A New Ring Expansion Reaction of 1-Acyl-2-vinylpiperidine and 1-Acyl-2-Vinylpiperazine via Aza-Claisen Rearrangement of Amide Enolate

Abstract

A new ring expansion reaction of 1-acyl-2-vinylpiperidines and 1-acyl -2-vinylpiperazines has been achieved. Amide enolate induced aza-Claisen rearrangements of 1-acyl-2-azacycles provide the corresponding lactams possessing various substituents at α-position of carbonyl in good yields.

Notes

Treatments of 1-acyl-2-vinylazacycles with sec-Buli, KHMDS or NHMDS provided much lower yields than those with LHMDS.

Use of benzene, xylene or dioxane provided relatively lower yield. Decane is less convenient solvent than tolune although it affords the same yield as tolune.

Spectral data for lactam 2c as a representative rearranged product: IR (neat) 3320, 1660 cm⁻¹; ¹HNMR (CDCl₃, 400 MHz) δ 5.97–5.95 (m, 1H),5.39–5.31 (m, 2H), 3.81 (t, 1H, J = 2.9 Hz), 3.67–3.59 (m, 1H), 3.29 (s, 3H), 2.81 (dd, 1H, J = 13.4, 8.1 Hz), 2.42 (br d, 1H, J = 11.7 Hz), 2.28–2.21 (m, 1H), 2.18–2.13 (m, 1H), 1.88 (ddd, 1H, J = 15.7, 7.8, 7.8 Hz), 1.82–1.76 (m, 1H), 1.67–1.63 (m, 1H), 1.49–1.40 (m, 1H), 1.24–1.15 (m, 1H); ¹³C NMR (CDCl₃, 400MHz) δ 171.5, 136.1, 124.6, 85.1, 57.8, 39.6, 35.9, 32.7, 29.6, 28.9; HRMS Calcd. for C₁₀H₁₇NO₂ 183.1259, found 183.1263.

The coupling constants between two olefinic protons were determined by decoupling studies.

The chair-chair-like transition state of the amide enolate is favored over the chair-boat-like transition state due to the repulsions between N-alkyl groups and the eclipsed allyic hydrogens of the chair-boat-like transition state.^1a Among the chair-chair-like transition states such as transition state A-D, transition states C and D are ruled out due to the preferred formation of Z-amide enolate^1a,11 and the aza-Claisen rearrangement proceeds through the energetically favorable transition state A to give E-olefin.

At present, ring expansions of other ring-sized 2-vinylazacycles by aza-Claisen rearrangement of amide enolate are not satisfactory or afford a trace amount of the desired products. Studies on ring expansion of 2-vinylaziridine, 2-vinylazetidine and 2-vinylpyrrolidine are in progress.