Silyl-Hilbert-Johnson nucleosidation

The example of a silyl—Hilbert—Johnson nucleosidation reaction in Section 25.3 is presumed to involve an intermediate ribosyl cation that is stabilized by intramolecular interactions involving the C2 benzoyl group. This intermediate blocks attack by the heterocyclic base from the a face of the ribose ring but allows attack on the j8 face, as required for formation of the desired product. Propose a structure for the ribosyl cation intermediate that explains the stereoselective bonding of the base. 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

The silyl-Hilbert-Johnson method of nucleoside synthesis, using trimethylsilyltriflate as catalyst, is useful for the preparation of N-3 nucleosides (e.g., from 4-carbamoylimidazolium-5-olate) <84JHC529>, and a similar silyl displacement method has been used to make 1-alkylthio- and 1-phenylthio-l-trimethylsilyloxyalkanes and -cycloalkanes. This latter process uses 1-trimethyl-silylimidazole (177) and trimethylsilyltriflate as catalyst <84CHE662, 90S104>. The use of two equivalents of the thiol prevents the formation of imidazole adducts (Scheme 116) <90S104>. 

P-D-Rihofuranosyl derivatives of various 1,2.4-triazoles have been reported, along with P-D-arabinofurano l and 2 - and 5 -deo3 - analogues. Ribofuranosylation of 1.2,3-triazoIe (4) gave the 2- substituted nucleoside, while the l,4-thlazin-3-one nucleoside (5), and its S-oxide, a potential tetrahedral intermediate analogue for enzymes in pyrimidine nucleoside metabolism, have been prepared by silyl-Hilbert-Johnson methods, Also available by standard methods are P-D-ribofuranosyl derivatives of... 

The second step of new nucleoside preparation was the modification at the pyrrole nitrogen, using standard techniques of nucleoside synthesis such as the silyl-Hilbert-Johnson (or Vorbriiggen) reaction [17a, c, 18], alkylation under basic conditions [17d, 19] or Mitsunobu reaction [17f, 20], By means of methods mentioned, a series of nucleosides 44-46 was prepared in moderate to good yields. 

Irreversible lactim-lactam tautomerization was recognized a long time ago and is generally achieved by either heat or catalysts. One of the synthetic applications was reported by Knorr as early as 1897. Later, this reaction was first applied to the synthesis of pyrimidine nucleoside by Johnson and Hilbert, thus being called the Hilbert-Johnson reaction (HJR). The reaction has been employed as one of protocols for the preparation of pyrimidine nucleosides. The biological and medicinal interest in pyrimidine affords further impetus to prepare new types of derivatives. Because of the synthetic utility of the HJR for synthesis of pyrimidine nucleosides, a more sophisticated version of the HJR has been developed by Vorbriiggen (the silyl HJR VHJR) employ-... 

The synthesis of pteridine nucleosides from pteridones can be considered as an electrophilic attack on a ring N-atom forming an 0,iV-acetal. A large number of N-l, N-3, and N-8 substituted ribo-, 2 -deoxyribo, arabino, xylo-, and gluconucleosides have been synthesized and described silyl-method based on the Hilbert-Johnson-Birkofer reaction. Lumazine (3) reacts with hexamethyldisilazane to 2,4-bis-trimethylsilyloxypteridine (85), which condenses with l-0-acetyl-2,3,5-tri-0-benzoyl-/ -i>ribo-furanose (86) under SnCl4, BF3 or trimethylsilyl triflate catalysis to a mixture of A(-l)-mono (87),... 

N-Alkylation in the azine ring is demonstrated by the preparation of 2-substituted 6-(jS-D-ribofuranosyl)oxazolo[5,4-rf]pyrimidin-7(6/T)-ones (181). In this case the silyl ether variant of the Hilbert-Johnson method for the synthesis of pyrimidine nucleosides has been used the pyrimidinone (180) is converted into its silyl ether using HMDS and the ether reacted with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide under Hg(II) catalysis. Deacetylation using methanolic ammonia gives the nucleoside with a /3-anomeric configuration (74JMC1282). 

---