Lipase‐catalyzed aza‐Michael addition of amines to acrylates in supercritical carbon dioxide

Abstract

BACKGROUND Aza‐Michael addition, a powerful method for the synthesis of β‐amino carbonyl derivatives, has been extensively studied in organic chemistry. In this study, the efficient and chemoselective aza‐Michael addition of amines to acrylates catalyzed by lipase in supercritical carbon dioxide (scCO2) was reported for the first time. RESULTS Under the optimal conditions [amine (1 mmol), acrylate (1 mmol), novozym 435 (20 mg), 40 °C, scCO2 (25 mL, 10 MPa)], the corresponding Michael adducts of amines to acrylates were exclusively obtained in high yields (60–93%) for a short reaction time (1 h). No aminolysis was observed when scCO2 was used as reaction medium. Moreover, novozym 435 showed high reusability in scCO2 for aza‐Michael addition. CONCLUSION The excellent chemoselectivity and reusability of novozym 435 in scCO2 indicate the method's great potential for practical application. © 2019 Society of Chemical Industry

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

“…Therefore, n -hexane was applied in the following process. Obtained results remain in agreement with the literature data for enzymatic aza-Michael addition [ 54 ]. In the next step, the impact of enzyme quantity was investigated.…”

“…Based on literature data regarding enzymes known—bioactivity [ 54 ], the model addition reaction of dimethyl phosphite (1 mmol) and vinyl cinnamate (1 mmol) was conducted in n -hexane at 40 °C ( Scheme 1 ) ( Table 1 , entry 1). A series of commercially available lipases and one domestically prepared pig liver acetone powder were screened as catalysts.…”

“…Among the derivatives studied, the compounds possessing methyl group at α-position 5 , 6 , 7 , 8, and 9 turned out to be the most active comparing to derivatives with aryl group at α-position ( Figure 2 ). The research results presented are important for understanding the biological properties of tested α-hydroxy phosphonate derivatives as a function of potential new antibiotics and their toxic effects on Gram-negative bacteria in the face of the growing drug resistance pandemic, in reference to our previous works related to the characteristics of the model E.coli K12 and R2-R4 [ 44 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Finally, the analyzed α-hydroxy phosphonate derivatives are more cytotoxic in the model bacterial cells than the commonly used antibiotics: ciprofloxacin, bleomycin, and cloxacillin.…”

Biocatalytic Aza‐Michael Addition of Aromatic Amines to Enone Using α‐Amylase in Water

“…Very recently, Chen et al . used lipase enzyme to catalysed the aza‐Michael addition of amines to acrylates in supercritical carbon dioxide . Moreover, the α‐amylase enzymes are known for catalyzing the hydrolysis of α‐glucosidic linkages of polysaccharides such as starch or glycogen in nature .…”

Aza‐Michael addition of 1,2‐diazoles to structurally diverse enones: Efficient methods toward β‐amino ketones

“…However, aza‐Michael addition approach is a standout protocol among the most essential and powerful route for C‐N bond formation; nevertheless addition of azoles to cyclic enones is quite troublesome because of less nucleophilic nature of the azoles and due to the structural complexity of the cyclic enones. [ 2 ] It is evident from the literature reports that metals, [ 3 ] lanthanides, [ 4 ] inorganic strong supports, [ 5 ] fluorides, [ 6 ] organocatalysts, [ 7 ] bases, [ 8 ] and even enzymes [ 9 ] were utilized toward the successful accomplishment of aza‐Michael addition reactions. In recent times, catalyst‐free aza‐Michael addition reactions have also been explored using azoles and β,γ‐unsaturated‐α‐keto esters/electron deficient olefins.…”