Synthesis and conformational analysis of chiral ureas incorporatingN‐1‐phenylethyl groups. Manifestation of allylic 1,3‐strain

Abstract

AbstractThe synthesis of novel chiral ureas (R,R)‐2, (S,S)‐3and (R)‐6incorporating the α‐phenylethyl group is described. Conformational analysis of these ureas, and of previously reported (R,R)‐1, was carried out computationally, both at semiempirical (AM1 and PM3) andab initio(HF and B3LYP) levels, and experimentally from x‐ray crystallographic analysis of (R,R)‐2and (S,S)‐3, and in the case of (R)‐6by means of NOE NMR spectroscopy. A substantial preference of 1.5–2.6 kcal mol−1in favor of conformations withsyn‐periplanar arrangements between the CH bond at the α‐phenylethylN‐substituent and the NC(O) segment was found, and this observation confirms the relevance of allylic A1,3strain in this system. The possibility of hydrogen bonding in thesyn‐periplanar CH···OCN arrangement was discarded in the light of topological analysis of (R,R)‐1, within the frame of Bader's atoms in molecules theory. Copyright © 2005 John Wiley & Sons, Ltd.