Michael Addition

Mechanism of the Michael Addition

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Reviews |
Sample reactions

Methyl Cyanoacetate
Cyclohexane, t-BuOH
RT, 48 h, 91%


NaSBn
MeOH
RT, 3 h, 77%


KOH
EtOH
100 °C, 5 h
"8 mg of strychnine was obtained from a mixture of 7 mg isostrychnine and 65 mg isostrychnine acetates."


t-BuOOH, Me3N+Bn HO-
THF
-15 °C, , 91%


BnSH, n-BuLi
THF
-50 °C, , 85% (4 steps)


Bz2O2, CuBr, MeLi
Et2O
-78 to 0 °C, 45 min, 75%



80 °C, 16 h


CuCN, t-BuLi, TMSCl
Et2O, Et3N
-78 to -10 °C, 3 h, 93%


Et3NBn+ i-PrO-, Ph3COOH
THF
-10 °C, 3 h, 72%



CuI, MeLi
THF
0 °C to RT, 45 min, 60%


CuI, MeLi, TMSCl
Et2O, Et3N
0 °C to RT, 3.5 h, 80%


CuI, (CH2NMe2)2, TMSCl, VinylMgBr
Et3N, THF
90%



TMS2NLi
DME, THF
-78 °C, 4.5 h, 71%


CuI, VinylMgBr
THF


KOt-Bu, NaOH, Ethyl vinyl ketone
H2O, t-BuOH
0 °C to RT, 10 h, 53%


Me3N+Bn HO-, VinylCN
H2O, PhH, t-BuOH
50 °C, 45 h


BF3.OEt2, CuCN, MeLi
THF



n-BuLi
THF
-78 °C to RT, 6 h, 67%


CuI, MeLi
Et2O
-78 °C to RT, ON, 97%


i-Pr2NLi, i-PrCO2Et
THF
-78 to 0 °C, 2.5 h



CuCN, t-BuLi
Et2O
-78 to 0 °C, 2 h, 92%
"99 % yield base on 93 % conversion."



i-Pr2NLi
THF
-78 °C to RT, 3 h, 64-85%


DBU, t-BuOOH
THF
RT, 72 h, 82%


CuCN, MeLi
Et2O
-78 °C, 2 h



Li, NH3
t-BuOH, THF
-78 to -5 °C, 75 min


KOt-Bu
t-BuOH



PhH
Reflux, 22 h, 76%



MeI, CuBr.Me2S
HMPA
66%


Me2CuLi, AllylCl
HMPA, THF
-78 °C to RT


Sc(OTf)3
Sealed tube
DCE, H2O
120 °C, 36 h, 73%



Et3N
CH2Cl2
RT, 12 h


n-BuLi, Ph3COOH
THF
-78 °C, 2 h


BnNHMe
RT, 16 h


Et3N, TMSCl, Vinyl2CuMgCl
THF
-78 °C to RT



K2CO3
THF
Reflux, 4 h, 98%


KOt-Bu, VinylCN
THF
0 °C, 20 min, 74%


CuI, Et3N, TMSCl, TMSCH2MgCl
HMPA, THF
-78 °C to RT, 2 h



TASF
CH2Cl2
-78 °C, 5 min, 79%


MeMgBr, TMSCl, CuBr.Me2S
HMPA, THF
-78 °C to RT, 2.5 h
"The starting material was 90:10 er."




HMPA, (n-Bu3PCuI)4
THF
-50 °C to RT, 3 h, 60%


Me2CuLi
Et2O
-78 °C, 30 min


Me2CuLi
Et2O
-78 °C, 30 min



CuBr.Me2S
THF, Me2S
-78 to 0 °C, 6 h



CuBr.Me2S
THF, Me2S
-78 to 0 °C, , 68%


Et3N
Sealed tube
Ethylene Glycol
225 °C, 24 h, 8-12%
"The yield was 10-15 % brsm."


Me2CuLi
Et2O
-20 °C, 40 min, 96%



AcCl, t-BuLi, (n-Bu3PCuI)4
Et2O
-78 to 0 °C, , 84%



VinylMgBr, (n-Bu3PCuI)4
HMPA, THF
-45 °C to RT, 3 h, 54%



TiCl4
CH2Cl2
-78 °C to RT, 40 min
"R = H, t-Bu."


TsOH, Morpholine
PhH
Reflux, , 92%


NaOH, t-BuOOH
H2O, MeOH
RT, , 89% (2 steps)


Tf2O, Et2AlCN, n-Bu4N+ Ph3SiF2-
PhH
0 °C to RT, 19.5 h, 81%


H2O2, NaOH
CH2Cl2, H2O, MeOH
0 °C, 2 h, 75%
"Also isolated was the TES-deprotected product (16 % yield)."


TMSCl, VinylMgBr, CuBr.Me2S
THF
-78 °C, 2 h, 92%



CuBr.Me2S
THF, Me2S
-78 to 0 °C, 24 h


VinylMgBr, CuBr.Me2S
50%
"Also isolate was the C3-epimer (15 % yield)."



Mg
Et2O
Reflux, , 13%
"Also isolated was the C3-epimer (40 % yield)."



i-Pr2NLi
THF
-100 to -78 °C, , 50%
"For the synthesis of this enone, see : J. Am. Chem. Soc. 1984, 106, 6690."


Et3N, K3Fe(CN)6, NCCH2CO2Et
EtOH, H2O
RT, 11 min, 84%


NaOCl
H2O, Pyr
0 °C, 60 min, 90%


HCl
EtOH, H2O
Reflux, 4 h, 50% (2 steps)




ClCH2CO2H
CH2Cl2
0 °C to RT, 3.5 h


p-MePhSH
EtOH
-15 °C, 36 h, 70% (2 steps)


Et3N, Methyl propynoate
THF
-20 to 0 °C, 3.5 h, 89%


TMS2NNa, CuBr.Me2S
NMP
0 to 65 °C, 95 min, 10%


NaH
THF
0 °C, 105 min, 98%


Dimethyl malonate, KOt-Bu
4Å MS
THF
4 °C to RT, 24 h, 91%



i-Pr2NEt, Tf2O
CH2Cl2
-78 °C, 90 min



Br3CCO2H
PhMe
-60 °C to RT, 23 h, 82%



CuBr.Me2S, Mg
THF
-50 °C to RT, 80 min, 58%



TiCl4
CH2Cl2
71%


TMS2NLi
THF
0 °C to RT, 100 min, 100%



BF3.OEt2, CuI, t-BuLi
Et2O, HMPT
-120 to -20 °C, 9 h, 60%
"The yield was 74 % brsm."



AcCl, i-Pr2NLi
HMPA, THF
-78 °C, 105 min, 86%



Li, CuI.Me2S
Et2O
-30 °C to RT, 2.5 h, 85%
"Also isolated was the C6'-epimer (5 % yield)."



AcOH
100 °C, 60 min, 63%



CuBr.Me2S
THF
-78 °C, 15 h



KOt-Bu
DMSO
RT to 100 °C, 10 h, 60%



NaOMe
MeOH
RT, 12 h, 58%


CuI, MeLi
-78 to -40 °C, 80 min, 93%


VinylMgBr
THF
-78 to 0 °C, 12.5 h, 90%


CuI, MeLi.LiBr
Et2O
0 °C, 30 min, 80%


CuI, VinylMgBr
THF
-78 °C to RT, 30 min, 55%


Et3N, Methyl vinyl ketone
MeOH
RT, 105 min, 74%


Me3N+Bn HO-
DME
-20 °C, 2.5 h, 44%
"Also isolated was the C2-epimer (14 % yield)."



K2CO3
MeCN
Reflux, 42 h, 95%


Me3N+Bn HO-, Methyl acrylate
Dioxane
50-70 °C, 60 min, 88%


Me2NH
H2O
0 °C, 2 h


CuCN, VinylMgBr
THF
-78 to -40 °C, 40 min, 98%



LDA
THF
-78 to -20 °C, 17.5 h, 79%
"another diastereomer was also isolated (6% yield)"


Me2CuLi
Et2O
-78 to -34 °C, , 99%


CuI, Et3N, TMSCl, VinylMgBr, HMPA
THF
-60 °C to RT, 3 h, 89%


AcOH, H2O, Methyl acrylate, Hydroquinone, THF
RT to 65 °C, 2 d, 78% (2 steps)
"94:06 e.r.; the enantiomeric purity was improved to >99:01 e.r. by crystallization of the corresponding semicarbazone."



LDA
THF
-78 °C to RT, 2 h, 75%
"66:33 dr"


H2O, HCl, NaOEt
EtOH
10 °C to Reflux, 20 min, 90%


TMSCl, AllylMgBr, CuBr.Me2S
THF
-78 °C, 2 h, 75%


KOt-Bu, VinylCO2t-Bu
t-BuOH, THF
-10 to 0 °C, 2 h, 62%
"91:09 dr"
