Fluoride ion catalyzed

Polymerization of methacrylates is also possible via what is known as group-transfer polymerization. Although only limited commercial use has been made of this technique, it does provide a route to block copolymers that is not available from ordinary free-radical polymerizations. In a prototypical group-transfer polymerization the fluoride-ion-catalyzed reaction of a methacrylate (or acrylate) in the presence of a silyl ketene acetal gives a high molecular weight polymer (45—50). 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Fluoride ion-catalyzed polyfluoroalkylation is a powerful method for introducing RF groups into polyfluoroazaaromatics. Trichloro-1,2,3-triazine is such a reactive system that fluorination and polyfluoroalkylation... 

Fluoride ion catalyzed reaction of the cyclic nitronate 1 with benzaldehyde provides a cyclic hcmiaeetal 2 in 95% diastereoselectivity18 with tra ,v,tr u.v-relationship of the protons in positions 2, 3 and 4. The relative configuration of the hemiacetal carbon position was not assigned. Upon reaction of the diastereomeric nitronate 3 at 25 °C the 4a-stereocenter is epimerized by fluoride ion such that hemiacetal 2 is once again obtained. In contrast, reaction of 3 at 0°C furnishes the diastereomeric product 4 in 23% yield 8. 

Davis has described an approach to related 1,3-diol synthons [49] (Eq. 20). Silylation of the -hydroxy ester 129 with diisopropylchlorosilane, followed by fluoride ion-catalyzed intramolecular hydrosilylation generated a 1 1 diastere-omeric mixture of acetals 131. These acetals were shown to undergo diastereo-selective nucleophilic additions vide infra). 

Fluoride ion catalyzes the hydrosilylation of both alkyl and aryl aldehydes to silyl ethers that can be easily hydrolyzed to the free alcohols by treatment with 1 M hydrogen chloride in methanol.320 The most effective sources of fluoride are TBAF and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). Somewhat less effective are CsF and KF. Solvent effects are marked. The reactions are facilitated in polar, aprotic solvents such as hexamethylphosphortriamide (HMPA) or 1,3-dimethyl-3,4,5,6-tetrahydro-2(l //)-pyrirnidinone (DMPU), go moderately well in dimethylformamide, but do not proceed well in either tetrahydrofuran or dichloromethane. The solvent effects are dramatically illustrated in the reaction of undecanal and dimethylphenylsilane to produce undecyloxyphenyldimethylsi-lane. After one hour at room temperature with TBAF as the source of fluoride and a 10 mol% excess of silane, yields of 91% in HMPA, 89% in DMPU, 56% in dimethylformamide, 9% in tetrahydrofuran, and only 1% in dichloromethane are obtained (Eq. 164).320... 

Fluoride ion catalyzed 1,3-dipolar cycloaddition of bromo nitrile oxide, obtained in situ from dibromoformaldehyde oxime 184, to nonactivated alkynes provides a new approach to the synthesis of neuroactive isoxazoles. However, the regioselectivity of cycloaddition in this case is not high—products 185 and 186 are obtained in a 1 1 to 1 1.4 ratio (equation 80). Cycloaddition reaction of hydroximoyl chlorides and acetylene was snc-cessfully carried out also in the presence of NaHCOs as a base. For instance, a-keto oximes 187 were reacted with acetylene and NaHCOs to give isoxazoles 188 in good yields (equation 81). 

Nitro-aldol reaction (9, 444).5 The /J-amino alcohol obtained hy fluoride ion catalyzed a Idol condensation of aldehydes with silyl nitronales (1) is the practically pure (RS,SR)-diastereoisomer (3),... 

Some Michael additions of unsaturated reagents to imidazoles involve the neutral species of the heterocycles, but others may be reactions of the anion. Fluoride ion catalyzed addition of 2-methyl-4-nitroimidazole (113) to a suitable Michael acceptor gives almost quantitative yields of the 1-substituted 4-nitroisomers (114) (90JOC3702,91JCR(S)35o). 

Intramolecular conjugate allylation (12, 25).2 Fluoride ion catalyzes intramolecular Michael additions of allyltrimethylsilane to a,p-enones as well as a,p-unsaturated esters, nitriles, and amides Lewis acid catalysis is not effective. The method is particularly suited to cyclopentane annelations.2... 

Majetich reports that the fluoride ion catalyzed carbocyclization of ally anion equivalents to a, 3-enones is sensitive to the structure of the a,p-enone in which competing 1,2- and 1,4-addition processes occur.116 For example, a,(3-enones (135) afford predominantly the jyn-bicyclo[4.3.0]nonan-3-ones (136)... 

Corriu and coworkers have reported an alternative procedure for the conjugate addition of ketones to a.P-unsaturated acceptors which employs CsF-(RO)4Si (Scheme 56) 126 this procedure affords adducts with a,3-enones, oc.fj-unsaturated esters and a,3-unsaturated amides. Mechanistically, silyl enol ether formation occurs initially, followed by fluoride ion catalyzed enolate formation. 

The fluoride ion-catalyzed reduction of 2-methylcyclohexanone by various hydrosilanes gives the corresponding silyl ethers in 40-99% yields (equation 27)41. The reactivity, markedly influenced by the steric bulk of hydrosilanes (see entry 30 of Table 1), decreases in the order of Ph2SiH2 >>PhMe2SiH > Ph2MeSiH > Ph3SiII. 

Further examination of the fluoride ion-catalyzed asymmetric aldol reaction of the enol silyl ethers prepared from acetophenones and pinacolone with benzaldehyde using 4b and its pseudoenantiomer 4c revealed the dependence of the stereochemistry of the reactions on the hydroxymethyl-quinudidine fragment of the catalyst (Table 9.3) [10,15]. 

The first pentalene to be synthesized free of fused rings was the hexaphenyl derivative (752).232) The approach involved fluoride ion-catalyzed Michael addition-Knoevenagel dehydration of 1,2,3-triphenylcyclopentadiene with 1,2,3-triphenyl-propenone and subsequent oxidation with N-bromosuccinimide in CCI4. 

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. ... 

Intramolecular conjugate additions/ This fluoride ion-catalyzed Michael addition is particularly useful for cyclization of suitably substituted allyltrimethylsilanes with a Michael acceptor. In the examples cited, BE, is not useful, because its use results in desilylation or isomerization. 

Aldol condensation (8, 467). Complete details have been published concerning the fluoride-ion-catalyzed aldol reaction of enol silyl ethers with aldehydes. I hc primary product is the silyl ether of the aldol, and yields can be markedly improved by addition of FSi(CHj), to the reaction. The reaction exhibits only slight anti-syn selectivity, but does show high axial selectivity when the substituent is added to the a-position of a cyclohexanone (equation I). 

Noyori, R., Yokoyama, K., Sakata, J., Kuwajima, I., Nakamura, E., Shimizu, M. Fluoride ion catalyzed aldol reaction between enol silyl ethers and carbonyl compounds. J. Am. Chem. Soc. 1977, 99, 1265-1267. 

The fluoride ion-catalyzed aldol reaction can be utilized for asymmetric synthesis... 

The Hosomi-Sakurai reaction is a powerful method for conjugate allylation of a,fi-unsaturated ketones [425], In the presence of TiCl4 the allylation occurs smoothly at the y-position of allylsilanes and the / -position of a, -unsaturated ketones. This highly regioselective process has been widely used for introduction of functionalized carbon chains and construction of carbocycles in natural product synthesis [6, 426]. When TBAF is used as catalyst, both conjugate addition and 1,2-addition occur competitively [333]. The fluoride ion-catalyzed procedure is, however, effec-... 

Mechanistic investigation of the reaction of vinylsilacyclobutanes has suggested the presence of a silanol-fluoride adduct as the actual vinyl donor [545]. Similar species can be generated from vinylsilanols and bis(vinyl)disiloxanes by the action of TBAF. Consistently with the reactivity of vinylsilacyclobutanes, these silicon reagents work as effective vinyl donors (Scheme 10.210) [546-54B]. Vinylhydrosi-lanes [547] and vinyl(2-pyridyl)silanes [549] also can be successfuUy used for the Pd-catalyzed coupling, because they are readily converted into vinylsilanols by fluoride ion-catalyzed hydrolysis. 

The fluoride ion-catalyzed addition of alkoxymethylthiomethylsilanes to aldehydes followed by acid-catalyzed cyclization affords 1,3-oxathiolanes (Scheme 10.220)... 

The Lewis acid-promoted aldol-type reaction of thiomethylsilanes with silyl enolates and subsequent fluoride ion-catalyzed cyclization leads, on the other hand, to tetrahydrothiophenes. In these reactions the thiomethylsilanes serve as thiocarbonyl ylide equivalents. 

The readily available diethyl 1,1 -dilluoro-1 -(irimcthylsilyl)mcthylphosphonate -- is particularly suited to fluoride-ion-catalyzed reactions. In the presence of CsF, it reacts with aromatic or heteroaromatic aldehydes in THF at room temperature to produce silylated adducts, which are readily hydrolyzed to produce diethyl l,l-difluoro-2-hydroxy-2-arylethylphosphonates in 57-87% yields. " Further applications of diethyl l,l-difluoro-l-(trimethylsilyl)methylphosphonate have been demonstrated in the synthesis of [l- C]2,2-difluoroethene. The fluoride-ion-induced desily-lation of diethyl l,l-drfluoro-l-(trimethylsilyl)methylphosphonate with catalytic amount of anhydrous CsF has been accomplished in the presence of conunercial [ C]formaldehyde. The key intermediate undergoes a Horner-Wadsworth-Emmons reaction to give the highly volatile [l-"C]2,2-difluoroethene, which is collected in 10-15% yields with a purity exceeding 97% (Scheme 2.16). "... 

In fluoride ion catalyzed reactions of allylsilanes, aldehydes are the only carbon electrophiles that work well protodesilylation is unavoidable with most other electrophiles, even in the most rigorously dried media. The most commonly used fluoride ion source, which only needs to be present in catalytic amounts, is TBAF in THF at room temperature or under reflux, benzyltrimethylammonium fluoride may be better, and cesium fluoride in DMF, potassium fluoride with 18-crown-6 in THF, and TASF in polar... 

Table 2 Ratio of Diastereoisomers in the Fluoride Ion Catalyzed Reactions of Enol Silanes with Aldehydes...

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