Oxazolidines, ring-chain tautomerism

An important feature of saturated oxazolo[3,4- ]pyridines is their easy epimerization at the aminal C-l stereocenter. A quite explicit example has been reported by Moloney et al. and is depicted in Scheme 46. The reaction between lactam 157 and benzaldehyde produces a mixture of hexahydro-oxazolo[3,4- ]pyridines, the kinetic product 158 being the major one. Equilibration of the mixture with boric acid allows the ratio of diasteroisomers to be reversed since /rarcr-oxazolidine 159 is now the major product <1998TL1025> the equilibration of epimeric oxazolidines via ring-chain tautomerism has been investigated in detail and explains the epimerization observed for some hexahydro-oxazolo[3,4-4]pyridines <1993JOC1967>. 

The ring-chain tautomerism of tetrahydro-l,3-oxazines is very sensitive to the stability differences, the substituents and the ring-fusion effect (Section IV,A). It also reveals a considerable stability difference in favor of the cis isomers. In the reactions of the cis- and trans-2-amino-l-cyclohexanols, as compared with the hydrindane analog systems, where the heteroatoms form an oxazolidine ring cis- or tra 5-fused with cyclohexane, the corresponding stability differences were again found to be in favor of the cis isomer (93JOC1967). 

The oxazolidine system proved a good protecting group with which to mask the ethanolamine moiety in the a-formylation and a-benzoylation of 558, and it could also be used as an aldehyde donor in the rearrangement, based on the ring-chain tautomeric character of 559, under acidic conditions to yield 3-(2-hydroxyethyl)-substituted 1,3-oxazin-4-ones 560 (Scheme 106) <1996JOC3358>. 

The ratio of 33A and 33B proved to be slightly solvent-dependent (Table V). The reactions of 3-amino-l,2-propanediol with substituted aromatic aldehydes in CDC13 resulted in five-component ring-chain tautomeric equilibria. Besides the open-chain form 34A, two epimeric oxazolidines (34B and 34B ) and two epimeric tetrahydro-l,3-oxazines (34C and 34C ) were identified in the tautomeric mixture. The proportions of the tautomers in the equilibrium for X = p-NC)2 were [34A] [34B] [34B ] [34C] [34C ] = 40.7 7.0 5.9 9.7 36.7 (94MI1, 94MI2). 

The ring-chain tautomerism of oxazolidines is discussed in Section 4.18.2.5.2. Oxazolidines form unstable salts which are easily hydrolyzed (equation 80) (77RRC1413). IV-Substituted oxazolidines react with enamines in the presence of trifluoroacetic acid to yield 1,4-oxazepines in a ring-opening 1,5-cycloaddition reaction (equation 8,1) (80LA1573). 

Oxazolidines 288 are subject to ring-chain tautomerism. The process can be considered as a reversible intramolecular nucleophilic addition to the C=N bond. A variety of substituted oxazolidines exist in the open-chain form 289 in the solid state <1985T5919, 1992T4979>. In solution, the two forms are in equilibrium, the position of which depends on the solvent and the substituents. 

In oxazolidines, the extent of ring chain tautomerism is also governed both by the acidity of its a-CH and by stereoelectronic stabilization of acyclic tautomers. Deprotonation at the a-carbon of the C-2 appendage induces ring opening of the oxazolidine to its chain tautomer. In 27a and 27b, steric hindrance to deprotonation and possible nonplanarity of the carbanion system due to the orthogonal disposition... 

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