Efficient catalysts for asymmetric Mannich reactions

Abstract

Efficient chiral catalysts for direct asymmetric three-component Mannich reactions of ketones, aldehydes and an amine (p-anisidine) have been developed. The corresponding β-amino carbonyl compounds (Mannich adducts) were obtained in good chemical yields and excellent enantio- and diastereoselectivities. The reaction conditions have been optimized by invoking ultrasonication and the influence of some structural moieties of the catalysts on the chemical yield and stereoselectivity of the Mannich products has been evaluated.

Highly efficient chiral polydentate sulfinyl ligands/catalysts containing prolinol moiety

“…Also in this case the absolute configuration of the major diastereomeric product depended on the enantiomer of prolinol used (Table 3) and the efficiency of the catalysts was very high, resembling the results obtained by us earlier. 6 Moreover, the product was obtained with very high diastereoselectivity and each enantiomer of the product was available using easily accessible enantiopure catalysts.…”

“…Nevertheless, the presence of all the coordinating centers, i.e., the hydroxyl, sulfinyl groups and the amine nitrogen atom, was proven to be essential for the efficiency of the catalysts and allowed us to conclude that the ligands 4 demonstrated a tridentate character. 4,6 Particularly, the presence of the stereogenic sulfinyl group proved crucial for the outcome of all the reactions since its replacement with the corresponding sulfide or sulfone moiety resulted in a substantial decrease of both the yield and enantiomeric excess of the products. Interestingly, the hydroxyl group in 4 could be replaced by the identical enantiomeric amine moiety, but in order to achieve high catalytic activity of the newly formed ligand 5 (Fig.…”

“…1) and stereoselectivity of the reactions in which it was used as catalyst, it was necessary to retain in its molecule the sulfinyl moiety, even if the latter lost in this case its stereogenic character. 4,6 Looking for other chiral amine-type substituents that could be useful in the designing of new ligands we focused our attention on prolinol, which seemed particularly interesting due to the presence of the hydroxyl group, capable of acting as an additional coordinating centre. In this context it should be mentioned that proline and its analogs are widely used as chiral organocatalysts.…”

Highly efficient conjugate additions of diethylzinc to enones promoted by chiral aziridine alcohols and aziridine ethers

“…It is worth noting that small-molecule amine ether ligands are scarcely reported in the chemical literature. [13][14][15][16] In continuation of our interests in the field of asymmetric synthesis, [17][18][19][20][21] and taking all of the aforementioned results into account, we decided to extend the scope of the applicability of aziridine alcohols 11 and aziridine ethers 12 using them as chiral catalysts for the conjugate Michael additions of diethylzinc to enones.…”

ChemInform Abstract: Highly Efficient Asymmetric Aziridination of Unsaturated Aldehydes Promoted by Chiral Hetero‐Organic Catalysts.

“…[21] Previously,w eh ave reportedasynthesis of chiral tridentate ligands, whichc ontain hydroxy,s ulfinyl, and amine moieties, with two stereogenic centers at the sulfinyl sulfur atom and on the carbon atom in the amine function (Scheme 1). [22,23] Ligands that bear open-chain amine functionalities are very effective catalysts for the enantioselective Henry [24] and aza-Henry [25] reactions, direct aldol condensation, [26] and Mannich reaction, [27] whereas their analogs that contain an aziridine ring as the amine moiety exhibited high catalytic activity in diethyl-and phenylethynylzinc additions to aldehydes, [23,28] in the conjugate addition of diethylzinc to a,b-unsaturated carbonyl compounds (enones), [29] and in the asymmetric Simmons-Smith cyclopropanation. [30] An easy access to both enantiomeric products using diastereomeric forms of the ligand was demonstrated.…”