SYNTHESIS OF CHIRAL BICYCLIC BIS-LACTAM COMPONENTS FOR THE CONTROLLEDSELF-ASSEMBLY OF HYDROGEN-BONDED ARRAYS

The chiral biyclic bis-lactams of structures 3 and 4 were synthesized from the key intermediate 2'b, the N,N'-bis(4-methoxybenzyl)derivative of 2(X = MeO) (Scheme 6). The synthesis of this intermediate involved two key steps: 1) a double condensation of glyoxylic acid/anisamide ( = oxoacetic acid/4-methoxybenzamide) adduct 11c with veratrole (1,2-di methoxybenzene; 10) allowed the introduction of two glycine units at t he 4,5-positions of the veratrole ring to give 18c (Schemes 3 and 4); 2) in order to circumvent the hydrolysis of 4-methoxybenzoyl protectiv e groups which proved to be unfeasible, these groups were transformed into 4-methoxybenzyl groups through a sequence involving thiocarbonyla tion followed by reduction (Scheme 5). Thereafter, the double intramol ecular cyclization of the resulting diamino diester 22c proceeded easi ly to afford 2'b, This intermediate may be transformed via the tetrol 2'g or the diol 2'h into the, N-protected derivatives of 2 (X = OR) an d of 3 (X = OCOR). Cleavage of the 4-alkoxybenzyl groups was achieved by eerie ammonium nitrate. However. when the aromatic ring bore ether functions (N-protected 2). this normal reaction was accompanied by the oxidative ring cleavage to give the diene-diester structure 4 (Scheme s 5 and 6).