Synthesis and stereochemical analysis of 2-amino-1,2,3,4-tetrahydro-1,4-methanonaphthalene-2-carboxylic acid, a conformationally rigid phenylalanine derivative

Abstract

A rigid phenylalanine analogue, 2-amino-1,2,3,4-tetrahydro-1,4-methanonaphthalene-2-carboxylic acid (3) of unknown stereochemistry was obtained as the sole amino acid product from a Strecker reaction with 1,2,3,4-tetrahydro-1,4-methanonaphthalen-2-one (4). Compound (4) was initially treated with benzylamine and potassium cyanide to give 2-benzylamino-2-cyano-1,2,3,4-tetrahydro-1,4-methanonaphthalene (5), which was then converted into 2-benzylamino-2-carboxamido-1,2,3,4-tetrahydro-1,4-methanonaphthalene (6) by treatment with 70% sulphuric acid. N-Debenzylation of (6) by hydrogenolysis with 5% palladium-on-charcoal catalyst afforded 2-amino-2-carboxamido-1,2,3,4-tetrahydro-1,4-methanonaphthalene (7) which gave the acid (3) on heating in 10% sulphuric acid. A Stereochemical analysis of (3) by ¹H n.m.r., ¹³C n.m.r, and auto-correlated two-dimensional n.m.r. spectroscopy, determined the structure to be 2-endo-amino-1,2,3,4-tetrahydro-1,4-methanonaphthalene-2-exo-carboxylic acid (1a). Treatment of 1,2,3,4-tetrahydro-1,4-methanonaphthalene-2-spiro-5′-hydantoin (9)[obtained from a Bucherer reaction with (4)] with aqueous barium hydroxide also afforded (1a) as the only amino acid product.