Green Synthesis Of Trisubstituted Tetrahydrothiophenes,Isoquinuclidine,and Chiral ?-aminoketones

Green Chemistry,an important and attractive research field,plays a vital role for environmental protection as it encourages the design of products and processes that minimize the use and generation of hazardous waste.In our research the recent development of green chemistry was reviewed.We also report a catalyst-free synthetic method for trisub stituted tetrahydro thiophenes and bio catalytic protocols for isoquinuclidine derivatives and chiral a-aminoketones.A simple,efficient,eco-friendly and catalyst-free procedure was developed for the construction of trisubstituted tetrahydrothiophenes via a sulfa-Michael/aldol(Henry)cascade reaction in water.The protocol,simply utilizing readily-available starting materials under clean reaction conditions,provided an alternative and highly attractive approach to a series of tetrahydrothiophene derivatives from a wide range of substrates in good yields(up to 93%)with excellent diastereoselectivities(up to>99:1).The powder of a crude extract from earthworms was used as a catalyst in three-component cascade Mannich-Michael reactions for the preparation of isoquinuclidine(azabicyclo-[2.2.2]-octane)derivatives.The effects of molar ratio of substrates,solvents,water content,catalyst loading,temperature,and reaction time were investigated.The developed system had excellent substrate adaptability.Various isoquinuclidines were obtained in yields of up to 99%with ratios of endo/exo of up to 7624.This method provides a good example of the benefits of using naturally existing catalysts for organic synthesis.The catalytic promiscuity of pepsin from porcine gastric mucous was observed in the catalysis of asymmetric a-amination reactions for C-N bond formation.Pepsin showed favorable catalytic activity with good adaptability to different substrates.Enantioselectivities up to 90%ee and yields up to 95%were achieved.This work offers a novel use of enzyme catalytic promiscuity and a potential alternative synthetic method for organic chemistry.