Efficient Baylis--Hillman reaction using stoichiometric base catalyst and an aqueous medium.
A practical and efficient set of conditions were developed using stoichiometric base catalyst, 1,4-diazabicyclo[2,2,2]octane (DABCO), and an aqueous medium to overcome problems commonly associated with the Baylis--Hillman reaction, such as low reaction yields and long reaction time. These simple modifications to the classical conditions, using more base catalyst and an aqueous medium, proved to be successful in converting a variety of aliphatic and aromatic aldehydes to their corresponding Baylis--Hillman products. The inclusion of environmentally friendly water in the reaction solvent was critical for achieving the high yield of Baylis--Hillman adducts. Our deuterium-exchange experiments suggest that the Michael addition adduct formed between DABCO and methyl acrylate is the active intermediate for the Baylis--Hillman reaction in aqueous conditions, and its hydrolysis, a nonproductive side reaction facilitated by the quaternary ammonium ion, leading to the formation of a stable betaine product, consumes both the catalyst and methyl acrylate, making it necessary to add more base catalyst and methyl acrylate.
Yu
C
C
Department of Pharmaceutical Chemistry, College of Pharmacy, Rutgers, the State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8020, USA.
Liu
B
B
Hu
L
L
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D010879:Piperazines / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship
D000447:Aldehydes; D010879:Piperazines; D012997:Solvents; C007306:triethylenediamine