Premium
Expedient Synthesis of Homochiral 1‐Aryl‐Substituted 4,5‐Dihydro‐1 H ‐imidazoles and Their Modification to N‐Heterocyclic Carbene Precursors
Author(s) -
Latham Christopher M.,
Lewis William,
Blake Alexander J.,
Woodward Simon
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.201403560
Subject(s) - chemistry , carbene , deprotonation , aryl , alkylation , medicinal chemistry , ligand (biochemistry) , organic chemistry , stereochemistry , catalysis , ion , biochemistry , alkyl , receptor
The amidoamines ( S )‐Ar 1 CONHCHRCH 2 NHAr 2 [Ar 1 = o ‐C 6 H 4 SO 3 H, R = Bn, i Bu, i Pr; Ar 2 = 2,6‐ i Pr 2 C 6 H 4 , 2,6‐Et 2 C 6 H 4 , 2,4,6‐Me 3 C 6 H 2 ] cyclise to ( S ) 1‐aryl‐substituted 4,5‐dihydro‐1 H ‐imidazolinium species with HC(OEt) 3 in moderate‐to‐excellent yields on heating to 150–175 °C (nine examples, four isolated yields of 48 to >97 %). They are attained as their o ‐C 6 H 4 (SO 3 – )(CO 2 Et) salts. The latter are readily deprotonated to afford analytically pure ( S ) 1‐aryl‐substituted 4,5‐dihydro‐1 H ‐imidazoles (imidazolines). The purification of the intermediate sulfonate salts is not always necessary, and analytically pure imidazolines are isolated by simple kugelrohr distillation (nine examples, 45–95 %) after basification. Imidazoline alkylation provides a library of ( S )‐ N ‐alkylimidazolinium salts (23 examples, 74–97 %). As the initially required amidoamines are available in simple one‐pot reactions, the overall approach constitutes a rather efficient approach to this useful family of chiral N‐heterocyclic carbene (NHC) ligand precursors (effectively three steps from commercial N ‐Boc‐α‐amino alcohols; BOC = tert ‐butyloxycarbonyl).