Synthesis of Chiral Bicyclic Bis‐lactam Components for the controlled self‐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‐dimethoxybenzene; 10 ) allowed the introduction of two glycine units at the 4,5‐positions of the veratrole ring to give 18c ( Schemes 3 and 4 ); (2) in order to circumvent the hydrolysis of 4‐methoxybenzoyl protective groups which proved to be unfeasible, these groups were transformed into 4‐methoxybenzyl groups through a sequence involving thiocarbonylation followed by reduction ( Scheme 5 ). Thereafter, the double intramolecular cyclization of the resulting diamino diester 22c proceeded easily 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) and of 3 (X = OCOR). Cleavage of the 4‐alkuxybenzyl groups was achieved by ceric 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 ( Schemes 5 and 6).