660861-63-2Relevant academic research and scientific papers
Asymmetric synthesis of 1-substituted 1,2,3,4-tetra-hydroisoquinolines by asymmetric electrophilic α-amidoalkylation reactions
Ludwig, Matthias,Polborn,Wanner, Klaus T.
, p. 299 - 326 (2007/10/03)
An efficient method for the asymmetric synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via chiral N-acyliminium ions is presented. The N-acyl-1,2-dihydroisoquinolines (8) and (9) underwent smooth oxidation reactions with Ph3C+BF4- to give the chiral N-acylisoquinolinium ions (10) and (13), respectively. Stereoselective addition of organomagnesium and organozinc compounds to intermediates (10) and (13) provided the corresponding 1-substituted N-acyl-1,2-dihydroisoquinolines (11/12) and (14/15) in good yields. The diastereoselectivity of these reactions appeared to be dependent on the structure of the N-acyliminium ion intermediates (10) and (13) and on the nature of the trapping reagent with the zinc reagents in general leading to markedly improved stereoselectivities. Pure diastereomers were obtained by preparative HPLC and readily transformed into enantiopure 1-substituted 1,2,3,4-tetrahydroisoquinolines by catalytic hydrogenation and reductive removal of the chiral auxiliary.
