Enantioselective reduction of heterocyclic ketones with low level of asymmetry using carrots

Abstract

A whole spectrum of biocatalysts for asymmetric reduction of prochiral ketones is well known including the Daucus carota root. However, this type of reaction is still challenging when pro-chiral ketones present low level of asymmetry, like heterocyclic ketones. In this work, 4,5-dihydro-3(2H)-thiophenone (1), 2-methyltetrahydrofuran-3-one (2), N-Boc-3-pyrrolidinone (3), 1-Z-3-pyrrolidinone (4) and 1-benzyl-3-pyrrolidinone (5) were studied in order to obtain the respective enantioselective heterocyclic secondary alcohols. Except for 5, the corresponding alcohols were obtained in high values of conversion and with high selectivity. In order to circumvent the low isolated yield of the corresponding chiral alcohol from 2, we observed that the use of carrots in the absence of water is feasible. Addition of co-solvents was needed to the water-insoluble ketones 3 and 4. Comparatively, baker’s yeast was used for bio reductions of 1, 3 and 4. And in terms of conversion, selectivity and work-up, the use of carrots were a more efficient biocatalyst, as well as a viable method for obtaining 5-member heterocyclic secondary alcohols.

Keywords:

• Carrot
• bioreduction
• heterocyclic ketones
• chiral heterocyclic alcohols

Acknowledgements

The authors thank the Multiuser Central Facilities (UFABC) for the experimental support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors are grateful to the Fundação de Amparo à Pesquisa do Estado de São Paulo (2017/18007-2) for financial support.