Sila-Pummerer

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-]. 

Silylation of the 2-qfclohexanone phenylsulfoxide 1213 with the O-silylketene-acetal 1214 in the presence of Znl2 gives 75% of the Sila-Pummerer product 1215, whereas the 2-cyclooctanone phenylsulfoxide 1216 affords a ca. 1 1 mixture of the Sila-Pummerer products 1217 and the olefin 1218 [31] (Scheme 8.12). 

Nucleophilic Substitutions and Cyclizations via Sila-Pummerer Reactions... 

Cyclization of the sulfoxide 1248 with TMSOTf 20/DlPEA affords a 4 1 mixture of the tetrahydroquinolines 1249 and 1250, in 97% yield, and HMDSO 7 [49]. On heating of the sulfoxide 1251 to 80 °C Brook rearrangement then Sila-Pummerer rearrangement-cyclization gives, via 1252, 17% 1253 [50] (Scheme 8.19). 

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). 

The Sila-Pummerer reaction of a-alkoxy sulfoxides such as 1269 with excess tri-mefhylsilyl cyanide 18 and Znl2 affords, in quantitative yield, the a-cyanoether 1270 and trimethylsilyl methylsulfenate 1271 [58] (Scheme 8.24). 

DMSO or other sulfoxides react with trimethylchlorosilanes (TCS) 14 or trimefhylsilyl bromide 16, via 789, to give the Sila-Pummerer product 1275. Rearrangement of 789 and further reaction with TCS 14 affords, with elimination of HMDSO 7 and via 1276 and 1277, methanesulfenyl chloride 1278, which is also accessible by chlorination of dimethyldisulfide, by treatment of DMSO with Me2SiCl2 48, with formation of silicon oil 56, or by reaction of DMSO with oxalyl chloride, whereupon CO and CO2 is evolved (cf also Section 8.2.2). On heating equimolar amounts of primary or secondary alcohols with DMSO and TCS 14 in benzene, formaldehyde acetals are formed in 76-96% yield [67]. Thus reaction of -butanol with DMSO and TCS 14 gives, via intermediate 1275 and the mixed acetal 1279, formaldehyde di-n-butyl acetal 1280 in 81% yield and methyl mercaptan (Scheme 8.26). Most importantly, use of DMSO-Dg furnishes acetals in which the 0,0 -methylene group is deuter-ated. Benzyl alcohol, however, affords, under these reaction conditions, 93% diben-zyl ether 1817 and no acetal [67]. 

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

Phenylthio-l-trimethylsilylalkanes are easily prepared by the alkylation of (phenylthioXtrimethylsilyl)mcthane as shown in Scheme 10 [40], The treatment of (phenylthio)(trimethylsilyl)methane with butyllithium/tetramethylethylene-diamine (TMEDA) in hexane followed by the addition of alkyl halides or epoxides produces alkylation products which can be oxidized electrochemically to yield the acetals. Since acetals are readily hydrolyzed to aldehydes, (phenylthioXtrimethylsilyl)methane provides a synthon of the formyl anion. This is an alternative to the oxidative transformation of a-thiosilanes to aldehydes via Sila-Pummerer rearrangement under application of MCPBA as oxidant [40, 41]. 

Tetrahydrothiophene-fused Cgg can be generated by its reaction with the thio-carbonyl ylide precursor bis(trimethylsilylmefhyl) sulfoxide 262 [314, 315]. Thermal sila-Pummerer rearrangement leads in situ to the ylide 263, which is readily added to CgQ (Scheme 4.45). 

The formation of 29, the product of a sila-Pummerer rearrangement, as a minor reaction product points to the intermediacy of the ion pair 28. 

Formaldehyde anion synthon ( CHO). The anion of 1 (n-BuLi, THF, 0°) is readily alkylated, particularly by primary halides. The products can he converted into aldehydes under very mild conditions. Oxidation with m-chloroperbenzoic acid gives an unstable sulfoxide, which undergoes an sila-Pummerer rearrangement to an acetal. Addition of water liberates the free aldehyde. Epoxides can also be used as electrophiles.2 3 Example ... 

Salicylate annelation, 279-280 Salutaridines, 593 Samarium(ll) iodide, 464-465 Sarkomycin, 457, 458 Schweizer s reagent, 597 Selenium, 465-466 Selenones, 123 Selenuranes, 223 Shapiro reaction, 563-565 Sharpless epoxidation, 263, 600 Shikimic acid, 3, 4, 548 Sibirinone, 596 Sila-Pummerer reaction, 576 Silica, 466... 

The first example of the sila-Pummerer rearrangement, which consists in the thermal conversion of sulfoxide 169 into O-silylated cyclic 0,S-acetal 170, has been described <1999TL185>. As shown in Scheme 29, a 1,3-migration of silicon atom to a sulfoxide oxygen resulted in ring expansion. 

Ethoxyvinyllithium also adds stereoselectively to 1 to provide an adduct that is converted in several steps to the < n/(-carboxylic aeid 4. The, vvn-isomer 5 is available by addition of methyllithium, trapping with QH SeCI, and a sila-Pummerer rearrangement (Scheme 11). 

Ketone synthesis. The intermediate a in the synthesis of aldehydes can be alkylated in the presence of TMEDA to give the ketone equivalent 2. The silanes are converted into ketones (3) by a sila-Pummerer rearrangement (10, 314). Unfortunately, only primary alkyl halides give satisfactory yields. 

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