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Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co I ‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes
Author(s) -
Garcia Pierre,
Moulin Solenne,
Miclo Yves,
Leboeuf David,
Gandon Vincent,
Aubert Corinne,
Malacria Max
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802301
Subject(s) - intramolecular force , trimethylsilyl , chemistry , aminopyridines , cycloaddition , alkyne , nitrile , catalysis , medicinal chemistry , cobalt , combinatorial chemistry , organic chemistry
Three‐ring circus : An expedient route to tricyclic fused 2‐trimethylsilyl‐3‐aminopyridines exhibiting unprecedented skeletons is described. The key step is a very efficient cobalt‐catalyzed [2+2+2] cycloaddition of a polyunsaturated compound displaying an ynamide, an alkyne, and a nitrile functionality (see picture).The first [2+2+2] cocyclizations between ynamides, nitriles, and alkynes are reported. They open a new access to unprecedented nitrogen‐containing heterocycles of type 2‐trimethylsilyl‐3‐aminopyridines. Such frameworks, which can be found in various compounds of biological interest, are very difficult to prepare by conventional methods. However, using [CpCo(C 2 H 4 ) 2 ] (Cp=cyclopentadienyl) as catalyst, the intramolecular cyclizations could be achieved in up to 100 % yield. The presence of the trimethylsilyl group allowed a rare type of Hiyama cross‐coupling: one of the silylated pyridines could be coupled with p ‐iodoanisole to give a new type of biaryl system.