Dcc Coupling
16
DCC Coupling Dicyclohexylcarbodiimide (DCC) N C N O OH N N cat. OH , O O N,N-dimethylaminopyridine (DMAP) OH O DCC , 2-butanol , DMAP OH O DCC , BuNH 2 , DMAP O O N O H
-
Upload
wookyoung-lee -
Category
Documents
-
view
154 -
download
1
description
DCC-coupling
Transcript of Dcc Coupling
DCC Coupling
Dicyclohexylcarbodiimide (DCC)
N C N
O
OH
N Ncat.OH,
O
O
N,N-dimethylaminopyridine (DMAP)
OH
ODCC , 2-butanol , DMAP
OH
ODCC , BuNH2 , DMAP
O
O
N
O
H
DCC Mechanism
N C N
H O
O
N C N
H O
O
O
H
Et
H
O CHMe2
Me2HCMe2HC
N C N N C N
O
O
H
H
O
O
!+ !+
CHMe2
Me2HC
C
O
N
H
N
H
O
O CHMe2
+Me2HC
Dicyclohexyl ureaH2N
O
NH2
UreaDCC used for coupling amino acids to form peptides
DCC Coupling
OH
OPhPh
C6H13
N
Et
H
DCC
N
OPhPh
C6H13
Et
DCC coupling to couple amino acids to make peptides
H2N CO2Et
HN COOH
MeH
Ph H
O
O
+DCC
N
MeH
H
O
O
O
N CO2Et
H
Ph
H
Ethyl ester of phenylalaninetert-butyl carbamate (Boc) of alanine
Boc
A protected dipeptide, phe-ala
Imides
O
O O NH3
OH
O
H2N
O
Via acyl substitution
Cl
O
HN
O O
H2N
O
H2N
O
+Li–HN
OBuLi
Cl
O
NH
O O
Cyclic Anhydrides
CO2H
CO2H200°C
– H2O
O
O
O
CO2H
CO2H 200°C
– H2O
O
O
O
CO2H
CO2H200°C
– H2O
O
O
O
Succinic anhydride
Glutaric anhydride
Phthalic Anhydride
Cyclic Imides
O
O
O
NH3
N
O
O
H
O
O
O
MeNH2
N
O
O
Me
O
O
O
PhNH2
N
O
O
Ph
succinimide
N-methylglutarimide
N-phenylphthalimide
Lactams and Lactones
NN
N
H
O
H
O
H O
a !-lactam
N
S
O
CO2H
Me
Me
HHN
HO
H2N
HOamoxicillin (a penicillin)
OO
O
O O O
O
O
O
Me
HO
Me
Me
Me
O OHO
H
Me
Me2N
methymycin ( a macrocyclic lactone)
Acyl Substitution With Carbon Nucleophiles
Grignard reagents
1. 2 equiv. MeMgI 2. H3O+
CO2Et
OH
Me
Me 88%
O
Me
MeMgI MeMgI
and then hydrolysis
C7H15
O
Cl
C7H15
O
Cl
Bu
BuMgBr
C7H15
O
Bu
- Cl
C7H15
O
Bu
Bu
BuMgBr
C7H15
OH
Bu
Bu
H3O+
Other Acid Derivatives
CO2Et1. 2 PhMgBr , THF
2. H3O+
Ph
Ph
OH
OH
1. PBr3
2. Mg , THF
3. PhCO2Me
4. H3O+
Ph
OH
OH
PBr3Br
Mg
etherMgBr
1. PhCO2Me
2. H3O+
Ph
OH
OH
1. CrO3 , aq H+
acetone , heat
2. SO Cl2
3. EtMgCl , ether
4. H3O+
OH
EtEt
OH CrO3 , aq H+
acetone , heat
OH
O
SOCl2Cl
O
EtMgCl
ether
OH
EtEt
Dialkylcadmium Reagents
2 RLi + CdCl2 R2Cd + 2 LiCl
A dialkyl cadmiumMe2Cd dimethylcadmiumBu2Cd dibutylcadmium
Me Cl
O
1.
2. H3O+
Et-MgX +2
Et2Cd
CdCl2 Et2Cd
Also with Grignard reagents
React with acid chlorides to give ketones
Me
O
Cl
OLi
1. 0.5 CdCl2
2.
O
Other Carbon-Carbon Forming Reactions
Et
Et
O
O
Br
1. NaCN , DMF
2. H3O+ , heat
3. 2-propanol , cat. H+
O
O
New C-C bond
CN
O
OH
Cl
O
Ph2CuLi , ether
Cl
O
Bu2CuLi , ether
–10°C
Ph
O
O
Friedel-Crafts
organocuprates
Cyanide SN2
OH
O1. SOCl2
2. ethylbenzene
AlCl3
Reduction
Cl
O 1. LiAlH4 , ether
2. H3O+ OH
H2 , Pd-C
EtOH
OH
O
O O
1. LiAlH4 , ether
2. H3O+
OH HO
CO2Et
1. LiAlH4 , ether
2. H3O+ OH+ EtOH
NH2
O1. LiAlH4 , ether
2. H3O+ NH2
CN
1. LiAlH4 , ether
2. H3O+
CH2NH2
NH2
H2 , Pd-C
EtOH
NH2
Dibal
H+ EtOH
O
Al
HDiisobutylaluminum hydrideDibal orDibal-H
• Milder reducing agent• Converts esters to aldehydes at low temperature
CO2Et
1. Dibal , THF , –78°C
2. H3O+
Spectroscopy
IR: acid chloride C=O, 1810 (PhCOCl , 1770) anhydride 1820 + 1760 ester 1770 amide 1690 + 1650
NMR: a C=O 2.1 - 2.6 CO2H >12 (exchange with D2O)
NH2 1-6 (slow exchange with D2O) O=C-OCH 3.5-4.0
Acid chloride , 1806 Acid anhydride , 1832 , 1761
Methyl acetate , 1748
acetamide , 1681
acetamide , 1655 + 1653
1700Methyl acrylate , 1732
IR
Chapter 22. Enols and Enolate Anions
C
OH
C
O
Keto-enol tautomerismenol
C
OH
X C
O
X
H
:Base
C
O
C
O
C=C of an enol can react with an electrophile
An enol can react with a base to form a resonance stabilized enolate anion
