Rules of the Day 4-02-07

Click here for today's lecture mechanism sheet

1. There are four new concepts associated with chapter 19. Click on these one at a time to get more information.

A) Reactions favor the formation of weaker bases at equilibrium (provides a motive), so you need to have a Table of pKa values

B) Enolates as nucleophiles

C) Beta-Dicarbonyl species are especially acidic

D) Conjugate addition to alpha,beta unsaturated carbonyl species.

2. alpha,beta-unsaturated carbonyl species are electrophilic functional groups in which the enolate (or aenamine) nucleophile attacks the b carbon atom, not the carbonyl carbon (also known as "1,4 conjugate addition"). This process, referred to as a Michael reaction, creates a new carbon-carbon bond and retains the carbonyl in the product.

3. The alpha,beta-unsaturated carbonyl species can be an aldehyde, ketone, ester, amide or even a nitrile.

4. The nucleophile is generally an enolate deroved fom a beta-dicarbonyl species, but enamines and Gilman reagents work as well.

5. The mechanism of the Michael reaction involves attack by the enolate at the beta-carbon atom to generate a new enolate intermediate, that is reprotonated during the reaction to give an enol, that tautomerizes to the keto form. If a beta-dicarbonyl species is used, then the final step is deprotonation at the remaining alpha hydrogen. In this case, the chemists opens up the flask and adds mild acid to give the final product. A catalytic amount of base is used. You can see the first part of the Michael reaction (everything before the tautomerization of the enol) by clicking here.

6. The key synthetic recognition element of the Michael reaction is a carbonyl with a nucleophile derived from an enolate (usually a beta-dicarbonyl enolate) attached to the beta-carbon atom. These can be tough to spot so practice.

7. The Robinson annulation is a Michael reaction followed by an aldol reaction to make a six-membered ring. Talk about a basketball reaction!!! This reaction is important because it helps make steroid rings, and steriods are important pharmaceuticals; hormones such as birth control pills and corticosteroids such as prednisone are steroids.

Homework: There is no homework to turn in this Wednesday because I want you to concentrate on doing the following homework. These are great problems, on the challenging side, and there is no need to make more for you to do. PLEASE DO THE READING AND THESE PROBLEMS EVEN THOUGH YOU DO NOT NEED TO TURN THEM IN!!! Read: Chapter 20 Problems 19.58, 19.59 Take your time on these two problems, and realize that they contain variations on the reaction themes (aldols, Michael reactions, etc.) that we have been covering. Even if you have trouble answering these on your own, make sure you read the study guide solutions and understand what is going on. It is just enolate chemistry, taken in a couple of new directions.