| Abstract
| - Mono- (5) and dithio (4) analogues of3,4,7,8-tetramethylglycoluril (2) are readily preparedusingLawesson's reagent (1 equiv or excess, respectively). This novelapplication of Lawesson's reagentto glycolurils can be extended to N-acylglycolurils.Thus the N-acetyl and N-butanoylderivativesof 2 are converted into the monoacyl-monothio analogues8 and 9 in which thionation occurs attheleast hindered urea carbonyl. Compared to the parent glycoluril2, the thio analogues are morereadily acylated; initial acylation of 5 occurs exclusivelyon the NH site adjacent to sulfur to give13, while 4 is converted to either the monoacetyl(11) or diacetyl (12) derivative by aceticanhydride,depending on temperature. Unlike 2, acylation of4 can be accomplished with tert-butoxideasbase and then acyl halide. Further acetylation of 11gives 12, while 8 gives theunsymmetricaldiacetyl-monothioglycoluril 15 or acetyl butanoylthioglycoluril 17, and 9 gives the isomericacetylbutanoyl thioglycoluril 16. Derivative 12undergoes a crossed Claisen-like condensation betweenthe two acetyl groups to give acetoacetyldithioglycoluril(18), in a manner similar to the diacetylderivative of the parent glycoluril, while 15 undergoesselective crossed-Claisen condensation,predominantly by deprotonation of the acetyl group adjacent to oxygen(2.2:1 ratio of 19:20). Incrossed-Claisen condensations, both isomers ofacetylbutanoylmonothioglycoluril rearranged to3-ketohexanoyl and 2-ethyl-3-ketobutanoyl thioglycolurils(16 to 24 and 25; 17 to26 and 27,respectively). When the selectivities for deprotonation of theacetyl moiety over the butanoyl moiety,and for deprotonation of the acyl group adjacent to oxygen over thatadjacent to sulfur, reinforcedeach other, highly selective crossed-Claisen condensation was achieved(26:27 6:1). In contrast,when these two selectivities worked in opposition, reversal of theregiochemical outcome occurred(24:25 0.75:1). The results show thatthionation provides a more sophisticated and selectivetemplate for development of intramolecular crossed-Claisen methodologyusing the glycoluriltemplate-directed approach.
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