Chapter 21 Ester Enolates

Transcription

1 hapter 21 Ester Enolates

2 Introduction R R' H H The preparation and reactions of β-dicarbonyl compounds, especially β-keto esters, is the main focus of this chapter. A proton on the carbon flanked by the two carbonyl groups is relatively acidic, easily and quantitatively removed by alkoxide ions.

3 Introduction R R' pk a ~ 11 H H 3 H 2 H R R' H

4 Introduction R R' R R' H H The resulting carbanion is stabilized by enolate resonance involving both carbonyl groups.

5 Introduction R R' R R' H H The resulting carbanion is stabilized by enolate resonance involving both carbonyl groups.

6 21.1 The laisen ondensation

7 The laisen ondensation 2RH 2 R' 1. NaR' 2. H 3 + RH 2 HR' + R'H R β-keto esters are made by the reaction shown, which is called the laisen condensation. Ethyl esters are typically used, with sodium ethoxide as the base.

8 Example 2H 3 H 2 H 3 1. NaH 2 H 3 2. H 3 + H 3 H 2 H 2 H 3 (75%) Product from ethyl acetate is called ethyl acetoacetate or acetoacetic ester.

9 Mechanism Step 1: H 3 H H 2 H H 2 H 2 H 3

10 Mechanism Step 1: H 3 H H 2 H H 2 H 2 H 3 H 3 H 2 H H 2 H 2 H 3

11 Mechanism Step 1: Anion produced is stabilized by electron delocalization; it is the enolate of an ester. H 2 H 2 H 2 H 3 H 2 H 3

12 Mechanism Step 2: H 3 H 2 H 3 H 2 H 2 H 3

13 Mechanism Step 2: H 3 H 2 H 2 H 3 H 2 H 3 H 3 H 2 H 3 H 2 H 2 H 3

14 Mechanism Step 2: H 3 H 2 H 2 H 3 H 2 H 3

15 Mechanism Step 3: H 3 H 2 H 2 H 3 H 2 H 3 H 3 H 2 H 2 H 3 + H2 H 3

16 Step 3: Mechanism The product at this point is ethyl acetoacetate. However, were nothing else to happen, the yield of ethyl acetoacetate would be small because the equilibrium constant for its formation is small. Something else does happen. Ethoxide abstracts a proton from the H 2 group to give a stabilized anion. The equilibrium constant for this reaction is favorable. H 3 H 2 H 2 H 3 + H2 H 3

17 Mechanism Step 4: H 3 H H 2 H 3 + H H 2 H 3 H 3 H 2 H 2 H 3 + H2 H 3

18 Mechanism Step 5: H 3 H H 2 H 3 In a separate operation, the reaction mixture is acidified. This converts the anion to the isolated product, ethyl acetoacetate.

19 Mechanism Step 5: H 3 H H 2 H 3 H + H H H H 3 H H 2 H 3 + H H

20 Another example 2H 3 H 2 H 2 H 3 Reaction involves bond formation between the α- carbon atom of one ethyl propanoate molecule and the carbonyl carbon of the other. 1. NaH 2 H 3 2. H 3 + H 3 H 2 HH 2 H 3 H 3 (81%)

21 21.2 Intramolecular laisen ondensation: The Dieckmann Reaction

22 Example H 3 H 2 H 2 H 2 H 2 H 2 H 2 H 3 1. NaH 2 H 3 2. H 3 + H 2 H 3 (74-81%)

23 via H 3 H 2 H 2 H 2 H 2 H 2 H 2 H 3 NaH 2 H 3 H 3 H 2 H 2 H 2 H 2 HHH 2 H 3

24 via H 3 H 2 H 2 H 2 H 2 HHH 2 H 3

25 via H 3 H 2 H 2 HHH 2 H 3 H 2 H 2 H 3 H 2 H 2 H 2 H 2 HHH 2 H 3

26 via H 3 H 2 H 2 HHH 2 H 3 H 2 H 2

27 via H 3 H 2 H 2 HHH 2 H 3 H 2 H 2 H 3 H 2 + H 2 HHH 2 H 3 H 2 H 2

28 21.3 Mixed laisen ondensations

29 Mixed laisen ondensations As with mixed aldol condensations, mixed laisen condensations are best carried out when the reaction mixture contains one compound that can form an enolate and another that cannot.

30 Mixed laisen ondensations These types of esters cannot form an enolate. HR RR R R R

31 Example H 3 + H 3 H 2 H 3 1. NaH 3 2. H 3 + HH 3 (60%) H 3

32 21.4 Acylation of Ketones with Esters

33 Acylation of Ketones with Esters Esters that cannot form an enolate can be used to acylate ketone enolates.

34 Example H 3 H 2 HH 2 H NaH 2. H 3 + H 2 H 3 (60%)

35 Example H 2 H 3 + H 3 1. NaH 2 H 3 2. H 3 + H 2 (62-71%)

36 Example H 3 H 2 H 2 H 2 H 2 H 3 1. NaH 3 2. H 3 + H 3 (70-71%) 71%)

37 21.5 Ketone Synthesis via β-keto Esters

38 Ketone Synthesis RH 2 HH RH 2 H 2 R + 2 R β-keto acids decarboxylate readily to give ketones (Section 19.17).

39 Ketone Synthesis RH 2 HR' H 2 RH 2 HH + R'H R R β-keto acids decarboxylate readily to give ketones (Section 19.17). β-keto acids are available by hydrolysis of β- keto esters.

40 Ketone Synthesis 2RH 2 R' 1. NaR' 2. H 3 + R β-keto acids decarboxylate readily to give ketones (Section 19.17). β-keto acids are available by hydrolysis of β- keto esters. β-keto esters can be prepared by the laisen condensation. RH 2 HR' + R'H

41 Example 2 H 3 H 2 H 2 H 2 H 2 H 3 1. NaH 2 H 3 2. H 3 + H 3 H 2 H 2 H 2 HH 2 H 3 H 2 H 2 H 3 (80%)

42 Example H 3 H 2 H 2 H 2 HH H 2 H 2 H 3 1. KH, H 2, H 3 + H 3 H 2 H 2 H 2 HH 2 H 3 H 2 H 2 H 3

43 Example H 3 H 2 H 2 H 2 HH H 2 H 2 H H 3 H 2 H 2 H 2 H 2 H 2 H 2 H 3 (81%)