Synthesis, lipase catalyzed kinetic resolution, and determination of the absolute configuration of enantiomers of the Morita-Baylis-Hillman adduct 3-hydroxy-2-methylenebutanenitrile

Abstract

3(RS)-Hydroxy-2-methylenebutanenitrile was synthesized from acetaldehyde and acrylonitrile with DABCO as a catalyst. Optimization of the reaction conditions was conducted because some literature procedures were not reproducible. Asymmetric transesterification of the Morita-Baylis-Hillman adduct was carried out using ten lipases. The hydroxyl-nitrile was also esterified chemically and subjected to enzymatic hydrolysis with the same set of enzymes. The best results were obtained with lipase from Candida antarctica and Novozyme 435. The absolute configuration of an optically pure hydroxyl-nitrile was determined by Mosher's method.

Synthesis and Characterization of Cyanobutadiene Isomers—Molecules of Astrochemical Significance

“…Morita−Baylis−Hillman addition of acrylonitrile ( 14) and acetaldehyde using catalytic 1,4-diazabicyclo[2.2.2]octane (DABCO) afforded 3-hydroxy-2-methylenebutanenitrile (15) in quantitative yield. 72 Subsequent dehydration of 15 was performed using catalytic K 2 CO 3 . The resulting 2-cyano-1,3butadiene (3) was distilled from the reaction mixture under vacuum and collected as an aqueous emulsion that separated upon cooling.…”

“…Although 2-cyano-1,3-butadiene ( 3 ) has been prepared previously, synthetic routes often involve a pyrolysis reaction as the last step. ,− Preferring to avoid a pyrolysis reaction, we prepared 2-cyano-1,3-butadiene ( 3 ) using a combination of literature procedures from Strub et al and Nonaka et al − (Scheme ). Morita–Baylis–Hillman addition of acrylonitrile ( 14 ) and acetaldehyde using catalytic 1,4-diazabicyclo[2.2.2]­octane (DABCO) afforded 3-hydroxy-2-methylenebutanenitrile ( 15 ) in quantitative yield . Subsequent dehydration of 15 was performed using catalytic K 2 CO 3 .…”

The Application of Biocatalysis in the Preparation and Resolution of Morita‐Baylis‐Hillman Adducts and Their Derivatives

“…Strub and co-workers were able to demonstrate resolution of the MBH adduct derived from acetaldehyde and acrylonitrile using both transesterification and hydrolysis of the corresponding acetate (Scheme 19). [84] The enzyme giving the best E value of 91 for transesterification was Novozyme 435, with this same enzyme performing very well in the hydrolysis reaction (E > 200). Lipase A from Candida antarctica was also found to be effective for resolution by hydrolysis.…”

“…Strub and co‐workers were able to demonstrate resolution of the MBH adduct derived from acetaldehyde and acrylonitrile using both transesterification and hydrolysis of the corresponding acetate (Scheme 19). [84] …”

Lipase‐Catalysed Enzymatic Kinetic Resolution of Aromatic Morita‐Baylis‐Hillman Derivatives by Hydrolysis and Transesterification

“…reported only 9 % conversion after 35 days for the transesterification reaction of benzaldehyde‐derived MBH adducts [14] . Interestingly, there are literature reports on the EKR of MBH adducts derived from aliphatic aldehydes by transesterification [8,15] . The earlier success we achieved in the EKR of MBH acetates by hydrolysis prompted us to expand the substrate scope for the EKR reactions using different substrates, acyl groups and enzymes and we were also motivated to try and achieve EKR using transesterification on aromatic MBH substrates for the first time.…”