Efficient synthesis of alpha-aryl esters by room-temperature palladium-catalyzed coupling of aryl halides with ester enolates

A catalytic amount of Pd(dba)(2) ligated by either carbene precursor N,N'-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolium (1) or P(t-Bu)(3) mediated the coupling of aryl halides and ester enolates to produce alpha-aryl esters in high yields at room temperature. The reaction was highly tolerant of functionalities and substitution patterns on the aryl halide. Improved protocols for the selective monoarylation of tert-butyl acetate and the efficient arylation of alpha,alpha-disubstituted esters were developed with LiNCy(2) as base and P(t-Bu)(3) as ligand. In addition, tert-butyl esters, such as those of Naproxen and Flurbiprofen, were prepared from tert-butyl propionate and aryl bromides in high yields in the presence of Pd(dba)(2) and the hindered, saturated heterocyclic carbene ligand precursor.     

Palladium-catalyzed alpha-arylation of esters and amides under more neutral conditions

Two procedures for the alpha-arylation of carbonyl compounds under conditions that are more neutral than those of reactions of aryl halides with alkali metal enolates are reported. The first procedure rests upon the development of catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) and the highly reactive dimeric Pd(I) complex {P(t-Bu)3]PdBr}2. By this procedure, zinc enolates prepared from alpha-bromo esters and amides react with aryl halides to form alpha-aryl esters and amides in high yields under mild conditions with 1-2 mol % catalyst and with remarkable functional group tolerance. By the second procedure, silyl ketene and silyl ketimine acetals react with aryl bromides in the presence of substoichiometric zinc fluoride, 1 mol % Pd(dba)2, and 2 mol % P(t-Bu)3 in DMF solvent at 80 degrees C. Reactions of zinc tert-butyl acetate and propionate enolates and trimethylsilyl ketene acetals of tert-butyl propionate and methyl isobutyrate with aryl bromides bearing electron-donating and potentially reactive, base-sensitive electron-withdrawing groups and with pyridyl bromides are reported. In addition, the diastereoselective coupling of phenyl bromide with an imide enolate bearing the Evans auxiliary is reported, and this study shows that racemization of base-sensitive stereocenters does not occur during the coupling process under these more neutral conditions.     

5-(4-叔丁氧基羰基哌嗪基)苯并呋喃-2-甲酸乙酯的合成

5-溴苯并呋喃-2-甲酸乙酯与4-叔丁氧基羰基哌嗪进行Buchwald-Hartwig偶联反应,若催化剂是Pd(OAc)2/BINAP,碱是Cs2CO3,则产物主要是5-(4-叔丁氧基羰基哌嗪基)苯并呋喃-2-甲酸乙酯,转化率达70%;若催化剂是Pd(dba)2/P(t-Bu)3,碱是叔丁醇钾,则产物中几乎没有5-(4-叔丁氧基羰基哌嗪基)苯并呋喃-2-甲酸乙酯.文中讨论了影响这个Buchwald-Hartwig偶联反应的因素.     

Suzuki-Miyaura coupling reaction using pentafluorophenylboronic acid

[reaction: see text] We have found new conditions for the Suzuki-Miyaura coupling reaction applicable to pentafluorophenylboronic acid (C(6)F(5)B(OH)(2)) (1), which is an inactive substrate under normal conditions. The reactions of 1 with phenyl iodide or bromide under Pd(PPh(3))(4)/CsF/Ag(2)O or Pd(2)(dba)(3)/P(t-Bu)(3)/CsF/Ag(2)O catalytic system conditions gave 2,3,4,5,6-pentafluoro-1,1'-biphenyl (3a) in more than 90% yields. Combination of CsF and Ag(2)O was essential for promoting these reactions.     

Controlled Pd(0)/t-Bu(3)P-Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with PhPd(t-Bu(3)P)I or Pd(2)(dba)(3)/t-Bu(3)P/ArI as the Initiator

Controlled Pd(0)/t-Bu(3)P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with an ArPd(t-Bu(3)P)I complex as the initiator are described. ArPd(t-Bu(3)P)I complexes, either prepurified or generated in situ from Pd(2)(dba)(3)/t-Bu(3)P/ArI (dba = dibenzylideneacetone) without separation/purification, were found to be efficient initiators in general for the controlled Suzuki cross-coupling polymerization, with narrow polydispersity indexes (PDIs) of 1.13-1.35 being observed. The Pd(2)(dba)(3)/t-Bu(3)P/p-BrC(6)H(4)I combination was identified as a highly robust initiator system, with PDIs of ≤1.20 in general and as low as 1.13 being obtained. Higher number-average molecular weights (M(n)) were achieved without a significant increase in the PDI (from 1.14 for a polymer with a M(n) = 9500 to 1.20 for a polymer with M(n) = 31?400) by using a smaller amount of the Pd(2)(dba)(3)/t-Bu(3)P/p-BrC(6)H(4)I initiator in the polymerization.     

1,2-Bis(diphenylphosphino)carborane as a dual mode ligand for both the Sonogashira coupling and hydride-transfer steps in palladium-catalyzed one-pot synthesis of allenes from aryl iodides

[reaction: see text] One-pot allene synthesis from aryl iodides 1 and propargyldicyclohexylamine 2 proceeded in the presence of Pd(2)(dba)(3).CHCl(3) catalyst (2.5 mol %), 1,2-bis(diphenylphosphino)carborane 5 (10 mol %), CuI (15 mol %), and Et(3)N (150 mol %) to give the corresponding allenes 4 in good to high yields. Electron-deficient bidentate phosphines, such as 1,2-bis(diphenylphosphino)carborane 5 and (C(6)F(5))(2)PC(2)H(4)P(C(6)F(5))(2), play the role of a dual mode ligand for both the Sonogashira coupling and hydride-transfer reactions.     

Palladium-catalyzed aminoallylation of activated olefins with allylic halides and phthalimide

The three-component aminoallylation reaction of the activated olefins 2 with the phthalimide 1a and allyl chloride proceeded very smoothly in the presence of Pd(2)dba(3).CHCl(3) (5 mol %)/P(4-FC(6)H(4))(3) (40 mol %) and Cs(2)CO(3) (3 equiv against 2) in dichloromethane at room temperature to give the corresponding aminoallylated products, N-pent-4-enylphthalimides 3, in 58-99% yields. The reaction of oxazolidinone 1b also proceeded very smoothly to give N-(2,2-dicyano-1-phenylpent-4-enyl)oxazolidinone in a quantitative yield; however, the Tsuji-Trost-type allylation products 4 were obtained in the case of dibenzylamine, N-tosylaniline, and pyrrolidin-2-one. Further, 2 underwent cycloaddition with N-tosylvinylaziridine 9a in the presence of Pd(2)dba(3).CHCl(3) (5 mol %)/P(4-FC(6)H(4))(3) (40 mol %) in THF at room temperature, giving the corresponding pyrrolidines 11 in 69-99% yields.     

Palladium-catalyzed highly stereoselective synthesis of N-aryl-3-arylmethylisoxazolidines via tandem arylation of O-homoallylhydroxylamines

The palladium-catalyzed tandem arylation of O-homoallylhydroxylamines with 2 equiv of aryl bromides was examined. With Pd2(dba)3 (1 mol %) as the catalyst, Xantphos (2 mol %) as the ligand, and NaOt-Bu as the base, the reactions of O-homoallylhydroxylamines with aryl bromides via sequential N-arylation/cyclization/C-arylation in toluene afforded the corresponding N-aryl-3-arylmethylisoxazolidines in good yields with excellent diastereoselectivity.     

Palladium-catalyzed synthesis of arylamines from aryl halides and lithium bis(trimethylsilyl)amide as an ammonia equivalent

[reaction: see text]. A simple, palladium-catalyzed method to convert aryl halides to the parent anilines using lithium bis(trimethylsilyl)amide (LiN(SiMe3)2) is reported. The reaction is catalyzed by Pd(dba)2 and P(t-Bu)3 and can be run with as little as 0.2 mol % of catalyst. The reaction is faster than competing generation of benzyne intermediates and, therefore, provides the aniline products regiospecifically.     

Synthesis of novel tetracycles via an intramolecular Heck reaction with anti-hydride elimination

[reaction: see text] The catalytic combination of Pd(2)(dba)(3)/HP(t-Bu)(3).BF(4) and DABCO gives an unusual intramolecular Heck reaction with dihydronaphthalene substrates, yielding formal anti-hydride elimination products in good to excellent yields under mild conditions. For dibromo substrates, multiple Heck reactions are possible when an external acceptor is added to afford more highly functionalized products.     

Unusual palladium-catalyzed silaboration of allenes using organic iodides as initiators: mechanism and application

A highly regio- and stereoselective method for the synthesis of various 2-silylallylboronates 7 from allenes 1 and 2-(dimethylphenylsilanyl)-4,4,5,5-tetramethyl[1,3,2]dioxaborolane (5) catalyzed by palladium complexes and initiated by organic iodides is described. Treatment of monosubstituted aryl and alkylallenes RCH=C=CH(2) (1a-m) and 1,1-dimethylallene (1n) with borylsilane 5 in the presence of Pd(dba)(2) (5 mol %) and organic iodide 3a (10 mol %) afforded the corresponding silaboration products 7a-n in moderate to excellent yields. This catalytic silaboration is totally regioselective with the silyl group of 5adding to the central carbon and the boryl group to the unsubstituted terminal carbon of allene. Furthermore, the reactions show very high E stereoselectivity with the Z/E ratios lying in the range from 1/99 to 7/93. In the absence of an organic iodide, silaboration of 1 with 5 still proceeds, but gives products having completely different regiochemistry as that of 7. The silaboration chemistry can be applied to the synthesis of homoallylic alcohols. Treatment of allenes (1) with borylsilane 5 and aldehydes 14 in the presence of Pd(dba)(2) (5 mol %) and 3a (10 mol %) at 80 degrees C in ethyl acetate for 5 h afforded homoallylic alcohols 15a-p in one pot in good to excellent yields, with exceedingly high syn selectivity (>93%). Mechanistic pathways involving an unusual palladium-catalyzed three-component assembling reaction of dimethylphenylsilyl iodide, allene 1, and borylsilane 5 were proposed to account for these catalytic reactions.     

Palladium-catalyzed synthesis of 1-alkylphosphonium salts from 1-alkenes

A palladium(0) complex catalyzes the addition reaction of a triarylphosphine and a protic acid to a 1-alkene, giving a 1-alkylphosphonium salt. The treatment of atmospheric ethylene, triphenylphosphine, and (CF3SO2)2NH in the presence of Pd2(dba)3.CHCl3 (dba = dibenzylideneacetone) (0.1 mol %) in chlorobenzene at 65 degrees C for 5 h gave ethylphosphonium salt in 98% isolated yield. The anti-Markovnikov adduct 1-propylphosphonium salt was obtained by the reaction of atmospheric propene in 95% yield. 1-Butene was converted to 1-butylphosphonium salt in 92% yield in the presence of 1 mol % catalyst. This reaction competed with olefin isomerization, and a mixture of 2-butene and 1-butene (>20:1) was recovered. The reactions of 1-pentene and 1-hexene with triphenylphosphine gave modest yields of the products. The less reactive 1-alkenes, however, reacted effectively with tris(p-chlorophenyl)phosphine. The inner olefins, 2- and 3-pentene also gave a 1-pentylphosphonium salt in high yields via rapid olefin migration.     

Palladium(0)-catalyzed intramolecular [2+2+2] alkyne cyclotrimerizations with electron-deficient diynes and triynes

In the presence of 2.5 mol % of [Pd(2)(dba)(3)] (dba=dibenzylideneacetone) and 5 mol % of PPh(3), nearly equimolar amounts of dimethyl nona-2,7-diyne-1,9-dioate derivatives (diyne diesters) and dialkyl acetylenedicarboxylates were allowed to react in toluene at 110 degrees C to afford [2+2+2] cycloadducts in moderate-to-good yields. Similarly, dimethyl trideca-2,7,12-triyne-1,13-dioate derivatives (triyne diesters) were catalytically transformed into phthalic acid ester analogues in excellent yields. To gain insight into the mechanism of these intramolecular alkyne cyclotrimerizations, stoichiometric reactions of [Pd(2)(dba)(3)] with a diyne diester and a triyne diester bearing ether tethers were conducted in acetone at room temperature to furnish an oligomeric bicyclopalladacyclopentadiene and a Pd(0) triyne complex, respectively. The structures of these novel complexes were unequivocally determined by Xray structure analysis. The isolated triyne complex was heated at 50 degrees C or treated with PPh(3) in acetone at room temperature to afford the arene product. Furthermore, the same complex catalyzed the triyne cyclization with or without PPh(3).     

Palladium-catalyzed alpha-arylation of esters

A new and simple one-pot procedure for the palladium-catalyzed intermolecular alpha-arylation of esters is described. A number of esters can be functionalized with a wide range of aryl bromides using Pd(OAc)(2) or Pd(2)(dba)(3) and bulky electron-rich o-biphenyl phosphines 1-3. Under the reaction conditions, using LiHMDS as base, alpha-arylation proceeds at room temperature or at 80 degrees C with very good yields and high selectivities for monoarylation. Important nonsteroidal antiinflammatory drug derivatives such as (+/-)-naproxen tert-butyl ester and (+/-)-flurbiprofen tert-butyl ester can be prepared in 79% and 86% yield, respectively. The catalyst system based on the di-tert-butylphosphine (2) is also active for the alpha-arylation of esters using aryl chlorides. Furthermore, using (3) the alpha-arylation of trisubstituted ester enolates can be accomplished to provide compounds that have quaternary centers.     

Efficient palladium-catalyzed nucleophilic addition of triorganoindium reagents to carbocyclic derivatives

Palladium (0)-catalyzed allylic substitution reactions employing triorganoindium reagents have been investigated. In situ generated vinyl- and arylindiums react with substituted and unsubstituted cyclohex-2-enyl esters in the presence of 1-3 mol % Pd(2)(dba)(3) to produce vinyl- or arylcyclohexenes in moderate to excellent yields. The stereoselectivity of this process was also examined, and evidence is presented that the reaction proceeds with inversion of stereochemical configuration.     

Preferential oxidative addition in Suzuki cross-coupling reactions across one fluorene unit

The Suzuki-type cross-coupling reaction of 2,7-dihalofluorenes with 1 equiv of arylboronic acid and Pd2(dba)3/P(t-Bu3) as a catalyst system is investigated. The exclusive formation of the diarylated coupling product demonstrates that "preferential oxidative addition" is also applicable to fluorene monomers due to a controlled intramolecular motion of the regenerated Pd(0) catalyst across the "large" distance between the 2- and the 7-position of one fluorene monomer.     

Suzuki cross-coupling of solid-supported chloropyrimidines with arylboronic acids

The utility of the Suzuki cross-coupling to synthesize biaryl compounds is expanded herein to include reactions of resin-supported chloropyrimidines with boronic acids. In particular, an efficient method is described for the synthesis of a library of biaryl compounds from solid-supported chloropyrimidines. The Suzuki reaction was performed in an inert atmosphere using Pd(2)(dba)(3)/P(t-Bu)(3) as catalyst, spray-dried KF as base, and THF as solvent. The reaction was allowed to proceed overnight at 50 degrees C. Upon cleavage with acid, a library of 4-(substituted amino)-6-arylpyrimidines was obtained in moderate yield and high purity.     

Scope and limitations of Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Buchwald-Hartwig amination reactions of aryl chlorides

Proazaphosphatrane ligands in combination with Pd(2)(dba)(3) generate highly active catalysts for Buchwald-Hartwig amination of aryl chlorides. In particular, commercially available P(i-BuNCH(2)CH(2))(3)N is a highly general and efficient ligand, allowing the coupling of an electronically diverse set of aryl chlorides, including chloropyridines, with a wide variety of amines using 1 mol % of Pd at 100 degrees C. Either a 1:1 or 2:1 ratio of ligand to Pd was found to be effective. This catalyst system performs exceptionally well for sterically hindered substrates, even with only 0.25 mol % of Pd. It is shown that NaOH can also be used as the base (instead of NaO-t-Bu) allowing functionalized substrates to participate in these reactions.     

Scope and limitations of the Pd/BINAP-catalyzed amination of aryl bromides

Mixtures of Pd(2)(dba)(3) or Pd(OAc)(2) and BINAP catalyze the cross-coupling of amines with a variety of aryl bromides. Primary amines are arylated in high yield, and certain classes of secondary amines are also effectively transformed. The process tolerates the presence of several functional groups including methyl and ethyl esters, enolizable ketones, and nitro groups provided that cesium carbonate is employed as the base. Most reactions proceed to completion with 0.5-1.0 mol % of the palladium catalyst; in some cases, catalyst levels as low as 0.05 mol % Pd may be employed. Reactions are considerably faster if Pd(OAc)(2) is employed as the precatalyst, and the order in which reagents are added to the reaction has a substantial effect on reaction rate. It is likely that the catalytic process proceeds via bis(phosphine)palladium complexes as intermediates. These complexes are less prone to undergo undesirable side reactions which lead to diminished yields or catalyst deactivation than complexes of the corresponding monodentate triarylphosphines.     

苯并[de]蒽-7-酮类叔芳胺的合成及其发光性能的研究

芳基伯胺与芳基溴在Pd(dba)2/P(t-Bu)3催化下于80 ℃甲苯溶液中反应生成芳基仲胺, 芳基仲胺再与3-溴苯并[de]蒽-7-酮在Pd(OAc)2/P(t-Bu)3催化下于120 ℃邻二甲苯溶液中反应生成苯并[de]蒽-7-酮类叔芳胺有机电致发光材料; 3-二苯基氨基苯并[de]蒽-7-酮与丙二腈反应生成2-(3-二苯基氨基)苯并[de]蒽-7-基亚基丙二腈. 产物的结构经1H NMR, 13C NMR, 13C (DEPT), HRMS光谱所证实. 用UV-Vis, PL, DSC测定了化合物的发光性能.