Silyl-Hilbert-Johnson reaction

Because activated 4-0-trimethylsilylated-2, 3, 5 -0-acyluridines such as 3 are also obtained as reactive intermediates in the Friedel-Crafts-catalyzed silyl-Hilbert-Johnson reaction [59, 59 a] of persilylated uracils or 6-azauracils such as 227 with sugars such as l-0-acetyl-2,3,5-tri-0-benzoyl-/9-D-ribofuranose 228 in the presence of SnCl4, treatment of the reactive intermediate 229 with a large excess of pyrrolidine neutralizes the SnCLi. used and aminates 229 to afford the protected 6-aza-cytidine 230, although in 57% yield only [49, 59] (Scheme 4.20). 

Niedballa, U. and Verbruggen, H (1976) A general synthesis of N-Glyco-sides. 6 On the mechanism of the stannic chloride catalyzed Silyl Hilbert-Johnson reaction J Org Chem. 41,2084-2086. 

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 mechanism of the Friedel-Crafts-catalysed Hilbert-Johnson reaction has been reviewed, with particular reference to the reaction of silylated uracils and stannic chloride or trimethylsilyl trifluoromethanesulphonate. ... 

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. 

The triazine 2-deoxynucleoside (24) and its ribosyl analogue (25) have been synthesized by application of the silyl ether modification of the Hilbert-Johnson reaction. Compound (25) was shown to possess antiviral and antibacterial activity. Ribosylation of 6,7-diphenyl-2-thiolumazine (26) has been... 

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. 

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),... 

Imbach et al. have reported syntheses of 4 -thiothymidine (104) and 4 -thiouridine (105) starting fromL-lyxose, following the dithiobenzyl acetal cyclization method and the Hilbert-Johnson silyl condensation reaction of 103 with silylated thymine (77% yield, a p 43 57) and uracil (74% yield, a 47 53),... 

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