Syntheses Of (E)-Vinyl Alkylsulfones And Quinoline Sulfones

In pharmaceutical chemistry vinylsulfone compounds can act as inhibitors of cysteine proteases,sorting enzymes and HIV integrases,and neuroprotective agents.As for synthetic organic chemistry vinyl sulfones are used as a kind of intermediates.Traditional synthetic methods about vinylsulfone compounds mainly include(1)Knoevenagel condensations of sulfonylacetic acids with aromatic aldehydes,(2)wittig reaction of Sulfonyl phosphonates with carbonyl-containing compounds,(3)?-elimination of halosulfones and(4)Cross-coupling reaction.However,most of these methods suffer from some shortcomings,such as inaccessible starting materials,harsh reaction condition,tedious procedures,and large amount of unwanted byproducts.Thus,we developed an efficient method for the synthesis of vinyl sulfones from alkenes and tert-butylsulfinamide,using much cheap,easily available Cu SO4·5H2O catalytic system.The advantages of the synthetic routines of vinyl sulfones are obviously,such as accessible starting materials,mild reaction condition,simple procedures.Quinoline and derivatives have certain pharmacological activities such as antiviral,anti-malarial,anti-tumor.3-sulfonylquinoline compounds and4-sulfonylquinoline compounds can be used as receptor antagonists in the treatment of schizophrenia,Parkinson's,Alzheimer's disease.Most of the previous synthetic methods about 3-sulfonylquinoline compounds and 4-sulfonylquinoline compounds are cyclization reation.Previous synthetic methods about 3-sulfonylquinoline compounds and 4-sulfonylquinoline compounds are mainly cyclization reation.Most of these methods are achieved through multi-step synthesis,cumbersome operation,and the low utilization of raw materials.A directly method for the synthesis of 3-sulfonylquinoline compounds and4-sulfonylquinoline compounds from 2-blocked-quinoline N-oxides and sodium sulfite,with the help of H-phosphonate was developed.The advantages of of this method is obviously,less reaction steps,simple procedures and cheap reagents.The main contents of this paper are as follows:(I)A new method for synthesis of vinyllsulfone Compounds.1.The applications of vinylsulfone compounds in medicinal chemistry and organic chemistry,and the previous synthesis methods of vinylsulfone compounds;2.We optimized the reaction of styrene and tert-butyl sulfenamide;and then evaluated the substrates scope and limitations of our protocol.20 compounds were synthesized and elucidated structure by 1H NMR?13C NMR and HRMS.3.Finally,explore the mechanism of synthesis of vinyllsulfone compound s,by a variety of means such as nitrogen atomosphere,radical inhibitor,isoto pe labeling.(II)A new method for synthesis of 3-sulfonylquinoline and 4-sulfonylquinoline compounds.1.The applications of 3-sulfonylquinoline compounds and 4-sulfonylquinoline compounds in medicinal chemistry,and the previous synthesis methods of3-sulfonylquinoline compounds and 4-sulfonylquinoline compounds.2.We optimized the reaction of 2-methyl quinoline N-Oxide and Sodium benzenesulfinate;and then evaluated the substrates scope and limitations of our protocol.24 compounds were synthesized and elucidated structure by 1H NMR?13C NMR and HRMS.3.Finally,a plausible mechanism is proposed according previous reports.