Cross-coupling tetrabutylammonium fluoride

The palladium-catalyzed cross-coupling of alkenylsilanols has been extensively studied with respect to the structure of both the silicon component and the acceptor halide. The preferred catalyst for coupling of aryl iodides is Pd(dba)2 and for aryl bromides it is [allylPdCl]2. The most effective promoter is tetrabutylammonium fluoride used as a 1.0M solution in THF. In general the coupling reactions occur under mild conditions (room temperature, in 10 min to 12 hr) and some are even exothermic. 

The aryl bromide 40, prepared from cross-coupling between 1,2-dibromobenzene and (trimethylsilyl)acetylene, was converted to the corresponding arylzinc halide 41a and arylboronic acid 41b for subsequent coupling with the haloallenes 42 to produce the benzannulated enyne-allene 43 in -40% yield (Scheme 20.10) [38]. Desilylation with tetrabutylammonium fluoride (TBAF) then afforded 44 in 67% yield. 

The related cyclization of 2-ethynylanilines 67 also represents one of the usefiil methods for the synthesis of 2-substituted indoles since the precursors are easily prepared from 2-haloanilines 66 by Pd-catalyzed cross-coupling with terminal alkynes. Althou cyclizations of such alkynes are normally effected using Cu(I) or Pd(II) species, Sakamoto showed that in the absence of such metals, base catalysis (e.g., NaOEt) alone can accomplish the same goal. This author now reports that tetrabutylammonium fluoride (TBAF) is capable of inducing cyclization to the indoles 68 without affecting functionalities such as bromo, cyano, ethoxycarbonyl, and ethynyl <99JCS(P1)529>. 

The palladium catalyzed cross-coupling of organosilicon compounds and aryl halides found only limited application with azines compared to the Suzuki or Negishi coupling. In a recent paper DeShong reported the efficient coupling of bromopyridine derivatives with aryl siloxanes (7.44.) 62 The transmetalating ability of the siloxane was enhanced by the addition of tetrabutylammonium fluoride. 

Indeed, the cross-coupling of (5)-2-cyclohexenyl(difluoro)phenylsilane (64% ee) took place smoothly with 4-acetylphenyl iodide using tetrabutylammonium fluoride as the activator to give the coupled product (5)-3-(4-acetylphenyl)cyclohexene (52% ee). Thus, the stereochemistry of the reaction was retention of configuration, and the efficiency of the... 

Regardless of the solvent used, various additives have been explored in the Sonogashira reaction to increase yield, and reaction rates. Ammonium and silver salts have shown the most promise in this respect. Mori et al. [123] found that by using 2 equiv. of either tetrabutylammonium fluoride (TBAF) or tetrabutylammonium hydroxide (TBAOH), activation of the cross-coupling with... 

The Hiyama-Hatanaka cross-coupling reaction is a more recent arylation coupling reaction that was reported by these workers in 1988 [12e, 31]. These workers demonstrated that trimethylsilylethy-lene reacts with aryl halides in the presence of a Pd(0) catalyst, a base, and a source of fluoride ion to give styrene derivatives [12e]. The source of Pd can be (it-CjHjPdCOj, Pd(Ph3P)4, or even Pdjfdbalj the base could be a hydroxide, an acetate, a phosphane, or a phosphite and the source of the fluoride ion could be tris(diethylamino)sulfonium difluoro(trimethyl)silicate (TASF), tetrabutylammonium fluoride (TBAF) or even KF (See Scheme 1.14a). The role of this reagent is shown in the catalytic cycle... 

The resultant alkenyl(2-pyridyl)silanes can be subjected to further transformations. For example, the treatment of alkenyl (2-pyridyl)silanes with aryl iodides in the presence of tetrabutyl-ammonium fluoride and palladium catalyst affords substituted oleflns in good yields (eq 3). This cross-coupling reaction is suggested to proceed through the intermediacy of a highly reactive alkenylsilanol. The treatment of alkenyl(2-pyridyl)silanes with tetrabutylammonium fluoride effects simple protodesilyl-ation (eq The reaction with acetyl chloride in the presence of aluminum chloride affords the corresponding Q ,/3-unsaturated enones (eq 5). ... 

The most commonly accepted mechanism for this coupling was initially proposed by Hiyama and Hatanaka, which involves three steps.The first step is the oxidative addition of the aryl halide to the palladium(O) catalyst to give arylpalladium complex 1. The second step involves the transmetallation of the arylpalladium complex 1 with the anionic arylsilicate 2 to give bis(aryl)palladium complex 3. Finally, the cross-coupled product 4 is produced and the palladium(O) catalyst is regenerated through reductive elimination of the bis(aryl)palladium(II) complex 3. The key intermediate to this process is the requirement for the pentacoordinate arylsilicate anion 2, typically formed by treatment of the tetracoordinate silane with the activating anion, such as tetrabutylammonium fluoride (TBAF). 

Xerulinic acid (151) inhibited the biosynthesis of cholesterol in HeLa S3 cells by blocking HMG-CoA synthase. Bisstannane 147 was transmetallated to the zincate intermediate and was Negishi cross-coupled with butenolide 148 to give the all tra 5-polyene 149. The Stille reaction of 149 with enediyne 150 followed by deprotection of the silyl group with tetrabutylammonium fluoride afforded xerulinic acid (151). 

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