Please don’t do problem 31a, but please do problem 32c

Chapter 22 Alpha Substitutions and Condensations of Enols and Enolate Ions Actually this the chemistry of  hydrogen atoms Aldehydes, ketones and esters enolate ion IMPORTANT: enolate is a nuke; attacks via of its alpha carbon

Reactions of Enolates with Electrophiles

ALDOL REACTION - Borodin

C

EXAMPLES Dangle the group attached to alpha carbon nuke portion Electrophilic portion

MECHANISM OF ALDOL REACTION + H

In general: Designing Self Aldol Synthesis break bond; add H to left portion remove H from OH then form C=O +

Acid Catalyzed Aldols Conjugated enones quite stable Also called  - unsaturated aldehyde

Overall Reaction

Other conditions for dehydration of beta hydroxy aldehydes 1. Base plus heat 2 heat

Planning a Self Aldol synthesis of  -Unsaturated aldehyde Add O Add 2 H CH 3 CH 2 CH=O

Aldols Involving Ketones Much slower than aldehydes - need special gimmicks DIACETONE ALCOHOL!!!! mesityl oxide!!!

Crossed Aldol Condensations- Problems Two different aldehydes or ketones PROBLEM - if both have alpha hydrogens

Problem, con’t Also self aldol product of acetaldehyde and propionaldehyde

How to get a single crossed aldol product? 1.Treat one of the aldehydes or ketones with  -hydrogens with another aldehyde or ketone without  -hydrogens. Commonly used carbonyl compouds without  - hydrogens Of course, these will serve as electrophilic centers

Examples Trick is to add compound with  hydrogen to basic solution containing the compound without  hydrogen. +

Problem Can the following compound be prepared in good yield by an aldol condensation?

Aldol Cyclizations OH _ 1,4-diketone Please do problem 22-30

Example 1 Site A to C=O leads to 4-membered ring Site B to C=O leads to 6-membered ring FAVORED

EXAMPLE -2 A B CD D to C=O give 6-membered ring

Example 3

Example Starting diketone? Show the diketone that would give the following 2 H O

Claisen Condensation IMPORTANT POINTS  PKA OF ALPHA H’S ON ESTER ARE AROUND 24 (RECALL KETONES ARE AROUND 20.  THIS REQUIRES THE USE OF A SLIGHTLY STRONGER BASE 3.USE ALKOXIDES RO - WHERE R IS SAME AS THE OR OF THE ESTER (RECALL PKA OF ALCOHOLS ARE AROUND 17 TO 18.

Claisen Condensations Involves Esters with Alpha Hydrogens  keto ester