Pd(0)/iodide salt-mediated Heck reaction of aryl nonaflates: Application to the synthesis of 2-(1-alkenyl)phenylphosphonates

Iodide salt, such as NaI, KI or n-Bu₄NI (TBAI), rather than bromide or chloride salt, was found to play a key role in the Pd(0)-catalyzed Heck reaction of aryl nonaflates and terminal alkenes. In the presence of PdCl₂(PPh₃)₂, NaI or TBAI in DMF, a class of 2-(1-alkenyl)phenylphosphonates was first synthesized via the reaction of o-phosphonylphenyl nonaflates with alkenes, the yields, regioselectivities and stereoselectivities were much dependent on the nature of the substituents. In case of the aryl nonaflates without bearing the sterically hindered phosphonyl group with the alkenes, the reactions proceeded more smoothly under the same conditions, leading to the linear products regioselectively in good to excellent yields. A rationale for this reaction is discussed.     

First comprehensive investigation of Suzuki couplings of alkenyl nonaflates with aryl and alkenyl boronic acid derivatives by using classical conditions and microwave heating

Alkenyl nonaflates (nonafluorobutanesulfonates) are excellent substrates in a variety of palladium-catalysed coupling reactions. We herein demonstrate that bicyclic nonaflates generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives can be coupled with aryl or alkenyl boronic acids in a very efficient manner. The resulting densely functionalised bicyclic skeletons are highly suitable for further synthetic elaboration. The thermal Suzuki couplings provided the expected products in moderate to good yields. Microwave (MW) irradiation dramatically shortened reaction times and gave superior results. Bisboronic ester 19 was also coupled with bicyclic nonaflates, for example, with 14, and double Suzuki-coupling products, such as 22, were isolated in good yields. We demonstrated the great synthetic potential of aryl-substituted 8-heterobicyclo[3.2.1]octene derivatives, such as 15, by the stereoselective conversion of this compound into highly substituted furanose 31 or substituted pyran derivative 33, which were obtained in short and efficient reaction sequences.     

Palladium-catalyzed amination of aryl nonaflates

The first detailed study of the palladium-catalyzed amination of aryl nonaflates is reported. Use of ligands 2-4 and 6 allows for the catalytic amination of electron-rich and -neutral aryl nonaflates with both primary and secondary amines. With use of Xantphos 5, the catalytic amination of a variety of functionalized aryl nonaflates resulted in excellent yields of anilines; even 2-carboxymethyl aryl nonaflate is effectively coupled with a primary alkylamine. Moderate yields were obtained when coupling halo-aryl nonaflates with a variety of amines, where in most cases the aryl nonaflate reacted in preference to the aryl halide. Overall, aryl nonaflates are an effective alternative to triflates in palladium-catalyzed C-N bond-forming processes due to their increased stability under the reaction conditions.     

An efficient Negishi cross-coupling reaction catalyzed by nickel(II) and diethyl phosphite

A combination of diethyl phosphite-DMAP and Ni(II) salts forms a very effective catalytic system for the cross-coupling reactions of arylzinc halides with aryl, heteroaryl, and alkenyl bromides, chlorides, triflates, and nonaflates. The choice of solvent is quite important and the mixture of THF-N-ethylpyrrolidinone (NEP) (8:1) was found to be optimal. The reaction usually requires only 0.05 mol % of NiCl₂ or Ni(acac)₂ as catalyst and proceeds at room temperature within 1-48 h.     

Functionalized 2,3-dihydrofurans via palladium-catalyzed oxyarylation of α-allyl-β-ketoesters

The palladium-catalyzed reaction of (hetero)aryl bromides, chlorides, and nonaflates with α-allyl-β-ketoesters provides ready efficient access to functionalized 2,3-dihydrofurans. The reaction tolerates several useful substituents including chloro, fluoro, ether, ketone, ester, cyano, and nitro groups.     

Palladium-catalyzed highly regioselective Heck reaction of aryl nonaflates with electron-rich olefins

Highly efficient palladium-catalyzed Heck coupling of aryl nonaflates with electron-rich vinyl ethers, and enamides is described. These reactions afforded exclusively the branched products in good yields. The results indicated that aryl nonaflates are effective alternative to the frequently employed aryl triflates.     

Pd‐Catalyzed Synthesis of α‐Aryl Vinylphosphonates via Suzuki Arylation of α‐Phosphonovinyl Nonaflates

The first palladium‐catalyzed method for the arylation of α‐phosphonovinyl nonaflates is described. Using a catalyst comprised of Pd(OAc)₂ and SPhos, terminal and internal α‐aryl vinylphosphonates could be efficiently accessed under mild conditions. The reaction features a broad coupling partner scope and tolerates many functional groups.     

Barbier–Negishi Coupling of Secondary Alkyl Bromides with Aryl and Alkenyl Triflates and Nonaflates

A mild and practical Barbier–Negishi coupling of secondary alkyl bromides with aryl and alkenyl triflates and nonaflates has been developed. This challenging reaction was enabled by the use of a very bulky imidazole‐based phosphine ligand, which resulted in good yields as well as good chemo‐ and site selectivities for a broad range of substrates at room temperature and under non‐aqueous conditions. This reaction was extended to primary alkyl bromides by using an analogous pyrazole‐based ligand.     

Expedited palladium-catalyzed amination of aryl nonaflates through the use of microwave-irradiation and soluble organic amine bases

[reaction: see text] Microwave-assisted, palladium-catalyzed C-N bond-forming reactions with aryl/heteroaryl nonaflates and amines using the soluble amine bases DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or MTBD (7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene) and ligands (1-3) resulted in good to excellent yields (71-99%) of arylamines in short reaction times (1-45 min).     

Pd-catalyzed Negishi coupling of pyrazole triflates with alkyl zinc halides

A mild, functional group tolerant palladium-catalyzed Negishi coupling of pyrazole triflates and nonaflates with alkyl, benzyl, and aryl zinc halides has been developed. It allows quick access to 3-substituted pyrazole analogs at late stage via common synthetic intermediates.     

One-pot synthesis of β-acetamido-β-arylpropiophenone employing trifluoroacetic acid as an efficient catalyst

Trifluoroacetic acid as an efficient catalyst promoting the Dakin–West reaction at ambient temperature is reported for the first time in this paper. A few efficacious auxiliary catalysts were also developed for the Dakin–West reaction. A variety of substituted aryl aldehydes and aryl ketones were found to be applicable to the preparation of some new β-acetamido-β-arylpropiophenones. This procedure has several advantages such as high yields, short reaction time, and smaller amount (0.30 mol%) of catalyst.     

PMHS-mediated couplings of alkynes or benzothiazoles with various electrophiles: application to the synthesis of (-)-akolactone A

Polymethylhydrosiloxane (PMHS) in combination with CsF facilitates the cross-coupling of alkynes or benzothiazoles with an array of vinyl, styryl, and aryl halides or nonaflates as well as acid chlorides. Experimental and spectroscopic evidence indicates that these reactions involve the in situ generation of a siloxyl intermediate. These cross-couplings proceed relatively quickly at room temperature and under amine-free conditions. To demonstrate the applicability of the method, a total synthesis of the cyctotoxic butanolide (-)-akolactone A was carried out.     

A general and mild Ullmann-type synthesis of diaryl ethers

[reaction: see text] An efficient method for the synthesis of diaryl ethers under particularly mild conditions is described. Inexpensive ligands were found to greatly accelerate the Ullmann-type coupling of aryl bromides or iodides with phenols. A series of diaryl ethers were obtained with excellent yields in acetonitrile in the presence of Cs(2)CO(3) and catalytic copper(I) oxide. The reaction tolerates substrates with unfavorable substitution patterns, such as sterically hindered coupling partners or electron-rich aryl halides.     

Well-defined,air-stable (NHC)Pd(Allyl)Cl (NHC = N-heterocyclic carbene) catalysts for the arylation of ketones

A number of palladium-N-heterocyclic carbene (NHC) complexes were found to be active catalysts for the arylation of ketones. A large number of substrates, both aryl halides and ketones, are compatible with the reaction conditions. The ketone arylation reactions are achieved with low catalyst loading in short reaction times using aryl chlorides and triflates as reactive partners. [reaction: see text]     

Pd‐Catalyzed Difluoromethylation of Vinyl Bromides,Triflates, Tosylates,and Nonaflates

Pd‐catalyzed difluoromethylation of di‐, tri‐ or tetra‐substituted vinyl bromides, triflates, tosylates and nonaflates under mild conditions is described. The reaction tolerates a wide range of functional groups, such as bromide, chloride, fluoride, ester, amine, nitrile, and protected carbonyl, thus providing a general route for the preparation of difluoromethylated alkenes.     

FeCl3催化Et2Zn与芳香醛的加成反应研究

以FeCl_3作为催化剂, 研究了Et_2Zn与芳香醛的加成反应, 考察了催化剂、溶剂、催化剂与Et_2Zn用量及温度对该反应的影响. 实验结果表明: 在60℃, 1.2当量Et_2Zn, 甲基环戊基醚为溶剂的反应条件下, 10 mol% FeCl_3可以较高效的将各种芳香醛转化为仲醇.     

Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.     

On the synthesis and functionalisation of the 4-aza-8,12-dioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrenium system

The preparative use of the reaction between tris(2,6-dimethoxyphenyl)carbenium tetrafluoroborate and excess of an arylamine such as 4-methylaniline or 4-bromoaniline to yield firstly the aryl functionalised acridinium derivatives and then further in situ reaction to yield the desired functionalised triangulenium salts was found to be problematic. A preparative route for the triangulenium salts is presented along with a demonstration of the further derivatisation by standard Suzuki coupling reaction.     

Cross-coupling reactions of (1-fluorovinyl)methydiphenylsilane(1) with aryl halides and aryl triflates

The cesium fluoride (CsF)-assisted cross-coupling reaction of (1-fluorovinyl)methyldiphenylsilane (1) with aryl halides and aryl triflates was examined. The reaction with aryl iodides smoothly proceeded to afford the corresponding (1-fluorovinyl)arenes in the presence of a catalytic amount of CuI and Pd(PPh(3))(4) in aprotic polar solvents such as DMF, DMI, DMA, and NMP in good yields. A variety of functional groups (nitro, ester, ketone, and ether) on the aromatic rings can be tolerated under these mild conditions. Aryl iodides are superior to aryl bromides as the coupling reaction partner. The cross-coupling reaction of 1 with aryl triflates instead of aryl halides was also accomplished in the presence of tetrabutylammonium iodide (n-Bu(4)NI) as the additive under similar conditions.     

Heck reactions of aryl halides with alk‐1‐en‐3‐ol derivatives catalysed by a tetraphosphine–palladium complex

cis,cis,cis‐1,2,3,4‐Tetrakis(diphenylphosphinomethyl)cyclopentane–[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of alk‐1‐en‐3‐ol with a variety of aryl halides. In the presence of hex‐1‐en‐3‐ol or oct‐1‐en‐3‐ol, the β‐arylated carbonyl compounds were selectively obtained. Turnover numbers up to 84 000 can be obtained for this reaction. Linalool and 2‐methylbut‐3‐en‐2‐ol led regio‐ and stereoselectively to the corresponding (E)‐1‐arylalk‐1‐en‐3‐ol derivatives. A minor electronic effect of the substituents of the aryl bromide was observed. Quite similar reaction rates were generally observed in the presence of activated aryl bromides such as bromoacetophenone and deactivated aryl bromides such as bromoanisole, indicating that, with these alkenols and this catalyst, the oxidative addition of aryl bromides to palladium is not the rate‐limiting step. It should be noted that this reaction also proceeds with sterically very congested aryl bromides such as 9‐bromoanthracene or 2,4,6‐triisopropylbromobenzene or with a vinyl bromide. On the other hand, low yields were obtained with aryl chlorides. Copyright © 2006 John Wiley & Sons, Ltd.