Reaction of alk-3-yn-1-ones with non-symmetricalo-phenylenediamines provides an effective method with high atom economy for the synthesis of diversely substituted 1,5-benzodiazepines and conjugated enaminones.

Reaction of alk-3-yn-1-ones with o-phenylenediamines provides an effective method with high atom economy for the synthesis of diversely substituted benzodiazepines and conjugated enaminones. This microwave-accelerated reaction proceeds in ethanol in the absence of a catalyst and leads to benzyl-substituted 1,5benzodiazepines with good yields (70-92%). A room temperature protocol with the same set of reagents (stabilized with triethylamine) leads to enaminones (3-amino-2-alkenones, 70-99%). The tautomer formed and the regio-and stereochemistry of the process are confirmed by the X-ray crystallographic structure determination of 2-(4-methylbenzyl)-4-phenyl-3H-benzo[b][1,5]diazepine and (Z)-3-[(2-amino-4,5-dimethylphenyl)amino]-4-(4-tert-butylphenyl)-1-(4-chlorophenyl)but-2-en-1-one. Scheme 1 The synthesis of 1,5-diazepines 3 from alk-3-ynones 1 and o-phenylenediamines 2. † Electronic supplementary information (ESI) available: 1 H and 13 C NMR spectra for diazepines 3, enaminones 4 and 6, and cif files for 3aa and 4cb. CCDC 929588 and 950049. For ESI and crystallographic data in CIF or other electronic format see

Lewis acid-catalyzed rearrangements of 4,5-dihydro-1,3-dioxepines have been investigated. Rearrangement of vinyl acetals under a variety of conditions resulted in cis- and trans-2,3-disubstituted tetrahydrofuran derivatives in a highly stereoselective manner. Rearrangements at lower temperatures typically provided the cis-2,3-disubstituted tetrahydrofuran carbaldehydes. At higher temperatures, the corresponding trans-2,3-disubstituted tetrahydrofuran carbaldehydes are formed. The requisite substrates for the vinyl acetal rearrangement were synthesized via ring-closing olefin metathesis of bis­(allyoxy)­methyl derivatives using Grubbs second-generation catalyst followed by olefin isomerization using a catalytic amount of RuCl2(PPh3)3. We examined the substrate scope using substituted aromatic and aliphatic derivatives. Additionally, the rearrangement was utilized in the synthesis of a stereochemically-defined bis-tetrahydrofuran (bis-THF) derivative, which is one of the key structural elements of darunavir, an FDA-approved drug for the treatment of HIV/AIDS.

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