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 arylation of heteroaromatic compounds is also achieved by aryl-aryl coupling reaction. The arylation of A-methylimidazole with bromobenzene occurs under palladium catalysis (Equation (62)).72 The arylation of thiazole with aryl iodide occurs at the 2-position under PdCl2(PPh3)2/CuI catalysis.73 In this case, tetrabutylammonium fluoride improves the activity of the catalyst. Alternatively, thiazoles and benzothiazole are efficiently arylated... 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

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. 

Conversion of the resulting separate D-seco D-E trans i-vincadiffor-mine diols 198-201 to their primary tosylates and tertiary trimethylsilyl-oxy derivatives 202-205 and coupling to vindoline by the chlorination-silver tetrafluoroborate-potassium borohydride sequence provided amino tosylates 206-209, which could be directly subjected to cyclization or, alternatively, converted to the C-20 -C-21 epoxides 178, 181, 210, and 211 by reaction with tetrabutylammonium fluoride (Scheme 53). While cyclization of the tosylates 206-209 led essentially only to quaternary salts which could be debenzylated to provide the lower energy atropi-somer of vinblastine (1), leurosidine (56), vincovaline (184), and its C-20 epimer (212) respectively, cyclization of the epoxides 178, 181, 210, and... 

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. 

This method has been extended to heterocycles bearing a hydroxymethyl-substituted nitrogen. Thus, ethyl l-(hydroxymethyl)pyrazole-4-carboxylate (10) is converted into ethyl 1-(fluoromethyl)pyrazole-4-carboxylate (11) in 76% yield with cesium fluoride/methanesulfonyl fluoride/18-crown-6 system.167 Potassium fluoride did not react at all and tetrabutylammonium fluoride leads to decomposition and formation of coupling products. 

Lithium butyldimethylzincate, 221 Lithium sec-butyldimethylzincate, 221 Organolithium reagents, 94 Organotitanium reagents, 213 Palladium(II) chloride, 234 Titanium(III) chloride-Diisobutylalu-minum hydride, 303 Tributyltin chloride, 315 Tributyl(trimethylsilyl)tin, 212 3-Trimethylsilyl-l, 2-butadiene, 305 Zinc-copper couple, 348 Intramolecular conjugate additions Alkylaluminum halides, 5 Potassium t-butoxide, 252 Tetrabutylammonium fluoride, 11 Titanium(IV) chloride, 304 Zirconium(IV) propoxide, 352 Miscellaneous reactions 2-(Phenylseleno)acrylonitrile, 244 9-(Phenylseleno)-9-borabicyclo[3.3.1]-nonane, 245 Quina alkaloids, 264 Tributyltin hydride, 316 Conjugate reduction (see Reduction reactions)... 

Tetrabutylammonium fluoride, 286 Titanium(IV) chloride-Diethylalumi-num chloride, 309 Vinylene carbonate, 342 Dihydroxylation (see Addition reactions to carbon-carbon multiple bonds) Dimerization (see Coupling reactions) Displacement reactions (see Substitution reactions)... 

Tetrabutylammonium fluoride trihydrate eventually proved to be the best activator for this goal, and various 1-trialkylsilyl-1-alkynes could be coupled under such conditions (Scheme 10.74).120,121... 

A limited number of vinyltrimethylsilanes and acetylenic trimethylsilanes couple with aryl and vinyl iodides in the presence of TASF (tris(diethylamino)sulfonium difluo-romethylsilicate) or TBAF (tetrabutylammonium fluoride) and ( 3-C3H5PdCl)2 catalyst249. Acetylenic trimethylsilanes couple with vinyl bromide under even milder conditions. In the absence of an organic trimethylsilane, TASF itself transfers a methyl group in reasonable yields to the aryl halide250. 

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... 

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