Chiral Cu(ii)-amino alcohol based complexes for asymmetric aza-Henry reaction of N-Ts imines

Abstract

A series of chiral dimeric ligands 1A-C, 2A-B, 3A-B and 4A derived from (S)/(R) 1,1′-bi(2-naphthol)-bis-aldehyde/piperazine-bis-aldehyde and various aminoalcohols viz., (1R,2S)-(−)-2-aminodiphenylethanol, (1S,2R)-(−)-2-aminodiphenylethanol, (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol and (R)-valinol were synthesized. In situ generated complexes 1A-C-, 2A-B-, 3A-B-, 4A-Cu(II)/Cu(I) of dimeric chiral ligands with different copper salts were used as catalysts for the asymmetric aza-Henry reaction of a variety of N-tosylimines as substrates with different nitroalkanes at RT to afford good yields of aza-Henry products (80% with respect to the imines) with excellent enantioselectivity (ee > 99%) in 24 h with nitromethane and high syn selective products with excellent enantioselectivity with nitroethane. The dimeric chiral Cu(II)complex 1A-Cu(II) retained its performance at the gram level and was expediently recycled for a number of times. The enantio-pure aza-Henry product was further used for the synthesis of (S)-levamisole (an anthelminthic agent) in good yield and ee in three steps.

New α-Hydrazinophosphonic acid: Synthesis, characterization, DFT study and in silico prediction of its potential inhibition of SARS-CoV-2 main protease

“…The one-pot multicomponent reactions such as Mannich-type reaction and Kabachnik-Fields reaction are largely and efficiently used in organic synthesis to prepare the biologically active compounds [20] , [21] , [22] , [23] , [24] . Several bioactive and pharmaceutical compounds have been synthesized using one-pot multicomponent reactions including antiviral [25] , anticancer [26] , anti-HIV [27] , antimalarial and antiinsecticidal [28] , antipsychotic [ 29 , 30 ], antiparasitic [31] , antidepressant [32] , antibacterial and antimicrobial [33] . The Kabachnik-Fields reaction is a three-component reaction including a carbonyl, an amine and a dialkylephosphite or a trialkylephosphite.…”

The Stereoselective Nitro-Mannich Reaction in the Synthesis of Active Pharmaceutical Ingredients and Other Biologically Active Compounds

“…The synthesis of imidazothiazole-derivative Levamisole, an anthelminthic agent, has been the subject of a few studies. In a formal synthesis of this molecule published in 2014 by Kureshy and coworkers, an enantioselective copper-catalyzed aza-Henry reaction is used to establish the chiral center in the molecule (Choudhary et al, 2014). Amino alcohol-based ligands, particularly 142, were found to promote the reaction between aliphatic N-tosylaldimines and aromatic N-benzenesulfonamide aldimines and nitromethane, providing products in high yields and very high enantio-and diastereoselectivities.…”

Peer Review #2 of "One-pot multicomponent nitro-Mannich reaction using a heterogeneous catalyst under solvent-free conditions (v0.1)"

“…The nitro functional group can also form other functionalities such as hydroxylamines [9], and oximes, or nitriles [10]. Indeed several natural products and pharmaceuticals have been synthesised via an intermediate nitro-Mannich reaction including antiemetic [11], analgesics [12], antimalarial and antiinsecticidal [13], antipsychotic [14,15], antiviral [16], anticancer [17,18], anti-HIV [19], antiparasitic [20], antidepressant [21], antibacterial and antimicrobial [22], and anaesthetic [23].…”