Notes_Enolates3

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Unformatted text preview: Extra Credit Opportunity #2 available at front (Same as one handed out on Wednesday) Enolates, Enols and Enamines Vollhardt: Chapter 17, Sec3on 179 Chapter 18, Sec3on 181 to 187 Lecture Supplements: pg. 4352 CFC, OWLS, PP: pg. 257280 All materials herein are copyright 2008 Stephanie L. Gould. Materials are intended for personal use in conjunc3on with Chemistry 14D at UCLA. Distribu3on is not permiSed. Chemical Structures O HOO- Enolate O H3O+ or HO- OH Enol O (CH3)2NH H2SO4 N(CH3)2 Enamine Copyright 2008 Stephanie L. Gould General Reactivity Nucleophiles! ON(CH3)2 OH > Enolates are Strong Nucleophiles Formal nega3ve Charge Adjacent O gives addi3onal electron density > Enamines are Moderate Nucleophiles No Formal Charge Adjacent N gives addi3onal electron density Enols Moderate Nucleophiles Adjacent O gives addi3onal electron density Electron rich PI BOND is the source of the nucleophilic character of all three Copyright 2008 Stephanie L. Gould Formation of Enolate and Enols O H H H Base- O H H O- H-Base OH Keto Enolate Enol Keto form stable Process called ketoenol tautomeriza3on Isomers that differ by one hydrogen loca3on Each structure called a tautomer Copyright 2008 Stephanie L. Gould Enolate vs. Substitution Products O H H H Base- O H H O- H-Base OH Keto Enolate Enol Want reactant to "act" as base not nucleophile Sterics favors base (Hydrogen easier to abstract than aSach at carbonyl Li Use a STERICALLY HINDERED base (ex. LDA) Copyright 2008 Stephanie L. Gould N Formation of Enols Acid Catalyzed O H H H OH H3O+ OH OH H H H H H H H2O Copyright 2008 Stephanie L. Gould Keto Enol Equilibrium O H3O+ or HOOH Keto form generally more stable Must use strong, hindered base to form enolate Enol forma3on favored when stabilized, ex: O OH Copyright 2008 Stephanie L. Gould Chemical Structures O HOO- Enolate O H3O+ or HO- OH Enol O (CH3)2NH H2SO4 N(CH3)2 Enamine Copyright 2008 Stephanie L. Gould Formation of Enamines H+ H O C R2NH OH C HO NR2 H2O H+ R N R'' R N R H2O NR2 HO NR2 H H2O R N R Copyright 2008 Stephanie L. Gould How do we know which hydrogen? O O O How many types of Hydrogen atoms are in this molecule? O H O O H 1 H H LDA CH3OCH3 H 3 H H 2 H Base reacts with MOST acidic proton Usually leads to MOST stable enolate Copyright 2008 Stephanie L. Gould Draw all of the possible enolates Rank in terms of stability of enolate O O O O O O LDA CH3OCH3 3 O O O 1 O O O 2 Copyright 2008 Stephanie L. Gould End of Lecture 1 Start of Lecture 2 Administrative Extra Credit #2 5 pts Due Wednesday, June 4th at 1pm. No excep3ons! Exam #2: Average: 67 High: 100 Low: 1 Regrade policy on VOH. Regrade requests will only be accepted before Monday, June 9th 3pm (Before your Final) Copyright 2008 Stephanie L. Gould Final Exam Monday June 9th That's only one week from now! Ackerman Ballroom 36pm Format ~910 pages Concepts (45 pages) Reac3ons (23 pages) Mechanisms (2 pages) Exam is Comprehensive (Weeks 110) Copyright 2008 Stephanie L. Gould Material Subs3tu3on Reac3ons (SN2/SN1) Elimina3on Reac3ons (E2/E1) Addi3on Reac3ons to CC PiBonds EAS Reac3on Radical Reac3ons Carbonyls Fundamentals and Reac3ons with Enolate, Enol and Enamines We will NOT cover Pharmaceu3cals Copyright 2008 Stephanie L. Gould Additional Study Materials Mechanism/Product Prac3ce on VOH Will post answers on Wednesday Thinkbook pg. 291292 Will post answers on Wednesday Review your second midterm Answers posted online today Review in class on Friday (Remember class is only 50 mintues long, this should not serve as your only studying!) Copyright 2008 Stephanie L. Gould Practice Provide the Enolate, Enol or Enamine product for the following reactions LDA Ethyl Ether O O H O NH N H+ H O LDA Ethyl Ether O O H H3O+ O O OH H Copyright 2008 Stephanie L. Gould Reactions Enolate Reac3ons with: Alkyl halides** (SN2/E2) Aldehydes and Ketones** (Aldol Reac3on) Esters** (Claisen and Dieckmann Condensa3on Reac3ons) **We will cover all of these mechanism Copyright 2008 Stephanie L. Gould Enolate Reaction with Alkyl Halide O NaOCH3 CH3I (1 eq) O O O CH3 Propose a reasonable mechanism for this product to form O H NaOCH3 CH3I (1 eq) O O O O H3C I O CH3 Copyright 2008 Stephanie L. Gould SN2 vs E2 O H NaOCH3 CH3I (1 eq) O O O O H3C I O CH3 SN2 H O H NaOCH3 CH3I (1 eq) O O Copyright 2008 Stephanie L. Gould O H2C H3C CH3 I O H + O E2 SN2 vs E2 SN2 E2 Electrophile CANNOT be Ter3ary Electrophile ter3ary Enolates are moderate Good Leaving Group bases (but good nuclephiles) Good Nucleophile Polar Solvent (Apro3c preferred) Copyright 2008 Stephanie L. Gould Revisiting the First Example O NaOCH3 CH3I (1 eq) O O NaOCH3 (2 eq) CH3I (2 eq) O CH3 O O CH3 O CH3 O Limita3on Polyalkyla3ons are possible Copyright 2008 Stephanie L. Gould Practice H3CH2CO2CH2C O LDA (excess) BrCH2CO2CH2CH3 (2eq) CH2CO2CH2CH3 O LDA CH2CH3Br (1eq) O Et O Et Et Et LDA CH2CH3Br O (both in excess) O Copyright 2008 Stephanie L. Gould Returning Exams Last Names: AF Outside of Lecture Hall with Chris Day GK Outside of Lecture Hall with Allison Rhodes OS Upper Right (North) Side of Lecture Hall with Yuen Lau LN and TZ and those who are not enrolled as per the registrar With me in the front of the Lecture Hall Copyright 2008 Stephanie L. Gould End of Lecture 2 Start of Lecture 3 Turn in Extra Credit Opportunity #2 at the front now! Include your Name and ID # No late assignments will be accepted Final Exam Monday June 9th That's only one week from now! Ackerman Ballroom 36pm If you want your exam mailed to you, please bring a selfaddressed, stamped (3 stamps) envelop to the final exam Copyright 2008 Stephanie L. Gould Reactions Enolate Reac3ons with: Alkyl halides** (SN2/E2) Aldehydes and Ketones** (Aldol Reac3on) Esters** (Claisen and Dieckmann Condensa3on Reac3ons) **We will cover all of these mechanism Copyright 2008 Stephanie L. Gould Aldol Reaction Ketones and Aldehydes O (H3C)3C + O H NaOH CH3OH (H3C)3C O H O OCH3 O (H3C)3C H -OH O (H3C)3C O H O H Ph (H3C)3C O (H3C)3C O (H3C)3C HO H Ph H Copyright 2008 Stephanie L. Gould -OH Things to consider Reac3on of Enolate with an Aldehyde Product is an Alcohol If Alcohol is adjacent to groups that would stabilize leaving (there is resonance stabiliza3on) then the alcohol group can leave in an an E2 elimina3on Reac3on can also occur with Ketones Reac3on can be intramolecular Copyright 2008 Stephanie L. Gould Practice O LDA 2 CH3OH O (H3C)3C HO C(CH3)3 O + H O O NaOH CH3OH H OH O O LDA CH3OH, heat CH Copyright 2008 Stephanie L. Gould 3 O Reactions Enolate Reac3ons with: Alkyl halides** (SN2/E2) Aldehydes and Ketones** (Aldol Reac3on) Esters** (Claisen and Dieckmann Condensa3on Reac3ons) **We will cover all of these mechanism Copyright 2008 Stephanie L. Gould Claisen and Dieckmann Reactions O 2 H3C OCH3 1. KOCH3 2. H+ (workup) O O OCH3 Ketoester O OCH3 O H3C OCH3 O H3CO O CH3 OCH3 O H3CO O CH3 H+ H3CO O O CH3 Still in Basic Conditions H3CO O O CH3 Copyright 2008 Stephanie L. Gould Dieckmann Reaction - Intramolecular What is the major Product? O O H3CO O OCH3 1. LDA 2. H+ OCH3 O Copyright 2008 Stephanie L. Gould Practice O OCH3 1. LDA (1eq) 2. PhCHO 3. H+ workup O O OCH3 1. LDA (1eq) 2. PhCO2CH3 3. H+ workup O OCH3 O O OCH3 O 2 OCH3 1. LDA (1 eq) 2. H+ workup Copyright 2008 Stephanie L. Gould Evaluations ...
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This note was uploaded on 08/20/2008 for the course CHEM 14D taught by Professor Hardinger during the Spring '08 term at UCLA.

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