Desilylation with cesium fluoride

Ring nitrogens in pyrazines and the benzo derivatives react with electrophiles to form quaternary ammonium species such as iV-alkylpyrazinium salts and pyrazine iV-oxides. N-Alkylation has generally been performed by treatment with a reactive alkyl iodide. The N-1 nitrogen in 2(l//)-pyrazinone 5 is methylated using chloro(chloromethyl)dimethyl-silane followed by desilylation with cesium fluoride to yield l-methyl-2(l//)-pyrazinone <2000TL4933>. 

Another study reported that desilylation occurs when a-triethylsilylated imminium perchlorates are irradiated. /V-AI ky I-a-enaminones are obtained after treatment of the photolysates with aqueous sodium bicarbonate ( 70% yield). These enones are also formed upon fluoride-induced desilylation with cesium fluoride in acetonitrile.128... 

In general S-alkylation of thioamides occurs much more readily and selectively than O-alkylation of amides. Thus, N-silylmethylthioamides obtained by the reaction of N-silylmethylamides with Lawesson s reagent (83JOC4773) are treated with methyl triflate to give C-methylthioiminium triflate ylide precursors. Their desilylation with cesium fluoride generates C-hetero-substituted azomethine ylides 35 (83JOC4773 85JOC2170). 

N-Alkoxymethyl(trimethylsilyImethyl)amines are convenient precursors for C-unsubstituted azomethine ylides 43 since the N-alkoxymethyl(trimeth-ylsilylmethyl)amines are readily available by the reaction of N-alkylated silylmethylamines with formaldehyde in alcohol solvents (84CL1117). Treatment of the amines with trimethylsilyl triflate in acetonitrile or tetrahy-drofuran brings about the elimination of alkoxy group R O to form N-silylmethyliminium trifiates 42. The subsequent desilylation with cesium fluoride generates C-unsubstituted azomethine ylides 43 (84CL1117). Both steps of the alkoxy elimination and subsequent desilylation of 42 are induced by trifluoroacetic acid (85CPB896, 85CPB2762), tetrabutylammonium... 

Desilylation with cesium fluoride has been the most common use of cesium compounds in organic synfhesis. HI and tetraalkylammonium fluoride are also commonly used for desilylation but these reagents are difficult to use under anhydrous conditions. The cesium fluoride-induced reaction can be performed easily under anhydrous conditions, so desilylation produces carbanion-equivalent species which can be used for further C-C bond-forming reactions. The reaction seems to... 

Desilylation with cesium fluoride also affords ylides, which can be used for the Wittig and Horner-Wadworth-Emmons reactions [18-20]. 

Similar to these results, but accompanied with ring opening, are the desilylation reactions of substituted aziridines. Treatment with cesium fluoride (1 equiv.) in HMPA (tetrabutylammonium fluoride in THF or DME gives lower yields) at room temperature followed by aqueous work-up, yields desilylated open-chain compounds.320... 

Triazines are trimers of unstable imines and may serve as imine precursors. Treatment of trimer of A1-pyrrol ine with a trimethylsilylmethyl triflate gives trimethylsilylmethyl-imonium triflate which may be desilylated by cesium fluoride, providing an ylid suitable for 1,3-dipolar cycloaddition reactions and constmction of the hexahydro-pyrrolizine framework.386 This strategy has been applied to prepare trachelanthamidine, supinidine and isoretronecanol alkaloids.387... 

Alternatively, trialkylstannylcesium compounds can be prepared by fluoride ion-induced desilylation. Treatment of (trimethysilyl)tributylstannane with cesium fluoride affords a tributylstanyl anion. The anion reacts with a C-I bond to form a vinyl anion that promotes intramolecular cyclization [6]. The spiro ketone obtained is converted into a natural sesquiterpene acorone (Scheme 2.3). 

Carbanion equivalents with anion stabihzing groups are prepared by desilylation of the corresponding materials with cesium fluoride [9-15]. In Scheme 2.6 treatment of aryltrimethylsilanes with cesium fluoride affords carbanion equivalents which add to the carbonyl compounds. The reactive species are not simple organocesium compounds but react as nucleophilic carbanion equivalents. 

Desilylation of silyl enol ethers with cesium fluoride also gives the corresponding enolate equivalent. Under the action of cesium fluoride 1,1-disiloxydiene reacts with aldehydes at the position (Scheme 2.30) [47]. 

Desilylation of some compounds can generate very reactive species such as benzynes, pyridynes, xylylenes, and benzofuran-2,3-xylylenes. 1,4-Elimination of o-(a-trimethyl-silylalkyljbenzyltrimethylammonium halides with TBAF in acetonitrile generates o-xylylenes, which undergo intermolecular and intramolecular cycloadditions (eq 15). Treatment of a-silyl disulfides with Cesium Fluoride or TBAF forms thioaldehydes, which have been trapped by cycloaddition with cyclopentadiene (eq 16). ... 

The parent thiocarbonyl ylide (39), generated by cesium fluoride-induced desilylation of (38), is trapped with alkenes bearing electron-withdrawing substituents and with DMAD to give tetra-hydrothiophenes (40) (58-86%) and dihydrothiophene (41) (56%), respectively (86CC1073). With alkenes the original stereochemistry of the alkenes is retained. 

Reaction of organosUanes with lactones and enonesf Certain carbanions, generated by desilylation, have been found to react not only with aldehydes and ketones, but also with some lactones and a,/ -enones. Cesium fluoride or tetrabutylam-monium fluoride supported on silica can be used as catalysts. 

The first article on the desilylative route to azomethine ylids appeared in 1979.385 It deals with the action of methyl trifluorosulfonate on iV-(trimethylsilylmethyl)benzylide-nimine to form the corresponding iminium salt which reacts with DMAD in the presence of cesium fluoride to yield corresponding A3-pyrroline. 

Destlylation. Anhydrous cesium fluoride desilylates trimethylsilylmethyl-sulfonium, trimethylsilylmethylammonium, and trimethylsilylmethylphosphonium salts at room temperature to produce ylides, which undergo various useful transformations. Use of potassium fluoride-18-crown-6 or a tetraalkylammonium fluoride gives products in low yield in these reactions. The trimethylsilylmethyl-onium salts are prepared by alkylation of sulfides, amines, imines, and phosphines with (trifluoromethanesulfonylmethyl)trimethylsilane (1). 

In addition to the generation of phosphonium ylides from phosphonium salts by deprotonation with bases in some instances ylides may result from pyrolysis of phosphonium salts, especially silylated salts (equation 17). Similar fluoride ion induced desilylation (equation 18) of phosphonium salts proved to be a very useful alternative for the synthesis of ylides which are difficult to synthesize by the conventional salt method (as in the case of R, R = alkyl). - The most effective fluoride source is cesium fluoride and the reaction proceeds at room temperature. 

It is possible for organosilyl compounds with a leaving group at the fi position to undergo E2-type reactions induced by cesium fluoride. In deprotonation-ehmina-tion, a strong base such as amide or alkoxide is required the conjugated acid produced by deprotonation (e.g. amine or alcohol) may react with the elimination product. In the case of cesium fluoride-induced desilylation-elimination, the formed conjugated acid is silyl fluoride which is unreactive. The production of unstable products such as cyclopropene (Scheme 2.13), cyclohexene-3-yne (Scheme 2.14), or orthoquinodimethane has been reported [24—29]. 

Similarly, the cesium fluoride-induced desilylation of a-trimethylsilylbenzylsulfonium alkyl triflate salts produces sulfur ylides, which rapidly equilibrate in DME solution to the thermodynamically more stable ylide prior to reaction with aromatic aldehydes to produce predominantly frons-diaryl epoxides in high yields. In the absence of an aldehyde trapping agent, Sommelet-Hauser rearrangements occur. 

More one example is connected with generation of unsubstituted ylides [35], As facile precursors for non stabilized pyridinium methylides N-(trimethylsilylmethyl) pyridinium triflates were synthesized. Cesium fluoride induced desilylation of the precursors liberated the nonstabilized pyridinium methylides which were trapped as the cycloadducts to dimethyl acetylenedicarboxylate. Trapping of 3-CF3-pyridinium ylide gave the mixture of isomers (50a 50b = 1 5) in 53 % overall yield. 

In order to avoid the requirement of high temperatures, Wender et al. have developed an alternative method and milder activation process to perform this type of cycloaddition, even at room temperature. This involved an initial 0-4 alkylation of the P-hydroxy-y-pyranone, to produce a highly reactive 4-aLkoxypyrylium salt, followed by 0-3 desilylation to give the desired oxidopyrylium intermediate. As shown in Scheme 20.34, alkylation of 78 with methyl triflate at 20 °C generated a pyrylium salt. Upon exposure of this salt to anhydrous cesium fluoride, the cycloaddition proceeded smoothly at room temperature to give the... 

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