Chemical Synthesis

CBHA Ligands

Introduction

Asymmetric synthesis have become one the most important tool for the synthesis of chiral molecules. The importance of these transformations is illustrated by the near endless discovery of chiral molecules used in various fields such as pharmaceuticals, flavors and fragrances and pesticides. Since the pioneering work of Knowles and Horner in the hydrogenation of prochiral olefins, a plethora of new ligands and catalysts have been developed for new asymmetric reactions. The common feature of these ligands is their C2 symmetry, reducing the number of possible isomeric metal complexes and the number of different substrates. These new transformations give access to molecules in fewer steps, high yields and high selectivities.

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 fine-tuning of the ligand potency. A variety of these ligands have been synthesized and the reactivity was probed in a variety of asymmetric oxidation reactions.

 

Advantages

  • Versatile ligands
  • Atom-economical
  • Low catalyst loading
  • Mild catalytic conditions
 

Representative Applications

Asymmetric Epoxidation of 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 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 with tert-butyl hydroperoxide (TBHP) under air at temperature between 0° C and –20° C afforded the desired epoxy alcohol with both high enantioselectivities and good yields. The procedure proved to be effective for small epoxy alcohols as well as more complex epoxy alcohols.

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

 

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 manganese-salen 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 coworkers 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.

Reference: Barlan, A. U. et al. Angew. Chem., Int. Ed. 2006, 45, 5849.

 

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 coworkers 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.

Reference: Basak, A. et al. Tetrahedron: Assymmetry 2006, 17, 508.



Prod. No. Product Name Structure
700592 (R)-CBHA-DPA  
700576 (S)-CBHA-DPA  
700584 (R)-CBHA-DMDA  
700568 (S)-CBHA-DMDA  
700541 (R)-CBHA-TPP  
700533 (S)-CBHA-TPP