Asymmetric Epoxidation of Allylic Alcohols

By: Josephine Nakhla, chemfiles volume 9 article 2

The catalytic asymmetric epoxidation of olefins has become the reaction of choice to generate diverse chiral building blocks used in the synthesis of natural products and biologically active molecules. The development of catalysts based on bis(hydroxamic acid) ligands for the vanadium-catalyzed asymmetric epoxidation of allylic alcohols was based on a desire to reduce the deceleration effect observed in some cases in related epoxidations with hydroxamic acid ligands. The deceleration observed was predicted to be a result of the formation of inactive species, which were formed from the binding of more than one ligand to the metal. It was predicted that since the bidentate ligand (bis(hydroxamic acid)) would be chelating to the metal, this deceleration effect could be resolved. Additionally, it was hypothesized that a larger R group would prevent the carbonyl oxygen coordination to the metal by favoring a conformation in which the carbonyl group was directed towards the cyclohexane (Figure 1). Thus, an ideal catalyst system was designed via control of the coordination number as well as the steric environment.

Figure 1.

The use of bis(hydroxamic acid) based ligands in combination with VO(O-iPr)3 proved effective in the efficient asymmetric epoxidation of various allylic alcohols (Scheme 1). Using only 1 mol% of the catalyst, Yamamoto and co-workers demonstrated a variety of allylic alcohols could be converted to the enantiopure epoxides with excellent enantioselectivity.

Scheme 1.

This methodology was also applied in the kinetic resolution of allylic alcohol 1, which resulted in high enantioselectivities of the epoxy alcohol as well as the allylic alcohol (Scheme 2).1

Scheme 2.

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  1. Zhang, W. et al. Angew. Chem., Int. Ed. 2005, 44, 4389.

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