Alcohols, Carbonyls and REDOX The Carbonyl Group (Section 12.1) Oxidation/Reduction Reactions: Review (Section 12.2) Reduction of Carbonyls to Alcohols (Section 12.3) Oxidation of Alcohols (Section 12.4) Organometallic Compounds (Section 12.5) Organolithium and Magnesium Compounds (Section 12.6) Reactions of Organolithium/Magnesium Species (Section 12.7) Alcohols from Grignard Reactions (Section 12.8) Lithium Dialkylcuprates (Section 12.9)

The Carbonyl Functional Group Carbonyl Features 1  and 1  Bond Carbonyl Group Quite Polarized (C  +, O  - ) Resonance Structure for Carbonyl Reflecting Bond Polarization??

General Reactions of Carbonyls Nucleophilic Addition to Carbonyl Groups: Oxidation of Alcohols/Reduction of Carbonyls: Less Hydrogen Content More Hydrogen Content

Oxidation/Reduction Reactions Commonly Termed ‘REDOX’ Reactions From General Chemistry, we Will Recall  Oxidation: Loss of Electrons  Reduction: Gain of Electrons Organic Chemists will Typically use Different Definitions  Reduction: Increase Hydrogen Content (Decrease Oxygen)  Oxidation: Decrease Hydrogen Content (Increase Oxygen) Oxidizing/Reducing Agents: Usually Inorganic Compounds (M + ) We will also Recall that in REDOX Reactions:  Oxidizing Agents get Reduced  Reducing Agents get Oxidized

Oxidation States of Carbon: Organics +1 For More Electronegative, -1 For Less, 0 For Bonded Carbon

Alcohol Synthesis: Carbonyl Reduction Carboxylic Acids, Esters, Aldehydes Reduced to 1° Alcohols Ketones Reduced to 2° Alcohols Several Hydrogen Sources Are Used In Organic Reactions: We’ve Already Seen NaBH 4

Reducing Agents: 1° and 2° Alcohols Sodium Borohydride: NaBH 4 Lithium Aluminum Hydride: LiAlH 4 (LAH) H 2 /Transition Metal Catalyst (z.b. CuOCuCr 2 O 4 ) NaBH 4 and LiAlH 4 are Hydride Transfer Agents Hydride (H¯) Acts as a Nucleophile Carbonyls Have Varying Degrees of Ease of Reduction: HardestEasiest

Selection of a Reducing Agent CarboxylateEsterKetoneAldehyde LiAlH 4 1° Alcohol 2° Alcohol1° Alcohol NaBH 4 No Reaction 2° Alcohol1° Alcohol Choice of Reducing Agent Impacts Reaction Products For Ketones/Aldehydes Either Reductant Suffices Carboxylates/Esters Only Reduced by LiAlH 4 For Compounds w/ Multiple Carbonyl F.G.s; Select Based on Which Group(s) Need to be Reduced

NaBH 4 /LiAlH 4 Reduction Examples

Oxidizing Agents in Organic Chemistry PCC Generally a Mild Oxidant (1° Alcohol  Aldehyde) Jones Reagent Harsher Oxidant (1° Alcohol  Carboxylic Acid) Alcohol Often Dissolved in Acetone While Jones Reagent Added Choose Oxidant Based on Desired Carbonyl Functional Group

General Oxidizing Agent Selection MeOH1° Alcohol2° Alcohol3° Alcohol PCCH 2 C=OAldehydeKetone No Reaction Cr 6+ H 2 SO 4 HCO 2 H Carboxylic Acid Ketone No Reaction Just as in Reductions, Oxidation Products Depend on Reagent Generally Don’t Oxidize 3° Alcohols (No Texas Carbons) PCC Good For Aldehydes From Primary Alchols Cr 6+ /H 2 SO 4 Reagents, KMNO 4 Primary  Carboxylic Acids Use What You Like For Most Ketones

Oxidation of 1°, 2° Alcohols

Oxidation Mechanisms: Chromate Esters

Organometallic Compounds Organic Compounds Containing Carbon—Metal Bonds Bonds Range From Ionic to Primarily Covalent Ionic C—M Bonds:  C—Na  C—K Primarily Covalent C—M Bonds:  C—Pb  C—Sn  C—Hg Inetermediate C—M Bonds Include C—Mg and C—Li Reactivity Increases with Ionic Character of C—M Bond

Organolithium Reagents Reactive, Carbanion-Like Species (React Slowly w/ Ethers) Halide Reactivity: RI > RBr > RCl (F Not Often Used)

Grignard Reagents Reactivity of Halides Same as for Organolithium Reagents Generally Exist as Complexes, We’ll Use RMgX for Simplicity

Organometallic Reactions: Notes Can Act as Nucleophiles Towards Polarized Carbonyl Groups Very Strong Lewis Bases (React with Acidic Protons) Basicity Necessitates Dry Conditions (Avoid Reaction w/ H 2 O) Reason For Basicity: Carbanion-Like Behavior (pK a ??) Strong Enough Bases to Deprotonate Terminal Alkynes (pK a ??) With No Acidic Protons, Can Do Nucleophilic Substitution Let’s Look at Some Representative Grignard Reactions

Grignard Reactions: Epoxides Grignard Reagents Nucleophilically Open Epoxides Generally Attack Less Substituted Carbon (Steric Hindrance) View This as Carbanion Attacking in S N 2 Reaction (O L.G.)

Grignard Reactions w/ Carbonyls Let’s Look at Some Specific Grignard Reactions w/ Carbonyls Grignard Reagents React With a Variety of Carbonyls  Formaldehyde  1° Alcohols  Higher Aldeydes  2° Alcohols  Ketones  3° Alcohols  Ester  3° Alcohols Attack of Grignard Generates Alkoxide; Protonate to get OH

Grignard Reactions: Carbonyls

Grignard Reactions: Esters Grignard Reagents React Twice w/ Esters  3° Alcohols Two Alkyl Groups of Alcohol Correspond to Grignard Reagent Grignard Reactions Quite Useful in Wide Range of Alcohol Syntheses (w/ Varying Degrees of Substitution)

Reactions of Organolithium Compounds Organolithium Reagents React Similarly to Grignards Also Strong Bases, Same Limitations Apply More Reactive Species Than Grignard Reagents Routine Syntheses: Prefer to use Grignard Reagents Sodium Alkynides (Triple Bond Anions) React in Same Manner w/ Aldehydes and Ketones Now We’ll Look at One More Organometallic: Lithium Dialkylcuprates (A Coupling Reagent)

Lithium Dialkylcuprates Quite Versatile C—C Bond Forming Reaction