1 -Aryl-1,2,3,4-tetrahydroisoquinoline

Oxidative coupling of aryl tetrahydroisoquinolines. This reagent is superior to thallium(III) trifluoroacetate or vanadium oxyfluoride for nonphenolic oxidative coupling of substrates such as 2 to provide aporphines and homoaporphines (3). 

Li and Li have reported Cu(I)-catalyzed enantioselective alkynylation of prochiral sp C-H bonds adjacent to a nitrogen atom [58]. In this approach, a combination of CuOTf and pybox (197) in the presence of t-BuOOH results in coupling of N-aryl tetrahydroisoquinolines (209) with terminal alkynes (Scheme 17.42). The desired coupling products (211) were generally isolated in moderate to good yields with moderate enantioselectivities. Although it is not clear if the catalytically active Cu(I) species acts as a Lewis acid in this protocol, the chemistry is, nonetheless, worthy of mention. 

On the other hand, novel photosensitizers were synthesized and applied in the visible-light-mediated oxidative hmctionalization of A-Aryl tetrahydroisoquinolines. A promising organogold complex was developed for aerobic oxidative C (sp )-H functionalization of secondary and tertiary amines (Scheme 3.5) [31]. Another feature of this novel gold complex was imderUned by production of... 

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. 

N-aryl-tetrahydroisoquinolines were the subject of a gold-catalyzed oxidative coupling with diarylphosphine oxides to provide the corresponding phosphinoyl derivatives (Scheme 26). ... 

A novel asymmetric synthesis of l-aryl-l,2,3,4-tetrahydroisoquinolines is based on the addition of chiral phenylacetaldehyde acetals to acyUmines <95TL(36)8003>. 

A short synthesis of 6-cyano-l,2,3,4-tetrahydroisoquinoline used an improved method of aryl triflate cyanation that employs zincfll) cyanide as the cyanide source <95SC(25)3255>. 

R3R4NH = r)-C8H17NH2, BunNHMe, PhNHMe, Ph2NH, morpholine, or piperidine For 970 R1R2NH = PhNHMe, Ph2NH, morpholine, or 1,2,3,4-tetrahydroisoquinoline R5 = aryl or heteroaryl... 

Peroxidase and laccase enzymes were used to catalyze the decarboxylation of various tetrahydroisoquinoline-1-carboxylic acids to give high yields of the corresponding 3,4-dihydroisoquinolines (204). Compounds such as 125 (Scheme 29) are derived from Pictet-Spengler ring closure via a-keto acid and aryl amine condensation and are of biogenetic importance. The possible relevance of iso-... 

Anodic regioselective fluorination of a-phenylsulphenylated ethyl acetates, 1-naphthalene and 2-pyridine derivatives [80], l-aryl-3-(phenylthio)oxindoles and 2-substituted-3-oxo-4-(phenylthio)-l, 2, 3,4-tetrahydroisoquinolines [81], 2-benzo-thiazolyl and 5-chloro-2-benzothiazolyl sulfides [82], a-(phenylsulfenyl)lactams [83], as well as various heterocycles such as thiolanones, oxathiolanones, dithi-olanones, 3Fl-l,4-benzoxathian-2-ones [84] in Et3N-3HF or Etr NF- HF [n = 3,4), has been reported. 

In 2004, Taylor and Jacobsen suggested a procedure for the enantioselective acetyl-Pictet-Spengler reaction, that is the cyclization of electron-rich aryl or heteroaryl groups onto N-acyliminium ion enabling access to substituted tetrahydro-P-carbolines and tetrahydroisoquinolines that are core structure elements in natural and synthetic organic compounds [202, 203]. Screening various thiourea catalyst candidates such as 47 in the formation of model product Np-acetyl-... 

The anodic oxidation of 4-(3,4-dimethoxybenzyl)6,7-dimethoxy-2-methyl-l,2,3,4-tetrahydroisoquinoline does not afford the intramolecularly aryl-aryl coupled prod-... 

The Heck reaction continues to be a popular route to tetrahydroisoquinolines. Intramolecular reaction of 2-iodo-Ar-phenylbcnzamidc with methyl acrylate yields l-oxotetrahydroisoquinoline-3-carboxylic acids <1997J(P1)2577>, while the intramolecular reaction of an aryl bromide with an enaminone also forms the tetrahydroisoquinoline ring <1997TL2829>. 

The Pictet-Spengler reaction, the cyclization of an electron-rich aryl or heteroaryl group onto an imine electrophile, is the established method for the synthesis of tetrahydroisoquinoline and tetrahydro-/ -carboline ring systems. Catalytic asymmetric approaches to these synthetically important structures are mostly restricted to asymmetric hydrogenations of cyclic imines [77, 78]. In a noteworthy... 

The aporphine skeleton 21 can be synthesized through the SrnI mechanism by exploiting the bidentate behavior of phenoxide ions that allows one to obtain the ortho-arylation in good yields, as shown in Scheme 10.43 [59]. Tetrahydroisoquinoline precursors that contained nitrogen-based EWGs (i.e., amides, sulfonamides,... 

The synthesis of 1-substituted tetrahydroisoquinolines using an intramolecular Pd-catalyzed a-enolate arylation was described. Treatment of a-amino esters such as 71 and 73 with LiOr-Bu, Pd2(dba)3 and ligand 75 or 76 afforded the corresponding isoquinolines 72 and 74. Investigations to develop an asymmetric version of this reaction were reported to be ongoing <02JOC465>. 

Copper diacetate-catalyzed arylation of heterocyclic amines such as piperidine, tetrahydroisoquinoline 76101 or 1,6-diazacyclodecane 77104 by aryllead triacetates gave only modest to moderately good yields of the iV-aryl derivatives (Equation (76) and (77)). The reactions with aliphatic amines lead to particularly poor yields of the derived anilines101 (Equations (78) and (79)), although the arylation of cyclooctylamine 78 with an electron-rich aryllead triacetate afforded the aniline derivative 79 in a moderately good yield (52%) (Equation (80)).1O5 1O5a... 

A practical ligand-free palladium-catalyzed intramolecular reductive Heck cyclization was developed by Liu et al. <07TL2307>. The authors found that water was an essential component of the reaction mixture. Using a series of aryl halide intermediates this cyclization resulted in the desired 1,2,3,4-tetrahydroisoquinolines in high yields. Cook and co-workers found that InCU was an efficient catalyst for an intramolecular Friedel-Crafts cyclization of Ar-(4-bromobut-2-enyl)-A-(bcnzyl)-4-methylbcnzcncsulfonamidc to form the desired 3-substituted tetrahydroisoquinolines <07OL1311>. 

The aromatic, tetramethoxy-substituted, tetrahydroisoquinoline alkaloid weberine has been isolated recently from extracts of the Mexican cactus Pachycereus weberi (38). The rare occurrence of four adjacent methoxy groups on an aryl moiety prompted the synthesis and examination by crystal-structure analyses of analogs and derivatives with four and five adjacent methoxy groups on the phenyl ring. In contrast to the problem with... 

Glushkov VA, Arapov KA, Minova ON et al (2006) Synthesis and anticoagulant activity of l-aryl derivatives of tetrahydroisoquinolines. Pharm Chem J 40 363-366... 

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