Jacobsen epoxidation

The Jacobsen epoxidation, also known as the Jacobsen-Katsuki epoxidation, is a chemical reaction that enables the enantioselective epoxidation of unfunctionalized alkyl- and aryl-substituted alkenes. It serves as a complement to the Sharpless epoxidation, which is used for forming epoxides from the double bonds of allylic alcohols. The stereoselectivity of the Jacobsen epoxidation is derived from a C₂-symmetric manganese(III) salen-like ligand, employed in catalytic amounts. The manganese center facilitates the transfer of an oxygen atom from an oxidant, such as chlorine bleach. Named after its inventor, Eric Jacobsen, and sometimes including Tsutomu Katsuki, this reaction is crucial for organic chemists who aim to control the stereochemistry of biologically active compounds and develop enantiopure drugs.

Numerous improved methods for this reaction have been developed. A general reaction scheme is provided below.

Reference

  • Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. Enantioselective Epoxidation of Unfunctionalized Olefins Catalyzed by Salen Manganese Complexes. J. Am. Chem. Soc. 1990, 112 (7), 2801–2803. https ://doi .org /10.1021 /ja00163a052 .

  • Irie, R.; Noda, K.; Ito, Y.; Katsuki, T. Catalytic Asymmetric Epoxidation of Unfunctionalized Olefins Using Chiral (Salen)Manganese(III) Complexes. Tetrahedron: Asymmetry 1991, 2 (7), 481–494. https ://doi .org /10.1016 /S0957 -4166 (00 )86102 -9 .

 

 

Application to Crixivan Intermediate (-)-cis-(1S,2R)-1-aminoindan-2-ol

It required a significant amount of development to synthesize the (-)-cis-(1S,2R)-1-aminoindan-2-ol ((-)-CAI).  A number of different routes including biotransformations.  Both the epoxide (shown below) and the diol undergo a unique Ritter reaction with acetonitrile (CH3CN) to afford enantiopure cis-aminoindanol.