Substituted proline derivatives as organocatalysts in Michael reaction

Abstract

Chiral, polysubstituted proline esters, obtained via cycloaddition reactions of azomethine ylides, were studied as organocatalysts in the Michael reaction of aldehydes/ketones and vinylsulphones. Under optimised reaction conditions employing 10 mol % of the catalyst in wet CH 2 Cl 2 , the yields of the products were generally good while the enantioselectivity varied, reaching up to 52 %.

Menthols as Chiral Auxiliaries for Asymmetric Cycloadditive Oligomerization: Syntheses and Studies of β-Proline Hexamers

“…The developed cycloadditive oligomerization method differs conceptually from traditional protecting-group-use (PGU) β-peptide synthesis methods , and is based on a 1,3-dipolar cycloaddition of azomethine ylide and acrylamide components . Despite that various chiral auxiliaries including menthols, lactates, and optically active amines were successfully used for diastereoselective synthesis of monomeric pyrrolidine products, it is us who applied acrylamides, derived from enantiomerically pure 3-PCA esters, as dipolarophiles for the construction of chiral poly-β-proline framework . Moreover, we observed that these unusual β-peptides influenced the progression of tumor cell cycles and revealed potent anticancer activity in PC-3 cell tests .…”

Organocatalysts Derived from Unnatural α‐Amino Acids: Scope and Applications

“…the performance of whichi nM ichael additions was relatively low in terms of stereocontrol (Scheme 40). [95] Polycyclic unnatural prolines Catalytic unnatural proline derivatives with fused rings have been reported by different authors, although only in af ew cases have the organocatalytic properties of these polycyclic prolinesh ave been provedt ob es ynthetically relevant. Yu, Han, and co-workers [96] described organocatalytic pairs formed by trans-4,5-methano-l-proline 200 and alkaloids,s uch as 201, as efficient promoters of Biginelli reactions between cinnamaldehydes 202,t hiourea 203,a nd b-keto esters 204.T his concept of cooperative catalysis between amino acids and modified alkaloids is similar to that described forp henylglycine in Scheme 36.…”

“…In all the precedent cases that involve monocyclic unnatural proline scaffolds, the pyrrolidine moiety was the only source of chirality. Attempts to introduce additional chiral substituents into unnatural prolines by means of (3+2) cycloadditions involving menthyl acrylates led to organocatalysts 195 a and b , the performance of which in Michael additions was relatively low in terms of stereocontrol (Scheme ) …”

A novel thiourea type organocatalyst possessing a single NH functionality

“…Our interest in organocatalysed reactions prompted a study in this area and the initial results are discussed in this article. 44,45…”