Chapter 18: Carbonyl Compounds IILearning Objectives:1. Recognize and assign names to aldehydes and ketones.2. Write the mechanism for nucleophilic addition and nucleophilic addition-elimination reactions of aldehydes and ketones, and be able to predict the products of such reactions.3. Be able to explain the relative reactivity of carbonyl compounds toward nucleophilic addition.4. Be able to describe the concept of employing protecting groups.5. Predict the products of the reactions of carbonyl compounds with Grignard reagents, hydride iondonors, sulfur nucleophiles, and with phosphonium ylides (the Wittig reaction).6. Be able to recognize Re and Si faces of carbonyl compounds, and the stereochemistry outcomes from a nucleophilic addition.7. Predict the products of addition reactions to -unsaturated carbonyl compounds.Sections:18.1 Nomenclature18.2 Relative Reactivities of Carbonyl Compounds*18.3 How Aldehydes and Ketones React*18.4 Reaction of Carbonyl Compounds with Carbon Nucleophiles*18.5 Reaction of Carbonyl Compounds with Hydride Ion*18.6 Reaction of Aldehydes and Ketones with Nitrogen Nucleophiles*18.7 Reaction of Aldehydes and Ketones with Oxygen Nucleophiles*18.8 Protecting Groups*18.9 Addition of Sulfur Nucleophiles18.10 The Wittig Reaction*18.11 Stereochemistry of Nucleophilic Addition Reactions: Re and Si Faces#18.12 Designing a Synthesis V: Disconnections, Synthones, and Synthetic Equivalents18.13 Nucleophilic Addition to -Unsaturated Aldehydes and Ketones*18.14 Nucleophilic Addition to -Unsaturated Carboxylic Acid Derivatives18.15 Enzyme-catalyzed Additions to -Unsaturated Carbonyl Compounds#* Sections that will be focused# Sections that will be skippedRecommended additional problems8.40 – 8.55, 8.58 – 8.61, 8.63 – 8.67, 8.69 – 8.72, 8.741Class Note18.1 NomenclatureOHOHOHOHH HO OOHOHHOH OCH2CH3O OOCH2CH3CHO OCl2HOOHO OOO OOOCH3OO318.2 Relative Reactivities of Carbonyl CompoundsNucleophilic addition 18.3 How Aldehydes and Ketones ReactA. In basic conditionR H (R)OR H(R)O NuNu ( Z)tetrahedral intermediateR H(R)O NuH4B. In acidic conditionH BB+HR H (R)OR H(R)O BHR H (R)OH518.4 Reaction of Carbonyl Compounds with Carbon NucleophilesA. Carbon nucleophile (basic or acidic?)B. Reaction of aldehydes and ketones with Grignard reagent 6C. Reactions of ester and carboxylic acid with Grignard reagent7D. Reactions of aldehydes and ketones with acetylide ions(i) pKa of CH2CH2HRCH CH HR C C HR(ii) Mechanism8E. Reactions of aldehydes and ketones with hydrogen cyanide(i) pKa of H-CN(ii) Mechanism(iii) Synthesis of -hydroxy carboxylic acid918.5 Reaction of Carbonyl Compounds with Hydride IonA. Source of hydride B. Reduction of aldehydes and ketones10C. Reduction of esters11D. Reduction of carboxylic acids12E. Reduction of amides1318.6 Reaction of Aldehydes and Ketones with Nitrogen NucleophilesA. pKa of aminesB. Addition of primary amines14C. Addition of secondary aminesD. Addition of hydrazine, hydroxyamine15E. Mechanism of Wolff-Kishner reduction1618.7 Reaction of Aldehydes and Ketones with Oxygen NucleophilesA. Addition of water (formation of hydrate, gem-diol, geminal diol)R H (R)OR H(R)HO OHH2O(i) Consideration of pKa(ii) Stability consideration17B. Addition of alcohol (formation of hemiacetal, acetal, hemiketal, and ketal)R HOR HR'O OR'HOR'R HR'O OH(2 equivalents)H2OR ROR RR'O OR'HOR'R RR'O OH(2 equivalents)H2O18C. Mechanism1918.8 Protecting GroupsA. Stability of acetals and ketalsB. ExampleOHOCH2CH2OH+OO+H2O(i)OOCH3O?OOH20C. More examples(i)NH2?NH2NO2(ii)NH2?NH2CO2H2118.9 Addition of Sulfur Nucleophiles18.10 The Wittig ReactionA. Wittig reagents(C6H5)3P CH2phosphonium ylide(C6H5)3P CH2B. Formation of Wittig reagents22C. Reactions(i) Synthesis of (ii) Synthesis of 23D. Stereoselectivity (E vs. Z)E. Arbuzov (Perkow) reaction and Horner-Emmons reaction(i) Horner-Emmons reaction24(ii) Arbuzov (Perkow) reaction2518.12 Designing a Synthesis V: Disconnections, Synthones, and Synthetic EquivalentsA. Retrosynthetic analysisExampleOHOHsynthesis offrom2618.13 Nucleophilic Addition to -Unsaturated Aldehydes and KetonesA. Analysis of -unsaturated aldehydes and ketonesROB. Direct addition (1,2-addition) and conjugate addition (1,4-addition)27C. Examples(i)O1) CN2) HCl(ii)O+HSCH3(iii)CH3O+(CH3)2NH28(iv)O1) NaBH4, CeCl32) H2O, H+(v)HO1) CH3MgBr2) H2O, H+(vi)O1) CH3MgBr2) H2O, H+29(vii)1) (CH3)2CuLi2) H2O, H+O18.14 Nucleophilic Addition to -Unsaturated Carboxylic Acid DerivativesClOHOCH3+NHCH3OHOCH3+OCH3O1) LiAlH42) H2O, H+ClONH3