高等有机化学5[1]3碳-杂重键的加成反应

1、5.3 Addition to C,O multiple bondsBase catalyzedStep 1.Step 2.CAOBNuslowCAO-BNuCAO-BNuH+CAOHBNuMechanism No matter which species attack first, the rate-determining step is usually the one involving Nu attack!Acid catalyzedStep 1.Step 2.CAOBH+CAOHBCAOHBNuslowCAOHBNuCompeted procedure: SubstitutionCAO

2、BH+CAOHBCAOHBNuCAOHBNuStep 3.CAOHNuCAONuH+Step 4.CAOHBNuCAOHNuCAOHNuB-Step 2.Step 1. When A, B are H, R, Ar, the substrate is an aldehyde or ketone, these almost undergo addition! For carboxylic acids and their derivatives (B = OH, OR, NH2, X, etc), the substitution is major procedure! Activity Elec

3、tronic effectC=ORHRC=ORRC=OArCCl3-CH=O + HOHCCl3-CH(OH)2CH3CHOCH3CHOHCNHCNPhCHOCPhHOHCNHCNK 104K = 210 Steric effectOHCNOHCNK= 104OHCNOHCNK= 103 NucleophilicityC N OStereochemistryOcamphorNaBH4OHHHOH86%14%t-BuOt-BuHOHt-BuHOH+LiAlH4 88% 12%LiAl(s-BuO)3H 7% 93%C CC2H5HC6H5CH3OetherLiAlH4H2OC CC2H5HC6H

4、5CH3OHHC CC2H5HC6H5CH3OHH+75%25%Aldol condensationH3CROHO-RCHOCH3RH2CROHHO-H2OH2CRO-H3CRORCH2OCH3O-RRCHOCH3OHR-RCHOCH3RBase-catalyzedCH3CCH3OCH3C-CH2-H+OHCH3C=CH2OHCH3CCH3+OHOHCH3-C-CH2-C(CH3)2+OH-H+OHCH3-C-CH2-C(CH3)2O-H2OCH3-C-CH=C(CH3)2O烯醇化烯醇化亲核加成亲核加成H+-H+Acid-catalyzedClaisen-Schemidt reactionCH

5、O + CH3CC(CH3)3OH2O-C2H5OHNaOH88 % -93%C=CHHCC(CH3)3OCH C NOEt-2CH CNHC CNH3O+CH COC CNThorpe ReactionKnoevenagel reactionZZCH2BZZCHRRC=OZZCH-CRRO-HBZZCH-CRROHZZC CRROHZZC=CRRBC=ORRH2 CZZ+C=CRRZZ弱碱苯, 分水Z: CHO, CR, COOR, CN, NO2等OCHO + CH2(CO2H)2O2N吡啶CH=C(CO2H)2O2NCH=CHCO2HO2N-CO274-80 %CH3CCH2CH3 +

6、NCCH2CO2EtO丙氨酸 - HOAc苯, 分水CH3CH2C = CCO2EtCH3CN85 %eg 1.eg 2.eg 3.制备各种类型的制备各种类型的,-不饱和化合物不饱和化合物.CHOOHCOH3CCH2COEtOBOOCOCH3Mannich reactionCH3-C-CH2-H + CH2O + HNORRH+CH3-C-CH2-CH2NORRPrimary or secondary amineActive hydrogen compounds CH EWGOHHHRC CHROHNCHCH2=ONHRRRRH+HCH2=OHN-CH2OHRRRR-H2ON=CH2N-CH2

7、-OH2OORRCH2=NRRHO HCH3-C=CH2CH3-C-CH2-CH2-NCH3C-CH2+ H+H+转移转移 Acid catalyzedOCH3CH2O + (CH3)2NH+HCl, H2OOCH3CH2N(CH3)2OCH3(CH3)2NCH267 %+33 %NHN+ CH2O + HN(CH3)2NHCH2N(CH3)2H2OHAc95 %CHOCHOMeNH2H3CCOCH3NMeOH2NCH2CH2COCH(CH3)2H2C CH COCH(CH3)2制备制备,-不饱和醛酮不饱和醛酮Wittg reactionPh3P=CH2(I)(II)Ph3P-CH2Ylide

8、Ph3P + CH3XPh3P+-CH3X-C6H5LiPh3P+-CH2-Ph3P + XCH2COOC2H5Ph3P+-CH2COOC2H5 X-K2CO3Ph3PCHCOOC2H5+-C=O + Ph3P-CR2Ph3P=CR2 C=CR2 + Ph3P=OPh3P-CR2+-O=CPh3P-CR2+-O-CPh3P-CR2O-CPh3P CR2O CC=CR2 + Ph3P=OMechanism内鏻盐内鏻盐OPh3P CHR_+CHRPh3P OReformatsky ReactionC OCH2CO2Et-卤卤代代羧羧酸酸酯酯ZnXCOHCH2CO2Et H3O+-羟羟基基羧羧酸酸酯

9、酯COZnXCH2CO2EtZnCH2CO2EtXZn有有机机锌锌试试剂剂COCCHCO2Et -不不饱饱和和羧羧酸酸酯酯-H2OR C NC COOEtBrZnC COOEtCRNZnBrH2OC COOEtCRODarzens ReactionC=O + BrCH2CO2EtCOCH CO2EtNaNH2or RO-*CHCHOOH-H+,-环氧酸酯环氧酸酯* CH2 生成醛生成醛 CHR 生成酮生成酮BrCH2COOEtNaNH2BrCHCOOEtC=OCH3C6H5C CCH3C6H5BrO-C CCH3C6H5BrO-CO2EtHCO2EtH+CH3C6H5COCH COOHCH3C

10、6H5C=CH-OHCH3C6H5CHCHOOH-COCHCO2EtC6H5CH3-Br-H+Mechanism-CO2Benzoin Condensation2 ArCHOArCH-CArOH OKCN醇-水CH + CN-OCO-CNHC-CNOHCHOCO-HCCNOHCHCCNOHOCHCOHO-H+安息香安息香X. Linghu, J. S. Johnson, Angew. Chem., 2003, 115, 2638ROSiEt3CN_ROSiEt3CNO-RRO-CNOSiEt3RKey Intermediate:NCHOCH3CH3CHO+KCN醇-水NCH3CH3NCCH3C

11、H3OHHCOCOHHCO+C6H5C CC6H5OOOH-140 oCC6H5CCOO-OHC6H5CH5C6H5C6CO-OOH(C6H5)2COHCOO-H+(C6H5)2COHCOOH二苯乙醇酸重排二苯乙醇酸重排OOOCCO OOC COOH2OH-H+acceptor(donor)donor(acceptor)Cannizzaro Reaction (Disproportionation)CHO2NaOH C2H5OH50oCCH2OHCOONa+H+COOH反应机理反应机理ArCHO + OHArCOHOHCArHOArCOOH+ ArCOHHArCOO-+ ArCOHHHH+Ar

12、COOH+ ArCOHHH交错的交错的Cannizzaro 反应反应：HOCH2CCH2OHCH2OHCHO + HCHOCa(OH)260HOCH2CCH2OHCH2OHCH2OH+ 1 / 2 (HCOO)2Ca季戊四醇季戊四醇羧酸衍生物与亲核试剂的反应羧酸衍生物与亲核试剂的反应RCH2CX RCH2COCR RCH2CH RCH2CR RCH2COR RCH2CNH2OO OOOOO减小减小反应活性：反应活性：加成加成-消除历程消除历程酯的水解酯的水解OOC2H5CO18C2H5 + H2OCH3CONa + C2H5O18HNaOHOORCOR + -OHRCOH + -ORR-C-O

13、ROHO-RCO- ONa+RCONaOROH +BAC2Or H+R具有手性时，构型保持具有手性时，构型保持- ROH+R-C-OR+R-C-ORR-C-OR-H+OHHOH2OOH+OHRCORH+RCOH+OHOHOH2RCOHORCOROHAAC2AAL1CH3CO18OC(CH3)3H+CH3CO18OHC(CH3)3CH3C+O18C(CH3)3OHSN1CH3CO18OH + (CH3)3C+H2O(CH3)C3COH2+(CH3)3COH + H+R具有手性时，外消旋化具有手性时，外消旋化Claisen CondensationC2H5OHCH3COONaCH3COOHOOCH3CCH2COC2H5 +Na+OOCH3CCHCOC2H5C2H5ONaC2H5O-OCH3COC2H5OC2H5O-CH2COC2H5C2H5ONaOCH3CCH2COC2H5OOOCH3COC2H5OCH3CCH