:Jacobsen's catalyst

Jacobsen's catalyst consists of a salen ligand, tetradentate, meaning it binds to the central manganese metal through four bonds, one to each oxygen and nitrogen atom of the salen backbone. Its chirality is conferred from the diamine-derived backbone. The aryl groups are decorated with tert-butyl substituents, which amplify the asymmetry around the Mn center.

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.{{OrgSynth | author = Larrow, JF | author2 = Jacobsen, EN | title = (R,R)-N,N'-Bis(3,5-Di-tert-Butylsalicylidene)-1,2-Cyclohexanediamino Manganese(III) Chloride, A Highly Enantioselective Epoxidation Catalyst | volume = 75 | pages = 1 | year = 1998 | prep = v75p0001}} The synthesis has been adapted for undergraduate level chemistry courses in order to stress the importance of enantiomerically pure compounds.{{cite journal | author = Hanson, J | journal = J. Chem. Educ. | year = 2001 | volume = 78 | issue = 9 | pages = 1266 | title = Synthesis and Use of Jacobsen's Catalyst: Enantioselective Epoxidation in the Introductory Organic Laboratory | doi = 10.1021/ed078p1266| bibcode = 2001JChEd..78.1266H }}

:File:Synthesis of (R,R)-Jacobsen's catalyst.png

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.{{cite journal | author = McGarrigle, EM | author2 = Gilheany, DG | journal = Chem. Rev. | year = 2005 | volume = 105 | issue = 5 | pmid = 15884784 | pages = 1563–1602 | doi = 10.1021/cr0306945 | title = Chromium- and Manganese-salen Promoted Epoxidation of Alkenes}}

File:Oxidation des Katalysators V4.svg

After the addition of the oxidant to the system, O=Mn(V) is generally accepted to be the active oxidant species formed (step A). The substrate is thought to approach the metal-oxo bond from the side at a perpendicular orientation in relation to the catalyst in order to allow favorable orbital overlap. This mechanism, which was originally proposed by John Groves to explain porphyrin-catalyzed epoxidation reactions,{{cite journal | author = Groves, JT | author2 = Nemo, TE | journal = J. Am. Chem. Soc. | year = 1983 | volume = 105 | issue = 18 | pages = 5786–5791 | doi = 10.1021/ja00356a015 | title = Epoxidation Reactions Catalyzed by Iron Porphyrins - Oxygen Transfer from Iodsylbenzene| bibcode = 1983JAChS.105.5786G }} is commonly referred to as a "side-on perpendicular approach". The approach is over the diamine bridge, where the steric bulk of the tert-butyl groups on the periphery of the ligand do not interfere with the alkene's approach (see below). However, as is the case with the overall mechanism, the pathway of alkene approach is also debated.

File:Approach of Substrate 1.png

The ease with which Jacobsen's catalyst selectively epoxidizes cis-alkenes has been difficult to replicate with terminal and trans-alkenes. Structural changes to the ligand and adaptations to the protocol for the epoxidation reaction, however, have led to some successes in these areas. For example, derivatives of Jacobsen's catalyst with small structural changes to the salen backbone have been used in conjunction with low temperatures and the oxidant m-chloroperbenzoic acid (m-CPBA) to epoxidize the terminal alkene styrene.{{cite journal | author = Palucki, M | author2 = Pospisil, PJ | author3 = Zhang, W | author4 = Jacobsen, EN | journal = J. Am. Chem. Soc. | year =1994 | volume = 116 | issue = 20 | pages = 9333–9334 | doi = 10.1021/ja00099a062 | title = Highly Enantioselective, Low-Temperature Epoxidation of Styrene| bibcode = 1994JAChS.116.9333P }} The low temperature of the reaction favors only one pathway, the cis pathway, while m-CPBA is used because of water's high freezing point. Little success has occurred with the epoxidation of trans alkenes by manganese compounds but other salen coordination compounds, such as oxochromium complexes, can be used.{{cite journal | author = Daly, AM | author2 = Renehan, MF | author3 = Gilheany, DG | journal = Org. Lett. | year = 2001 | volume = 3 | issue = 5 | pmid = 11259031 | pages = 663–666 | doi = 10.1021/ol0069406 | title = High Enantioselectivities in an (E)-Alkene Epoxidation by Catalytically Active Chromium Salen Complexes. Insight into the Catalytic Cycle}}

The ligand structure of Jacobsen's catalyst is easily modified for use over a wide range of reactions, such as epoxide-ring openings, Diels-Alder reactions, and conjugate additions.{{cite journal | author = Jacobsen, EN | journal = Acc. Chem. Res. | year = 2000 | volume = 33 | pmid = 10891060 | issue = 6 | pages = 421–431 | doi = 10.1021/ar960061v | title = Asymmetric Catalysis of Epoxide Ring-Opening Reactions}}{{cite journal | author = Yoon, TP | author2 = Jacobsen, EN | journal = Science | year = 2003 | volume = 299 | issue = 5613 | pmid = 12637734 | pages = 1691–1693 | doi = 10.1126/science.1083622 | title = Privileged Chiral Catalysts| bibcode = 2003Sci...299.1691Y }} For example, an analogous catalyst with an aluminum center has been used for the carbonylation of epoxides in order to obtain beta-lactones.{{cite journal | author = Getzler, YDYL | author2 = Mahadevan, V | author3 = Lobkovsky, EB | author4 = Coates GW | journal = J. Am. Chem. Soc. | year = 2002 | volume = 124 | issue = 7 | pages = 1174–1175 | doi = 10.1021/ja017434u | title = Synthesis of beta-lactones: A highly active and selective catalyst for epoxide carbonylation| pmid = 11841278 | bibcode = 2002JAChS.124.1174G }}

• Asymmetric catalysis
• Enantiomers
• Jacobsen epoxidation
• Salen ligand

{{reflist}}

Category:Manganese(III) compounds

Category:Catalysis

Category:Metal salen complexes

Category:Tert-butyl compounds

Category:Catalysts