Enantioselective anti-Mannich reaction catalyzed by modularly designed organocatalysts

Abstract

A highly stereoselective method for achieving the anti-Mannich reaction of aldehydes and ketones with ethyl (4-methoxyphenylimino)acetate was realized using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and (A)-pyrrolidien-3-carboxylic acid in the reaction media. The desired anti-Mannich products were obtained in good to excellent yields (up to 93%), excellent diastereoselectivities (up to 99:1 dr), and good to high enantioselectivities (up to 99% ee).

Designing a novel tetradentate polyoxometalate eco-catalyst for the synthesis of β-aminocyclohexanone derivatives in water

“…The Mannich reaction is one of the most useful strategies for C-C bond formation in organic synthesis. 1,2 It is a practical and efficient method for the construction of both allylic and benzylic amines, important targets that are found in many biologically active molecules and which are useful synthetic intermediates employed in the total syntheses of alkaloids and other complex molecules. [3][4][5][6][7] This reaction is considered to be a very effective strategy for the synthesis of useful compounds as building blocks in pharmaceuticals and natural products such as antimicrobial, 8 cytotoxic, 9 anticancer 10 and analgesic activity.…”

Recent Advances in Solvent‐Free Asymmetric Catalysis

“…Recently, the Zhao group developed the anti-Mannich reaction of aldehydes and ketones with ethyl (4-methoxyphe-nylimino)acetate using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and (R)-pyrrolidine 3-carboxylic acid in the reaction media. [59] The authors found that MDOs self-assembled could deliver the desired anti-Mannich products in high yields (up to 93 %), excellent diastereoselectivities (up to 99 : 1 dr), and good to high enantioselectivities (up to 99 % ee) under neat conditions, without the need of using large excesses of the aldehyde or ketone substrates (Scheme 40). It should be noted that common organic solvents were also screened but the results were not so promising with respect to those in neat conditions.…”

“…In 2009 the group of Jacobsen used (salen)Co(III) catalyst with monomeric (58) and oligomeric (59) forms to the enantioselective formation of tetrahydrofuran and benzodihydrofuran by intramolecular oxetane ring openings. [66] This intramolecular reaction was carried out with 1 mol % of catalyst 58 in the absence of solvent or with small amount of methyl tert-butyl ether (TBME) and 0.01 mol % catalyst 59 in MeCN.…”

Theoretical evidence for the enantioselectivity of Mannich reactions with fluorinated aromatic ketones

“…3 The asymmetric Mannich reaction has also been explored extensively, whether with organometallic catalysts 4 or with organocatalysts. 5…”