Jacobsen's catalyst

Jacobsen's catalyst (S,S).png
Jacobsen's catalyst is the common name for N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) chloride, a coordination compound of manganese and a salen-type ligand. It is used as an asymmetric catalyst in the Jacobsen epoxidation, which is renowned for its ability to enantioselectively transform prochiral alkenes into epoxides. Prior to its development, catalysts for the asymmetric epoxidation of alkenes required the substrate to have a directing functional group, such as an alcohol as seen in the Sharpless epoxidation. This compound has two enantiomers, which give the appropriate epoxide product from the alkene starting material.

Enantiomerically pure epoxides are desirable as building blocks for complex molecules with specific chirality. Biologically active compounds can exhibit radically different activity based on differences in chirality and therefore the ability to obtain desired stereocenters in a molecule is of great importance to the pharmaceutical industry. Jacobsen's catalyst and other asymmetric catalysts are particularly useful in this field; for example, Jacobsen's catalyst was used to synthesize phenylisoserine, a side chain to the famous anti-cancer drug Taxol, in a four-step synthesis as early as 1992.

Jacobsen’s catalyst is typical of a transition metal oxidation catalyst: it has a high-valent metal center in a nitrogen and oxygen donor environment. The chelating salen ligand of Jacobsen’s catalyst is tetradentate, meaning it binds to the central manganese metal through four bonds, one to each oxygen and nitrogen atom of the salen backbone. It belongs to a class of chiral diimine ligands that are synthesized via the Schiff base condensation.

Both enantiomers of Jacobsen's catalyst are commercially available. Jacobsen's catalyst can be prepared by separating 1,2-diaminocyclohexane into its component enantiomers and then reacting the appropriate tartrate with 3,5-di-tert-butyl-2-hydroxybenzaldehyde to form a Schiff base (see intermediate formed in the reaction scheme below). Reaction with manganese(II) acetate in the presence of air gives the manganese(III) complex, which may be isolated as the chloro derivative after the addition of lithium chloride. Shown below is the preparation of the (R,R)-enantiomer. The synthesis has been adapted for undergraduate level chemistry courses in order to stress the importance of enantiomerically pure compounds.

In general, two mechanisms have been suggested. Because Jacobsen’s catalyst epoxidizes conjugated alkenes (i.e. those in which there are multiple double bonds on alternating carbons) most effectively, the generally accepted mechanism is based on a radical intermediate which is stabilized due to the conjugated nature of the substrate. For non-conjugated alkenes, the substrate is far less able to stabilize a radical, making a radical intermediate more unlikely. In this case, a concerted mechanism in which the bond to the oxygen is simultaneously broken with metal-center while it is formed with the substrate is probable. However, more recent studies have indicated a radical intermediate is possible, challenging the assumption that non-conjugated alkenes undergo concerted mechanisms.

In the original catalytic reaction, iodosylarenes (PhIO) were used as the stoichiometric oxidant, but soon after it was found that chlorine bleach (NaClO), a cheaper alternative, works as well. While other oxidants subsequently have been used, bleach continues to be the most common.

This page was last edited on 8 August 2017, at 18:16.
Reference: https://en.wikipedia.org/wiki/Jacobsen%27s_catalyst under CC BY-SA license.

Related Topics

Recently Viewed