化学应用与污染控制

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1、1何何 龙龙西华师范大学化学化工学院西华师范大学化学化工学院Brnsted Acid-Catalyzed Asymmetric Three-Component 1,3-Dipolar Cycloaddition Reaction化学应用与污染控制技术重点实验室年会化学应用与污染控制技术重点实验室年会，2010，12，122NOHn-C5H11IepadiformineNMeOMeOOOH(-) coccinineNMeCO2CH3OBzcocaineNHMeOOMeMeMesembraneMeNOHOOHOAc3-acetyltrachelanthamineNMeHMeHHMe(+)-benz

2、ohydrindanHNNHHHCOOHHCOOHOHOOCacromelic acid ANHCO2HCO2HKainic acidThe Importance of Pyrrolidine in Natural and Unnatural Biologically Active Products3R1NR2MOOR3EWGNHEWGR4R3O2CR2R1NR2MOOR3R1IaIb*LL*L*L*R4NR2OOR3R1ML*n (Cat)Base (Cat)uControl of Stereochemistry with Chiral LA-Bonded Dipole.M = Cu, Ag

3、, Zn, Ni, Co; L= chiral diphosphines, N-P ligands Early examples: (a) Longmire, J. M.; Wang, B.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 13400. (b) Gothelf, A. S.; Gothelf, K. V.; Hazell, R. G.; Jorgensen, K. A. Angew. Chem., Int. Ed. 2002, 41, 4236. Reviews: Njera, C.; Sansano, J. M. Angew. Chem., I

4、nt. Ed. 2005, 44, 6272. Coldham, I.; Hufton, R. Chem. Rev. 2005, 105, 2765. (d) Pandey, G.; Banerjee, P.; Gadre, S. R. Chem. Rev. 2006, 106, 4484. (e) Nair, V.; Suja, T. D. Tetrahedron 2007, 63, 12247.u 1,3-Dipolar Addition via Iminium CatalysisNHCHOR4R3O2CR2R1+CHOR4NHArArORNRR4NR2OOR3R1NR2OOR3R1Vic

5、ario, J. L.; Reboredo, S.; Bada, D.; Carrillo, L. Chem. Int. Ed. 2007, 46, 5168; Ibrahem, I.; Rios, R.; Vesely, J.; Cordova, A. Tetrahedron. Lett. 2007, 48, 6252 Previous Representative Achievements4u 1,3-Dipolar Addition by Bifunctional CatalystPrevious Representative AchievementsNHNO2R4R3O2CR2R1+N

6、O2R4NR2OOR3R1NHNNHNOCF3CF3MeOXue, M.-X.; Zhang,X.-M.; Gong, L.-Z. SYNLETT 2008, 691-694 ; Liu, Y.-K.; Liu, H.; Du, W.; Yue, L.; Chen, Y.-C. Chem. Eur. J. 2008, 14, 9873. Control of Stereochemistry with the Proposed Chiral BH-Bonded DipoleR1NR2NHEWGR4R3O2CR2R1IIaEWGR4CO2R3HPOO*ROOR*HNR2CO2R3HPOO*ROOR

7、*HR1NR2OOR3R1P*RO*ROOOHIIbH5Up to 99% eeOOOOPOHOOPOOH two hydrogen-bonding donors1aRCHO10 mol% 1aCH2Cl2, RT 3A MS+NHCO2EtCO2EtRCO2MeCO2MeCO2MeMeO2CH2NCO2EtCO2EtGong, L. Z. J. Am. Chem. Soc. 2008, 130, 5652Brnsted Acid-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition Reaction6OOOOPOHOOPOOHXOOOPOHOOPOOH

8、1d. X = NAc1e. X = S1f. X = SO2OOOPOHOOPOOH1b. n = 11c n = 01aOOOOPOHOOPOOHPhPh1gnBinaphthol-derived Bisphosphoric Acids7entrycatalystsolventTemp (oC)Yield (%)Ee (%)11aCH2Cl2RT969821bCH2Cl2RT339231cCH2Cl2RT794541dCH2Cl2RT271051eCH2Cl2RT742361fCH2Cl2RT267671gCH2Cl2RT5059Evaluation of the Catalysts+H2

9、NCO2C2H5CO2C2H5+CO2CH3CO2CH33AMS, RTNHCO2C2H5CO2C2H5RCO2CH3H3CO2C10 mol% 1a-g, CH2Cl2CHONO2R = 4-NO2C6H48The Reaction of Vinyl ketones and Esters +H2NCO2C2H5CO2C2H5+10 mol % 1a CH2Cl2, 3A MS, RTNHCO2C2H5CO2C2H5R1R2OOR2R1CHO234R3R3entryR1R2R3Time (h)Yield (%)ee (%)14-NO2C6H4CH3H48779624-CNC6H4CH3H744

10、79634-BrC6H4CH3H72589544-ClC6H4CH3H74649154-FC6H4CH3H72439462-NO2C6H4CH3H64859673-NO2C6H4CH3H74639784-NO2C6H4OCH3H48829592-NO2C6H4OCH3H729192104-CNC6H4OCH3H649696113-NO2C6H4OCH3H488497124-BrC6H4OCH3H648097134-NO2C6H4OCH3Ph488594144-BrC6H4OCH3Ph728597154-ClC6H4OCH3Ph726594164-CNC6H4OCH3Ph727196172-NO

11、2C6H4OCH3Ph608598Manusript in preparation9+ catalyst 1 or 5, CHCl33AMS, 50oCNHPhCO2CH3CO2CH3H3CO2CO2NH2NPhCO2CH3+CO2CH3CO2CH3CHONO2uOptimization of conditions for the reaction involving a a-phenylglycine methyl ester 5a, Ar= Ph 45% yield, 12% ee5b, Ar= 4-t-BuC6H4 34% yield, 12% ee5c, Ar= 4-NO2C6H4 4

12、1% yield, 59% ee5d, Ar= 3,5-(CF3)2C6H3 42% yield, 14% ee5e, Ar= 4-ClC6H4 65% yield, 26% ee8f, Ar= 2-naphthyl 98% yield, 62% ee5g, Ar= 2,4,6-(iPr)3C6H2 65% yield, 0% ee5h, Ar= Ph3Si 28% yield, 0% eeArArOOPOOHXOOOPOHOOPOOH11a, 92% yield, 97% ee1b, 78% yield, 98% ee1c, 33% yield, 11% ee1d, 22% yield, 1

13、1% ee1e, 73% yield, 35% ee1f, 13% yield, 75% ee1g, 56% yield, 82% ee10uScope of Aldehydes entryR1R2R3Yield (%)bee (%)c14-CF3C6H4CH3CH3989424-BrC6H4CH3CH3939734-ClC6H4CH3CH3969444-FC6H4CH3CH3869453-CNC6H4CH3CH3659262-NO2C6H4CH3CH3989672-BrC6H4CH3CH3969182-Cl,4-FC6H3CH3CH3949693-Cl,4-FC6H3CH3CH3878810

14、4-Cl,3-FC6H3CH3CH3849811c-C6H11CH3CH3587512c-C3H5CH3CH36174134-MeOPhCH=CHCH3CH39696144-NO2PhCH=CHCH3CH38998154-NO2C6H4CH3C2H59592164-NO2C6H4C2H5CH39595+NHPhCO2R2R1CO2R3R3O2CH2NCO2R2Ph+CO2R3CO2R320 mol %1a, CHCl33AMS, 50oCR1CHOManusript in preparation11NHCO2CH3O2NCO2CH3H3CO2CClNHCO2CH3O2NCO2CH3H3CO2C

15、ClNHCO2CH3O2NCO2CH3H3CO2CClNHCO2CH3O2NCO2CH3H3CO2CFNHCO2CH3O2NCO2CH3H3CO2CFNHCO2CH3O2NCO2CH3H3CO2CFNHCO2CH3O2NCO2CH3H3CO2COCH3NHCO2CH3O2NCO2CH3H3CO2CClOCH3NHCO2CH3O2NCO2CH3H3CO2COCOCH396%yield, 97% ee96%yield, 94% ee95%yield, 98% ee94%yield, 95% ee93%yield, 95% ee96%yield, 98% ee91%yield, 96% ee92%y

16、ield, 91% ee97%yield, 95% eeuScope of a a-arylglycine methyl ester Manusript in preparation12NHCO2CH3O2NCO2CH3H3CO2CClNHCO2CH3O2NCO2CH3H3CO2CBrNHCO2CH3O2NCO2CH3H3CO2CFNHCO2CH3O2NCO2CH3H3CO2CNHCO2CH3O2NCO2CH3H3CO2CNHCO2CH3O2NCO2CH3H3CO2COAc82% yield ,97% ee88% yield ,97% ee65% yield ,97% ee91% yield

17、,96% ee73% yield ,98% ee92% yield ,98% eeFFNHCO2CH3O2NCO2CH3H3CO2C79% yield ,94% eeNHCO2CH3O2NCO2CH3H3CO2COCH3NHCO2CH3O2NCO2CH3H3CO2COCH392% yield ,98% ee96% yield ,98% eeClu Scope of a a-arylalanine methyl ester CHONO2+H2NR2CO2CH3+CO2CH3CO2CH3NHR2CO2CH3CO2CH3H3CO2C20mol% 1a3 A MS ,70oC, ClCH2CH2ClR

18、1R1 = 4-NO2C6H4Manusript in preparation13entryAr Yield (%)dree (%)14-NO2C6H4828.5/19724-BrC6H48910/19534-ClC6H4779/19144-CNC6H4838/19653-NO2C6H4809.5/19762-NO2C6H4938/192uGenerality for Fumarate +H2NCO2C2H5CO2C2H5+10mol %1a, Toluene 3AMS, RTNHCO2C2H5CO2C2H5ArH3CO2CCO2CH3H3CO2CCO2CH3ArCHOManusript in

19、 preparation14OOOOPOOOPOOHH1.7151.632(0.00 0.00)Complex-maleate-major ( -16.32, 8.14 )1.7511.7092.5601.6711.6941.9192.1092.439TS-maleate-major ( 0.00, 0.00 )2.976uTransition States Located by DFTManusript in preparation15Conclusion R2 = CH3, C2H5R3 = CO2CH3, Ar, BnR4 = CH3, OCH3R6 = H, CO2CH3R5 = H,

20、 Phup to 98% ee, 98% yield, 99:1 dr+H2NCO2R2R3+COR4R6NHR3CO2R2R6R4OC1a, Solvent3 A MS , TempR1R1CHOR5R51.6711.6941.9192.1092.439TS-maleate-major ( 0.00, 0.00 )2.976DFT计算表明：双磷酸催化剂催化计算表明：双磷酸催化剂催化的本体系的的本体系的1,3-偶极环加成反应，经偶极环加成反应，经历一种新型的双功能催化活化与立历一种新型的双功能催化活化与立体控制模式。体控制模式。u1.u2.Manusript in preparation16 致致 谢谢u龚流柱龚流柱 （教授）（教授）u西华师范大学化学化工学院西华师范大学化学化工学院u中国科学技术大学化学系中国科学技术大学化学系