Sulfoxides, silyl

Thomas investigated the chemistry of 8-azabicyclo[1.2.1]octanes, the core structure of the tropane alkaloids, and unexpectedly observed a Grob fragmentation instead of the predicted elimination reaction. Upon treatment of mesylate 27 with potassium /-butoxide in dimethyl sulfoxide, silyl cleavage affords alkoxide 28 which fragments to yield formaldehyde, a mesylate anion, and bicycle 29. Exposure of 27 to DBU in acetonitrile leads to the desired E2 reaction with complete suppression of the Grob fragmentation. ... 

Whereas conversion of sulfoxides to the corresponding a-acyloxysulfides by acid anhydrides, for example acetic anhydride, the Pummerer reaction [1], has been known for quite a time, the conversion of sulfoxides with silylating reagents via the unstable intermediate O-silyl compounds to a-silyloxysulfides, the Sila-Pummerer reaction is a relatively new reaction, which has recently been reviewed [1—4-]. 

Sulfoxides containing an a-chloro group 1191 or an a-trimethylsilyl group 1193 rearrange on silylation with TMSOTf 20/triethylamine or with LDA followed by TCS 14 to the olefins 1192 and 1194 in 86 and 75% yield and HMDSO 7 [22, 23], whereas a sulfoxide with an a-cyano or a-carbomethoxy group as in 1195 reacts... 

Treatment of the allylic sulfoxide 1227 a with diisopropylethylamine (DIPEA) or of 1227 b with N-trimethylsilyldiethylamine 146 and TMSOTf 20 leads in ca. 90% yield to the quaternary amino derivatives 1228 and 1229 and HMDSO 7 [36] (Scheme 8.15). Tetramethylene sulfoxide 1230 reacts with silylated thymine 1231 in the presence of three equivalents of TMSOTf 20 to give the 4 -thio-nucleoside analogue 1232 and HMDSO 7 [37]. Other silylated pyrimidine, pyridine, and purine bases react analogously with cyclic sulfoxides to give 4 -thio-nucleoside analogues [37, 37a, 38]. 

HMDSO 7 [39]. With 20/DIPEA sulfoxide 1233 affords 76% of 1235 [40]. Analogous silylation of the S-oxide function in 1237 with the O-silylketene acetal 1214 and subsequent cyclization with ZnCl2 or Znl2 affords 1238, a precursor of thie-namycin [41-43] (Scheme 8.16). 

Sila-Pummerer reaction of the /1-ketosulfoxide 1257 with the enol silyl ether of acetophenone 653 in the presence of BSA 22 a and stannous triflate affords the C-substituted sulfide 1258 in 82% yield and HMDSO 7 [52]. The allylic sulfoxide 1259 reacts with 653 in the presence of TMSOTf 20/DIPEA to give the unsaturated sulfide 1260 in 62% yield or, with the enol silyl ether of cyclohexanone 107a , the unsaturated sulfide 1261 in 63% yield and HMDSO 7 [53] (Scheme 8.21). 

In the presence of Znl2 in acetonitrile the saturated sulfoxide 1262 is converted by the O-trimefhylsilylketene acetal 663 into the sulfide 1263 in 55% yield and HMDSO 7 [54] whereas the unsaturated sulfoxide 1264 affords with excess O-silyl-ketene acetal 663 the bis-addition product 1265 in 45% yield [55, 56] (Scheme 8.22). 

On treatment of the silylated dichloromethyl alcohols 1585 with butyUithium, lithium trimethylsilanolate, MesSiOLi, 98 is ehminated and the 1,1-dichloroolefins 1586 are formed in 40-82% yields [5, 6]. Likewise, treatment of sulfoxide 1587 at -30 °C with excess LDA results in ehmination of trimethylsilanol 4 to afford nearly... 

Polar functional groups such as carbonyl, cyano, and sulfoxide, as well as silyl and stannyl groups, exert a strong directing effect, favoring proton removal from the geminal methyl group.171... 

The problem of the nucleophilicity of amides in glycosylation reactions is not limited to the sulfoxide method and has been shown to result in the formation of glycosyl imidates from intermolecular reaction with activated donors. It appears that this problem may be suppressed by the prior silylation of the amide [348,349]. Accordingly, it may be sufficient to operate the sulfoxide method with an excess of triflic anhydride when amides are present so as to convert all amides into O-triflyl imidates, which are then hydrolyzed on work-up. Despite these problems, several examples have been published of successful sulfoxide glycosylation reactions with acceptors carrying remote peptide bonds [344,345] and with donors coupled to resins via amide-based linkages [346,347], with no apparent problems reported. Sulfonamides and tertiary amides appear to be well tolerated by the sulfoxide method [340,350],... 

Sulfoxides have also been used in the synthesis of nucleoside analogs (Scheme 3.2). Chanteloup and Beau reported the synthesis of ribofuranosyl sulfoxide 13 and its use in the glycosylation of a series of silylated pyrimidine and purine bases.7 Although 16 is not an anomeric sulfoxide, its reaction with cytosine derivative 17 is conceptually related.8... 

The silylation reactions were performed by treatment of a solution of the substrate (1 mol. equiv.) in oxolane [or a A 1 (v/v) mixture of oxolane—dimethyl sulfoxide for substrates insoluble in oxolane] with (l.A—1.5 mol. equiv.) and trlphenylphosphine (0.5 mol. equiv.). The structures of the substrates employed and of the products obtained, and yields, are shown in Figure 1. Under the particular reaction conditions employed secondary hydroxyl groups are either not silylated or are silylated distinctly slower. 

The proposed mechanism of the oxidative cleavage of S-protecting groups by the chlorosilane/sulfoxide procedure is outlined in Scheme 8. 95 The first reaction is considered to be formation of the sulfonium cation 9 from diphenyl sulfoxide (7) and the oxygenophilic silyl compound 8. The formation of a sulfonium ion of this type is known and has been utilized for the reduction of sulfoxides. 97 Subsequent electrophilic attack of 9 on the sulfur atom of the S-protected cysteine residue leads to the formation of intermediate 10, whereby the nature of the silyl chloride employed should be the main factor that influences the electrophilicity of 9. The postulated intermediate 10 may then act as the electrophile and react with another S-protected cysteine residue to generate the disulfide 11 and the inert byproduct diphenyl sulfide (12). This final step is analogous to the reaction of a sulfenyl iodide as discussed in Section 6.1.1.2.1. 

Amino-ketone lassen sich in z.T. guten Ausbeuten auch durch Umsetzung der O-Silyl-enole von Ketonen mit Chlor-jod-melhan und Bis-[dimethylamino]-methan in Di-methyl-sulfoxid erhalten2. 

Before concentration, acid hydrolyzates are neutralized, most commonly with barium carbonate, although such organic bases as methyldioctylamine has been used.81 This step normally causes little loss, except by adsorption on, for example, barium sulfate,82 but the following points are of interest. Neutralization with ammonia has been recommended,83 as the neutral solution may be evaporated directly to dryness without filtration, and the ammonium sulfate formed is insoluble in methyl sulfoxide, a solvent used for trimethyl-silylation. The authors83 also found that, when hydrolyzates are neutralized with ion-exchange resins, the pH of the concentrated solutions may differ by as much as 2 units of pH. D-Fructose has been found to be epimerized by barium carbonate or pyridine, and lead... 

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