Chapter 21 Lecture Notes - CEM 252 at MSU Spring 1997

Chapter 21 - Enolate Anions and Enamines

Common Reactivity: Nucleophilic attack

Chapter 21-Slide 1

Enolate Formation: A Stronger Base

• From Chapter 17: NaOH
  
• LDA (Lithium Diisopropylamide)
  

Chapter 21-Slide 2

LDA: Why is it Better?

• N is left of O on the periodic table
  Since they both have minus charge LDA is stronger base
• LDA is sterically hindered
  It will not act as a nucleophile (nucleophiles can add to carbonyl carbon)

Chapter 21-Slide 3

Regioselectivity of Enolate Formation

Which enolate is more stable?

Which enolate forms faster?

Chapter 21-Slide 4

Steric Hindrance Affects Rate

Chapter 21-Slide 5

Establishing Thermodynamic Conditions

In order to reverse the reaction, proton transfer is needed - the keto form (if present) can act as a proton donor

Chapter 21-Slide 6

Using LDA for Directed Aldol Reactions

Chapter 21-Slide 7

The Acetoacetic Ester Synthesis

Chapter 21-Slide 8

The Malonic Ester Synthesis

Chapter 21-Slide 9

Enamines: Preparation

Preparation: any 2^o amine and carbonyl compound with an a-hydrogen

Chapter 21-Slide 10

Enamines - Similar to Enolate in Reactivity

• Intermediates for alkylating aldehydes/ketones
  
• Intermediates for generating b-diketones
  

Chapter 21-Slide 11

The Michael Reaction - Another Example of 1,4 Addition

Chapter 21-Slide 12

1,4-Addition versus 1,2-Addition

• Extremely strong bases:
  
• Somewhat weaker bases:
  

Chapter 21-Slide 13

CHALLENGE

Will stronger or weaker bases react faster?

Is a compound more stable with a C=C or a C=O? (consider what you know about keto-enol tautomerism)

Discuss these questions with the people around you.

Chapter 21-Slide 14

Robinson Annulation - Forming Cyclohexenones

Chapter 21-Slide 15

Michael Reaction - a Biological Example

(Gutierrez & Siva, Chemical Research in Toxicology, 1995, 8, 455-464)

Chapter 21-Slide 16