Ways to make esters

RCO2H + R'-I base

RCO2R'

RCO2H + R'OH DCC

RCO2R'

N C N

N,N'-Dicyclohexylcarbodiimide (DCC)

H
N C N N C N RCO2R'

H
R O
H +
O
O O R' O
R O
N N
H H
Dicyclohexyl urea

Sometimes its difficult to separate product from DCU,

in that case use EDCI instead of DCC

7/25/13   1  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Ways to make esters
Baeyer-Villiger oxidation Favorskii rearrangement
O O Br CO2Et
NaOEt/EtOH
mCPBA O
O

Mitsunobu  reaction
DEAD, PPh3
RCO2H + R'OH RCO2R'

Ph3P R H
CO2Et O
N N Ph3P CO2Et
EtO2C N N
EtO2C
H Ph3P CO2Et + RCO2
O N N
EtO2C H
O R

R O PPh3

H CO2Et
RCO2R' O
O PPh3 + N N +
EtO2C H
7/25/13  
R O 2  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Ways to make esters
CO2R
R= iPr, DIAD N N R = Et, DEAD
Diisopropyl azodicarboxylate RO2C Diethyl azodicarboxylate

O
OH
R2CO2H
O R2
R R1 PPh3, DIAD
R R1

O O
?

O O O O
OBn OBn

H+, H2O O
PPh3, DEAD
BnO
HO O
HO
7/25/13   3  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Ways to make esters
Primary Alcohols

Reduction:

NaBH4
RCHO

LiAlH4
RCO2R Primary alcohols

LiAlH4
RCO2H

OH
BH3
NaOH, H2O2 R
R

RMgX
HCHO RCH2OH

7/25/13   4  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Ways to make esters
Secondary Alcohols
O
reduction
R R'
RMgX
RCHO 2  o  Alcohol  
Oxymercuration
R

RMgX
HCO2R symmetrical 2o alcohol

formate ester

Tertiary Alcohols
O
RMgX
R R'

Oxymercuration 3  o  Alcohol  
R
RMgX
RCO2R

7/25/13   5  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan  
 Ways to make esters
Pyridine, Mscl
ROH R OMs Mesylate

Pyridine, Tscl
ROH R OTs Tosylate

Pyridine, Brcl
ROH R OBs Brosylate

Pyridine, Nscl
ROH R ONs Nosylate

Pyridine, Tf2O
ROH R OTf Triflate

NaBr
R OTs R Br Finkelstein reaction
Acetone

7/25/13   6  
CH-­‐423  Course  on  Organic  Synthesis;  Course  Instructor:  Krishna  P.  Kaliappan