I'd like to reduce enantioselectively a ketone in presence of an ester (which should NOT be reduced to an aldehyde and further to an alcohol).

  • Adding $\ce{LiAlH4}$ would also reduce the ester and gives no enantioselective reduction of the ketone.

  • In the following reaction (Frater-Seebach Alkylation) they used Bakers yeast: enter image description here

  • Probably S-BINAP also give 2. I think there is a $\ce{RuCl2BINAP}$ transition metal complex in combination with $\ce{H2}$ used.

  • I would first use KOH, then adding Evans auxiliary, adding LiCl for chelation of acid carbonyl to Evans auxiliar carbonyl, then adding $\ce{NaBH4}$ and to a standard Felkin Anh reduction. And as a last step I would use $\ce{LiOEt}$. Does this work or will the chelating ketone also be reduced?

May be my own suggestion is easier to reproduce in lab than the use of asymmetric reduction using $\ce{H2}$ under high pressure.

I'm looking for further ways to get the (S)-hydroxy compound 2. Are there easier ways?

  • $\begingroup$ "Probably S-BINAP also give 2." Under what conditions? BINAP is just a ligand. $\endgroup$ – jerepierre Jul 29 '15 at 16:50
  • $\begingroup$ You're right. I get this reaction condition from a slide from Google. I've edited my question. $\endgroup$ – laminin Jul 29 '15 at 22:20

I have had great results for enantioselective ketone reduction using the Noyori Ru-TsDPEN system. This has advantages through being catalytic with low stoichiometry and doesn't require high pressure, or molecular hydrogen for that matter. The downside might be the initial cost of the catalyst / chiral ligand but you don't need very much. The typical reduction reagents are triethylamine and formic acid, making this a very mild system to work with in terms of conditions.
It might be cheaper to purchase the RuCl2(p-cymene) and chiral TsDPEN separately. That way you can also play with the ligand-metal ratio if you need to. This saves a lot of hassle rather than adding on and removing chiral auxiliaries

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  • $\begingroup$ +1 to Beerhunter's answer. The Noyori $\ce{Ru-TsDPEN}$ transfer hydrogenation can work really well. As alluded to,the catalyst can be made fairly easily, just involving stirring several components together, drying, filtration and concentration. The whole procedure is relatively insensitive and making it yourself makes the whole process enormously cheaper $\endgroup$ – NotEvans. Oct 20 '15 at 7:33

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