Proton magnetic resonance studies of compounds with bridgehead nitrogen atoms—XVIII Configurational and conformational studies with derivatives of hexahydroindolizin‐2(3H)‐one

Abstract

A series of substituted hexahydroindolizin-2(3H)-ones and some related ketones have been prepared by Dieckmann condensation of the appropriate diesters. Utilising spectral data, the configurations of these compounds have been assigned, and their conformations discussed with particular reference to the magnitude of the geminal coupling constant (Jgem) for the N-CH,-C(0) protons. With the exception of tetrahydropyrrolizin-2(3H)-one, all the ketones in this study are shown to exist in predominantly tuans-fused conformations. In the case of hexahydroindolizin-2(3H) one and hexahydro-2H-quinolizin-3 (4H)-one, the separate contributions to Jgem from the adjacent N lone pair and the carbonyl T electrons are discussed.PMR studies of compounds with bridgehead nitrogen atoms-XVIII 26 1 I. H202 2. AczO I. POCIS 3. NaOH 2. NaCN Na in dry toluene conc. HCI * Jsem is assumed negative.

Novel synthesis of 5,6,7,8-tetrahydroindolizines

“…2-Formyl-3-carboxy-1,2,3,4-tetrahydroisoquinoline (3) was prepared in 98% yield by the same procedure, starting from 3-carboxy-1,2,3,4-tetrahydroisoquinoline prepared by us according to the procedure of Julian et al10 (recrystallized from ethanol): mp 114-116 °C; NMR (CDClg) 9.60 (s, 1, -COOH), 8.60 (s, 1, -CHO), 7.30 (s, 4, aromatic protons), 5.25 (t, l,J = 6 Hz, proton on Cg), 4.90 (s, 2, protons on Cg), 3.45 (d, 2, J = 6 Hz, protons on C4); IR (KBr) 1715,1720 cm™1.…”

“…Caled for CgHi iNO-,: C, 47.76; H, 5.47; N, 6.96. Found: C, 47.65; , 5.60; N, 6.83. JV-Acetyl-2-piperidinecarboxylic Acid (5). The solution of 0.645 g (5 mmol) of 2-piperidinecarboxylic acid in 10 ml of acetic anhydride was stirred for 1 h. Water (10 ml) was added and the solution evaporated to dryness to give an oil.…”

“…A thin-walled glass tube containing 820 mg (5 mmol) of 11 was introduced in a bath at 240 °C until gas evolution ceased (5 min), leaving a brown oil. Chromatography on 60 g of silica gel using benzene as eluent afforded 520 mg (88%) of 12 as a colorless oil, which was homogeneous on TLC (benzene-ethyl acetate, 1:1): NMR (CDC13) 6.50 (d, 1, proton on Ci), 6.10 (t, 1, proton on C2), 5.80 (d, 1, proton on C3), 3.95 (broad t, 2, protons on Cg), 2.80 (broad t, 2, protons on Cg), 1.85 (m, 4, protons on Cg and C7). This compound was not stable enough to be analyzed.…”

Stereochemistry, conformational analysis, and transannular cyclizations of nine-membered ring azaolefins

“…Cahill and Crabb used NMR to determine the stereochemistry of substituted indolizinones. 26 The chemical shifts of the axial and equatorial protons adjacent to the nitrogen atom may be used to assign structure. A comparison of their data (Table II) with the chemical shifts obtained from the spectra of 22 and 23 allows assignment of the stereochemistry of the cyclization.…”

“…In an attempt to learn more about the factors controlling the stereochemistry of the transannular cyclization, lactam 20a was reduced to the unsaturated amine 26 with lithium aluminum hydride. The NMR spectrum of amine 26 shows CQ"…”