Fluoride-catalyzed carbonyl addition

Bis(trimethysilyl)methane derivatives react with aldehydes and ketones in the presence of a fluoride ion to afford di- and trisubstituted alkenes in one pot [56]. The reaction involves the fluoride-catalyzed carbonyl addition followed by Peterson elimination. For example, a,a-bis(trimethylsilyl)acetonitrile 153 produces /3-phenylacrylonitrile 154 with high -selectivity, whereas tris(trimethylsilyl)-methane 155 reacts with anisaldehyde at room temperature to give alkenylsilane 156 (Scheme 5.39). 

The anions, generated in situ by desilylation of silylacetylenes, allylsilanes, propargylsilanes, a-silyloxetanones, bis(trimethylsilylmethyl) sulfides, and other silane derivatives,can undergo nucleophilic addition to ketones and aldehydes (eq 11). Al-(C,C-bis(trimethylsilyl)methyl) amido derivatives can add to aldehydes followed by Peterson alkenation to form acyl enamines. Treatment of 2-trimethylsilyl-l,3-dithianes can generate dithianyl anions, which are capable of carbocyclization via direct addition to carbonyl or Michael addition (eq 12). The fluoride-catalyzed Michael additions are more general than Lewis acid-catalyzed reactions and proceed well even for those compounds with enolizable protons and/or severe steric hindrance (eq 13). ... 

Besides rhodium catalysts, palladium complex also can catalyze the addition of aryltrialkoxysilanes to a,(3-unsaturated carbonyl compounds (ketones, aldehydes) and nitroalkenes (Scheme 60).146 The addition of equimolar amounts of SbCl3 and tetrabutylammonium fluoride (TBAF) was necessary for this reaction to proceed smoothly. The arylpalladium complex, generated by the transmetallation from a putative hypercoordinate silicon compound, was considered to be the catalytically active species. 

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Aromatic systems arc fluorinated by reagents containing an O-F bond, in particular by tri-fluoromethyl hypofluorite, and acetyl hypofluoritc. Trifluoromethyl hypofluorite is a commercial reagent which is prepared by the reaction of elemental fluorine with carbon monoxide. The initial product is carbonyl fluoride 10 formed by a spontaneous and highly exothermic reaction. This product is passed through a bed of cesium fluoride which catalyzes the addition of a second mole of fluorine to give trifluoromethyl hypofluorite. 

Alfhough direct nucleophilic addition is limited because of the low nucleophilicity of fhe fluoride ion, a palladium-catalyzed reaction enables the weak nucleophile to participate fhe addition reaction. In the presence of cesium fluoride, palladium-catalyzed carbonylation of an aryl halide gives fhe acyl fluoride in good yield (Scheme 2.5) [8]. 

Addition of silylacetylenes to carbonyl compounds This salt catalyzes the addition of l-phenyl-2-trimethylsilylacetylene (1) to aldehydes or ketones at room temperature to form adducts which can be isolated in the silylated form (2) or as alcohols (3). The reaction of (a) with ,)S-unsaturated carbonyl compounds is generally not useful. See Ethyl trimethylsilylacelate-Tetra-ii-butylannnoniani fluoride, this volume. 

Ragaini and associates found that fluorides can promote the palladium-phe-nanthroline catalyzed carbonylation of nitroarenes to carbamates. The effect was more evident on the rate of the reaction at short reaction times, but a positive effect on selectivity is also observed under certain conditions. The effect was observed even under conditions in which chloride inhibits the reaction. The reason for these results might be that fluoride can avoid the formation of inactivating byproducts that deactivate the catalyst. Additionally, tetraethylammonium fluoride was found to be better than sodium fluoride. 

The effect of silver salts, copper acetate and mercury acetate as an additive was studied in the palladium-catalyzed carbonylation of nitrobenzene [17]. The combination of palladium acetate, sliver fluoride, 1,10-phenanthroline and p-toluen-sulfonic acid were found to be highly active and selective yielding nitrobenzene conversion up to 96 %. Copper acetate and mercury acetate are also effective as additives and gave good results. A-phenylcarbamate was produced in the presence of alcohol. 

Fluoride catalyzed addition of silylacetylenes to carbonyl compounds. E. Nakamura and I. Kuwajima, Angew. Chem. Int. Ed., 75, 498 (1976)... 

The conversion of alcohols to the corresponding alkyl fluorides by the pyridine or boron trifluoride catalyzed decomposition of alkyl fluoroformates formed by the addition of 2, or of carbonyl chloride fluoride, to alcohols has been reported.47,48... 

Conjugate addition to acyclic Michael acceptors. Sakurai and Hosomi (9, 445-446) reported one example of the fluoride ion-catalyzed reaction of allyltrimethylsilane with an acyclic enone. In that case (reaction with C6H5CH=CHCOCH,). 1.2- and 1,4-adducts are obtained in the ratio 2 1.1,4-Addition is enhanced by use of DMF and HMPT as solvent and by increase in the size of the group adjacent to the carbonyl group. 1,4-Addition is the main or predominant reaction with a,3-unsaturated esters or nitriles. In this case, it is superior to or competitive with allylation with lithium diallylcuprate. Yields in 1,4-additions to a,p-enones can compare favorably with those obtained with reactions catalyzed by TiC. ... 

Silylated cyanohydrins have found considerable utility in the regioselective protection of p-qui-nones, as intermediates for the preparation of 3-amino alcohols and as precursors to acyl anion equivalents. Such compounds are typicdly prepared in high yield by either thermal or Lewis acid catalyzed addition of TMS-CN across the carbonyl group. This cyanosilylation has a variety of disadvantages and modified one-pot cyanosilylation procedures have been reported. - The carbonyl group can be regenerated by treatment with acid, silver fluoride or triethylaluminum hydrofluoride followed by base. ... 

Treatment of 2 with 3 equiv of 3-phenyl-2-propenal in refluxing toluene-t/g while the reaction progress was monitored by H NMR spectroscopy resulted in the disappearance of the aldehyde hydrogen peak (6 1.56). The IR spectrum of 4 shows a new absorption due to a Vco stretch at 1448 cm. The mass spectrum of the product shows a molecular ion at m/z 538. To our surprise, an X-ray study of 4 showed it to be the insertion product of the two carbonyl ligands into the C-Si bond in 2. The reaction has the potential for developing a new method for double C-C bond formation between the carboranyl unit and carbonyl conqwunds. Such an insertion of the carbonyl functionality into the o-carborane has been observed in Yamamoto s work on the chemoselective addition of o-carborane to the aldehyde groups by a pedladium-catalyzed or a fluoride-promoted reaction. ... 

The carbonyl group of oxazolidinones undergoes a clean addition of Ruppert s reagent (trifluoromethyl trimethylsilane). jhe reaction catalyzed by cesium fluoride is quantitative (Eq. 24). The cleavage of the TMS ether (see p. 148 for other silyl group removal) liberates a-amino trifluoromethyl ketones. 

Unsymmetrical sulfides possessing carbonyl groups beta to sulfur have been prepared by Michael addition of thiols to a,i8-unsaturated aldehydes, ketones, and esters in tetrahydrofuran under phase transfer conditions [17] (see Eq. 13.8). This reaction is catalyzed by fluoride ion. In this application, tetrabutylammonium fluoride (TBAF)... 

Silver(I) complexes with Tol-BINAP (270) were used by Yamamoto and coworkers for mediating diastereoselective and enantioselective Mukaiyama aldol additions. According to the authors conclusion, the mechanism does not involve transmetallation to silver enolates but follows the usual carbonyl group activation [135]. Hoveyda and coworkers used silver(II) fluoride in the presence of a dipeptide-type ligand for enantioselective additions of silyl enol ethers to a-keto esters [136]. The reaction of 2-trimethylsilyloxyfuran with aromatic and aliphatic aldehydes was catalyzed with chromium salen complex in the presence of protic additives like isopropanol [137]. Various protocols of enantioselective Mukaiyama aldol reactions that use water as cosolvent have been elaborated ... 

A copper fluoride phosphine complex catalyzes the cyanomethyl addition to ketone carbonyls using trimethylsilylacetonitrile possibly through transmetalation aided by triethoxyfluorosilane (Scheme 3-136). ... 

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