In 2001, Prof. R. Noyori received the Nobel prize for his development of stereoselective reductions — Organic Chemistry Chemistry Question
Stereoselective Reduction
In 2001, Prof. R. Noyori received the Nobel prize for his development of stereoselective reductions of C=C and C=O double bonds.
Let us consider a simplified model reaction to understand some of the basic control elements necessary to achieve a stereoselective hydrogenation reaction. For example, racemic β-ketoester A can be reduced by hydrogen to racemic B with a high diastereoselectivity in the presence of a metal catalyst that will chemoselectively hydrogenate C=C double bonds. Enantiomerically pure β-ketoester C is diastereoselectively reduced to racemic B. An additive (1 equivalent) such as lithium chloride proved to be highly important for the high diastereocontrol in the reaction.
[VISUAL]
Draw the structures of the enantiomers forming racemic B.
Model Answer
The structures of the two enantiomers forming racemic B (the syn-diastereomers of methyl 3-hydroxy-2-methyl-3-phenylpropanoate) are shown in the solution visual [VISUAL]. One enantiomer has both the hydroxyl (-OH) and methyl (-CH3) groups on dashed bonds, while the other has both on wedged bonds, representing the (1R, 2R) and (1S, 2S) syn-isomers.
There are two diastereomers to the compounds of 30.1 that form a racemic B*. Draw their structures.
Model Answer
The structures of the two enantiomers forming racemic B* (the anti-diastereomers of methyl 3-hydroxy-2-methyl-3-phenylpropanoate) are shown in the solution visual [VISUAL]. One enantiomer has the hydroxyl (-OH) on a wedged bond and the methyl (-CH3) on a dashed bond, while the other has the hydroxyl on a dashed bond and the methyl on a wedged bond, representing the (1R, 2S) and (1S, 2R) anti-isomers.
Develop a model showing that in the reaction described above only B (but no B*) forms .
Model Answer
Obviously, A and C must be reduced by a common, achiral intermediate, since C is racemized in the process. The racemization of C can be understood by the formation of the enolate D1, which forms with a higher preference than D2, because of the strong chelation effect of Li+ present as an additive in the reaction mixture. The donation of hydrogen by the metal in the usual way (syn–addition) from the top or the bottom of D1 leads to racemic E1/E2 as single diastereomers. Hydrolysis leads to racemic B.
The mechanism of the model is shown in the visual [VISUAL].