Fluoride ion-catalyzed reactions

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). 

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. 

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. ... 

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...

Kuroboshi, M. Shinozaki, T. Ishihara, T. Ando, T. A convenient synthesis of fluorine-containing highly-substituted furans through new fluoride ion-catalyzed reaction of l-alkyl-F-l-alkenyl phosphates. Chem. Lett. 1987, 1621-1622. 

Alkylation of cyclic azaanions is also well studied. It can be exemplihed by the reactions of 81 reported by Banks group.The fluoride ion-catalyzed reaction of... 

As a Carbon Nncleophile in Fluoride Ion-Catalyzed Reactions. The reactions with aldehydes, ketones (eq 23), and o , -unsaturated esters (eq 24) can also be catalyzed by fluoride ion, usually introduced as tetra-n-butylammonium fluoride (TBAF), or other silicophihc ions such as alkoxide. These reactions produce silyl ether intermediates, which are usually hydrolyzed before workup. The stereochemistry of attack on chiral ketones can sometimes be different for the Lewis acid- and fluoride ion-catalyzed reactions. In addition some electrophiles only react in the fluoride-catalyzed reactions, as with the addition to trinitrobenzene giving an allyl Meisenheimer complex . ... 

The inoeased ability of polyfluorinated compounds to undergo fluorine substitution was used for the synthesis of trifluoromethyl-substituted furans. Reaction of perfluorobut-2-ene 131 with acetylacetone or acetoacetic ester furnished 2,3-bis(trifluoromethyl)furans 132 through two sequential fluorine substitutions [97]. Similarly, fluoride-ion catalyzed reaction of fluorinated enol phosphates 133 led to dihydrofurans 134 which treatment with a base produced furans 135 in 44-56 % yields [98]. 

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 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). 

Silver ion also catalyzes nucleophilic reactions of thiol esters, including reactions of acetylhomocysteine thiolactone (12) and diethylethylphosphonothiolate (52). In the first reaction, an insoluble complex of silver ion and the substrate was first produced at pH 7.5, which then reacted with the nucleophile, in this case an amino group of a protein. In the second reaction silver ion complexes of the substrate were also postulated, on the basis that silver ion complexes with sulfur are much more stable than those with oxygen (I). The complexes postulated were 1 1 and 2 1 silver ion-substrate complexes. These complexes were suggested to react with the nucleophiles, water and fluoride ion, giving as products phos-phonic acid and phosphonyl fluoride, respectively, and silver mercaptide. It is evident that the last reaction at least must involve only the direct interaction of a silver ion with the sulfur atom of the thiol ester without chelate formation. Therefore it appears the metal ion-catalyzed reactions of thiol esters are unique, in that they involve complex formation, but not chelate formation in their catalytic mechanism. 

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). 

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]. 

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 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. 

---