Asymmetric Michael Addition Organocatalyzed by α,β-Dipeptides under Solvent-Free Reaction Conditions

Abstract

The application of six novel α,β-dipeptides as chiral organocatalysts in the asymmetric Michael addition reaction between enolizable aldehydes and N-arylmaleimides or nitroolefins is described. With N-arylmaleimides as substrates, the best results were achieved with dipeptide 2 as a catalyst in the presence of aq. NaOH. Whereas dipeptides 4 and 6 in conjunction with 4-dimethylaminopyridine (DMAP) and thiourea as a hydrogen bond donor proved to be highly efficient organocatalytic systems in the enantioselective reaction between isobutyraldehyde and various nitroolefins.

Organocatalytic Asymmetric Conjugate Addition of Aldehydes to Maleimides and Nitroalkenes in Deep Eutectic Solvents

“…3-(2-Bromophenyl)-2,2-dimethyl-4-nitrobutanal ( 13ai ) [41]. Yellow oil (42 mg, 70%); 1 H NMR (CDCl 3 ): δ H = 9.55 (s, 1H), 7.61 (dd, J = 8.0, 1.2 Hz, 1H), 7.36–7.25 (m, 2H), 7.15 (ddd, J = 8.0, 6.8, 2.2 Hz, 1H), 4.84 (dd, J = 13.2, 11.3 Hz, 1H), 4.72 (dd, J = 13.2, 4.1 Hz, 1H), 4.62 (dd, J = 11.3, 4.1 Hz, 1H), 1.17 (s, 3H), 1.09 (s, 3H) ppm; 13 C-NMR (CDCl 3 ): δ C = 203.9, 135.7, 134.0, 129.6, 128.5, 128.0, 127.2, 76.6, 49.2, 45.4, 21.1, 18.9 ppm; HPLC: Chiralcel OD-H, λ = 230 nm, n -hexane/2-propanol, 80:20, 1.0 mL/min, t r ( major ) = 10.5 min, t r ( minor ) = 25.6 min.…”

Recent Advances in Solvent‐Free Asymmetric Catalysis

“…In 2017, Juaristi and co-workers considered six noveldipeptides 83 a-f as potential chiral organocatalysts in the asymmetric Michael addition (Scheme 61). [83] Initial studies revealed that for the Michael addition of N-arylmaleimides as substrates, catalyst 83 b could afford better yield and selectivity with NaOH as a base additive than other organocatalyst based α,α-dipeptide under neat condition (Scheme 61A). Furthermore, to examine the effect of solvent the reaction was conducted in solution and only dichloromethane afforded results comparable in yield and selectivity relative to the neat conditions.…”

“…In 2017, Juaristi and co‐workers considered six novel‐dipeptides 83 a – f as potential chiral organocatalysts in the asymmetric Michael addition (Scheme ) . Initial studies revealed that for the Michael addition of N ‐arylmaleimides as substrates, catalyst 83 b could afford better yield and selectivity with NaOH as a base additive than other organocatalyst based α,α‐dipeptide under neat condition (Scheme A).…”

Asymmetric Intermolecular Heck Reaction of Aryl Halides by Pd-histidine Organocatalysts

“…Amino acids are well-known as safe and green ligands for preparing asymmetric catalysts [7][8][9][10], such as proline/cyclobutane which used in asymmetric aldol additions, amino acid-containing peptide organocatalysts applying in asymmetric Michael addition [11], and conjugate addition reactions of aldehydes to maleimide [12][13][14][15][16].…”