17.14 Stereoselective Addition to Carbonyl Groups Nucleophilic addition to carbonyl groups sometimes leads to a mixture of stereoisomeric products.

NaBH 4 80% 20% Example CH 3 H3CH3CH3CH3CO OH H H3CH3CH3CH3COH H H3CH3CH3CH3C

H 3 B—H – this methyl group hinders approach of nucleophile from top preferred direction of approach is to less hindered (bottom) face of carbonyl group preferred direction of approach is to less hindered (bottom) face of carbonyl group Steric Hindrance to Approach of Reagent

Biological reductions are highly stereoselective pyruvic acid  S-(+)-lactic acid O CH 3 CCO 2 H NADH H+H+H+H+ enzyme is lactate dehydrogenase CO 2 H HO H CH 3

carboxylat e binding site H3CH3CH3CH3C O O C O C – carbonyl binding site NAD–H Pyruvate is bound at the active site of the enzyme Figure 17.11

carboxylat e binding site H3CH3CH3CH3C O O C C – OH H NAD + carbonyl binding site where it is reduced to (S)-(+)-lactate. Figure 17.11

in aqueous solution RCH RCH RCOHOOH OH H2OH2OH2OH2OO Oxidation of Aldehydes

K 2 Cr 2 O 7 H 2 SO 4 H2OH2OH2OH2O O O CH O O COH (75%) Example

K 2 Cr 2 O 7 H 2 SO 4 H2OH2OH2OH2O O O CH O O COH (75%) via O OH CH OH Example

17.16 Baeyer-Villiger Oxidation of Ketones Oxidation of ketones with peroxy acids gives esters by a novel rearrangement.

R"COOH O RCR' O + R"COH O + KetoneEster ROCR' O General

C 6 H 5 COOH O (67%) Oxygen insertion occurs between carbonyl carbon and larger group. Methyl ketones give acetate esters. CHCl 3 Example CCH 3 O OCCH 3 O

C 6 H 5 COOH O (66%) Reaction is stereospecific. Oxygen insertion occurs with retention of configuration. CHCl 3 Stereochemistry O CCH 3 H3CH3CH3CH3C HH OCCH 3 O H3CH3CH3CH3C HH

R"COOH O RCR' O + ROCR' O R"COH O + Mechanism

R"COOH O RCR' O + ROCR' O R"COH O + O O C OHR R' OCR" First step is nucleophilic addition of peroxy acid to the carbonyl group of the ketone. Mechanism

R"COOH O RCR' O + ROCR' O R"COH O + O O C OHR R' OCR" Second step is migration of group R from carbon to oxygen. The weak O—O bond breaks in this step. Mechanism

Certain bacteria use hydrocarbons as a source of carbon. Oxidation proceeds via ketones, which then undergo oxidation of the Baeyer-Villiger type. Biological Baeyer-Villliger Oxidation O OO bacterial oxidation O 2. cyclohexanone monooxygenase, coenzymes