Chapter 18: Carbonyl Compounds II Learning bjectives: 1. ecognize 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 ion donors, sulfur nucleophiles, and with phosphonium ylides (the Wittig reaction). 6. Be able to recognize e and Si faces of carbonyl compounds, and the stereochemistry outcomes from a nucleophilic addition. 7. Predict the products of addition reactions to α,β-unsaturated carbonyl compounds. Sections: 18.1 Nomenclature 18.2 elative eactivities of Carbonyl Compounds* 18.3 ow Aldehydes and Ketones eact* 18.4 eaction of Carbonyl Compounds with Carbon Nucleophiles* 18.5 eaction of Carbonyl Compounds with ydride Ion* 18.6 eaction of Aldehydes and Ketones with Nitrogen Nucleophiles* 18.7 eaction of Aldehydes and Ketones with xygen Nucleophiles* 18.8 Protecting Groups* 18.9 Addition of Sulfur Nucleophiles 18.10 The Wittig eaction* 18.11 Stereochemistry of Nucleophilic Addition eactions: e and Si Faces # 18.12 Designing a Synthesis V: Disconnections, Synthones, and Synthetic Equivalents 18.13 Nucleophilic Addition to α,β-unsaturated Aldehydes and Ketones* 18.14 Nucleophilic Addition to α,β-unsaturated Carboxylic Acid Derivatives 18.15 Enzyme-catalyzed Additions to α,β-unsaturated Carbonyl Compounds # * Sections that will be focused # Sections that will be skipped ecommended additional problems 8.40 8.55, 8.58 8.61, 8.63 8.67, 8.69 8.72, 8.74 1
Class Note 18.1 Nomenclature Cl C 2 C 3 C 2 C 3 C 2
C 3 3
18.2 elative eactivities of Carbonyl Compounds Nucleophilic addition 18.3 ow Aldehydes and Ketones eact A. In basic condition Nu Nu () () () Nu ( Z) tetrahedral intermediate 4
B. In acidic condition B B + B () () () 5
18.4 eaction of Carbonyl Compounds with Carbon Nucleophiles A. Carbon nucleophile (basic or acidic?) B. eaction of aldehydes and ketones with Grignard reagent 6
C. eactions of ester and carboxylic acid with Grignard reagent 7
D. eactions of aldehydes and ketones with acetylide ions (i) pka of C 2 C 2 C C C C (ii) Mechanism 8
E. eactions of aldehydes and ketones with hydrogen cyanide (i) pka of -CN (ii) Mechanism (iii) Synthesis of α-hydroxy carboxylic acid 9
18.5 eaction of Carbonyl Compounds with ydride Ion A. Source of hydride B. eduction of aldehydes and ketones 10
C. eduction of esters 11
D. eduction of carboxylic acids 12
E. eduction of amides 13
18.6 eaction of Aldehydes and Ketones with Nitrogen Nucleophiles A. pka of amines B. Addition of primary amines 14
C. Addition of secondary amines D. Addition of hydrazine, hydroxyamine 15
E. Mechanism of Wolff-Kishner reduction 16
18.7 eaction of Aldehydes and Ketones with xygen Nucleophiles A. Addition of water (formation of hydrate, gem-diol, geminal diol) () () 2 (i) Consideration of pka (ii) Stability consideration 17
B. Addition of alcohol (formation of hemiacetal, acetal, hemiketal, and ketal) ' ' ' ' (2 equivalents) 2 ' ' ' ' (2 equivalents) 2 18
C. Mechanism 19
18.8 Protecting Groups A. Stability of acetals and ketals B. Example + C 2 C 2 + 2 (i)? C 3 20
C. More examples (i) N 2? N 2 N 2 (ii) N 2? N 2 C 2 21
18.9 Addition of Sulfur Nucleophiles 18.10 The Wittig eaction A. Wittig reagents (C 6 5 ) 3 P C 2 phosphonium ylide (C 6 5 ) 3 P C 2 B. Formation of Wittig reagents 22
C. eactions (i) Synthesis of (ii) Synthesis of 23
D. Stereoselectivity (E vs. Z) E. Arbuzov (Perkow) reaction and orner-emmons reaction (i) orner-emmons reaction 24
(ii) Arbuzov (Perkow) reaction 25
18.12 Designing a Synthesis V: Disconnections, Synthones, and Synthetic Equivalents A. etrosynthetic analysis Example synthesis of from 26
18.13 Nucleophilic Addition to α,β-unsaturated Aldehydes and Ketones A. Analysis of α,β-unsaturated aldehydes and ketones β α B. Direct addition (1,2-addition) and conjugate addition (1,4-addition) 27
C. Examples (i) 1) CN 2) Cl (ii) + SC 3 (iii) + (C 3 ) 2 N C 3 28
(iv) 1) NaB 4, CeCl 3 2) 2, + (v) 1) C 3 MgBr 2) 2, + (vi) 1) C 3 MgBr 2) 2, + 29
(vii) 1) (C 3 ) 2 CuLi 2) 2, + 18.14 Nucleophilic Addition to α,β-unsaturated Carboxylic Acid Derivatives Cl + C 3 NC 3 + C 3 1) LiAl 4 2) 2, + C 3 Cl + N 3 (excess) 30