The Jacobsen Epoxidation allows the enantioselective formation of epoxides from various cis-substituted olefins by using a chiral Mn-salen catalyst and a stoichiometric oxidant such as bleach. Compared to the Sharpless Epoxidation, the Jacobsen Epoxidation allows a broader substrate scope for the transformation: good substrates are conjugated cis-olefins (R: Ar, alkenyl, alkynyl; R': Me, alkyl) or alkyl-substituted cis-olefins bearing one bulky alkyl group.
Mechanism of the Jacobsen-Katsuki Epoxidation
For a good overview of mechanistic proposals please refer to T. Linker (Angew. Chem. Int. Ed., 1997, 36, 2060. DOI) and references cited therein.
A simplified catalytic cycle shows the formation of an Mn(V)-oxo complex. L could be a counterion or an amine N-oxide ligand, the addition of which has a slight beneficial effect on enantioselectivity, reaction rate and product yield:
Discussions of the mechanism of the oxygen transfer to the double bond have led to controversy. Depending on the substrate and additives, the formation of side products with trans stereochemistry points to a radical mechanism, whereas alkyl-substituted olefins stereoselectively give only cis products via a concerted mechanism. The suggested formation of manganaoxetanes receives support from calculations on a theoretical level, and from experiments reported by Katsuki using derivatives of the Jacobsen catalyst.
Two different models exist for the approach of the substrate, which help to explain the stereoselectivity of the nearby flat catalyst (a: according to Jacobsen, b: according to Katsuki):
In a simple model, steric repulsion accounts for rate differences and lowered selectivity:
However, Jacobsen was able to show that, after addition of a pyridine N-oxide derivative, trisubstituted alkenes are in fact excellent substrates. A simplified model by Jacobsen (J. Org. Chem., 1994, 59, 4378. Abstract) that includes the formation of radicals is based on the assumption that the dissymmetry of the chiral salen ligand can effectively orient the radical selectivity:
A discussion of recent advances in metallosalen chemistry can be found in a review by Katsuki (Synlett 2003, 281. DOI). This paper shows many oxene, nitrene and carbene transfer reactions using well-designed chiral first- and second-generation metallosalen complexes as catalysts.