The Role of Proximal, Lewis Basic Functional Groups in Carbonyl Reduction

3 The Role of Proximal, Lewis Basic Functional Groups in Carbonyl Reduction 

If chelation to a neigbouring group is possible, the use of HMPA is often not required for reduction of the carbonyl and reactions can be carried out under mild conditions. To examine the impact of chelation, Flowers studied the rate of reduction of 2-butanone, methyl acetoacetate and /V,/V-dimethylacetoace-tamide by Sml2.20 Reduction of the (1-keto ester or amide was several orders of magnitude faster than that of the unsubstituted ketone, which is consistent with chelation playing a major role. Further rate and mechanistic studies on the reduction of acetophenone and a series of 2 - and 4 -substituted acetophenone derivatives showed that both chelation and coordination provide highly 

In addition to accelerating the rate of carbonyl reduction, chelation can be used to control the diastereoselectivity of reductions and carbon-carbon bondforming reactions through highly organised transition states. Keck showed that appropriately subsituted p-hydroxy ketones are stereoselectively reduced by 

Even though the model shown above is consistent with the stereochemical outcome, Flowers has shown that changing the reaction conditions or the substituents in the (3-hydroxy ketone substrates can have an impact on the stereochemical outcome of the chelation-controlled reaction.23,24 A more detailed discussion of the mechanism of this reduction can be found in Chapter 4, Section 4.3. 

Although the above examples show the role played by substituents (3 to the ketone carbonyl, it is important to recognise that more distant, Lewis basic 

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