Tetrahydroisoquinolines, asymmetric hydrogenation

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. 

The optically active isoquinoline derivative 30 was prepared by asymmetric hydrogenation of the l-benzylidene-l,2,3,4-tetrahydroisoquinoline 29 catalysed by 27, and optically pure tetrahydropapaverine (31) is synthesized by this method [28]. 

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... 

Scheme 6.6 Synthesis of 1,2 dimethyl 1,2,3,4 tetrahydroisoquinoline via iridium catalyzed asymmetric hydrogenation.

Scheme 9.19 Asymmetric hydrogenation of N acetyl 1 methylene 1,2,3,4 tetrahydroisoquinoline.

The asymmetric hydrogenation of 1-alkyl 3,4-dihydroisoquinolines catalyzed by Ir/(5, i ,i )-17b was developed, providing chiral 1 -alkyl tetrahydroisoquinolines with high yields (88-96%) and good to excellent enantioselectivities (85-99% ee) (Scheme 26) [84]. 

Two molecules with comparable geometry in an asymmetric unit were found for 3,4-bis(4-fluorophenyl)-l,2,5-oxadiazole 2-oxide. The bond length of the dipolar N-O bond is 1.107 (7) A <2006AXEo4827>. In the molecule of 5-(6,7-dimethoxy-l,2,3,4-tetrahydroisoquinolin-2-yl)-4-phenyl-l,2,5-oxadiazole Ar-oxide, the six-membered heterocyclic ring has a flattened boat form. Intermolecular C-H- O hydrogen bonds link the molecules into dimers, which may be effective in the stabilization of the crystal structure <2006AXEo3130>. 

Enantioselective hydrogenation of certain a- and 3-(acylamino)acrylic acids or esters in alcohols under 1-4 atm H2 affords the protected a- and 3-amino acids, respectively (eqs eq 3 and eq 4). Reaction of N-acylated 1-alkylidene-1,2,3,4-tetrahydroisoquinolines provides the IR- or 15-alkylated products. This method allows a general asymmetric synthesis of isoquinoline alkaloids (eq 5). ... 

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%. 

DL-Dimethylcoclaurine was synthesized by the Bischler-Napieralski method starting with homoveratrylamine and p-methox3q)henylacetyl chloride. The 3,4-dihydroisoquinoline derivative first obtained was hydrogenated in the presence of palladium. The necessary comparison with material from the optically active alkaloid was achieved by subjecting the synthetic dimethylcoclaurine to exhaustive methylation, which robs Ci of the tetrahydroisoquinoline system of its asymmetric character. The meth-... 

The high performance of 64 compared to Hantzsch ester 39 was demonstrated by Akiyama and coworkers in the asymmetric transfer hydrogenation of trifluor-omethylacetophenone derivatives (Scheme 11.17a) [31]. Benzothiazoline 64c afforded 68 in 89% yield with 96% ee. In contrast, a significant reduction of reactivity and enantioselectivity was observed when 39 was used (4% yield, 45% ee). Enders and coworkers also reported the superiority of benzothiazoline over Hantzsch ester in a symmetric synthesis of tetrahydroisoquinolines via the reductive amination/aza-Michael addition sequence (Scheme 11.17b) [32]. Benzothiazoline 64d had a beneficial effect on both chemical yield and selectivity (98% yield,... 

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... 

In 2005-2007, Drabowicz et al. reported on the enantio-selective total syntheses of some tetrahydroisoquinoline and tetrahydro-(3-carboline alkaloids (Scheme 30.44) (/ )-(-l-)-crispine A, (R)-(- -)-octahydroindolo[2,3-a]quinolizi-dine, (R)-(- -)-harmicine, and (7 )-(- -)-desbromoarboresci-dine A, employing the asymmetric transfer hydrogenation... 

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