Oganic II - Klein - chapter 22

3,491 views
3,414 views

Published on

Published in: Technology, Education
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
3,491
On SlideShare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
156
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Oganic II - Klein - chapter 22

  1. 1. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• For carbonyl compounds, Greek letters are often used to describe the proximity of atoms to the carbonyl center.• This chapter will primarily explore reactions that take place at the alpha carbon. Copyright 2012 John Wiley & Sons, Inc. 22-1 Klein, Organic Chemistry 1e
  2. 2. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• The reactions we will explore proceed though either an enol or an enolate intermediate. Copyright 2012 John Wiley & Sons, Inc. 22-2 Klein, Organic Chemistry 1e
  3. 3. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Trace amounts of acid or base catalyst provide equilibriums in which both the enol and keto forms are present.• How is equilibrium different from resonance?• At equilibrium, > 99% of the molecules exist in the keto form. WHY? Copyright 2012 John Wiley & Sons, Inc. 22-3 Klein, Organic Chemistry 1e
  4. 4. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• In rare cases such as the example below, the enol form is favored in equilibrium.• Give two reasons to explain WHY the enol is favored.• The solvent can affect the exact percentages. Copyright 2012 John Wiley & Sons, Inc. 22-4 Klein, Organic Chemistry 1e
  5. 5. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Phenol is an example where the enol is vastly favored over the keto at equilibrium. WHY? Copyright 2012 John Wiley & Sons, Inc. 22-5 Klein, Organic Chemistry 1e
  6. 6. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• The mechanism for the tautomerization depends on whether it is acid catalyzed or base catalyzed. Copyright 2012 John Wiley & Sons, Inc. 22-6 Klein, Organic Chemistry 1e
  7. 7. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• The mechanism for the tautomerization depends on whether it is acid catalyzed or base catalyzed. Copyright 2012 John Wiley & Sons, Inc. 22-7 Klein, Organic Chemistry 1e
  8. 8. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• As the tautomerization is practically unavoidable, some fraction of the molecules will exist in the enol form.• Analyzing the enol form, we see there is a minor (but significant) resonance contributor with a nucleophilic carbon atom.• Practice with CONCEPTUAL CHECKPOINTs 22.1 through 22.3. Copyright 2012 John Wiley & Sons, Inc. 22-8 Klein, Organic Chemistry 1e
  9. 9. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• In the presence of a strong base, an ENOLATE forms.• The enolate is much more nucleophilic than in the enol. WHY? Copyright 2012 John Wiley & Sons, Inc. 22-9 Klein, Organic Chemistry 1e
  10. 10. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• The enolate can undergo C-attack or O-attack.• Enolates generally undergo C-attack. WHY? Copyright 2012 John Wiley & Sons, Inc. 22-10 Klein, Organic Chemistry 1e
  11. 11. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Alpha protons are the only protons on an aldehyde or ketone that can be removed to form an enolate.• Removing the aldehyde proton, or the beta or gamma proton, will NOT yield a resonance stabilized intermediate.• Practice with SKILLBUILDER 22.1. Copyright 2012 John Wiley & Sons, Inc. 22-11 Klein, Organic Chemistry 1e
  12. 12. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Draw all possible enolates that could form from the following molecule. Copyright 2012 John Wiley & Sons, Inc. 22-12 Klein, Organic Chemistry 1e
  13. 13. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Why would a chemist want to form an enolate?• To form an enolate, a base must be used to remove the alpha protons.• The appropriate base depends on how acidic the alpha protons are .• What method do we have to quantify how acidic something is? Copyright 2012 John Wiley & Sons, Inc. 22-13 Klein, Organic Chemistry 1e
  14. 14. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Let’s compare some pKa values for some alpha protons. Copyright 2012 John Wiley & Sons, Inc. 22-14 Klein, Organic Chemistry 1e
  15. 15. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• When pKa values are similar, both products and reactants are present in significant amounts.• Which side will this equilibrium favor? Copyright 2012 John Wiley & Sons, Inc. 22-15 Klein, Organic Chemistry 1e
  16. 16. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• In this case, it is an advantage to have both enolate and aldehyde in solution so they can react with one another.• Show how the electrons might move in the reaction between the enolate and the aldehyde. Copyright 2012 John Wiley & Sons, Inc. 22-16 Klein, Organic Chemistry 1e
  17. 17. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• If you want the carbonyl to react irreversibly, a stronger base, such as H–, is necessary.• When is it synthetically desirable to convert all of the carbonyl into an enolate? Copyright 2012 John Wiley & Sons, Inc. 22-17 Klein, Organic Chemistry 1e
  18. 18. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• Lithium diisopropylamide (LDA) is an even stronger base that is frequently used to promote irreversible enolate formation.• Why is the reaction affectively irreversible?• LDA features two bulky isopropyl groups. Why would such a bulky base be desirable? Copyright 2012 John Wiley & Sons, Inc. 22-18 Klein, Organic Chemistry 1e
  19. 19. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• When a proton is alpha to two different carbonyl groups, its acidity is increased.• Draw the resonance contributors that allow 2,4-pentanedione to be so acidic. Copyright 2012 John Wiley & Sons, Inc. 22-19 Klein, Organic Chemistry 1e
  20. 20. 22.1 Introduction to Alpha Carbon Chemistry – Enols and Enolates• 2,4-pentanedione is acidic enough that hydroxide or alkoxides can deprotonate it irreversibly.• Figure 22.2 summarizes the relevant factors you should consider when choosing a base.• Practice with CONCEPTUAL CHECKPOINTs 22.6 through 22.8. Copyright 2012 John Wiley & Sons, Inc. 22-20 Klein, Organic Chemistry 1e
  21. 21. 22.2 Alpha Halogenation of Enols and Enolates• H3O+ catalyzes the ketoenol tautomerism. HOW?• The enol tautomer can attack a halogen molecule.• The process is AUTOCATALYTIC: – The regenerated acid can catalyze another tautomerization and halogenation. Copyright 2012 John Wiley & Sons, Inc. 22-21 Klein, Organic Chemistry 1e
  22. 22. 22.2 Alpha Halogenation of Enols and Enolates• When an unsymmetrical ketone is used, bromination occurs primarily at the more substituted carbon.• The major product results from the more stable (more substituted) enol.• A mixture of products is generally unavoidable. Copyright 2012 John Wiley & Sons, Inc. 22-22 Klein, Organic Chemistry 1e
  23. 23. 22.2 Alpha Halogenation of Enols and Enolates• This provides a two-step synthesis for the synthesis of an α,β-unsaturated ketone.• Give a mechanism that shows the role of pyridine.• Other bases, such as potassium tert-butoxide, can also be used in the second step.• Practice with CONCEPTUAL CHECKPOINTs 22.9 and 22.10. Copyright 2012 John Wiley & Sons, Inc. 22-23 Klein, Organic Chemistry 1e
  24. 24. 22.2 Alpha Halogenation of Enols and Enolates• The Hell-Volhard Zelinsky reaction brominates the alpha carbon of a carboxylic acid.• PBr3 forms the acyl bromide, which more readily forms the enol and attacks the bromine.• Hydrolysis of the acyl bromide is the last step.• Draw a complete mechanism.• Practice CONCEPTUAL CHECKPOINTs 22.11 and 22.12. Copyright 2012 John Wiley & Sons, Inc. 22-24 Klein, Organic Chemistry 1e
  25. 25. 22.2 Alpha Halogenation of Enols and Enolates• Alpha halogenation can also be achieved under basic conditions.• The formation of the enolate is not favored, but the equilibrium is pushed forward by the second step.• Will the presence of the α bromine make the remaining α proton more or less acidic? Copyright 2012 John Wiley & Sons, Inc. 22-25 Klein, Organic Chemistry 1e
  26. 26. 22.2 Alpha Halogenation of Enols and Enolates• Monosubstitution is not possible. WHY?• Methyl ketones can be converted to carboxylic acids using excess halogen and hydroxide.• Once all three α protons are substituted, the CBr3 group becomes a decent leaving group. Copyright 2012 John Wiley & Sons, Inc. 22-26 Klein, Organic Chemistry 1e
  27. 27. 22.2 Alpha Halogenation of Enols and Enolates• Once all three α protons are substituted, the CBr3 group becomes a decent leaving group.• The last step is practically irreversible. WHY? Copyright 2012 John Wiley & Sons, Inc. 22-27 Klein, Organic Chemistry 1e
  28. 28. 22.2 Alpha Halogenation of Enols and Enolates• The carboxylate produced on the last slide can be protonated with H3O+.• The reaction works well with Cl2, Br2, and I2, and it is known as the haloform reaction.• The iodoform reaction may be used to test for methyl ketones, because iodoform can be observed as a yellow solid when it forms.• Practice with CONCEPTUAL CHECKPOINTs 22.13 and 22.14. Copyright 2012 John Wiley & Sons, Inc. 22-28 Klein, Organic Chemistry 1e
  29. 29. 22.2 Alpha Halogenation of Enols and Enolates• Give the major product for the reaction below. Be careful of stereochemistry. Copyright 2012 John Wiley & Sons, Inc. 22-29 Klein, Organic Chemistry 1e
  30. 30. 22.3 Aldol Reactions• Recall that when an aldehyde is treated with hydroxide (or alkoxide), an equilibrium forms where significant amounts of both enolate and aldehyde are present.• If the enolate attacks the aldehyde, an aldol reaction occurs.• The product features both aldehyde and alcohol groups.• Note the location of the –OH group on the beta carbon. Copyright 2012 John Wiley & Sons, Inc. 22-30 Klein, Organic Chemistry 1e
  31. 31. 22.3 Aldol Reactions• The aldol mechanism: Copyright 2012 John Wiley & Sons, Inc. 22-31 Klein, Organic Chemistry 1e
  32. 32. 22.3 Aldol Reactions• The aldol reaction is an equilibrium process that generally favors the products:• How might the temperature affect the equilibrium? Copyright 2012 John Wiley & Sons, Inc. 22-32 Klein, Organic Chemistry 1e
  33. 33. 22.3 Aldol Reactions• A similar reaction for a ketone generally does NOT favor the β-hydroxy ketone product.• Give a reasonable mechanism for the retro-aldol reaction.• Practice with SKILLBUILDER 22.2. Copyright 2012 John Wiley & Sons, Inc. 22-33 Klein, Organic Chemistry 1e
  34. 34. 22.3 Aldol Reactions• Predict the products for the follow reaction, and give a reasonable mechanism. Be careful of stereochemistry. Copyright 2012 John Wiley & Sons, Inc. 22-34 Klein, Organic Chemistry 1e
  35. 35. 22.3 Aldol Reactions• When an aldol product is heated under acidic or basic conditions, an α,β-unsaturated carbonyl forms.• Such a process is called an ALDOL CONDENSATION, because water is given off.• The elimination reaction above is an equilibrium, which generally favors the products.• WHY? Consider enthalpy and entropy. Copyright 2012 John Wiley & Sons, Inc. 22-35 Klein, Organic Chemistry 1e
  36. 36. 22.3 Aldol Reactions• The elimination of water can be promoted under acidic or under basic conditions.• Give a reasonable mechanism for each: Copyright 2012 John Wiley & Sons, Inc. 22-36 Klein, Organic Chemistry 1e
  37. 37. 22.3 Aldol Reactions• When a water is eliminated, two products are possible.• Which will likely be the major product? Use the mechanism to explain. Copyright 2012 John Wiley & Sons, Inc. 22-37 Klein, Organic Chemistry 1e
  38. 38. 22.3 Aldol Reactions• Because the aldol condensation is favored, often it is impossible to isolate the aldol product without elimination.• Condensation is especially favored when extended conjugation results. Copyright 2012 John Wiley & Sons, Inc. 22-38 Klein, Organic Chemistry 1e
  39. 39. 22.3 Aldol Reactions• At low temperatures, condensation is less favored, but the aldol product is still often difficult to isolate in good yield.• Practice with SKILLBUILDER 22.3. Copyright 2012 John Wiley & Sons, Inc. 22-39 Klein, Organic Chemistry 1e
  40. 40. 22.3 Aldol Reactions• Predict the major product of the following reaction. Be careful of stereochemistry. Copyright 2012 John Wiley & Sons, Inc. 22-40 Klein, Organic Chemistry 1e
  41. 41. 22.3 Aldol Reactions• Substrates can react in a CROSSED aldol or MIXED aldol reaction. Predict the four possible products in the reaction below.• Such a complicated mixture of products is not very synthetically practical. WHY? Copyright 2012 John Wiley & Sons, Inc. 22-41 Klein, Organic Chemistry 1e
  42. 42. 22.3 Aldol Reactions• Practical CROSSED aldol reactions can be achieved through one of two methods: 1. One of the substrates is relatively unhindered and without alpha protons. Copyright 2012 John Wiley & Sons, Inc. 22-42 Klein, Organic Chemistry 1e
  43. 43. 22.3 Aldol Reactions 1. One of the substrates is relatively unhindered and without alpha protons.Copyright 2012 John Wiley & Sons, Inc. 22-43 Klein, Organic Chemistry 1e
  44. 44. 22.3 Aldol Reactions• Practical CROSSED aldol reactions can be achieved through one of two methods: 2. One substrate is added dropwise to LDA forming the enolate first. Subsequent addition of the second substrate produces the desired product.• Practice with SKILLBUILDER 22.4. Copyright 2012 John Wiley & Sons, Inc. 22-44 Klein, Organic Chemistry 1e
  45. 45. 22.3 Aldol Reactions• Describe a synthesis necessary to yield the following compound. Copyright 2012 John Wiley & Sons, Inc. 22-45 Klein, Organic Chemistry 1e
  46. 46. 22.3 Aldol Reactions• Cyclic compounds can be formed through intramolecular aldol reactions.• One group forms an enolate that attacks the other group.• Recall that 5 and 6-membered rings are most likely to form. WHY?• Practice CONCEPTUAL CHECKPOINTs 22.25 through 22.27. Copyright 2012 John Wiley & Sons, Inc. 22-46 Klein, Organic Chemistry 1e
  47. 47. 22.4 Claisen Condensations• Esters also undergo reversible condensations reactions.• Unlike a ketone or aldehyde, an ester has a leaving group. Copyright 2012 John Wiley & Sons, Inc. 22-47 Klein, Organic Chemistry 1e
  48. 48. 22.4 Claisen Condensations• Esters also undergo reversible condensations reactions.• The resulting doubly-stabilized enolate must be treated with an acid in the last step. WHY?• A beta-ketoester is produced. Copyright 2012 John Wiley & Sons, Inc. 22-48 Klein, Organic Chemistry 1e
  49. 49. 22.4 Claisen Condensations• There are some limitations to the Claisen condensation: 1. The starting ester must have two alpha protons because removal of the second proton by the alkoxide ion is what drives the equilibrium forward. 2. Hydroxide cannot be used as the base to promote Claisen condensations because a hydrolysis reaction occurs between hydroxide and the ester. 3. An alkoxide equivalent to the –OR group of the ester is a good base because transesterification is avoided.• Practice CONCEPTUAL CHECKPOINTs 22.28 and 22.29. Copyright 2012 John Wiley & Sons, Inc. 22-49 Klein, Organic Chemistry 1e
  50. 50. 22.4 Claisen Condensations• Crossed Claisen reactions can also be achieved using the same strategies employed in crossed aldol reactions.• Practice with CONCEPTUAL CHECKPOINT 22.30. Copyright 2012 John Wiley & Sons, Inc. 22-50 Klein, Organic Chemistry 1e
  51. 51. 22.4 Claisen Condensations• Intramolecular Claisen condensations can also be achieved.• This DIEKMANN CYCLIZATION proceeds through the expected 5-membered ring transition state. DRAW it.• Practice with CONCEPTUAL CHECKPOINTs 22.31 and 22.32. Copyright 2012 John Wiley & Sons, Inc. 22-51 Klein, Organic Chemistry 1e
  52. 52. 22.4 Claisen Condensations• Give reagents necessary to synthesize the following molecules. Copyright 2012 John Wiley & Sons, Inc. 22-52 Klein, Organic Chemistry 1e
  53. 53. 22.5 Alkylation of the Alpha Position• The alpha position can be alkylated when an enolate is treated with an alkyl halide.• The enolate attacks the alkyl halide via an SN2 reaction. Copyright 2012 John Wiley & Sons, Inc. 22-53 Klein, Organic Chemistry 1e
  54. 54. 22.5 Alkylation of the Alpha Position• When 2° or 3° alkyl halides are used, the enolate can act as a base in an E2 reaction. SHOW a mechanism.• The aldol reaction also competes with the desired alkylation, so a strong base such as LDA must be used.• Regioselectivity is often an issue when forming enolates.• If the compound below is treated with a strong base, two enolates can form. Copyright 2012 John Wiley & Sons, Inc. 22-54 Klein, Organic Chemistry 1e
  55. 55. 22.5 Alkylation of the Alpha Position• What is meant by kinetic and thermodynamic enolate? Copyright 2012 John Wiley & Sons, Inc. 22-55 Klein, Organic Chemistry 1e
  56. 56. 22.5 Alkylation of the Alpha Position• For clarity, the kinetic and thermodynamic pathways are exaggerated below.• Explain the energy differences below using steric and stability arguments. Copyright 2012 John Wiley & Sons, Inc. 22-56 Klein, Organic Chemistry 1e
  57. 57. 22.5 Alkylation of the Alpha Position• LDA is a strong base, and at low temperatures, it will react effectively in an irreversible manner.• NaH is not quite as strong, and if heat is available, the system will be reversible.• Practice with CONCEPTUAL CHECKPOINTs 22.33 and 22.24. Copyright 2012 John Wiley & Sons, Inc. 22-57 Klein, Organic Chemistry 1e
  58. 58. 22.5 Alkylation of the Alpha Position• Give necessary reagents to synthesize the compound below starting with carbon fragments with five carbons or less. Copyright 2012 John Wiley & Sons, Inc. 22-58 Klein, Organic Chemistry 1e
  59. 59. 22.5 Alkylation of the Alpha Position• The malonic ester synthesis allows a halide to be converted into a carboxylic acid with two additional carbons.• Diethyl malonate is first treated with a base to form a doubly-stabilized enolate. Copyright 2012 John Wiley & Sons, Inc. 22-59 Klein, Organic Chemistry 1e
  60. 60. 22.5 Alkylation of the Alpha Position• The enolate is treated with the alkyl halide.• The resulting diester can be hydrolyzed with acid or base, and using heat. Copyright 2012 John Wiley & Sons, Inc. 22-60 Klein, Organic Chemistry 1e
  61. 61. 22.5 Alkylation of the Alpha Position• One of the resulting carboxylic acid groups can be DECARBOXYLATED with heat through a pericyclic reaction.• Why isn’t the second carboxylic acid group removed? Copyright 2012 John Wiley & Sons, Inc. 22-61 Klein, Organic Chemistry 1e
  62. 62. 22.5 Alkylation of the Alpha Position• Here is an example of the overall synthesis. Copyright 2012 John Wiley & Sons, Inc. 22-62 Klein, Organic Chemistry 1e
  63. 63. 22.5 Alkylation of the Alpha Position• Double alkylation can also be achieved:• Practice with SKILLBUILDER 22.5.• The acetoacetic ester synthesis is a very similar process. Copyright 2012 John Wiley & Sons, Inc. 22-63 Klein, Organic Chemistry 1e
  64. 64. 22.5 Alkylation of the Alpha Position• Give a complete mechanism for the process below.• Practice with SKILLBUILDER 22.6. Copyright 2012 John Wiley & Sons, Inc. 22-64 Klein, Organic Chemistry 1e
  65. 65. 22.6 Conjugate Addition Reactions• Recall that α,β-unsaturated carbonyls can be made easily through aldol condensations.• α,β-unsaturated carbonyls have three resonance contributors.• Which contributors are electrophilic? Copyright 2012 John Wiley & Sons, Inc. 22-65 Klein, Organic Chemistry 1e
  66. 66. 22.6 Conjugate Addition Reactions• Grignard reagents generally attack the carbonyl position of α,β-unsaturated carbonyls yielding a 1,2 addition.• In contrast, Gilman reagents generally attacks the beta position giving 1,4 addition, or CONJUGATE ADDITION. Copyright 2012 John Wiley & Sons, Inc. 22-66 Klein, Organic Chemistry 1e
  67. 67. 22.6 Conjugate Addition Reactions• Conjugate addition of α,β-unsaturated carbonyls starts with attack at the beta position.• WHY does the nucleophile generally favor attacking the beta position? Copyright 2012 John Wiley & Sons, Inc. 22-67 Klein, Organic Chemistry 1e
  68. 68. 22.6 Conjugate Addition Reactions• More reactive nucleophiles (e.g. Grignard) are more likely to attack the carbonyl directly. WHY?• Enolates are generally less reactive than Grignards but more reactive than Gilman reagents, so enolates often give a mixture of 1,2- and 1,4-addition products.• Doubly-stabilized enolates are stable enough to react primarily at the beta position. Copyright 2012 John Wiley & Sons, Inc. 22-68 Klein, Organic Chemistry 1e
  69. 69. 22.6 Conjugate Addition Reactions• When an enolate attacks a beta carbon, the process is called a Michael addition. Copyright 2012 John Wiley & Sons, Inc. 22-69 Klein, Organic Chemistry 1e
  70. 70. 22.6 Conjugate Addition Reactions• Give a mechanism showing the reaction between the two compounds shown below.• Practice with CONCEPTUAL CHECKPOINTs 22.44 through 22.46. Copyright 2012 John Wiley & Sons, Inc. 22-70 Klein, Organic Chemistry 1e
  71. 71. 22.6 Conjugate Addition Reactions• Because singly-stabilized enolates do not give high yielding Michael additions, Gilbert Stork developed a synthesis using an enamine intermediate.• Recall the enamine synthesis from Chapter 20. Copyright 2012 John Wiley & Sons, Inc. 22-71 Klein, Organic Chemistry 1e
  72. 72. 22.6 Conjugate Addition Reactions• Enolates and enamines have reactivity in common.• The enamine is less nucleophilic and more likely to act as a Michael donor. Copyright 2012 John Wiley & Sons, Inc. 22-72 Klein, Organic Chemistry 1e
  73. 73. 22.6 Conjugate Addition Reactions• Water hydrolyzes the imine, and tautomerizes and protonates the enol. Copyright 2012 John Wiley & Sons, Inc. 22-73 Klein, Organic Chemistry 1e
  74. 74. 22.6 Conjugate Addition Reactions• Give reagents necessary to synthesize the molecule below using the Stork enamine synthesis .• Practice with SKILLBUILDER 22.7. Copyright 2012 John Wiley & Sons, Inc. 22-74 Klein, Organic Chemistry 1e
  75. 75. 22.6 Conjugate Addition Reactions• The ROBINSON ANNULATION utilizes a Michael addition followed by an aldol condensation.• Practice CONCEPTUAL CHECKPOINTs 22.49 and 22.50. Copyright 2012 John Wiley & Sons, Inc. 22-75 Klein, Organic Chemistry 1e
  76. 76. 22.7 Synthetic Strategies• Most of the reactions in this chapter are C–C bond forming.• Three of the reactions yield a product with two functional groups.• The positions of the functional groups in the product can be used to design necessary reagents in the synthesis.• Practice with SKILLBUILDER 22.8. Copyright 2012 John Wiley & Sons, Inc. 22-76 Klein, Organic Chemistry 1e
  77. 77. 22.7 Synthetic Strategies• Stork enamine synthesis  1,5-dicarbonyl compounds.• Aldol and Claisen  1,3-difunctional compounds. Copyright 2012 John Wiley & Sons, Inc. 22-77 Klein, Organic Chemistry 1e
  78. 78. 22.7 Synthetic Strategies• We have learned two methods of alkylation: 1. The alpha position of an enolate attacks an alkyl halide. 2. A Michael donor attacks the beta position of a Michael acceptor.• These two reactions can also be combined:• Give a reasonable mechanism.• Practice with SKILLBUILDER 22.9. Copyright 2012 John Wiley & Sons, Inc. 22-78 Klein, Organic Chemistry 1e
  79. 79. 22.7 Synthetic Strategies• Give reagents necessary for the following synthesis. Copyright 2012 John Wiley & Sons, Inc. 22-79 Klein, Organic Chemistry 1e

×