R. Jeyaraman et al., Influence of A(1,3)-strain on the conformational preferences and stereodynamics of N-formyl-cis-2,6-diarylpiperidines, I J CHEM B, 38(3), 1999, pp. 325-336
Citations number
18
Categorie Soggetti
Organic Chemistry/Polymer Science
Journal title
INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY
Ten N-formyl-cis-2,6-diarylpiperidines have been prepared and their preferr
ed conformations are determined using NMR spectral studies and semiempirica
l calculations (AM1 and PM3 of MOPAC 6). The severe A(1,3)-strain due to th
e interaction between the N-C=O group (coplanar to the C2-N1-C6 plane) and
the adjacent aryl group forces the N-formyl-cis-2,6-diarylpiperidines 19-28
to prefer flattened boat conformations with nitrogen at one of the base po
sitions (VIA and VIE; Figure 1). Employing variable temperature NMR studies
, the barriers for N-C rotation in the N-formylpiperidin-4-one 19 and the N
-formylpiperidine 28 are found to be 72.5 and 65.8 kJ mol(-1), respectively
, which are in general, lower than those of the corresponding N-nitrosopipe
ridines. The lower energy barrier (Delta G(#)) of the N-formylpiperidine 28
compared to the N-formylpiperidin-4-one 19 (by 6.7 kJ mol(-1)) is attribut
ed to the larger ground state destabilization of N-formylpiperidine 28 than
19. Semiempirical calculations show a hydrogen bond type of attraction bet
ween the electron-rich oxygen atom of N-C=O group and the electron deficien
t hydrogen at alpha-position (H2).