1 -Phenylethyl tetrahydroisoquinolines

A third method is exemplified by the cyclization of N-oxide intermediate 162 to give isomers 163 and 164 they are analogs of couple 160/161 and can just like these be independently obtained from a 1-phenylethyl tetrahydroisoquinoline (80H(14)817). 

The synthesis of solefinacin (2) as shown in Scheme 14.7 [27] starts with 1-substi-tuted 1,2,3,4-tetrahydroisoquinoline (S)-30 which was synthesized from the corresponding N-(2-phenylethyl)carboxamide 29 using a Bischler-Napieralski synthesis. A resolution afforded desired enantiomer (S)-30, which was reacted with ethyl chloro forma te/potas slum carbonate to afford the carbamate. 

Condensation of two phenylethyl units derived independently from the same or different aromatic amino acid(s) leads to a variety of benzyl-tetrahydroisoquinolines, which, with additional structural modifications, produce a diverse range of alkaloids. (5)-Reticuline occurring in several plant species of Annonaceae is an important benzyl-tetrahydroisoquinoline alkaloid that acts as a precursor to several pharmacologically active... 

The condensation of dopamine (4) with phenylethyl units and subsequent cyclization result in the formation of benzyltetrahydroisoquinoline alkaloids. These initial reaction steps are identical to those discussed for the formation of simple tetrahydroisoquinoline alkaloids. However, the additional aromatic ring allows further modification, and a variety of structurally diverse classes of alkaloids are obtained via different aryl-aryl coupling reactions. Among others, protoberberine alkaloids, porphine alkaloids, and the most important class of opium alkaloids can be summarized as modified benzyltetrahydroisoquinoline alkaloids. 

The first method using the j-BuLi-sparteine aggregate was successfully applied to the asymmetric protonation of 2-(l-phenylethyl)pyridine 5 to afford (S)-5 in good yield with 50% ee. The 4-aryl-tetrahydroisoquinoline backbone 6, which is of considerable interest because of its presence in several natural or bioactive products such as sertraline or nomifensine, was obtained in good yield with 88% ee. Although the backbone of bioactive compounds was synthesized in an asymmetric fashion, the total synthesis of the corresponding drugs or natural products has not yet been achieved to date. 

Martinez, E., Estevez, J.J.C., Estevez, R.J.J., and Castedo, L., PhotochemicaUy induced cyclization of N-[2-(o-styryl) phenylethyl]acetamides and 5-styryl-l-methyl-1,2,3,4-tetrahydroisoquinolines new total syntheses of l-methyl-l,2,3,4-tetrahydronaphtho[2,l-f]isoquinolines. Tetrahedron, 57, 1981, 2001. 

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