Azabrendanes. III. Synthesis of stereoisomeric exo‐ and endo‐5‐acylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and their reduction by lithium aluminum hydride

Abstract

A number of stereoisomeric N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethylbicyclo[2.2.1]hept‐2‐enes have been synthesized from bicyclo[2.2.1]hept‐2‐en‐exo(endo)‐5‐carbonitrile via reduction of the latter by lithium aluminum hydride and subsequent reactions of the resulting amines with aryl(alkyl, cycloalkyl)carbonyl chlorides and anhydrides. The direction of reaction of amides with peroxy acids does not depend on orientation of substituents in the bicyclic fragment: that is, for both exo‐ and endo‐isomers the epoxidations are completed by the formation of N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1] heptanes. The reduction of stereoisomeric epoxides by lithium aluminium hydride proceeds in different directions; that is, isomers with an exo‐oriented amido group form the substituted exo‐5‐alkylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and the reactions of epoxides of endo‐amides are accompanied by intramolecular cyclization and completed by the formation of N‐[aryl(alkyl, cycloalkyl)]‐exo‐2‐hydroxy‐4‐azatricyclo[4.2.1.03,7]nonanes. The structures and stereochemical homogenity of the products have been confirmed by the analysis of 1H and 13C NMR spectra, correlation spectroscopy, and nuclear Overhauser enhancement spectroscopy experiments. We discuss the behavior of epoxides and provide an analysis of the coefficients of the atomic orbitals in the molecular orbital–linear combination of atomic orbitals equation (AM1 method). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:119–130, 2001

Azabrendanes V. Synthesis and reactions of stereoisomeric exo- and endo-5-aminomethylbicyclo[2.2.1]hept-2-ene-based ureas

“…The 1 H and 13 C NMR spectra of exo-and endo-ureas were found to be very similar to those of sulfonamides [15,16,[18][19][20], carboxamides [21,22], and previously studied ureas of the norbornene series [12]. The signals were assigned by comparison with the 1 H NMR spectrum of initial amine 2a, for which a two-dimensional (COSY) spectrum was obtained.…”

“…In particular, arylsulfonamides 17a, give heterocyclization products on reaction with peroxyacids (N-(arylsulfonyl)-exo-2-hydroxy-4-azatricyclo[4.2.1.0] nonanes [3,7]) 18]. Furthermore, amides 17b react with peroxy acids to produce alternative products, namely endo-5-acylaminomethyl-exo-2,3-epoxybicyclo[2.2.1] heptanes (Scheme 5) [21].…”

“…The IR spectra are not substantially informative for structural confirmation of compounds (18)(19)(20)(21)(22)(23)(24)(25)(26) as both characteristic absorption bands (860-850 cm -1 , ν C-O, 3040-3020 cm -1 , ν C-H of the epoxynorbornane fragment) occupy the same regions as the benzenering bonds vibrations. However, the signals of the H 2 and H 3 protons of the epoxide cycle, in the 2.9-3.1 ppm region of the 1 H NMR spectra, are characteristic of epoxy compounds [23,24,29,30].…”

Synthesis and Reactivity of Amines Containing Several Cage-like Fragments

“…,,,G Crystalline amides IVaIVf were obtained by reactions of acyl chlorides IIaIIc with amines IIIa IIId in the presence of triethylamine by procedure [7]. The preparation of amide IVb was formerly described in [10].…”

Synthesis and aminolysis of N-(4-chlorophenyl)- and N-(2,4-dichlorophenylsulfonyl)-N-(glycidyl)bicyclo-[2.2.1]hept-5-en-endo-ylmethylamines

“…For comparison substituted benzamides IVc and IVd were synthesized and subjected to the reaction with epichlorohydrin under the same conditions [12]. Both compounds were passive in this reaction.…”