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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
Author(s) -
Scarpi Dina,
Begliomini Stefano,
Prandi Cristina,
Oppedisano Alberto,
Deagostino Annamaria,
GómezBengoa Enrique,
Fiser Béla,
Occhiato Ernesto G.
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500205
Subject(s) - dig , chemistry , selectivity , triple bond , stereochemistry , combinatorial chemistry , scope (computer science) , reaction mechanism , reaction conditions , medicinal chemistry , double bond , organic chemistry , catalysis , computer security , computer science , programming language
Abstract The gold(I)‐catalysed reaction of N ‐Boc‐protected 6‐alkynyl‐3,4‐dihydro‐2 H ‐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.