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Abstract: The reactions between dimethylsulfonium methylide and 1,3-diene- or 1,3,5-triene-1,1-dioates under specific conditions enable the highly regioselective tandem ylide addition–eliminative olefination to provide 1,3-butadien-2-yl- or 1,3,5-hexatriene-2-yl-malonates. Alkylation at malonate methine carbon of 1,3-butadien-2-ylmalonates with a suitable alkyl halide having in-built functionalities for a dienophile generation led to quick assembly of precursors for type 2 intramolecular Diels–Alder reaction. Syntheses of functionalized bicyclo[n.3.1] alkenes (n=5 or 6) with the double bond at the bridgehead position have been achieved via the IMDA. An asymmetric version of this reaction has been developed using a MacMillan''s imidazolidinone catalyst, which provided a bicyclo[5.3.1] alkene with very high enantioselectivity. In situ methylation at malonate methine carbon of 1,3,5-hexatriene-2-yl-malonates followed by intermolecular Diels–Alder reaction with N-methylmaleimide provided the cycloadduct with complete regiocontrol and high diastereoselectivity. [Copyright &y& Elsevier]

The hydrolytic stability of norcantharidine derived conformationally constrained diamides in acidic media is solely governed by the type of amide. Tertiary diamides underwent smooth acid catalyzed hydrolysis due to anchimeric assistance whereas other diamides were stable. This was corroborated from conformational proximity of the amide groups for anchimeric assistance based on single crystal X-ray structure analysis. Theoretical calculations on the diamide structures also predict the similar proximity of the diamides in those conformations. Thus norcantharidine based diamides could probably serve as promising systems for delayed release of certain types of drugs which possess secondary amine component as exemplified by the release of m -chlorophenylpiperazine at a pH range of 1–2. Image 1 • Norcantharidine derived tertiary diamides hydrolyzed easily under acid catalysis. • Their primary, secondary and mixed diamides do not hydrolyze easily. • Hydrolysis of tertiary diamides occurred due to NGP of proximal amide carbonyls. • Hydrolysis of tertiary diamides has been supported by X-ray structure & calculations. • These tertiary diamides could serve for delayed release of certain types of drugs. [ABSTRACT FROM AUTHOR]