Tetrahydroisoqui nolines

Although secondary amines are common building blocks in the pharmaceutical industry, there are few examples of the resolution of secondary amines in the hterature. Preparation of substituted phenyl allylcarbonates allowed the resolution of 1-methyl-tetrahydroisoqui-noline (1-MTQ) to proceed with excellent enantioselectivity and recovery (Figure 3.1). 

Yi Hsiao, General Asymmetric Synthesis of 1-Substituted Tetrahydroisoqui-nolines via Enantioselective Hydrogenation, unpublished M.S. dissertation, Nagoya University, Nagoya, 1988. 

Quinoline and isoquinoline react in an analogous manner with benzene in conjugated superacids (HCI-AICI3, HBr-AlBr3) to yield predominantly cis-5,1-diphenyl-5,6,7,8-tetrahydroquinoline and <7,v-6,8-diphenyl-5,6,7,8-tetrahydroisoqui-noline, respectively (75-94% yield).297 The regioselectivity observed corresponds to the most stable dicationic intermediates 73 and 74. Unsaturated imides298 exhibit similar behavior in triflic acid (Scheme 5.33). 

The reaction of Ru-binap complexes applied to tetrahydroisoquinoline compounds that have an exocyclic enamide double bond produces 1-substituted tetrahydroisoqui-nolines nearly quantitatively and with optical yield close to 100%. This procedure served in industrial production of benzomorphans, morphinans, and various isoquinoline alkaloids ... 

Recently, Maruoka and coworkers reported the exploitation of C,iV-cyclic azomethine imines in highly enantiose-lective asymmetric 1,3-dipolar cycloadditions catalyzed by a titanium-binaphtholate (BINOLate) complex, which offers access to pharmaceutically attractive chiral tetrahydroisoqui-nolines and piperidines with a 1,3-diamine unit [13,14]. Not... 

Anionic Cyclodextrins Anionic CDs are often carbox-yalkylated, sulfoalkylated, sulfated, and phosphorylated. The most commonly used derivatives are S-p-CD, SBE-(3-CD, and sulfoethyl ether-p-CD. " Some examples from the literature are given below. Wu et al." describe a CE method with electrospray ionization-tandem MS (ESI-MS/MS) for the quantification of 1,2,3,4-tetrahydroisoqui-noline derivatives (TlQs). They performed the enantioseparation in a 50-p,m i.d., 75-cm-long fused-silica capillary filled with a 20-mM acetic acid/ammonium acetate buffer with pH 5.5 containing 1.0-mM S- -CD. The TIQ derivatives, i.e., salsolinol, 1-benzyl-TIQ, and A/-methyl salsoli-nol, could be baseline separated with resolutions ranging from 3 (for salsolinol) to 4.5 (for 1-benzyl-TIQ). 

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