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Facile and Versatile Annulation of the Imidazole Ring: Single and Sequential Cyclization Reactions of Fischer Carbene Complexes with 1,4‐Diazafulvenes
Author(s) -
Barluenga José,
GarcíaRodríguez Jaime,
Martínez Silvia,
SuárezSobrino Angel L.,
Tomás Miguel
Publication year - 2006
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.200501402
Subject(s) - chemistry , imidazole , carbene , nucleophile , annulation , pyridine , medicinal chemistry , adduct , reactivity (psychology) , stereochemistry , yield (engineering) , stereoselectivity , dimethylamine , organic chemistry , catalysis , medicine , materials science , alternative medicine , pathology , metallurgy
We examined the reactivity of dimethylaminodiazafulvene 1 toward Fischer alkenylcarbene 2 and alkynylcarbene 3 complexes. Diazafulvene 1 reacts with alkenylcarbenes 2 through a formal [6+3] heterocyclization in a regio‐ and stereoselective manner to afford dihydroimidazo[1,2‐ a ]pyridines 4 . Acid‐promoted dimethylamine elimination in compound 4 c gives rise to the aromatic imidazo pyridine 5 . A likely mechanism for this reaction is a 1,2‐nucleophilic addition/[1,2]‐shift metal‐promoted cyclization sequence. On the other hand, diazafulvene 1 and alkynyl carbenes 3 undergo a [6+2] cyclization to afford pyrrolo[1,2‐ a ]imidazole carbene complex 6 that can be readily oxidized to the corresponding esters 7 . When enynylcarbenes 3 e – i are treated with diazafulvene 1 , consecutive and diastereoselective [6+2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 8 , 9 , and 12 that can be appropriately demetallated to the corresponding imidazole‐based polyfused systems 10 , 11 , and 13 respectively. Finally, enynylcarbenes 3 d , f undergo consecutive [6+2]/[5+1] cyclization reactions with diazafulvene 1 and t BuNC, respectively, to yield tetracyclic adducts 14 and 15 . All these processes result in high yields and provide a route to the preparation of imidazopyridines and pyrroloimidazoles as well as other polycyclic molecules that contain imidazole groups, which are interesting from a pharmacological and biological point of view.