Studies Directed Towards the Total Synthesis of Anticapsin and Related Compounds. II. Diels-Alder Addition of N-Acyl Dehydroalanine Esters to 1-Trimethylsilyloxycyclohexa-1,3-diene

Abstract

In a study directed towards the total synthesis of anticapsin and related compounds, the Diels-Alder addition of N- acyl dehydroalanine esters (15)-(19) to 1-trimethylsilyloxycyclohexa-1,3-diene (6) was investigated. The cycloadditions were highly regioselective and provided 2-amino-1-trimethylsilyloxybicyclo[2.2.2]oct-5-ene-2-carboxylate derivatives (23)-(28) in moderate to good yields. A modest stereoselectivity was observed in the reactions, with the endo -adducts (23a)-(28a) favoured over the exo-adducts (23b)-(28b) by a ratio of 1.5-3.3:1. Adducts (23a) and (24a) underwent stereoselective epoxidation to the less hindered face of the olefinic double bond. Reaction of the resultant epoxides (31) and (32) with TiCl₄ afforded carbolactones (34) and (35), thereby allowing the assignment of endo stereochemistry to adducts (23a) and (24a). The stereochemistry of the remaining adducts was assigned by the use of ¹H n.m.r. spectroscopy.