Bases tetrabutylammonium fluoride

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

Reaction of the secondary silylnitronate 4 with acetaldehyde, catalyzed by anhydrous tetra-butylammonium fluoride, furnished only 20% of the desired product 5 as a 56 44 (R, S )j (R, R ) mixture. With tetrabutylammonium fluoride trihydrate as base the yield increased to 89% while the diastereoselectivity remained low16. 

As already discussed in Section 7.4, hexamethyidisiiane 857 (which is produced on a technical scale), in the presence of catalytic amounts of tetrabutylammonium fluoride di- or trihydrate in THF, reduces aromatic heterocyclic N-oxides such as pyridine N-oxide 860, quinoline N-oxide 877, or isoquinoline N-oxide 879 to the heterocycles [95] and nitrones to Schiff-bases. Aromatic nitro compounds such as nitrobenzene are reduced analogously to azo compounds such as azobenzene [96]. As mentioned in Section 7.5, secondary aliphatic nitro groups are reduced to oximes. 

Fluoride ion is effective as a base for the Flenry reaction, and potassium fluoride in isopropanol (Eq. 3.6)16 and tetrabutylammonium fluoride in THF (Eq. 3.7)17 have been widely used. 

Based on the early racemic synthesis of 4 (cis series), it had already been demonstrated that 2-azetidinone ring closure could be achieved via nucleophilic attack of a lithium amine anion on a (3-ester. Cyclization could be accomplished with other strong bases, but sodium bistrimethylsilylamide was found to effect efficient cyclization without significant racemization at C3. During the search for experimentally convenient bases, it was noted that Noyori (Nakamura et al., 1983) reported that tetrabutylammonium fluoride (TBAF) as well as LiF, KF, and CsF could serve as the base in Aldol reactions. Treatment of 17a or 17b with TBAF trihydrate in THF did not affect cyclization. After much experimentation it was found that addition of A,0-bistrimethylacetamide (BSA) to 19 followed by TBAF addition, effected 2-azetidinone ring closure. Further optimization found that use of catalytic TBAF (< 1%) in methylene chloride afforded near quantitative cyclization. 

The related cyclization of 2-ethynylanilines 67 also represents one of the usefiil methods for the synthesis of 2-substituted indoles since the precursors are easily prepared from 2-haloanilines 66 by Pd-catalyzed cross-coupling with terminal alkynes. Althou cyclizations of such alkynes are normally effected using Cu(I) or Pd(II) species, Sakamoto showed that in the absence of such metals, base catalysis (e.g., NaOEt) alone can accomplish the same goal. This author now reports that tetrabutylammonium fluoride (TBAF) is capable of inducing cyclization to the indoles 68 without affecting functionalities such as bromo, cyano, ethoxycarbonyl, and ethynyl <99JCS(P1)529>. 

For the removal of this protecting group, tetrabutylammonium fluoride in oxolane is the most frequently used [388, 389, 409-411]. A much simpler reagent to prepare, potassium fluoride — crown ether, has been introduced for the same purpose [427]. Silyl group at 0-2 of nucleosides is cleaved more rapidly [411] than at 0-5. Acyl migrations occurred under the tetrabutylammonium fluoride-catalyzed desilyla-tion [432, 434, 443], Differencies between the primary and secondary position were also observed for acid- or base-catalyzed solvolysis [391, 409-412], 5 -0-(7ert-butyl-dimethylsilyl)nucleosides are much more labile towards acid than either 2 - or 3 -silyl ethers [391, 410-412], whereas the situation is reversed for base hydrolysis [411], /V-Bromosuccinimide in aqueous DMSO is another alternative for the removal of this type of silyl group [444]. 

Silyl triflates may also be used as the catalyst to the same goal. In both cases, conjugated base induces desilylation to create the ylid (compare with the action of tetrabutylammonium fluoride on the same imine which led to the anion see Section VI.B.6.a).333,391... 

Schering-Plough uses (S)-4-phenyl-2-oxazolidinone in the large-scale production of their cholesterol absorption inhibitor Zetia (ezetimibe) (11) (Scheme 23.l).40 2 Condensation of the alcohol 12 with imine 13 in the presence of a Lewis acid such as TiCl4 and tertiary amine base yields compound 14. Silylation followed by intramolecular cyclization with tetrabutylammonium fluoride (TBAF) yields the protected ezetimibe 15. Removal of the protecting groups is carried out with weak acid to afford Ezetimibe (11). 

Treatment of a-chlorocodide (142 R = C1) with toluene-p-sulphonyl chloride yields -codeine tosylate (143 R = OTs), which is converted by SN1 reaction with lithium chloride, tetrabutylammonium fluoride, or piperidine into the 6-substituted compounds (142 R = Cl, F, or 1-piperidyl, respectively) and, by SN1 reaction, with retention of configuration, into the 8-substituted bases (143 R = Br, I, SCN,... 

Ethyl trimethylsilylacetate has also been used for the synthesis of a, (3-unsaturated esters.16 The chemistry of tetrabutylammonium fluoride as a base with mild reactivity has been reviewed.17... 

The usual procedure to remove the protecting silyl group (tetrabutylammonium fluoride in tetrahydrofuran) has caused acetyl rearrangements rather than to give a sialic acid derivative with a free C-9 primary hydroxyl function. Compound 5c, in which the free hydroxyl appears to be the secondary one at C-7, has been obtained as the sole reaction product in a 85% jdeld, after chromatographic purification. The overall yield of 5c based on 3a has been 83% [30]. 

Numerous methods are now available in the literature for the deprotection of TBS ethers under a variety of conditions. One of the most effective ways for the cleavage of silyl ethers is based on the exploitation of the high affinity of silicon towards fluoride ions. Thus, a number of reagents involving one form of fluoride or another, such as tetrabutylammonium fluoride [292], BF3-Et20 [301], hydrofluoric acid [302], fluorosilicic acid [303], ammonium fluoride [304], silicon fluoride [305], lithium tetrafluoroborate [306], and chlorotrimethylsilane/potassium fluoride dehydrate [307] have been developed for the deprotection of TBDMS ethers. Among these, TBAF is most frequently used but the strong basicity of the fluoride anion makes it inappropriate for base sensitive functionalities. 

Advances of the past three decades, however, have produced alternatives to the heavy metal-based cellulose solvents. Prominent among them are dimethylacetamide/LiCl (DMAc/LiCl) N,MMN-0 hydrate (NMMO) tetrabutylammonium fluoride/DMSO (TBAF/DMSO) and potassium thiocyanate/DMSO [48]. While many of these solvents have gained significant popularity among laboratory chemists, only the amine oxide solvent, N,MMNO, has achieved industrial practicality. This will be discussed in the section on regenerated cellulose fibers. Several other important physical properties of cellulose are given in O Table 4. 

The dithymidine phosphorothiofluoridates 67 have been prepared as a mixture of diastereoisomers following treatment of the methylselenyl ester precursors 68 with tetrabutylammonium fluoride. The base-catalysed hydrolysis of the phosphorothiofluoridates was found to be about four times slower than the corresponding phosphorofluoridates. The conversion of dinucleoside phosphorothioates 69 and dinucleoside phosphorodithioates 70 into the corresponding phosphorofluoridates 71 and phosphorothiofluoridates 72 respectively using iodine and triethylamine trishydrofluoride in acetonitrile has also been described. The conversions are rapid and occurred in excellent yield. 

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