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Shvo’s Catalyst

chemfiles volume 6 article 10

In catalytic asymmetric synthesis enzyme-mediated kinetic resolution is an important area. Lipases are particularly successful in kinetic resolutions and hence are manufactured on commercial scale. However, conventional kinetic resolution has a maximum theoretical yield of 50%. Dynamic kinetic resolution (DKR) circumvents this limitation by epimerizing the slow-reacting enantiomer concurrently with the kinetic resolution. In this way, one enantiomer of the epimerized substrate is converted faster to the product (e.g. by transesterification) by the enzyme, and the yield can theoretically be increased to 100% using DKR (Scheme 22).1


Scheme 22

Diruthenium complex 3, first reported by Shvo,2 has found numerous applications as a versatile catalyst in organic synthesis, including the reduction of aldehydes and ketones to alcohols, bimolecular disproportionation reaction of aldehydes to esters, isomerization of allylic alcohols and oxidation of alcohols.3 Under thermal conditions, the Shvo catalyst dissociates into the catalytically active 16-electron species 4 and 18-electron complex 5 (Scheme 23).


Scheme 23

Bäckvall has successfully used Shvo’s complex as an efficient epimerization catalyst in several enzyme mediated DKRs.4 In the first step of the proposed epimerization mechanism of secondary alcohols, one of the oxygens on 4 abstracts a proton (removing the need of an external base as cocatalyst) and the ruthenium metal acts as a hydride acceptor, subsequently leading to ketone formation. The ketone generated is then reduced in reverse fashion, resulting in an overall epimerization of the corresponding alcohol (Scheme 24).


Scheme 24

The nature of acyl donor is critical to take into account for successful chemoenzymatic DKR, and Bäckvall and co-workers have discovered certain aryl esters are efficient acyl donors in the DKR of several alcohols. An efficient protocol using immobilized Candida antarctica lipase B (CALB) is shown in Scheme 25. Based on the use of CALB in combination with Shvo’s ruthenium catalyst and p-chlorophenyl acetate as acyl donor, a number of secondary alcohols were successfully transesterified and obtained in good to high yields and excellent enantioselectivities (Scheme 26). In the case of the DKR of the racemic a-hydroxy esters, immobilized Pseudomonas cepacia lipase (PS-C) in cyclohexane was used.


Scheme 25


Scheme 26

The chemoenzymatic DKR was also applied to symmetrical diols, hydroxy esters, azido alcohols, hydroxy nitriles, halo alcohols and hydroxy phosphonates (Table 7). Similarly, using a slightly higher amount of Shvo’s catalyst, various β-hydroxy esters were obtained in a tandem aldol-deracemization-transesterification reaction sequence in good yields and enantioselectivities (Scheme 27).


Table 7


Scheme 27

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References

  1. Ward, R. S. Tetrahedron: Asymmetry 1995, 6, 1475.
  2. Shvo, Y. et al. J. Am. Chem. Soc. 1986, 108, 7400.
  3. Prabhakaran, R. Synlett 2004, 2048, and reference citation therein.
  4. For a review, see: Pàmies, O.; Bäckvall, J.-E. Chem. Rev. 2003, 103, 3247.

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