15.2 The michael reaction OH OH Nu. RHC=C HCR RHCEC HCR+ RHC-C-CR RHC-C HCR 22)H ueno Nu(keto 1.2-addition 1, 4-addition(conjugate addition) Micheal reaction:亲核的碳负离子对亲电的共轭体系进行共轭加成 A CH2-R A一CHR A H-i-i-i-H A, A=CHO, COR COOR, AA
19 15.2、The Michael reaction RHC C HCR 1) Nu-; 2) H + RHC C HCR 1 2 4 3 + RHC C H2CR 1 4 Nu 1,2-addition 1,4-addition (conjugate addition ) RHC H C 4 Nu CR 1 OH 2 O OH Nu O (enol) (keto) A CH2 R B: A CH R A' R CH A C C A' HB H C R A C C H A' A, A' = CHO, COR, COOR, NO2, CN, SO2Ph Micheal reaction: 亲核的碳负离子对亲电的共轭体系进行共轭加成
Some Common Micheal Donors and Acceptors Micheal Donors(给体) Micheal Acceptors(受体) R-C-CH-C-R B-diketone H2C=CH-C-H conjugate aldehyde R-C-CH-C-OR' P-keto ester H2 C:CH-C-R conjugate ketone l■●● R2CuLi dialkyl cuprate H2C=CH-C-OR conjugate ester enamine H2C=CH-C-NH2 conjugate amide 烯胺 R-C-CH-CEN B-keto nitrile H2 C-C-CEN conjugate nitrile R→c-CH-N a-nitro ketone H2C=CH-NO2 nitroethylene R-C-CH-S-Ph a-keto sulphone H2C:CH-SO2Ph vinyl sulphone
20 Some Common Micheal Donors and Acceptors R C CH C O O R' R C CH C O O OR' R 2CuLi C C N R C CH C O N R C CH N O O O R C CH S O O Ph O β-diketone β-keto ester dialkyl cuprate enamine 烯胺 β-keto nitrile α-nitro ketone α-keto sulphone H 2 C CH C O H H 2 C H C C N H 2 C CH NO 2 H 2 C CH SO 2Ph H 2 C CH C O R H 2 C CH C O OR H 2 C CH C O NH 2 conjugate aldehyde conjugate ketone conjugate ester conjugate amide conjugate nitrile nitroethylene vinyl sulphone Micheal Donors (给体) Micheal Acceptors（受体）
Conjugate Addition of amine H R- C=CH H2CTNR2 The mannich reaction an eno ole R an iminium ion -8c1+,m比 C-C-CHaNR2 a B-aminoketone The Micheal reaction a mannich base
21 Conjugate Addition of Amine R' C O H 2 C CH 2 NR 2 R' C '' O H C CH 2 HNR'' 2 + a β-aminoketone a Mannich base H 2 C NR 2 R' C '' OH CH an enole R an iminium ion + The Mannich Reaction The Micheal Reaction
The michael addition reaction 1,5-二羰基化合物的合成 H C、CH3 CHo Na 人。人 C2H5O CH OCH C2H5O CH2 H2C'C CHOH COOC2H5 H2C CH o〓C. CH3 H3C CH2 H2CC"O2H5 C2H50 Na* 0 H2 OC2H5 L C-C CHOH H3CCH-C o pKa 11 cOoC,H H2 CHOOC
22 The Michael Addition Reaction: 1 ，5-二羰基化合物的合成 C 2 H 5 O C H 2 O H 3 C C H 2 O p Ka 11 COOC 2 H 5 + H 2 C H C C CH 3 O C 2 H 5O Na C 2 H 5 O C H O OC 2 H 5 O H 2 C CH 2 C CH 3 O + H 2 C H C C OC 2 H 5 O C 2 H 5OH C 2 H 5O Na C 2 H 5OH H 3 C CH O C 2 H 5OOC C H 2 H 2 C C OC 2 H 5 O COOC 2 H 5
The michael addition reaction 1,5-二羰基化合物的合成 CNOOC COOCh 2 H H C-C-CH3-C2H5O-C-C-C-C-C-CH3 c2H5Occ° malonic ester enolate 1c1。0-H cooC. 2. Tautomerization C2H5o-- CH2 CH2 CCH3 1, 4-addition product, 90% H0-C-C-CH2CH2CCH3 1.5-keto acid COOC2H5 COOH heat C2H50-C-C-CH2CH2CCH3- HO-C-CH-CH2CH2CCH3 HO 23
23 The Michael Addition Reaction: 1 ，5-二羰基化合物的合成 C 2 H 5 O C C O COOC 2 H 5 C C C CH 3 H O H H malonic ester enolate C CH C 2 H 5 O O C 2 H 5OOC H 2 C H C C CH 3 O H C CH C 2 H 5 O O CH 2CH 2CCH 3 COOC 2 H 5 O 1,4-addition product, 90% C C H C 2 H 5 O O CH 2CH 2CCH 3 COOC 2 H 5 H, heat H 2 O O HO C CH O CH 2CH 2CCH 3 COOH O C H 2 HO C O CH 2CH 2CCH 3 O 1,5-keto acid H 1. C 2 H 5 O 2. Tautomerization