Chem 250 Lab -- Fall 2008
Synthesis and Use of Jacobsen's Salen(Co) Catalyst:
Hydrolytic Kinetic Resolution of Epoxides

Chem 250 Lab Schedule
Chem 250 Lab Introduction

In addition to teaching you important laboratory techniques and reinforcing important lecture concepts, we also like to use the lab as an opportunity to introduce you to modern, cutting-edge chemistry. This semester you will synthesize and use an important catalyst described in a recent paper by Professor Eric Jacobsen and his research group at Harvard. (Schaus, S.E.; Brandes, B.S.; Larrow, J.F.; Tokunaga, M.; Hansen, K.B.; Gould, A.E.; Furrow, M.E.; Jacobsen, E.N. "Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)CoIII Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols" J. Am. Chem. Soc. 2002, 124, 1307-1315.) The structure of the catalyst you will prepare is shown below:

This catalyst is composed of a large organic ligand complexed to cobalt. This type of organic ligand is referred to as a "salen", so for shorthand we can refer to this as Jacobsen's salen(Co) catalyst. There are a number of related catalysts in which the cobalt is replaced with another metal, for example, Mn, Al, or Cr.

In order to understand why these catalysts are important, you need to know that many molecules are chiral. This means that they can exist in two different forms (called enantiomers) that are mirror images of each other. Two enantiomers have very similar chemical properties, but usually have dramatically different biological properties.

Normally, a reaction that produces a chiral molecule will produce a 50:50 mixture of enantiomers (called a racemate or racemic mixture). But if you are making a molecule to use in a biological system (for example as a pharmaceutical) one of the enantiomers may have a desired effect, but the other enantiomer may cause some undesired side-effect. Thus, one of the most important and exciting areas of modern organic chemistry is the search for ways to make chiral molecules in only one of their mirror image forms.

This is where the salen catalysts come in. They are able to promote reactions that produce mostly one enantiomer of a molecule, or alternatively react with only one enantiomer in a racemic mixture. Professor Eric Jacobsen has been a major figure in this field of asymmetric catalysis.

What Professor Jacobsen and his group found was that when a racemic mixture of an epoxide (a molecule with a 3-membered ring containing 2 carbons and an oxygen) is treated with water and a catalytic amount of the salen(Co) catalyst 1, one of the epoxide enantiomers reacts much more rapidly than the other (Scheme 1). Thus, the product produced is predominantly one enantiomer, and the unreacted epoxide left behind is predominantly one enantiomer (i.e., "enantioenriched").

This catalyst is already important industrially, and you will get a chance to use it this semester. But first you have to make it!

Scheme 2 illustrates the steps you will perform to synthesize Jacobsen's salen(Co) complex 2, which is readily converted to the desired catalyst 1 by exposing it to air and acetic acid. In the first step, during week three, you will combine a mixture of 1,2-cyclohexadiamine stereoisomers with tartaric acid to form a salt and then selectively crystallize the stereoisomer shown. During week 5 you will react the now isomerically pure diamine with two equivalents of a phenolic aldehyde to give the organic diimine backbone of the salen catalyst. Then in week 9 you will prepare the cobalt salen complex 2. During weeks 11 and 12 you will convert this complex to the active catalyst and perform a highly selective hydrolytic kinetic resolution of an epoxide.