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

Abstract

AbstractThe gold(I)‐catalysed reaction of N‐Boc‐protected 6‐alkynyl‐3,4‐dihydro‐2H‐pyridines, which gives synthetically useful vinylogous amides (β‐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°) at C‐6. The same selectivity was observed with N‐Cbz‐protected 2‐alkynylpiperidines. With these compounds, β‐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.