N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

Viera Poláčková,Boglárka Némethová,Radovan Šebesta,Mária Mečiarová,Renata Górová,Dominika Krištofíková

doi:10.3762/bjoc.17.176

Viera Poláčková, Boglárka Némethová + Show 4 more

Open Access

https://doi.org/10.3762/bjoc.17.176

Copy DOI

Abstract

The synthesis of bifunctional N-sulfinylureas and thioureas with an appended pyrrolidine unit is presented. These organocatalysts were evaluated in Michael additions of aldehydes to nitroalkenes both under solvent-free conditions and in solution. The N-sulfinylurea catalyst was more efficient than the corresponding thiourea. For some substrates, enantioselectivities reached 98% ee. The stereogenic center on the sulfur did not have a considerable influence on the catalytic reactions. Under ball-milling conditions, the Michael adducts were obtained in good yields but with slightly lower enantiomeric purities than in solution. DFT calculations elucidated its mode of action and confirmed a dual activation mode, which combines enamine activation of aldehydes and hydrogen-bond activation of nitroalkenes.

Highlights

Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]
We describe the synthesis of new pyrrolidine appended sulfinylurea and thiourea organocatalysts and their assessment in Michael additions of aldehydes to nitroalkenes
We have started the synthesis of the catalysts from Boc-protected (S)-prolinol (1), from which the key intermediate, pyrrolidine derivative 2, can be obtained in three steps according to the literature procedure [32]

Summary

Introduction

Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]. An amine unit with a hydrogen-bond donating skeleton is highly efficient from among various possible combinations of catalytic moieties within an organocatalyst. This idea has been inspired by proline catalysis itself, in which the carboxylic function acts as an ancillary hydrogen-bond donor for the direction of one of the reagents [9]. Pyrrolidine became a privileged structural motif central to many catalyst designs [12] This fact stems from the success of diarylprolinol silyl ethers as chiral organocatalysts, which were independently introduced by Hayashi [13] and Jørgensen [14].

Methods

Results

Conclusion