Fluoride-induced elimination

Fluoride-induced /S-elimination reactions of silanes having leaving groups in the position are important processes in synthetic chemistry, as, for, example in the removal of / -trimethylsilylethoxy groups. 

Scheme 4.54 Formation of chiral allene via fluoride-induced elimination of chiral allylic silyl triflate213.

The o-quinodimethane (40) may also be generated by fluoride-induced 1/4/elimination of trimethyl(2-[(trimethylsilyl)methyl]-benzyl) ammonium iodide (43). When this elimination is carried out at low temperature, the reaction conditions are ecjually compatible with the presence of 27, and this provides an additional route to 42. ... 

The reactive indolo-2,3-quinodimethanes are generated in situ generally from N-protected 2,3-disubstituted indoles (514,515). Generation of reactive indolo-2,3-quinodimethanes was achieved by fluoride-induced, 1,4-elimination of silylated indolyl ammonium salts, and was applied in the synthesis of substituted tetrahydrocarbazoles (516). Subsequently, the iodide-induced 1,4-elimination of ]V-benzoyl-2,3-bis(bromomethyl)indole (534) methodology was developed for the synthesis of reactive indolo-2,3-quinodimethanes and was applied for the first time in the synthesis of substituted carbazoles (e.g., 536) (517) (Scheme 5.14). 

Dimethylene-2,3-dihydrofuran derivatives, which are produced by fluoride-induced 1,4-conjugative elimination of trimethylsilyl acetate from the [(trimethylsilyl)methyl]-3-furan precursor 207, undergo subsequent [4-1-4] dimerization reactions to produce cycloocta[l,2-3 6,5-. ]difuran derivatives as a mixture of isomers (Equation 137) <1995JA841 >. A methyl substituent at the 3-methylene position was found to retard the rate of dimerization, an observation which is consistent with the proposed two-step mechanism involving the initial formation of a diradical intermediate in the rate-determining step (Table 16). 

The driving force for the Diels-Alder reaction is, in part, due to the rearomatization process. Fluoride-induced elimination creates the same opportunity ... 

Few examples have been described of nucleophilic cleavage of carbonate- or carbamate-linked alcohols from insoluble supports. A serine-based linker for phenols releases the phenol upon fluoride-induced intramolecular nucleophilic cleavage of an aryl carbamate (Entry 2, Table 3.36). A linker for oligonucleotides has been described, in which the carbohydrate is bound as a carbonate to resin-bound 2-(2-nitrophen-yl)ethanol, and which is cleaved by base-induced 3-elimination (Entry 3, Table 3.36). Trichloroethyl carbonates, which are susceptible to cleavage by reducing agents such as zinc or phosphines, have been successfully used to link aliphatic alcohols to silica gel (Entry 4, Table 3.36). These carbonates can also be cleaved by acidolysis (Table 3.22). 

This method has been reviewed by Kocienski [420J, together with his own fluoride-induced elimination of -trimethylsiIyl sulfones. 

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. ... 

Fluoride-induced -elimination of p-(trimethylsily )ethyl ethers, which is the cornerstone of the 2-(trtmethylsilyl)ethoxymethyl (SEM) protecting group for hydroxyl functions (see section 4.4.5), has been modified for use in deprotecting cyclic acetals. For example, 4-(trimethylsilyl)methyM,3-dioxolanes46 and 5-tri-methylsilyl-13-dioxanes47 cleave on heating with lithium tetrafluoroborate [Scheme 2.16], The method works well for unhindered aldehydes and ketones. 

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... 

Fluoride-induced condensation of the 5-deoxy-5-nitro furanoside 85 with the a-C-furanosyl formaldehyde 55 obtained by ring contraction of glucosamine and subsequent functional group manipulation lead to a diastereomeric mixture of the nitroaldols 86. An acetylation-elimination sequence followed by reduction of the alkene, denitration and hydrogenolysis provide the C-disaccharide 88. 

For the liberation of acetal-masked alcohols under nonacidic conditions, p-eliminations, already mentioned in Section 3.1.2.1, were adopted. Following this concept the 2,2,2-trichloroethoxymethyl (35) and the 2-(trimethylsilyl)ethoxymethyl (SEM) ethers (36) were proposed. Both are introduced via Williamson syntheses and their removal is initiated by treatment with Zn or Zn/Cu in methanol or by fluoride-induced P-elimination respectively. Similarly, the trichloroethyl ether had already been applied in carbohydrate chemistry (Scheme 26). ... 

At the end of the chapter we briefly consider some reactions such as the fluoride-induced elimination of 3-silyl sulfones, which are not reductive eliminations but which have been included because of their relation to the Julia alkenation. 

The fluoride-induced elimination of P-trimethylsilyl sulfones to give terminal alkenes was first reported in 1979. The p-silyl sulfone (120 Scheme 42), prepared by the alkylation of the readily available crystalline sulfone (119), undergoes elimination on warming with TBAF in THF to give 1-decene in 80% yield. A second alkylation-elimination sequence can then be performed to give a 1,1-dialkyle-thylene derivative (121). Thus, the sulfone (119) may serve as a synthon for CH2=CH" or in... 

A fluoride-induced 1,4-elimination reaction illustrates the use of l-trimethylsilyl-4-phenylsulfony 1-2-butene (129) as a synthon for a butadiene anion (Scheme 46). The elimination is stereoselective, giving the ( )-diene (130) exclusively. 

BU3S11CH2I (600), MesSnCHd and Bu"I (10 000). Fluoride-induced elimination takes place at 0 °C in less than 5 minutes (Scheme 47). Nitrile anions adkylate even faster than sulfones with BusSnCHiI, but the subsequent elimination requires MeLi. Both reactions proceed in good yield (Scheme 48). Silica gel is also effective in causing elimination of 3-trialkylstannyl sulfones to alkenes. ... 

Fluoride-induced fragmentation reactions were used in two stages of a synthesis of hexahydrocannabi-nol methyl ether (144 Scheme 52). One of the phenolic hydroxy functions in the resorcinol derivative (140) was selectively liberated from the SEM ether to give the diol (141), which was converted to the bis (trimethylsilyl) ether (142). Subsequent treatment with CsF resulted in a 1,4-elimination to the o-quinone methide (143) intermediate, which underwent an intramolecular [4 -i- 2] cycloaddition to give the product in good yield. 

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... 

Alternatively, the o-benzoquinodimethane may be generated by fluoride-induced 1,4-elimination from trimethyl[2-(trimethylsilylmethyl)benzyl]ammonium iodide (13a). Interception with l-bromo-2-chlorocyclopropene gave the adduct 15a in 38% yield.Tetrahalocy-clopropenes were, however, unreactive. This method of o-quinodimethane generation has also been applied to pyridine derivatives, and provided a short route to l//-cyclopropa[g]quino-linc (16b).The interception was unsuccessful when the approach was applied to cyclo-propaisoquinoline. ... 

Bromo-2-trimethylsilylcyclopropene underwent addition to 2-methoxyfuran. After hydrolysis and oxidation, the cycloadduct 8a underwent fluoride-induced elimination to form a benzo-cyclopropcne-2,5-quinone 9a as a reactive intermediate which was trapped with furan. The adducts 10a and 11a were isolated with a combined yield of 64%. An analogous sequence gave cyclopropa[/)]naphtho-2.7-quinone 9b isolated as mixture of furan adducts 10b and 11b (74%). 3 ... 

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]. 

Until recently, attempts to trap the unstable o-quinone methide imines generated by this fluoride-induced 1,4-elimination in inter-molecular Diels-Alder reactions with typical dienophiles were unsuccessful.388... 

Fig. 5.15. Anti and syn transition states for fluoride-induced E2 elimination in (a) cyclopentyl and (b) cyclohexyl systems. Reproduced from J. Org. Chem., 59, 7046 (1994), by permission of the American Chemical Society.

Generation of benzocyclobutadiene by fluoride-induced elimination has permitted the NMR spectrum to be observed under flow conditions. All the peaks are somewhat upfleld of the aromatic region, suggesting polyene character. 

The exclusive formation of a single diastereomer with a trans ring fusion in the intramolecular Diels-Alder reaction of the o-quinone methide is consistent with the cycloaddition reaction proceeding through a preferred exo transition state from a chair conformation possessing an equatorial methyl substituent. The similar preference for a chair-exo transition state in the intramolecular [4 -t- 2] cycloadditions of substituted a,/3-unsatu-rated carbonyl compounds and substituted o-quinodimethane has been observed. A variant of these observations utilizes the room temperature fluoride-induced 1,4-elimination of trimethylsilynol for the in situ generation of an o-quinone methide enroute to the total synthesis of (+)-or (-)-hexahydrocannabinols [Eq. (48)]. ... 

Other 1,4-Eliminations Fluoride ion induced desilylation is a very mild method that allows generation of heterocyclic o-quinodimethanes at ambient temperature and is suitable for inter- and intramolecular Diels-Alder adduct formation (Scheme 17). However, the presence of F can be a problem, leading to epimerisation of optically active centres <85CJC3526>. Long routes required for the synthesis of the silylated precursors and purification problems detract somewhat from this otherwise excellent method. 

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