Synthesis and conformational analysis of 2-amino-1,2,3,4-tetrahydro-1-naphthalenols

Abstract

Synthesis and conformational analysis of several cis- and (or) trans-2-amino-1,2,3,4-tetrahydro-1-naphthalenols are described. Introduction of the nitrogen atom at the C(2) position of the starting tetralones 3 has been carried out through nitrosation followed by reduction of the intermediate hydroxyimino tetralone and (or) Neber rearrangement of the tosyloxy derivatives 7a–e. Stereoselective reduction of the C(1) carbonyl group of acetamidotetralones 5a–e or aminotetralones 8a–e afforded the corresponding acetamido or aminotetralols, respectively, of OH/N trans stereochemistry whereas an opposite stereoselectivity was observed in reduction of C(8)-OCH3 derivatives 5f and 8f under the same experimental conditions. Finally, acid hydrolysis of trans-acetamidotetralols led to cis-aminoalcohols in high yields. Conformational analysis has been carried out by 1H nuclear magnetic resonance techniques and MM2 theoretical calculations. All cis derivatives showed a major conformation in which the C(1)-OH group adopts a pseudoaxial disposition. On the other hand, trans-aminoalcohols in CDCl3 showed a major or exclusive OH/N trans-dipseudoequatorial conformation in which stabilization by intramolecular OH/N hydrogen bonding is possible. The only exception was found in C(8)-OCH3trans-aminoalcohols in DMSO-d6 solution, which showed a major OH/N trans-diaxial conformation.