1,2,3,4-tetrahydroisoquinoline 1 - arene

The Noyori asymmetric transfer hydrogenation was utilized in the synthesis of the chiral 1,2,3,4-tetrahydroisoquinolines by R.A. Sheldon et al. These compounds are important intermediates in the Rice and Beyerman routes to morphine. The "Rice imine" was exposed to a series of chiral Ru " complexes, which was prepared from r -arene-Ru " chloride dimeric complexes and A/-sulfonated 1,2-diphenylethylenediamines along with the azeotropic mixture of HCOOH/NEts. With the best catalyst the desired tetrahydroisoquinoline was isolated in 73% yield and the enantiomeric excess was 99%. 

Similarly, chromium-complexed benzylic cations are also stabilized and organic reactions based on the benzylic cation species have been developed. For example, planar chiral o-substituted benzaldehyde dimethylacetal chromium complexes 4 were treated with 3-buten-l-ol in the presence of TiCl4 to give tet-rahydropyran derivatives with high diastereoselectivity (Eq. 5) [5]. The chromium-complexed benzylic oxonium ion 6 would be also generated and subsequent intramolecular cyclization afforded the cyclization product 7. Furthermore, the chromium-complexed benzyl alcohol derivative having electron-rich arene ring at the side chain produced tetrahydroisoquinoline skeleton by treatment with Lewis acid with stereochemical retention at the benzylic position (Eq. 6) [6]. 

The Pictet-Spengler (PS) reaction is an important method to construct biologically important tetrahydroisoquinoline and tetrahydro- 3-carboline skeletons. Since it represents the intramolecular Friedel-Crafts cyclization of arenes and imines, we cover the asymmetric organocatalytic PS reaction in this chapter [61]. 

Chiral 1-alkyl-substituted tetrahydroisoquinolines have been obtained in excellent yield and with ee up to 95%, using A-sulfonylated diamines containing ruthenium arene complexes as catalysts (Fig. 80) (341). 

Focusing on benzene-like arenes, Shu-Li You described an efficient intramolecular Ir-catalyzed nucleophilic allylic substitution of phenols, addressing meto-substituted hydroxyarene with allylic carbonate side chains 31 as acyclic precursors [20]. A range of tetrahydroisoquinolines 33 was isolated in good yields (up to 90%) and ee up to 96% in the presence of chiral phosphoramidite ligand (5,5,5 )-32 (4mol%) and [IrCKCOD)] as the metal source (Scheme 5.10). The use of DMAP as an additive (200 mol%) in THF (rt to 50°C) allowed the regiochemical ortho aromatic C—H replacement (33 vs. 33 ) prevalently. 

Cyclization of iminium ions onto arenes were first described by Pictet and Spengler in 1911, with the formation of tetrahydroisoquinoline 152 (Equation 10) [125]. This versatile transformation has been widely used in the diastereoselective synthesis of polycyclic aromatic alkaloids of biological interest, in particular of tetrahydro-/5-carbolines 154 (Equation 11) [126]. A few selected examples that highlight stereoselective Pictet-Spengler reactions are discussed below [9, 103, 127]. 

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