Jacobsen hydrolytic kinetic resolution

Y—Nuc / solvent H2O (catalytic) Cr(lll)salen catalyst R = alkyl, aryl, H Y = cationic species Nuc = anionic species 

The mechanism of the Jacobsen HKR and ARO are analogous. There is a second order dependence on the catalyst and a cooperative bimetallic mechanism is most likely. Both epoxide enantiomers bind to the catalyst equally well so the enantioselectivity depends on the selective reaction of one of the epoxide complexes. The active species is the Co(lll)salen-OH complex, which is generated from a complex where L OH. The enantioselectivity is counterion dependent when L is only weakly nucleophilic, the resolution proceeds with very high levels of enantioselectivity. 

In the laboratory of J. Mulzer, the total synthesis of laulimalide, a microtubule stabilizing antitumor agent, was accomplished. The C9 stereochemistry of the natural product was introduced using the Jacobsen HKR on a diastereomeric mixture of a terminal epoxide. The epoxide mixture was prepared via the Corey-Chaykovsky epoxidation of citronellal. The HKR proceeded in high yield and high selectivity at room temperature, and the products were easily separated by flash chromatography. The did was converted into the diastereomerically pure epoxide in three steps. 

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R,9Z)-oetadec- 9-en-4-olide Currant stem girdler (Janus integer) Fs Sharpless asymmetric dihydroxylation and Jacobsen hydrolytic kinetic resolution (HKRL [204]... 

Following the examples of Schemes 2.5 and 2.7, the target may be synthesized from butyraldehyde as shown below. An altemative is radical addition of an enantiopure 2 hydroxy 1 pentyl group (perhaps from Jacobsen hydrolytic kinetic resolution of 1,2 epoxypentane,) to the N acylhydrazone derived from 5 chloropentanal. 

Industrialization studies of the Jacobsen hydrolytic kinetic resolution of racemic epichlorhy-drin... 

Industrialization Studies of the Jacobsen Hydrolytic Kinetic Resolution of Epichlorohydrin... 

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