Tetrahydroisoquinolines catalytic hydrogenation

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>. 

Enantioselective catalytic hydrogenation. The ruthenium(II) complexes of (R)- and (S)-l, bearing a chiral BINAP ligand, catalyze asymmetric hydrogenation of N-acyl-l-alkylidenetetrahydroisoquinolines to give (1R)- or (lS)-tetrahydroiso-quinolines in 95-100% ee.1 Thus the (Z)-enamide (2), prepared by acylation of 3,4-dihydropapaverine, is hydrogenated in the presence of (R)-l to (1R)-tetrahydroisoquinolines (3). The enantiomeric (lS)-3 is obtained on use of (S)-l as catalyst. 

IsoquinoUne was converted to 1,2,3,4-tetrahydroisoquinoline in 89% yield by reduction with sodium in liquid ammonia and ethanol [473], and to a mixture of 70-80% cis- and 10% trans-decahydroisoquinoline by catalytic hydrogenation over platinum oxide in acetic and sulfuric acid [474]. Without sulfuric acid the hydrogenation stopped at the tetrahydro stage. Catalytic hydrogenation of isoquinoline and its derivatives is the topic of a review in Advances in Catalysis [439]. 

Isoquinoline itself hydrogenates less readily than does quinoline. Studies of the catalytic hydrogenation of isoquinoline over Raney nickel have shown that the reaction proceeds consecutively via 1,2,3,4-tetrahydroisoquinoline (161), 5,6,7,8-tetrahydroisoquinoline (162) and c/j-decahydroisoquinoline (163) to rrawj-decahydroisoquinoline (164). Acridine undergoes similar hydrogenative isomerizations with supported Pd. Both cis- and rrarzj-l,2,3,4,4a,9,9a,10-octahydroacridines were formed at 150 °C and only three (165, 166 and 167) of the six possible stereoisomers of perhydroacridine were found, with (165) and (166) predominant. Alumina was preferred to carbon as a support. 

As noted previously, 7,8-dioxygenated tetrahydroisoquinoline alkaloids may be synthesized by a modified Pomeranz-Fritsch reaction. Application of the Bischler-Napieralski or Pictet-Spengler reactions usually leads to cyclization in an undesired sense, e.g., in (29 X = H) to the 2- rather than to the 6-position. This can be avoided by blocking the 2-position with a bromine function. Thus homopetaline (30 R = CH2CH2C6H4-p-OMe) has been synthesized from (29 R = CH2CH2C6H4-p-OMe) in four steps, the bromo-substituent being removed by catalytic hydrogenation over Raney nickel in the final step.41... 

The catalytic and chemical reduction of the 3-methyl-3,4-dihydrobenzyliso-quinoline (56) has been studied (Scheme 2)3 Catalytic hydrogenation of (56) in acidic ethanol gave the ds-l,2,3,4-tetrahydroisoquinoline, c/5-(57), as the sole product whereas reduction with NaBH4 produced a 25 1 mixture in favour of trans- Sl). The same report also describes the Bischler-Napieralski cyciization of N-2-[l-(2,5-dimethoxy-4-methylphenyl)propyl]-3,4-dimethoxyphenylaceta-mide to give, in addition to the normal product (56), a number of neutral compounds which shed some light on the mechanism of this reaction." One of... 

A recent patent application describes, in part, a multikilogram scale synthesis of quinapril (Jennings, 2004). The carboxyanhydride of 26 is prepared by treatment with phosgene (Scheme 10.8) (Youssefyeh et al., 1987). This is next coupled with tetrahydroisoquinoline subunit 27 in the presence of catalytic acid. Without isolation of the resultant quinapril t-butyl ester, the reaction solution is treated with acetic acid and anhydrous hydrogen chloride to deprotect the ester. Amorphous quinapril hydrochloride is obtained via treatment with acetonitrile. 

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... 

Lee, Yun-Choi, et al. described the synthesis of optically active tetrahydroisoquinoline alkaloids, (R)-(+)-higen-amine, (5)-(—)-higenamine, and their optically active 1-naphthylmethyl analogs, via enantioselective hydrogenation of the dihydroisoquinoline intermediates 212 as a key step. Catalytic asymmetric reduction of imine was accomplished with Noyori s catalyst RuCl[(5, 5)-TsDPEN... 

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