Jacobsen's Catalyst

Biologically active compounds are known to  exhibit radically different activities based on their differences in chirality. These activities can readily be exploited by the pharmaceutical industry to develop drugs that cure diseases and promote wellness. The ability to obtain the desired stereocenters within a molecule would naturally be a drug designer’s delight, and of great importance to the pharmaceutical industry [[i]]. Enantiomerically pure epoxides are one of the building blocks for designing complex molecules exhibiting a specific chirality. Asymmetric catalysts, especially Jacobsen's catalysts can be used for efficient enantioselective epoxidation of alkenes [[ii], [iii]]. For example, Jacobsen's catalyst was used to synthesize phenylisoserine, a side chain to the famous anti-cancer drug Taxol [[iv]].

N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) chloride, a coordination compound of manganese and a salen-type ligand, is commonly called as Jacobsen’s catalyst. This compound has two enantiomers, the (R,R) (Figure 1) - & the (S,S) (Figure 2) enantiomers, which give the appropriate epoxide product from the starting compound (alkene).

While epoxidation of cis-alkenes with the Jacobsen’s catalyst is an easy and straightforward process, the epoxidation of trans and terminal alkenes are much harder to achieve. Structural changes to the salen ligand backbone or changes in epoxidation protocol did not give the desired results.  Salen complexes with other transition metals like chromium have been more successful than manganese for catalysing epoxidation of trans or terminal alkenes [iii,[v],[vi]].

The ligand structure of Jacobsen’s complex can be  easily modified for synthesizing catalysts for a wide range of reactions, including epoxide-ring openings, Diels-Alder reactions, and conjugate additions [[vii],[viii]].

For example

1)      Aluminium salen complex has been used for the carbonylation of epoxides to obtain beta-lactones [[ix]] 

2)      Cobalt salen complexes (Figure 3, and 4)  have been used in hydrolytic kinetic resolutions (HKR), for example, in resolving racemic epichlorohydrin to R- or S- epichlorohydrin (Figure 5). 

               

Synthesis with Catalysts Pvt. Ltd. (SWC) is the largest manufacturer in India of chiral Jacobsen’s complexes as well cobalt containing Jacobsen’s type complexes in their highest possible purities. SWC has the capabilities to manufacture custom designed metal salen complexes as per user requirement. SWC can also provide consultancy services to help the user in all their process or catalyst requirements. Please get in touch with SWC by visiting www.syntheiswithcatalysts.com or by writing to info@synthesiswithcatalysts.com

References:

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[i]) Dalton Transactions. 41 (41): 1563–1602

[ii]) Journal of the American Chemical Society. 112 (7): 2801–2803

[iii]) Journal of the American Chemical Society. 113 (18): 7063.

[iv]) J. Org. Chem. 57 (15): 4320–4323

[v])  Chem. Rev. 105 (5): 1563–1602

[vi]) Org. Lett. 3 (5): 663–666

[vii]) Acc. Chem. Res. 33 (6): 421–431

[viii]) Science. 299 (5613): 1691–1693

[ix]) J. Am. Chem. Soc. 124 (7): 1174–1175