Isoquinolines and isoquinolones are of particular interest to medicinal chemists, due to their prevalence in alkaloids and therapeutic agents. Traditional routes to 3,4-dihydro-isoquinolones involve the thermal rearrangement (>250 �C) of cinnamyl azides, generating potentially explosive intermediates in an energy-intensive reaction.1 In recent decades, transition-metal catalysed C-H activation methodologies have come to the fore and proved to be invaluable in providing alternate strategies for the synthesis of heterocycles. C-H activation using transition-metal catalysed processes with internal oxidants has considerably improved accessibility to these scaffolds, using alkynes and hydroxamic esters or oximes as typical precursors. Furthermore, the alkynes and alkenes used to intercept the arylmetal species in the aforementioned systems have been either electronically neutral or electron-deficient. The only exception to this is a single example of the annulation of an enol ether (dihydrofuran) to N-(pivaloyloxy)-benzamide using rhodium(III) catalysis.2We were inspired to investigate vinyl esters as acetylene synthons and vinyl ethers as acetaldehyde enolate or acyl anion equivalents. As a result, the synthesis of 3,4-dihydroisoquinolones and isoquinolines using vinyl acetate, a cheap bulk chemical, as an acetylene equivalent has been explored. To our knowledge, the use of gaseous acetylene or an acetylene synthon to furnish a 3,4-dihydroisoquinolone has not been previously exemplified.1Davenport, R. J. et al. Tetrahedron 2002  , 58, 5761.2Fagnou, K. et al. J. Am. Chem. Soc. 2011  , 133, 6449.

Vinyl esters as acetylene synthons:  Rhodium(III)-catalysed C-H activation for the synthesis of isoquinolones and isoquinolines

248th National Meeting (2014)

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