Mechanistic studies on the catalytic asymmetric Mannich-type reaction with dihydroisoquinolines and development of oxidative Mannich-type reactions starting from tetrahydroisoquinolines

作者：Dubs Christian; Hamashima Yoshitaka; Sasamoto Naoki; Seidel Thomas M; Suzuki Shoko; Hashizume Daisuke; Sodeoka Mikiko^*

来源：Journal of Organic Chemistry, 2008, 73(15): 5859-5871.

DOI：10.1021/jo800800y

Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)(2)O, and cooperative action of the Pd(II) complex as an acid-base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via alpha-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.

• 出版日期2008-8-1