Triflates vinyl substitutions

Stannyl cuprates couple with vinyl halides or triflates [16c-d, 85], and a vinyl stannane produced this way has been used in the synthesis of 7-[( )-alkylidene]-cephalosporins [117]. Vinyl substitution reactions starting from dihydrofurans are... 

Vinyl Substitution with Triflate Esters and Related Esters 858... 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

VINYL SUBSTITUTION WITH ORGANIC HALIDES, DIAZONIUM SALTS, ACID CHLORIDES, SULFINATE SALTS AND TRIFLATES... 

Table 2 Vinyl Substitution with Vinyl Triflates... 

Numerous aryl bromides, iodides [203], borates [204] and triflates [205, 206] have been successfully carbonylated. Triflates could serve as a route for the synthesis of arenecarboxylic acid derivatives from phenols. This carbonylation using dppf in a catalytic mixture generally shows higher efficiency than PPhj or P(o-Tol)3 [207]. Poor performance is also noted for PPhj in a Pd-catalyzed vinyl substitution of aryl bromides [208]. Side-reactions involving the formation of [PPhjAr]Br and ArH are responsible. A system which is catalyzed effectively by PdCljfdppf) under 10 atm CO is the desulfonylation of 1-naphthalenesulfonyl chloride 58 in the presence of Ti(OiPr)4. Formation of isopropyl 1-naphthoate 59 can be explained in a sequence of oxidative addition, SOj extrusion, carbonylation and reductive elimination (Fig. 1-27) [209]. A notable side-product is di-l-naphthyl disulfide. 

In the borylation of vinyl triflates (3-substituted by a carbonyl group, use of potassium carbonate (K2CO3) (207mg, 1.5 mmol) in dry 1,4-dioxane (4mL) at 80 °C gives better results. 

The stereochemistry of nucleophilic vinylic substitution via the AdN-E mechanism ranges from retention of configuration to stereoconvergence. For SnV 1-type reactions, often partial inversion has been observed. The inversion has been attributed to nucleophilic attack on an ion pair intermediate.As illustrative examples, results of the acetolysis of the vinyl triflates la-c in the presence of sodium acetate are given in Scheme The fraction of inversion ranges from 40 to 80%, and is smaller the more stable the intermediate cation /3-alkyl substitution... 

Taking into account the structural similarity between indoles and benzo[l>]furans, an analogous approach has been used to generate the benzo[i)]furan skeleton. In the presence of Pd(PPh3)4 and KOAc, under a balloon of carbon monoxide, o-alkynylphenol produced 2-substituted-3-acylbenzo[i)]furans 39 in moderate yields with vinyl triflates (Scheme 13.23) [49]. Nevertheless, when vinyl triflates were substituted with aryl iodides, the acylated o-alkynylphenol was obtained as the sole product. Moreover, depending on the substitution pattern of the reagents, variable amounts of 2,3-disubstituted-benzo[i)]furans and in some cases 2-substituted-benzo [fojfurans have also been isolated. 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

The Heck reaction consists in the Pd(0)-catalysed coupling of alkenes with an aryl or alkenyl halide or triflate in the presence of a base to form a substituted alkene (Scheme 7.1). The reaction is performed in the presence of an organopalladium catalyst. The halide or triflate is an aryl or a vinyl compound and the alkene contains at least one proton. 

Pretreatment with nickel bromide causes normally unreactive aryl chlorides to undergo Pd-catalyzed substitution,139 and aryl and vinyl triflates have been found to be excellent substrates for Pd-catalyzed alkenylations.140... 

The palladium-catalyzed annulation of alkynes by functionally-substituted aryl and vinylic halides or triflates provides a veiy convenient and efficient approach to a wide variety of heterocycles and carbocycles. This chemistry has lead to the discovery of a number of novel palladium-catalyzed processes in which the palladium migrates from one carbon to another within the molecule providing a unique way to form carbon-carbon bonds in remote locations within the same molecule. 

Boronic acids 96 and 97 couple very well with vinyl triflates 98 and 99 under typical Suzuki conditions (Pd(PPh3)4/Na2C03/LiCl/DME) to give indoles 100 and 101, respectively, in 76-92% yield [115, 116]. Enol triflates 98 and 99 were prepared in good yield (73-86%) from N-substituted 3-piperidones, wherein the direction of enolization (LDA/THF/-78 °C PhNTf2) is dictated by the tf-substituent. 

The research group of Cacchi made extensive use of these tandem cyclization-Heck reactions to prepare a wide variety of indoles [311-314], For example, vinyl triflates react with o-aminophenylacetylene to afford an array of 2-substituted indoles in excellent yield, e.g., 356 to 357 [312], and a similar reaction of 358 with aryl iodides leads to an excellent synthesis of 3-arylindoles 359 [313],... 

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