1,2,3,4-Tetrahydro isoquinoline, synthesis

Pictet-Spengler tetrahydro-isoquinoline synthesis Synthesis of tetrahydroisoquinolines and isoquinolines from B-arylethylamines. 348... 

An asymmetric synthesis of 1-aryltetrahydroisoquinolines 79 from chiral amide 78 was reported <96TL(37)4369>. Optically active cis- or rranj-1,3-disubstituted tetrahydro-isoquinolines can he prepared hy a modification of this procedure. 

A general synthesis of 8-oxo-protoberberines, e.g. (93), and their analogues has been developed, using the photolysis of N-benzoyl-l-methylene-tetrahydro-isoquinolines (92). In this way, lactams of structures (94)—(97) have been prepared. " ... 

Total synthesis of calycotomine, 1-hydroxymethyl-substituted tetrahydro-isoquinoline 05S339. 

The Pictet-Spengler reaction is a modification of the Bischler-Napieralski reaction. It is probably the most used method for the synthesis of 1,2,3,4-tetrahydro isoquinoline core. Therefore, phenylethyl amines are used in reaction with carbonyl compounds in the presence of protic or Lewis acids. 

Microwave synthesis In an argon-filled microwave reaction vessel, 7-phenyl-5,6,7,8-tetrahydro-isoquinoline (56, 0.25 g, 1.2 mmol) was dissolved in DMA (6.3 mL). Under an argon atmosphere, sodium amide pellets (0.16 g, 4.1 mmol) were crushed and added to the reaction mixture. The vessel was closed and heated to 180 °C in a microwave oven (Entry s optimizer power input 20-25 W pressure 7.1-8.5 bar) for 12 h. 

Corey, E.J. and Gin, D.Y. (1996) A convergent enantioselective synthesis of the tetrahydro-isoquinoline unit in the spiro ring of ecteinascidin 743, Tetrahedron Lett., 37, 7163-7166. 

Benz[g]isoquinoline, l,4-ethano-l,2,3,4-tetrahydro-nomenclature, 1, 20 Benz[g]isoquinolinequinone synthesis... 

Pomerantz synthesis, 2, 429 synthesis, 2, 413 from benzynes, 2, 432 Isoquinoline, 1,2,3,4-tetrahydro-mass spectrometry... 

Isoquinoline-l,3-dione, 5,6,7,8-tetrahydro-synthesis, 2, 408 Isoquinoline hydrobromide bromination, 2, 49 Isoquinolines adducts... 

Depending on the reaction temperature and reaction time, tetrahydroisoquinoline 357 afforded different mixtures of 1,2,3,4,11,11 a-hcxahydro-6//-pyrazino[ 1,2-3]isoquinolines 358-361 and tetracyclic compound 362 (Scheme 30) <2005JA16796>. Each of the individual diastereoisomers 358-361 could be transformed into the compound 362. z7r-3//,4a//-3-Phcnylpcrhydropyra/ino[ 1,2-7]isoquinoline-l,4-dione was prepared via automated parallel solid-phase synthesis on Kaiser oxime resin <1998BML2369>. l,2,3,5,6,7-Hexahydropyrido[l,2,3-r/f ]quinoxaline-2,5-dionc was obtained by catalytic hydrogenation of ethyl 3-(2-oxo-l,2,3,4-tetrahydro-5-quinoxalinyl)acrylate in the presence of TsOH over 5% Pd/C catalyst under 40 psi of hydrogen <1996JME4654>. 

The mechanism of palladium-catalyzed intramolecular cyclization of o-bromo(aminoalkyl)benzenes has been discussed earlier (see Scheme 50 in Section IV,A,4). An example illustrating the use of this approach for the synthesis of 2,3,4,5-tetrahydro-l//-2-benzazepin-l-ones is given in Scheme 17386 and examples indicating the synthesis of isoquinoline derivatives are given earlier (see Scheme 146 in Section V,A,4). 

Completion of the synthesis of quinapril involves amide bond formation between 26 and a tetrahydroisoquinoline fragment. Two complementary protected 1,2,3,4-tetrahydro-3-isoquinoline subunits 27 and 28, each available in a single step from commercially available (6)-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, were utilized (Scheme 10.7). Coupling with 26 using DCC and HOBt in dichloromethane afforded the penultimate compounds 29 and 30 as maleate salts. Cleavage of the f-butyl ester of 29 and treatment with HCl provided quinapril. Alternatively, hydrogenation of 30 under standard conditions cleanly removed the benzyl ester, and quinapril (3) was isolated after formation of the hydrochloride salt. 

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