Gold-Catalysed Synthesis of Exocyclic Vinylogous Amides and β-Amino Ketones: A Detailed Study on the 5-exo/6-endo-dig Selectivity, Methodology and Scope

The gold(I)-catalysed reaction of N-Boc-protected 6-alkynyl-3,4-dihydro-2H-pyridines, which gives synthetically useful vinylogous amides (-enaminones), has been studied in detail, in order to optimize the reaction conditions, enlarge the scope and gain insight into the mechanism and the structural features that selectively favour the 6-endo-dig oxyauration of the triple bond. Experimental studies and DFT calculations demonstrate that the 6-endo-dig approach is exclusive with substituted alkynes, whereas with terminal alkynes the 5-exo-dig cyclization prevails, despite the large angle (120 degrees) at C-6. The same selectivity was observed with N-Cbz-protected 2-alkynylpiperidines. With these compounds, -amino ketones are obtained as a consequence of the 6-endo-dig attack onto a substituted triple bond. Sedamine alkaloids are easily obtained by this approach.