CBHA Ligands

By: Dr. Daniel Weibel, Chemfiles Volume 10 Article 1

Yamamoto and his group developed a new type of ligands based on the C2-symmetric chiral bishydroxamic acid (CBHA). These bidentate ligands have pendant "arms" that can be substituted with a variety of substituents allowing for a finetuning of the ligand potency. A variety of these ligands have been synthesized and the reactivity was probed in a variety of asymmetric oxidation reactions.

Asymmetric Epoxidation of Allylic Alcohols

Chiral epoxides have become a common building block used in the synthesis of natural products and biologically active substances. These enantiomerically enriched compounds can be obtained through different protocols such as the Sharpless asymmetric epoxidation using a titanium-tartrate complex or the Jacobsen epoxidation catalyst using a salen-manganese complex. One of the drawbacks of these reactions is the use of high catalyst loading and long reaction time. Moreover, the scope of these catalysts is somewhat limited.

Yamamoto and co-workers used the CBHA ligands that were developed for the epoxidation of a variety of allylic alcohols. Using 2 mol % of the BHA ligand with 1 mol % of VO(O-iPr)3 404926 with tert-butyl hydroperoxide (TBHP, 458139) under air at 0 °C to –20 °C afforded the desired epoxy alcohol with both high enantioselectivities and good yields. The procedure proved to be effective for both small and complex epoxy alcohols (Scheme 3).1

Scheme 3

Scheme 3

Asymmetric Epoxidation of Olefins

The asymmetric epoxidation of olefins has become an important reaction to obtain essential chiral building blocks. One of the most practical methods reported for this reaction is the manganesesalen catalyst that Jacobsen and co-workers reported in 1990. However, the low reaction temperature required for the reaction and the lack of selectivity for Z olefins made this method limited. Yamamoto and co-workers expanded the use of their CBHA ligands with the asymmetric epoxidation of olefins using a molybdenum complex. This new method proved to be efficient for the asymmetric oxidation of mono-, di- and trisubstituted olefins. The reaction is performed under mild conditions and under air giving good yields and excellent selectivity.

Scheme 4

Scheme 4

Asymmetric Oxidation of Sulfides

The preparation of enantiopure sulfoxides has become of utmost importance as building blocks for the synthesis of drugs and natural products. Several methods exist to synthesize these chiral sulfoxides, but they usually require several steps, stringent conditions and in most cases, result in low enantioselectivity. Yamamoto and co-workers used their newly developed CBHA ligands with a molybdenum complex for the asymmetric oxidation of sulfides to generate chiral sulfoxides. The reaction is carried out under air with only 2 mol % of catalyst required for good yield.

Scheme 5

Scheme 5: (227749)

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  1. Zhang, W.; Basak, A.; Kosugi, Y.; Hoshino, Y.; Yamamoto, H. Angew. Chem. Int. Ed. 2005, 44, 4389.
  2. Barlan, A. U.; Basak, A.; Yamamoto, H. Angew. Chem., Int. Ed. 2006, 45, 5849.
  3. Basak, A.; Barlan, A. U.; Yamamoto, H. Tetrahedron: Asymmetry 2006, 17, 508.

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