Spirocyclic oxazolines

Oxazolines are generally resistant to basic hydrolysis. For example, the ester in the spirocyclic oxazoline ester 317 was quantitatively hydrolyzed under basic conditions to afford the corresponding acid 318 (Scheme 8.94). ... 

In a special case, the spirocyclic oxazoline 640 was found to be unstable and undergoes rearrangement to the thietane A -acylimine 641 (Scheme 8.202). ° A zwitterionic intermediate 642 was proposed to account for the formation of 641. A biradical 643 is also a possible intermediate for this rearrangement. 

Thus, oxidation of oxazoline derivatives of phenolic compounds 33 with IBD in trifluoroethanol leads to spirocyclic amides 34 [26]. The low yield of compound 34b is attributable to the carbamate carbonyl of 33b competing effectively with the oxazoline nitrogen to capture the electrophilic intermediate obtained by activation of the phenol (Scheme 14). 

ElectophUic iodination using I2 has also been employed to effect net oxidation of oxazolines to 2-substituted 4-oxazolecarboxylic acid esters. Koskinen and co-workers" " ° prepared an intermediate oxazole fragment of calyculin using this method (Scheme 1.18). Here, the oxazoline 57 was first treated with LiHMDS and TMSCl to protect the carbamate as a sUyl amide followed by treatment with KHMDS and iodine to generate the oxazole 58. Interestingly, the authors also isolated diastereomeric spirocyclic ortho ester aminals 59 in 25 to 30% yield under these reaction conditions. 

The oxidative spirocyclization of phenolic substrates containing an internal nitrogen nucleophile provides a useful tool for the construction of nitrogen heterocycles [287, 315-318], For example, the hypervalent iodine-induced cyclization of phenolic oxazolines 251 affords the synthetically useful spirolactam products... 

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