Vorbriiggen reaction

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. 

FMOC-Cl has been used for 3, 5 -hydroxyl protection of deoxyribose for the introduction of modified bases such as aza-cytidine using the classical Vorbriiggen reaction. While the carbonate protecting groups do not alter the stereoselectivity of the (V-glycoside formation, the FMOC groups can be removed under much milder conditions (EtyN/pyridine) than the typical 4-methylbenzoyl group (eq 9). 

The conceptually simple cyclodehydration of a carboxylic acid and a (3-amino alcohol to an oxazoline requires harsh conditions of high temperature with azeotropic water removal (e.g., boric acid in refluxing xylene). Nonetheless, good yields of the oxazoline can be obtained if sensitive functionalities are absent. " A much milder approach has been developed by Vorbriiggen where the reaction of carboxylic acids with (3-amino alcohols is carried out in the... 

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-... 

This type is a one-pot reaction widi all components present fix>m the beginning. The alcohol is first converted into an 5N-activated (HGA) species (43), which undergoes an OX displacement with the carboxylic acid to form the ester (equation 18). Two methods are known to fit into this general scheme the Mitsunobu reaction and die Vorbriiggen-Eschenmoser reaction. ... 

Cyclopropanation (5, 496). Vorbriiggen et al. have extended the cyclo-propanation procedure of styrene by Paulissen et al. to a, -unsaturated ketones and esters. The reaction proceeds stereospecifically cis to a,a- or a, 3-disub-stituted ketones and esters in excellent yield, but fails with trisubstituted carbonyl compounds. The reaction evidently Involves a carbenoid, since there is no evidence for formation of pyrazolines. 

S. An efficient synthesis of enantiomeric ribonucleic acids from D-glucose. Helv. Chim. Acta 1997, SO 2286—2314). The protected enantiomeric cytidine was produced in 94% yield by the above reaction. After adjusting protecting groups, solid-phase oligonucleotide synthesis methods (Section 25.7) were used with this compound and the other three nucleotide monomers (also derived from L-ribose) for preparation of the unnatural RNA enantiomer. See also Vorbriiggen, H. Ruh-Pohlenz, C., Handbook of Nucleoside SynlhestsTy Wiley Hoboken, NJ, 2001. 

An important reaction is used by many today to prepare many nucleosides. The Vorbriiggen glycosylation reaction (H. Vorbriiggen, Germany) couples a highly protected heterocycle, such as 116, protected as the trimethysilyloxy derivative. Reaction of 116 and tetraacetyl ribofuranose 117 in the presence... 

The use of trimethylsilyloxy derivatives, instead of other bases in the Hilbert-Johnson synthesis of nucleosides has resulted in better yields. Niedballa and Vorbriiggen have reported on the scope and limitations of this modified Hilbert-Johnson reaction. Thus, in the example shown in Scheme 120, stannic chloride in 1,2-dichloroethane was used to effect a... 

Silylation and Activation of Nucleobases. Base glycosi-dation, using the Vorbriiggen method. and its variations, has been a much exploited synthetic reaction in the formation of many important nucleoside analogs. BSA is used to activate the nucleobases by silylation. The persilylated nucleobases undergo nucleosidations with electrophiles in the presence of Lewis acids, generally tin(IV) chloride or trimethylsilyl trifluoromethane-sulfonate, while phenylselenenyl chloride, N-iodosuccinimide/triflic acid, and iodine have also been used to mediate these reactions. A typical nucleosidation reaction is shown in eq 27. Thymine 1 was treated with BSA in acetonitrile to form the silylated thymine 2 in situ, which is then reacted... 

Niedballa and Vorbriiggen have shown that the use of this a-chloro sugar (4) in the condensation with 5-ethyluracil in the presence of stannic chloride produced approximately a 1 1 (a P) anomeric mixture of 10 and 9 under a variety of reaction conditions (Scheme 3). This was apparently due to the use of stannic chloride which either causes anomerization of the chloro sugar or more likely formation of a carbocation that has an equal chance of a or p attack. 

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