Tetralone test

The use of such an oxazaborolidine system in a continuously operated membrane reactor was demonstrated by Kragl et /. 58] Various oxazaborolidine catalysts were prepared with polystyrene-based soluble supports. The catalysts were tested in a deadend setup (paragraph 4.2.1) for the reduction of ketones. These experiments showed higher ee s than batch experiments in which the ketone was added in one portion. The ee s vary from 84% for the reduction of propiophenone to up to >99% for the reduction of L-tetralone. The catalyst showed only a slight deactivation under the reaction conditions. The TTON could be increased from 10 for the monomeric system to 560 for the polymer-bound catalyst. 

The ether extract and the water layer may be tested for the presence of /3-tetralone or the bisulfite addition product by the tetralone blue test. 

Tetralone blue test. A few drops of the organic solvent layer or the aqueous phase is shaken in a test tube with 2 ml. of 95% ethanol, and 10 drops of 25% sodium hydroxide solution is poured down the side of the tube. In the presence of air a deep blue color appears at the interface within 1 minute. 

Encouraged by these successful results, Saigo and co-workers tested ligand 78 in the rhodium-catalyzed hydrosilylation of ketones.56 Indeed, asymmetric hydrosilylation of acetophenone and tetralone using 78 as a chiral source led to considerably improved enantioselectivities (94% and 89% ee, respectively) compared to reactions performed with valinol-derived phosphorous-containing oxazoline 66 (82% and 59%, respectively).59,60 The equal accessibility of the two enantiomers of the m-2-amino-3,3-dimethyl-l-indanol backbone in 78 represented an additional advantage over oxazoline 66, which is derived from an amino alcohol of the chiral pool because (5)-tetralol could easily be obtained using (-)-78 in 97% yield and 92% ee (Scheme 17.30).56... 

Scientists at Merck have reported a number of biocatalytic routes derived from screening various microorganisms targeted to produce key intermediates that are then combined with chemical reactions to prepare the target molecule. The biocatalytic step was often carried out by necessity as a result of poor chemical yield, low optical purity, or both. 6-Bromo-P-tetralone (2) was reduced to (S)-6-bromo-P-tetralol (3) by the yeast Trichosporon capitatum MY 1890 (Scheme 19.6).79 The tetralol 3 is a key intermediate for the synthesis of MK-0499 (4), a potassium channel blocker. The (S)-P-tetralol 3 was produced in gram quantities with an ee of >99% to support further development of MK-0499. Baker s yeast was tested for its ability to carry out this reduction but showed insignificant product formation. 

Alkalay(16) recognized this notable omission in the analgesic literature and approached the synthesis by an imaginative 1-tetralone route (Scheme 4.6). Analgesic activity of 53 (R = Me) in the rat tail-flick test was low (25 mg/kg). 

Access to optically active 2-fluoro-l-tetralone 53 was achieved using the same palladium-mediated cascade reaction [30]. The catalytic enantioseiective decarbox-ylative protonation of 2-fluoro benzyl P-keto ester 54 in the presence of 30 mol% of quinine 20 afforded enantioenriched (S)-tetralone 53 in 65% ee (Scheme 7.24). The reaction was very sensitive to the nature of the palladium catalyst used. Furthermore, a minor amount of defluorinated product was observed. Several other cinchona derivatives were tested including analogues of cinchonine described by Brunner in organocatalytic EDP (see Section 7.5.3), but these chiral inductors afforded low selectivities (<30% ee). 

To extend this powerful new dihydrofuran synthesis to more complex systems, related reactions with branched /1-dicarbonyl systems were investigated [20]. hi a similar fashion, the cfs-fused furanoids 40 and 41 were prepared from hexane-2,4-dione (37), ethyl isobutyryl acetate (38), and 2. These targets are important chiral synthons, since there are many natural products bearing ethyl and isopropyl residues on furanoid rings. The flexibility of this method was also tested with the aromatic /3-diketone 39 yielding furanoid 42, which is an important system for tetralone synthesis (Scheme 8). 

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