Orthoesters and Oxazolines

This knowledge led to the development of the orthoester and oxazoline methods for producing 1,2-trans glycosides. 

A reaction which is analogous to the orthoester synthesis but which utilises glycosyl oxazolines affords means of synthesising, 2-trans-2 amino-2-deoxy-glycoside derivatives. Treatment of the gluco compomd (17) with phenol in the presence of toluene- -sulphonic acid thus gave the glycoside (18), and it was also utilised in a nucleoside synthesis 48). 

The preparation of several glucofuran [2, l-t/] oxazolines 35 and 36 from reaction of 2-amino-2-deoxy-D-glucose 34 with HF has been described. Compounds 35a and 35b are formed when the reaction is carried out in formic acid, whereas the orthoesters 36a-c are formed when the reaction is carried out using anhydrides. Further reaction of 35 and 36 with methanol gives methyl glycosides. Thus, 35 and 36 may hnd use as potential glycosyl donors for the synthesis of 2-amino-2-deoxy sugars (Scheme 8.14). " ... 

Langlois and co-workers ° developed a stereoselective hetero-Claisen rearrangement of camphor-based oxazoline A -oxides 300, available from hydroxylami-noisobomeol 298 and orthoesters 299. The rearrangement, initiated by acylation of... 

The Claisen rearrangement has been instrumental in the synthesis of a number of natural products.279-289 Many useful derivatives have been prepared using the Claisen-type rearrangement including enol ethers,290 amides,291-293 esters and orthoesters,294-296 acids,297-298 oxazolines,299 ketene acetals,300-301 and thioesters.302 Many of these variants use a cyclic primer to control relative and absolute stereochemistry. The Claisen and oxy Cope provide the best candidates for scale up as a result of the irreversible nature of these reactions. 

Carboxylic acids and esters frequently must be protected against the attack of organometallic reagents, e.g. metal alkyls and hydrides, and reducing agents like LiAlH. For this purpose they usually are converted to orthoesters, oxazolines or oxazoles. 

The synthesis of block copolymers by sequential polymerization requires a living polymer prepared from the less nucleophilic monomer (first block) and the addition of a more nucleophilic monomer to the active species located on this first block. The general order of nucleophilicities of heterocyclic monomers is as follows Siloxanes orthoesters < acetals < ethers < sulfides < oxazolines < amines. Depending on substitution and ring strain some changes may occur in these positions. 

ISC [intramolecular substitution by the third atom of a carbonyl-containing NG under inversion of configuration at the position of the original activation and either entry of the nucleophile at the carbon of the original carbonyl group (to form an orthoester derivative) or eUmination of another substituent (to give an oxazoline, oxazolone, etc.)]... 

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