction occurs preferentially on vinyl bromides.     

Palladium-catalyzed selective carboelimination and cross-coupling reactions of benzocyclobutenols with aryl bromides

The palladium-catalyzed selective β-carboelimination and cross-coupling chemistry of benzocyclobutenols is described. In contrast to the base-mediated ring-opening reactions of benzocyclobutenols, this variant proceeds with exclusive cleavage of the proximal bond.     

Palladium-catalyzed reaction of allylic ammonium bromides with nucleophiles

The reactions of allylic triethylammonium bromides and dimethylsulfonium bromide with carbon nucleophiles were catalyzed by tetrakis(triphenylphosphine)palladium to afford olefinic esters and ketones.     

Aminomethylations via cross-coupling of potassium organotrifluoroborates with aryl bromides

[reaction: see text] The Suzuki-Miyaura cross-coupling reaction of N,N-dialkylaminomethyltrifluoroborates with aryl halides allows the construction of an aminomethyl aryl linkage through a disconnection based on dissonant reactivity patterns. A variety of these aminomethyltrifluoroborate substrates were prepared in good to excellent yields and then shown to cross-couple with equal facility to both electron-rich and electron-poor aryl halides as well as to a variety of heteroaromatic bromides.     

Palladium-catalyzed cross-coupling reactions of heterocyclic silanolates with substituted aryl iodides and bromides

[reaction: see text] Sodium silanolates derived from a number of heterocyclic silanols undergo cross-coupling with a variety of aromatic iodides and bromides under mild conditions. In situ deprotonation of the silanols with an equivalent amount of sodium hydride in toluene generates the sodium salt that couples with iodides under the action of Pd(2)(dba)(3).CHCl(3) in good yield at room temperature to 50 degrees C. The aromatic bromides also couple with these salts under the action of the Pd(I) catalyst 12.     

Palladium-catalyzed cross-coupling of trimethoxysilylbenzene with aryl bromides and chlorides using phosphite ligands

Phosphites were employed as ligands in palladium-catalyzed Hiyama coupling reactions. The optimized reaction conditions were equimolar amounts (5 mol % each) of Pd(acac)₂ and phosphite 1 in p-xylene at 80 °C with TBAF as an additive. This catalyst system exhibited high activities in the reactions with trimethoxysilylbenzene and aryl bromides that have electron-donating or electron-withdrawing groups. In the case of aryl chlorides, substrates possessing electron-withdrawing groups gave the coupled products in high yields.     

Palladium-catalyzed cross-coupling reaction of phenyl fluoroalkanesulfonates with organometallics

The palladium-catalyzed cross-coupling reaction of phenyl fluoroalkanesulfonates with organozinc, organotin and organoaluminum reagents in the presence of lithium chloride takes place to afford alkylbenzenes in good yields. However, the coupling reaction with organolithium and Grignard reagents proceeds unsatisfactorily with poor regioselectivity. On the basis of the isolation of an oxidative addition product of phenyl fluoroalkanesulfonate to palladium, a catalytic cycle in the reaction is suggested.     

Palladium-catalyzed cross-coupling reaction of resin-bound chlorotriazines

To introduce the biaryl structure as a triazine functionality, we have developed a new synthetic route via the Suzuki cross-coupling reaction of resin-bound chlorotriazines. The Suzuki cross-coupling reaction was achieved using various arylboronic acids, Pd(PPh₃)₄, Cs₂CO₃, and dioxane. With the integration of this chemistry and our previous orthogonal methodology, the triazine library is greatly expanded to a biaryl scaffold.     

Palladium-catalyzed cross-coupling reaction of alkynylzincs with benzylic electrophiles

The reaction of alkynylzinc bromides with benzyl bromides or chlorides in the presence of a catalytic amount of Pd(DPEphos)Cl₂ in THF at 23 °C cleanly produces the corresponding benzylated alkynes in 73-97% yields. With 10⁻³ mol % of Pd(DPEphos)Cl₂, the maximum turnover number of 7.1 × 10⁴ has been observed for the formation of PhCCCH₂Ph.     

Palladium-catalyzed cross-coupling reaction of ethynylstibanes with organic halides

The reaction of ethynylstibanes (1a-g) with vinyl halides or triflate in the presence of a palladium catalyst led to the formation of cross-coupling products (5a-g, 10-12) in good to moderate yield, along with homo-coupling products (6a-g). A similar reaction of ethynyldiphenylstibane (1a) with aryl iodides (13a-i) also gave cross-coupling products (14a-i), although the yields were relatively low. The yields of the cross-coupling products were highly dependent on the nature of the solvent employed, and good results were obtained when the reaction was carried out in HMPA or amines such as diethylamine and morpholine. The results imply that HMPA and amine used as solvents facilitate transmetallation of the ethynyl group on 1 to the palladium by intermolecular coordination between antimony and oxygen (for HMPA) or nitrogen (for amine).     

Palladium-catalyzed cross-coupling of pyrrole anions with aryl chlorides, bromides, and iodides

[reaction: see text] A general method for the conversion of pyrrole anions to 2-arylpyrroles has been developed. Using a palladium precatalyst and sterically demanding 2-(dialkylphosphino)biphenyl ligands, (pyrrolyl)zinc chloride may be cross-coupled with a wide range of aryl halides, including aryl chlorides and aryl bromides, at low catalyst loadings and under mild conditions. A high degree of steric hindrance is tolerated. Certain ring-substituted pyrrole anions have also been arylated with aryl bromide substrates.     

Nickel-catalyzed cross-coupling reaction of alkynyl bromides with Grignard reagents

We describe a convenient method for the synthesis of 1,2-disubstituted acetylenes via a cross-coupling reaction of （bromoethynyl）benzene with Grignard reagents. The reaction of （bromoethynyl）benzene （1 mmol） with Grignard reagent （1.3 mmol） mediated by NiCl2 （4 mol%） and （p-CH3Ph）3P （8 mol%） in THF could produce 1,2-disubstituted acetylenes in good yields at room temperature.     

Palladium-catalyzed cross-coupling reaction of aryl trimethoxysilanes with terminal alkynes

A palladium-catalyzed cross-coupling reaction of aryl trimethoxysilanes with terminal alkynes was described. Thus, di-substituted alkynes were prepared in moderate to good yields. The electron-deficient terminal alkynes also worked well in the procedure.     

Palladium-catalyzed direct cross-coupling reaction of glycals with activated alkenes

An efficient method for a Pd(OAc)(2)-catalyzed cross-coupling reaction of glycals with activated alkenes under mild conditions has been developed. This transformation provides an expedient synthetic method to C(2)-functionalized glycals, which are common structural building blocks in natural products and other biologically active compounds. The reaction scope includes different kinds of carbohydrates, protecting groups and substituents on alkene. Moderate to excellent yields and pure E configuration selectivity were obtained.