277-1,3-Oxazines, formation

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

In the condensation of /3-hydroxy aldehydes 303 with A -sulfonyl aliphatic aldimines 304 (which could also be prepared in situ from the aliphatic aldehyde and A -sulfinyl /i-toluenesulfonamide), 2,5,6-trisubstituted 3,6-dihydro-277-1,3-oxazines 306 were formed as single /ra r-stereoisomers (Scheme 57). No oxazine formation was observed in the... 

The configuration of Willstatter s a -cocaine has now been shown to be 3j8-benzoyloxy-3a-methoxycarbonyltropane by adopting the method of oxazine formation of the nor derivative of a -ecgonine methyl ester. This latter had been obtained from tropinone by the cyanohydrin route. Obviously the cyanide ion attacks the ketone from the a-direotion in contrast with metalloorganic compounds, which carry out nucleophilic attack from the nonhindered jS-position (130). 

Heterocyclization. 3-Butenyl ketoximes give either 1,2-oxazines or cyclic nitrones, depending on the relative configuration of the OH and the unsaturated side chain." Oxazine formation is possible only when the oxygen atom of the oximes is on the same side as the double bond. 

Microwave-assisted solvent-free synthesis of pharmacologically important pyrido fused-ring systems has recently been accomplished and is an improved method for assembly of a variety of pyridopyridazine and quinoline derivatives. Benz-1,3-oxazine formation has also been investigated in dry media using AI2O3-KF as a solid base (Scheme 8.75) [187]. 

PEG 400 was found to be the most favorable solvent for the Mannich reaction involving anilines, formaldehyde, and a- or p-naphthols affording 145 and 146 (Scheme 83) [116]. PEG 400 seemed also to play a role of catalyst in the reaction as no 1,3-oxazine formation was detected in the absence of PEG 400. 

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