Fluoride-induced desilylation

Methoxymethoxy)(phenyl)methylcesium has been generated at room temperature in di-methylformamide by fluoride-induced desilylation from optically active benzyltrimethylsilane and trapped in situ by 2-cyclohexenone with 89% racemization41. 

The reactions of a-methyl-branched acylsilanes with 2-propenylmagnesium bromide exhibit surprisingly high diastereoselectivilies, although further improvement is accomplished by application of allyltrimethylsilane/ titanium(IV) chloride (> 100 I)27. The fluoride-induced desilylation proceeds with retention of configuration. 

Fluoride-induced desilylation has also been used to effect ring closures.117... 

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. 

A related process involves fluoride-induced desilylation in HMPA at room temperature of benzyldi-methyl(trimethylsilylmethyl)ammonium halides (20) to (21 62-84% yields R = H, 2-Me, 4-Me, 2-C1,4-Cl, 4-OAc X = Cl, Br).9 100 Compunds (20) were prepared by reaction of the corresponding benzyl halide derivatives with (dimethylaminomethyl)trimethylsilane, Me3SiCH2NMe2. The product of Stevens rearrangement (22) formed competitively and predominantly from precursors (20) having strong electron-withdrawing substituents (R = 2-COMe, 2-CN, 4-CN, 2-NO2, and 4-NO2).100... 

The second step is a fluoride-induced desilylation to alcohol 15. 

The utility of the DePuy fluoride-induced desilylation reaction 38 for the regioselective generation of gas-phase carbanions from trimethylsilyl compounds (equation 13) has... 

In the second step a fluoride-induced desilylation furnishes the propargylic alcohol 38. 

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... 

The C-Si bond of an SMA can also be cleaved by oxidizing reagents like cerium ammonium nitrate (CAN). Starting from (V-bis(trimethylsilyl)methylazetidinones, treatment with CAN probably leads to the oxidation product of the two C-Si bonds, i.e., the corresponding disilylketal that is hydrolyzed into the formamide to give the N-H azetidinones (yields >80%). This constitutes an alternate and more efficient way to sequential fluoride-induced desilylation. Peterson olefination, ozonolysis, and formamide decomposition when deprotection of bis(trimethylsilyl)methylated azetidinones into NH-azetidinones is required.228,230... 

In the presence of two equivalents of silver fluoride, N-protected bis[(trimethylsi-lyl)methyl]amines lead also to azomethine ylids which can be trapped by dipolarophiles. The mechanism of the cycloaddition reaction involves sequential electron-Me3Si+-electron transfer process from the amine to silver fluoride, which forms silver metal, ruling out a fluoride-induced desilylation process. Although silver is recovered at the end of the reaction, a cheaper oxidizing reagent is still lacking.448,449... 

Among unique transformations on the metallacyclobutene framework, allene complexes of cobalt can be prepared by fluoride-induced desilylation of cobaltacyclobutene complex 39 three isomeric complexes bearing the same disubsituted allene are obtained (Equation 41) <1998JA1100>. 

Tin-mediated cyclizations were then carried out on halides 49D and 49E (Bu3SnH, AIBN, heat), followed by Tamao oxidation (for 49D KF, KHCO3, H2O2) or fluoride-induced desilylation (for 49E TBAF) [121, 124]. Here,... 

As an alternative to tin-mediated conditions, thiyl radicals are an attractive alternative they generate carbon-centered radicals upon reversible addition to a multiple bond. This was found to be effective for cyclizations of 49E and 49F (Scheme 13). Treatment with AIBN and PhSH, followed by fluoride-induced desilylation, afforded vinyl and 2-(thiophenyl)vinyl adducts 50E and 50F, respectively [122, 123, 125]. Interestingly, during fluoride-induced (TBAF) desilylation of the intermediate formed... 

Fluoride-induced desilylation of silylated thiiranes 15 with tetraethyl ammonium fluoride (TEAF) resulted in a concomitant desilylation and desulfurization13 (Scheme 22). 

Cycloaddition of thiazolium azomethine ylides with dialkyl acetylenedicarboxylates 61 provides another approach to pyrrolo[2,1 -bjthiazoles 64 <070L4099>. Quatemization of 2-methylthiothiazole with trimethylsilylmethyl trifluoromethanesulfonate (TMSChkOTf) and subsequent fluoride-induced desilylation of the resulting (trimethylsilyl)methylammonium salt generate the acyclic azomethine ylide 62. This ylide readily participates in 1,3-dipolar cycloadditions with acetylene derivatives 61 to give adducts 63, which undergo spontaneous elimination of methylmercaptan to give the A-fuse cl thiazoles 64. ... 

A facile generation of o-quinone methides by the fluoride-induced desilylation of o-silyloxybenzyl derivatives is the key step in a synthesis of a range of chromans, including those which contain part of the puupehedione structure <06T6012>. A formal synthesis of puupehedione is based on a Ti-catalysed cyclisation of epoxypolyenes <06EJO4115>. A quinone methide is also involved in a synthesis of robustadials A and B from 2,4,6-trihydroxybenzene-l,3-dicarboxaldehyde, 3-methylbutanal and (-)-P-pinene. The... 

The preparation of this class of dienes has received considerable attention during the last few years. Scheme 127 depicts the current approaches, such as 1,4-eliminations of o-xylene derivatives via reduction (544) - (M2), thermal dehydrohalogenation ( 5) (542), and fluoride-induced desilylation... 

Several limitations of this base-promoted rearrangement are worthy of mentioning (a) when structurally feasible, both Stevens and Sommelet-Hauser reactions will compete (b) certain substituents on the aromatic ring, e.g. Cl, CN, NO2, prevent the formation of the ylide and no rearrangement takes place (c) if a p-hydrogen is present on the ammonium salt, elimination becomes yet another undesirable side reaction, In an attempt to overcome these limitations, Sato has utilized the fluoride-induced desilylation of... 

Fluoride-induced desilylation-cyanation studies have been undertaken 138) with several electrophilic cyanogen type reagents. The best results were attained 138) when the 1-silyl-l-vinylcyclopropane shown in Scheme 65 was heated in a THF solution containing 4 equivalents of phenylcyanate. This reaction has been used 138> as a key step for the synthesis of ( )-hinesol and of (+)-P-vetivone (Scheme 65). 

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]. 

P, P] Seebach and Brock reported the dichlorodiisopropoxytitanium-mediated addition of the trimethylsilyl enol ether of cyclohexanone to /3-nitrostyrenes (83). The initial products generated are nitronic esters 39.1-39.3. Separation followed by fluoride-induced desilylation of these intermediates yields the corresponding syn and anti nitroketones. The results of this study are summarized in Scheme 39 and Table 12. Anti isomers are obtained in moderate diastereomeric excess. Moreover, the method is complementary to the additions of similar substrates by way of their lithium enolates (2) or enamines (vide supra), which provide the syn diastereomers. Further reactions of the intermediate nitronic esters were briefly explored. For example, addition of aldehydes and activated olefins provides stereoselectively the products from nitroaldol and [3 + 2] cycloadditions. 

Cesium fluoride induced desilylation of immonium salts provides reactive azomethine yields, which are capable of 1,3-dipolar addition to many a, 8-unsaturated compounds to form heterocycles. Examples utilizing... 

O-Alkylation of N-silylmethylamides with methyl triflate (80JA7993 83JOC4773 85JOC2170) or O-acylation of N-silylmethylenaminones (83JA6160) leads to N-(l-silylalkyl)iminium salt intermediates, respectively the fluoride-induced desilylation generates azomethine ylides 33 and 34. 

Besides the methods discussed above, other approaches for generating aryne species include Kitamura s and Cadogen s methods. The former involves the fluoride-induced desilylation of phenyl[o-(trimethylsilyl)phenyl]iodonium triflate... 

Scheidt recently reported that a-silyl alkoxides generated from a-silyl silylethers 79 by fluoride-induced desilylation instead of deprotonation of a-silyl alcohol can be trapped by primary alkyl and by allylic and benzylic electrophiles via a Brook rearrangement (Scheme... 

Kobayashi and co-workers introduced 2-(trimethylsilyl)phenyl triflate as an aryne precursor subject to benzyne formation without the need of a strong base. Fluoride-induced desilylation and rapid elimination of the sulfonate provide efficient access to benzyne in acetonitrile at room temperature (eq 1). Other solvents such as THF, acetone, dichloromethane, DME, and toluene may be used, but such conditions may require heating for benzyne formation and frequently afford diminished yields. Preparation of the benzyne intermediate is even possible in protic media, albeit with decreased efficiency and limited applicability in subsequent reaction steps. ... 

Condensed-phase mechanistic evidence of formation of a ttansient cyclopropenyl anion on fluoride-induced desilylation of a 3-trimethylsilylcyclopropene derivative has been presented and the UV spectrum of a long-lived cyclopropenyl anion in solution has been recorded. ... 

A neat procedure for effecting intramolecular cyclizations of mono-thioacetals of dicarbonyl compounds is to use the corresponding 2-silyldithianes (62) and to generate the required anion by fluoride-induced desilylation, leading to (63,... 

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. 

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