[taurean]

How can we reduce a cyclic beta-ketoester to beta-hydroxy ester, diastereoselectively?  Anyone know of any method other than biotransformation?  Please pour in your comments.

[a confused chiral girl]

  I want to help, but I have no idea of how to do it. have you tried to google and see if any methods will pop up?

[movies]

What is controlling the stereoselectivity?  If it's diastereoselective then you must have a stereocenter somewhere in your molecule already.

Also, is the ester in the ring, or outside the ring.  If it's outside the ring like in 2-carboxymethyl cyclopentanone, there are excellent enantioselective methods for reducing the ketone carbonyl.

[taurean]

What is controlling the stereoselectivity?  If it's diastereoselective then you must have a stereocenter somewhere in your molecule already.

Also, is the ester in the ring, or outside the ring.  If it's outside the ring like in 2-carboxymethyl cyclopentanone, there are excellent enantioselective methods for reducing the ketone carbonyl.

Please open the attachment.  This is the ketoester I am trying to reduce.

[movies]

How about sodium borohydride?

[taurean]

How about sodium borohydride?

The reaction with sodium borohydride results in the mixture of four diastereomers.  I tried changing the solvent system from methanol to isopropanol, it gives me the same result in each case.

[movies]

Really??  How about L-Selectride?

Do you know what the diastereomers are?

[taurean]

Really??  How about L-Selectride?

Do you know what the diastereomers are?

I will let you know shortly; working on that.

[taurean]

Really??  How about L-Selectride?

Do you know what the diastereomers are?

I need a diequatorial beta-hydroxy ester or a diequatorial 1,3-diol.  After reading through the literature, I came to a conclusion that use of sterically encumbered borohydride would give a thermodynamically less stable isomer.

Please let me know your comments as why did you think that L-selectride would work for my substrate?

[movies]

Well, usually bulky reducing agents give better levels of diastereoselectivity, although in this case I guess it would be in the wrong direction for your purposes.  If you want the thermodynamic product, I would recommend a Meerwein-Ponndorf-Verley reduction.  That reaction is usually under thermodynamic control.

[taurean]

Well, usually bulky reducing agents give better levels of diastereoselectivity, although in this case I guess it would be in the wrong direction for your purposes.  If you want the thermodynamic product, I would recommend a Meerwein-Ponndorf-Verley reduction.  That reaction is usually under thermodynamic control.

Thanks for suggesting MPV reaction.

 I would like to try someother stereoselective reductions along with MPV reaction.  I was unsuccessful in digging out the literature for stereoselective (diastereoselective) carbonyl reduction of cyclic beta-ketoester.  If possible can you let me know some good reading material for diastereoselective carbonyl reduction of cyclic beta-ketoesters.

[movies]

There should be lots of diastereoselective versions, certainly MPV has been used for this purpose as well as Selectrides and aluminum hydrides.  There may not be a whole lot of obvious beta-ketoester versions that are exactly like your case, but I would look for diastereoselective ketone reductions with reagents that aren't powerful enough to reduce esters.

Have you tried Pd/C with hydrogen gas?  You might be able to reduce the enol form and heterogeneous reductions often give pretty good dr.

[taurean]

There should be lots of diastereoselective versions, certainly MPV has been used for this purpose as well as Selectrides and aluminum hydrides.  There may not be a whole lot of obvious beta-ketoester versions that are exactly like your case, but I would look for diastereoselective ketone reductions with reagents that aren't powerful enough to reduce esters.

Have you tried Pd/C with hydrogen gas?  You might be able to reduce the enol form and heterogeneous reductions often give pretty good dr.

I cannot reduce with Pd/C-H2.  I want the double bond in the reactant to be retained in the product.

I would look for diastereoselective ketone reductions, thanks.

[movies]

Sorry, I forgot what the rest of the molecule looks like and the picture seems to be gone now.

You might be able to reduce with dissolving metals like Na/EtOH.  Those are kinda strange reactions, but they really work sometimes.  You might reduce off the sulfone you have, however.  I'm not sure.

[taurean]

Movies,

After reading different papers, I feel that there is no set rule that diastereoselective reduction of ketone with L-selectride or any other sterically hindered hydride would give kinetically stable product (axial alcohol in case of cyclic ketone).

What is your opinion?