DIASTEREOSELECTIVE AND REGIOSELECTIVE INTRAMOLECULAR HECK REACTION OFALPHA-AMINO ALCOHOL DERIVATIVES FOR THE SYNTHESIS OF ENANTIOMERICALLYPURE ISOQUINOLINES AND BENZAZEPINES AT AMBIENT AND HIGH-PRESSURE

Alkylation and acylation of the alkenes 9b, c and 10a, b, which are ea sily prepared from the corresponding alpha-amino alcohols, with 2-halo benzyl and 2-halobenzoyl halides respectively, gives 11-15. These comp ounds cyclize with excellent diastereo- and regioselectivity to the en antiomerically pure N-heterocycles 18-20 in an intramolecular Heck rea ction using 5 mol-% of Pd(OAc)(2) in the presence of PPh3, TPAB and KO Ac. Under the same conditions substrate 17 leads to the enantiomerical ly pure benzazepine 24. The reaction of the bromoarene derivatives 14- 15 must be performed under high pressure to give good results.