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

The gold(I)-catalyzed reaction of N-Boc-protected 6-alkynyl-3,4-dihydro-2H-pyridines, which affords synthetically useful vinylogous amides (beta-enaminones), has been studied in detail in order to optimize the reaction conditions, enlarge the scope and have insights into the mechanism and the structural features that selectively favor 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°) at C6. The same selectivity is observed with N-Cbz-protected 2-alkynyl piperidines. With these, beta-amino ketones are obtained as a consequence of the 6-endo dig attack to a substituted triple bond. Sedamine alkaloids are easily obtained by this approach.