Intramolecular Friedel-Crafts-type reactions involving N-acyliminium ions derived from glycine templates

Enantiomerically pure 4-substituted 2-aralkyl-2,4-dihydro-1H-pyrazino[2,1-b ]quinazoline-3,6-diones (lb-m) in which the alkyl chain is (CH2)(n), n = 1- 3, behave as glycine templates giving by treatment with [hydroxy(tosyloxy)i odo] benzene in ethyl acetate cis-1-tosyloxy derivatives, When these compou nds contain electron-rich aryl substituents with n = 2, they spontaneously cyclize through intramolecular Friedel-Crafts-type diastereoselective react ions to give penta- or hexacyclic compounds. Otherwise, they give by solvol ysis cis-1-alkoxy derivatives, which in a second step, may be cyclized in a cid if n = 2, 3. All these reactions must occur through N-acyliminium speci es in S(N)1-like mechanisms. 1-Alkoxy-2-arylmethyl derivatives are reluctan t to cyclize, giving trans-1-hydroxy compounds as the only isolated reactio n products.