A theoretical and NMR lanthanide induced shift (LIS) investigation of the conformations of lactams.

Molecular mechanics (MM) with MMFF94 and MMX force-fields and ab initio (RHF/6-31G*,RHF/6-311G** and B3LYP/6-311G** ) calculations are used with LIS to investigate the conformations of N-methyl-2-pyrrolidone 1, N-methyl-2-piperidone 2, e−caprolactam 3, γ-valerolactam (1,5-dimethyl-2-pyrrolidone) 4, 2-azetidinone 5, 4-methyl azetidinone 6, 4-phenyl azetidinone 7, and N-methyl-4-phenyl azetidinone 8. The Yb(fod)3 paramagnetic induced shifts of all the 1H and 13C nuclei are measured and the corresponding diamagnetic complexation shifts obtained by the addition of Lu(fod)3. The complexation model (two-, three- or four-site) used depends on the relative rates of the processes involved. The amide inversion is the same order as that of the five and six membered lactam rings and much faster than the lanthanide complexation and the inversion of the seven membered ring. Both MM and ab initio calculations give an envelope conformation for 1 with C-4 out of the ring plane in agreement with the LIS analysis. For the piperidone ring of 2 the half-chair is calculated as the most stable form. The LIS analysis confirms this but cannot exclude a small amount ( 1.5%). In 4-phenyl azetidinone 7 the MMFF94 geometry with 60% of the axial conformer gave Rcryst 1.2% but the other geometries Rcryst > 1.5%. In contrast the N-methyl-4-phenyl-2-azetidinone 8 gave good agreement for all the geometries. The butterfly conformation gave Rcryst 1.1% for 80% of the axial conformer and the planar geometries Rcryst 0.98%. The LIS results confirm the ab initio and MM optimised geometries but the conformer energies at times differ from the calculated values. They also differ considerably from the corresponding values for the lactones studied previously and possible reasons for this are discussed.