REARRANGEMENTS1【课件】有机合成(上海有机所)

OH2 OH
OH
pinacol
CH3 CH3 C C CH3
-H+
CH3 CH3 C C CH3
CH3 O H
CH3 O
pinacolone
Migratory aptitude Aryl > alkyl
CH3 C CH2 Cl CH3
CH3 C CH2 CH3
CH3 C CH2 CH3
H+
(CH3)3C=CHPh
O- O HO C C Ph
Ph
O OH H+
HO C C Ph Ph
O OHO C C Ph
Ph
Favorskii rearrangement
O R3 R1 C C R2
Cl
R4OOH-
O R4O C
R3
C R2
R1
O
HO C
NH2-
O R3
NH2 C C R2
R1
R3 C R2 R1
Cl PhCO
Cl EtONa
O
O OH-
Br
CO2Et CO2H
Ph
N Me
OH-
HO2C
N Me
Rearrangement involving diazomethane Preparation of diazomethane
CH3
NO CH3NCO
SO2 N CH3 NO
KOH TsOK + CH2N2
CONCH3 NO
NaOH CH2N2
With aldehyde and ketone
O-
O
R2CO CH2N2 R C CH2 N N
N2
R C CH2R
R
RCHO CH2N2 RCOCH3
Side reaction
O-
R C CH2 N N R
Ring expansion
O
CH2N2
O R C CH2
R
O
With acyl chloride: Wolff rearrangement.
CH3 N2 CH3 C CH2+
CH3
CH3 CH3 C CH2 CH2 H+
CH3
CH3 CH3 C CH+ CH3
CH3
Pinacol rearrangement
CH3 CH3 CH3 C C CH3
H+
CH3 CH3
CH3 CH3
CH3 C C CH3 H2O CH3 C C CH3
OH OH
Me Me
Me Me
phenyl migration
methyl migration
Ph CH3 C C*H CH3
CH3
Intermediates for above processes
Ph CH3 CH3 C CH OTs
H
H CH3 HOAc CH3 C CH Ph
OAc
CH3
Ph CH3
C
II. Nucleophilic rearrangement:
----rearrangement to electron-deficient carbon
W AB
W AB
SN, E
CH3 CH3 C CH2Br
CH3
CH3
CH3
CH3 C CH2+
CH3 C CH2 CH3
CH3
H2O-H+
-H+
OH
O
CH2NH2
HNO2
O
HO CH2NO2
HO CH2NH2
O
CH3NO2 base
reduction
HNO2
Br HO C R'
R i-PrMgBr
Br -O C R'
R
O R' R
Br AgNO3
Br
Br
H2O
OH
Benzilic acid rearrangement
Ph C C Ph OHOO
Anchimeric assistance or neighboring group participation
Me
Ph C C*H Me benzene Me C C* Ph
Me OTs
refluxing
Me Me
Me Ph C C*H CH2 H+
Me
CH3 C C*H CH3 CH3
Me C C* Ph + Me C* C Ph
CH3 CH3 C CH2 OTs
CH3
CH3 TsO- CH3 C CH2+
CH3
4. From an amine, by treatment with nitrous acid.
CH3
CH3
CH3 C CH2 NH2 HNO2 CH3 C CH2 N2+
CH3
CH3
5. From an olefin, by protonation
CH
NH2
HNO2 HOAc
CH3
H C
CH3
H
CH Ph + Ph C
CH3 CH CH3 + CH3
Ph CH3 C CH H
H
OAc
OAc
OAc
Migration of Ph, CH3, H
CH3CH2CH2NH2 HNO2 CH3CH2CH2N2+
CH3CH2CH2+
1,2-H shift CH3CH+CH3
RCOCl CH2N2 R C O
CH2N N
H+
R C CH N2+
O
R C CH N2+
O
N2 R CH=C=O
H2O RCH2CO2H R CH=C=O
R'OH RCH2CO2 R'
RCOCl CH2N2 H2O RCH2CO2H
Arndt-Eistert synthesis
OH
CH2NH2 HNO2
+
NH2 CH2OH HNO2
CH2+
Expansion: C3-C8 Contraction : C4, C6-C8,,
five membered ring can not be contracted
CH3 OH H+
CH3 OH
A cascade of ring expansions
CH3O
CH3 CH3
OCH3 Cl
500
15.7
1.95
1.00
0.7
0.3
Tol Tol
Tol
Ph
Ph C C Ph H2SO4 Ph C C Ph + Ph C C Tol
OH OH
Tol O
Tol O
94%
6%
Tol=p-tolyl
Ph CH3
Ph C
C CH3
H&#CH3 C CH2CH3
OH
CH3 C
CH3
CH3 C
H
Driving force: formation of more stable carbonium
H+
Cl-
Cl
Driving force: formation of less strained ring
Wagner-Meerwein rearrangement
W
AB
AB
Types of rearrangement
W AB
W AB
1. Nucleophilic rearrangement: with a pair of electrons in W
2. Electrophilic rearrangement: without electron in W 3. Free radical rearrangement: with a single electron in W
CH3
CH3 C CH2
OH H+ CH3
CH3 C CH2
O+H2
CH3
CH3
CH3 H2O CH3 C CH2+
CH3
3. From an alcohol, by conversion into a derivatives which provides a stable leaving group.
Molecular Rearrangements
I. Introduction
CH3
CH3 C CH2Br CH3
H+ EtOH-H2O
CH3
CH3 C CH2CH3 OH
CH3
+
C
CH3
CH3 C
H
Alteration of molecular backbone
CH3
CH3 C CH2OH
CH3
W
Generation of carbonium ion
1. From a halide, by treatment with Lewis acid, eg. Ag+ or HgCl2
CH3 CH3 C CH2 X Ag+
CH3
CH3 CH3 C CH2+
CH3
2. From an alcohol, by treatment with acid.
-H+
Ph C C CH3
OH
Ph Ph C C CH3
CH3 O
The stereochemistry of the rearrangement