Bifunctional Thio/Squaramide Catalyzed Stereoselective Michael Additions of Aldehydes to Nitroalkenes towards Synthesis of Chiral Pyrrolidines

Abstract

Bifunctional squaramide and thiosquaramide organocatalysts were assessed in a stereoselective Michael addition of aldehydes to nitroalkenes. Organocatalysts feature pyrrolidine unit for enamine activation of aldehydes and hydrogen bond donating fragment for nitroalkene activation. The corresponding Michael adducts were obtained in good yields and good to high enantiomeric purities. Solvent‐free conditions were also tested but did not provide any significant improvement. Michael adducts were transformed into chiral pyrrolidines via reductive cyclization.

Application of Proline-Derived (Thio)squaramide Organocatalysts in Asymmetric Diels–Alder and Conjugate Addition Reactions

“…35 Šebesta and co-workers prepared benzyl pyrrolidine-thiosquaramide 16 by using this strategy. 39 In our work, however, we prepared thiosquaramide organo-…”

“…35 Šebesta and co-workers prepared benzyl pyrrolidine-thiosquaramide 16 by using this strategy. 39 In our work, however, we prepared thiosquaramide organocatalyst 16 ·TFA by the direct thionation of squaramide analogue 10 using P 4 S 10 -pyridine complex, which thionating agent was successfully applied previously in the literature. 22 36 Since thiosquaramides are usually unstable on silica gel, by using the direct thionation of squaramides, several purification steps of thio intermediates can be avoided (Scheme 4 ).…”

Synthesis of Chiral 3,4‐Disubstituted Pyrrolidines with Antibacterial Properties

“…Stereoselective Michael additions with enolizable carbonyl compounds proceed well via enamine activation . This robust Michael addition provides key chiral intermediates, γ‐nitroaldehydes which are subjected to reductive cyclization (Scheme ) . In this paper, we present synthesis of a series of chiral 3,4‐disubstituted pyrrolidine derivatives and evaluation of their antibacterial activities.…”

Rhodium-Catalyzed Ring Expansion of Azetidines via Domino Conjugate Addition/N-Directed α-C(sp3)–H Activation

“…Reported yields refer to isolated material after purification via flash column chromatography. The enantiomeric excess (ee) was determined by chiral HPLC. b The absolute configuration of 2ba was determined by transforming it to trans -methyl 4-phenylpyrrolidine-3-carboxylate and comparison of the optical rotation value with known compounds c ( R , R )- L10 was used. …”

“… b The absolute configuration of 2ba was determined by transforming it to trans -methyl 4-phenylpyrrolidine-3-carboxylate and comparison of the optical rotation value with known compounds …”