1.2.3.4- Tetra hydroisoquinoline

This compound was prepared in the same manner as (R)-Tic, using benzyl (S)-1,2,3,4-tetra-hydroisoquinoline-3-carboxylate (S)-mandelic add salt (40A) as starting material yield of (S)-33 920 mg (81%) mp 322-327 °C. 

A second degradative approach was more informative, for the products obtained accounted for all thirty-seven carbon atoms of the alkaloid. Permanganate oxidation of 0,0-dimethylliensinine (LXIV) afforded p-methoxybenzoic acid, l-oxo-2-methyl-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline, and a compound (O-methylliensinic acid) which was found to have structure LXX, mainly by degradation to 4,5,5 -tri-carboxy-2,2 -dimethoxydiphenyl ether. Similarly the permanganate oxidation of 0,0-diethylliensinine (LXV) yielded p-ethoxybenzoic acid and the acid LXXI (0-ethylliensinic acid). The above data revealed the constitution of the alkaloid to be as indicated in formula LXIII. 

The alkaloid was synthesized by the Ullmann condensation of l-(3 -bromo - 4 - benzyloxybenzyl) - 2 - methyl - 6,7 - dimethoxy -1,2,3,4 - tetra-hydroisoquinoline (XXXIV) and l-(4 -benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline (IX) followed by removal of the benzyl groups (40). 

The addition of phosphorous acid to 3,4-dihydroisoquinoline gives 1,2,3,4-tetra-hydroisoquinoline-1-phosphonic acid (192), and that of diphenyl hydrogenphosphonate to 2/f-pyrroline yields the diphenyl ester of Pro (193). ... 

In 2007, Liu and co-workers reported a ligand-free palladium-catalyzed synthesis of heterocycles through reductive Heck cyclization. Five and six membered heterocycles, including indolines, 2,3-dihydrobenzofurans, chromans, isochromans, 1,2,3,4-tetrahydroquinolines, and 1,2,3,4-tetra-hydroisoquinolines, were produced in 70-99% yields under mild conditions (Scheme 2.34). Water was found to be essential for these reactions. This transformation was investigated further by Lamaty and co-workers in 2007. 3,3-Disubstituted-2,3-dihydrobenzofurans were prepared in good yields. 

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