Silylated heterocycles

For further Pummerer reactions with silylated heterocyclic bases see Refs. 414a—414i in Handbook of Nucleoside Synthesis , H. Vorbruggen, C. Ruh-Pohlenz, Wiley-Inter-science. New York, 2001... 

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

With thiazolines it is still possible to obtain silylated heterocycles, despite the initial reaction giving the ring-opened product, since like the situation with oxazole (Section II1,B, 1) the desired isomerization can be induced thermally (Scheme 140) [90H(31)1213]. However, the analogous isomerization cannot be induced in the oxazoline case (87S693). 

D Synthesis of Silylated Heterocycles 1 Ring Formations a) Pyrazoles... 

Besides the methods already described for synthesizing silylated heterocycles via cyclisation reactions another possible alternative is the direct silylation of heterocyclic substances. Very early investigations219 showed that the use of silylated amines219 and silylated carboxylic acid amides220 is a very appropriate choice221 when the direct silylation222 223 by means of a chlorosilane fails. 

After it was demonstrated that silylated sugars easily form diglycosides225 when they are applied to 1-halo-sugars, further studies followed. It became apparent that these silylated heterocycles are convenient intermediates, especially for the synthesis of nucleosides when acylated 1-halo-sugar are employed224,22S. ... 

Exposure of triacetate 7 to 5-methyl-2,4-bis(trimethylsilyloxy)-pyrimidine (23) in presence of TMSOTf (24) provides the protected yff-nucleoside 8. The reaction of silylated heterocyclic bases with peracylated carbohydrates in the presence of Friedel-Crafts catalysts yields selectively yff-nucleosides. 

Simplified nucleoside synthesis,8 The known synthesis of nucleosides from silylated heterocycles and a protected sugar derivative in the presence of (CHjijSiClO or (CH3)3SiOTf (6, 639-640) has been adapted to a one-pot synthesis based on in situ silylation and Lewis acid catalysis. The reagent (1) is prepared in situ (equation I) and is added to the free base and acylated sugar then triflic acid, potassium nonaflate, or SnCl4 is added as catalyst. The last Lewis acid is fhe most active and allows condensation to proceed at 24°. Acetonitrile is the most useful solvent. The method is generally applicable and yields are about the same as those obtained in the two-step procedure. 

Synthesis of nucleosides by condensation of sugars with silyl heterocycles and Lewis acids such as AICI3, SnCI4l Me3SiS03CF3 (see 1 edition)... 

Synthesis of nucleosides. Reaction of silylated heterocycles with a protected 1-O-acyl or 1-O-alkyl sugar in 1,2-dichloroethane with either trimethylsilyl perchlorate or trimethylsilyl trifluoromethanesulfonate, (CH3)3Si0S02-Cp3, as catalyst gives nucleosides in high yield. The reaction is formulated for the reaction of silylated uracil (1) with l-O-acetyl-2,3,5-tri-O-benzoyl-0-D-ribofuranose (2) either at 22° for a prolonged period or for 4 hr. at reflux temperature. The function of the catalyst is to convert the sugar into the glycosyl... 

Synthesis and stereoselective functionalization of silylated heterocycles as a new class of formyl anion equivalents 06CC4881. 

The reaction of silylated heterocyclic bases with peracylated sugars in the presence of Lewis acids to yield natural (3-nucleosides. If the sugar lacks a 2oc-acyloxy substituent, an anomeric mixture forms ... 

As regards synthetic methods, a full account has been given of the use of methyl 2,3,5-tri-O -benzoyl- D-ribofuranosyl carbonate in condensations with silylated heterocycles in the presence of silver salts and diphenyltin sulfide (see Vol. 27, p. 242), and similar condensatimis can also occur with high selectivity in the presence of tin(II) chloride in acetonitrile. Thp derivatives of heterocycles have been used in Vorbriiggen-type couplings, P-D-ribofuranosyl derivatives of purines, pyrimidines, imidazoles and pyrazoles being made in this way. ... 

Deoxy-p-D-rhreo-pentofuranosyl nucleoside derivatives of type 38 could be obtained by condensation of silylated heterocycles with the a-(phenylthio)glycoside, induced by NBS. With pyrimidines, good p-selectivity was found, whereas with purines longer reaction times were... 

Condensation of the oxetan derivative (15) with silylated heterocycles did not lead to oxetanocin-like compounds, but instead L-threofuranosyl derivatives, mostly of a-configuration (16), could be isolated.33... 

A new route to T, 2 -trans-nucleosides has been developed which involves the reaction of a carbohydrate 1,2-cyclic sulphite with a silylated heterocycle. The example in Scheme 2 is typical, and glycopyranosyl nucleosides were similarly prepared.29.30... 

Meyers, A. I. Heterocycles in Organic Synthesis Wiley-Interscience, 1974 (332 pages). DegITnnocenti, A. Pollicino, S. Capperucci, A. Synthesis and Stereoselective Functionalization of Silylated Heterocycles as a New Class of Formyl Anion Equivalents Chemical Communications 2006, 4881—4893. Yus, M. Najera, C. Foubelo, F. The Role of 1,3-Dithianes in Natural Product Synthesis Tetrahedron 2003, 59, 6147-6212. Albright, J. D. Reactions of Acyl Anion Equivalents Derived from Cyanohydrins, Protected Cyanohydrins and a-Dialkylaminonitriles Tetrahedron 1983, 39, 3207-3233. Seebach, D. Corey, E. J. Generation and Synthetic Applications of 2-Lithio-l,3-dithianes /. Orpi. Chem. 1975, 40, 231-237. 

S. K. Vasisht and V. Goyal, Inorg. Chim. Acta, 1980, 44, LI 15 Silyl heterocyclics with TiCU and FeCla. 

Of relevance to this section is the preparation of some new heterocyclic thiocarbonyl transfer reagents, analogous to l,l -thiocarbonyldi-imidazole, from an 7V-silylated heterocycle and thiophosgene some of these derivatives show considerably more reactivity than the currently used reagents. 

With regard to new methods fOT the synthesis of fl-D-ribofuranosyl nucleosides, it has been shown that the methyl carbonate 1 condenses in a highly stereoselective manner with silylated heterocycles in the presence of silver salts and diphenyltin sulfide. The use of pentenyl glycosides has been extrapolated to the nucleoside field the ycoside 2 coupled efficiently with various purines when activated by NIS and TfOH to give products P-linked at Af-9, but the method was less effective in the 2-deoxy series. ... 

The aziridinonucleosides 47 (B Ura, Thy) have been made by Vorbriiggen-type coupling of the sugar with silylated heterocycles. ... 

A series of silylated heterocycles using an intramolecular silicon version of the Matteson rearrangement give binuclear heterocycles via a pentaorganosilicate species (Scheme... 

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