Chapter 10 Pericyclic
Reactions（周环反应）
Pericyclic Reactions
• Continuous concerted reorganisation of electrons
• 5 major categories:
–
–
–
–
–
Electrocyclic ring opening/closure
Cycloaddition/cycloreversion reactions
Cheletropic reactions (e.g. carbene addition)
Group transfer reactions (e.g. H2 transfer)
Sigmatropic rearrangements
Sigmatropic Rearrangements
• Migration of a s-bond across a conjugated p-system
• [m,n] shift when the s-bond migrates across m atoms of
one system and n of another
2
2
3
[1,3]-shift
1
3
1
1'
R 1'
R
2
2
1
R
1'
3
3'
2'
1
[3,3]-shift
R
3
3'
1'
2'
Conjugated π Systems
Antibonding
4
3
p
3
2
nonbonding
2
p
1
1
2 p-orbitals
3 p-orbitals
Bonding
4 p-orbitals
Suprafacial/Antarafacial
• Suprafacial migration: Group moves across same face
R
R'
R'
R
R'
R
R
R
R'
R
R'
R'
• Antarafacial migration: Group moves from one face to the
other
R
R'
R'
R
R'
R
R'
R
R
R'
R
R'
FMO Analysis
• [1,3] Sigmatropic Rearrangements: H migration
+
H
H
R
R'
2 allyl anion HOMO
R'
R
R'
R
1s proton LUMO
H
H
R
R'
Suprafacial migration
FORBIDDEN
R
H
R'
Antarafacial migration
ORBITALLY ALLOWED BUT
H CANNOT BRIDGE DISTANCE
FMO Analysis
• [1,3] Sigmatropic Rearrangements: C migration
+
H3C
CH3
R
R'
CH3
2p Carbon LUMO
H
H
R'
R
R'
R
C H
H H
C
H
2 allyl anion HOMO
R
R'
R'
R
Suprafacial migration
Retention at carbon
Suprafacial migration
Inversion at carbon
FORBIDDEN
ALLOWED
FMO Analysis
• [1,5] Sigmatropic Rearrangements
X
R
X
+
X
R'
H
R'
R
R'
R
1s proton LUMO
Suprafacial migration Antarafacial migration
ALLOWED
FORBIDDEN
3 pentadienyl anion HOMO
C
2p carbon LUMO
3 pentadienyl anion HOMO
Suprafacial migration
Retention at Carbon
ALLOWED
C
Antarafacial migration
Inversion at Carbon
ALLOWED
Dewar-Zimmerman
• Dewar-Zimmerman model:
– Choose a set of 2p atomic orbitals and arbitrarily assign phase
– Connect the orbitals in the starting material
– Allow reaction to proceed according to postulated geometry and
connect reacting lobes.
– Count number of phase inversions: Odd = Möbius, Even = Hückel
– Assign transition state as aromatic or antiaromatic based on
number of electrons:
System
Aromatic
Antiaromatic
Hückel
4n + 2
4n
Möbius
4n
4n + 2
– Aromatic = Thermally allowed (Photochemically forbidden)
– Antiaromatic = Thermally forbidden (Photochemically allowed)
Dewar-Zimmerman
• [1,3]-H shift
H
H
R'
R
Suprafacial:
Two Phase Inversions
Hückel Topology
Four electrons
FORBIDDEN
H
H
• [1,5]-H shift
H
R
H
R'
R
Antarafacial:
Three Phase Inversions
Möbius Topology
Four electrons
ALLOWED
H
R'
R
H
R'
Suprafacial:
Zero Phase Inversions
Hückel Topology
Six electrons
THERMALLY ALLOWED
Woodward-Hoffman
• A ground-state pericyclic change is symmetry-allowed
when the total number of (4q+2)s and (4r)a components is
odd.
• [1,5]-H shift – suprafacial
H
H
s2s
• [1,5]-H shift – antarafacial
H
H
s2s
H
H
p4s
No. (4q+2)s = 1
No. (4r)a
=0
Total
=1
ALLOWED
p4a
No. (4q+2)s = 1
No. (4r)a
=1
Total
=2
FORBIDDEN
Woodward-Hoffman
• [1,7]-H shift – antarafacial
H
p6a
H
No. (4q+2)s = 1
No. (4r)a
=0
Total
=1
ALLOWED
H
s2s
• [3,3] rearrangement
R
R
Chair
Boat
s2 s
R
p2s
p2s
No. (4q+2)s = 3
No. (4r)a
=0
Total
=3
ALLOWED
p2s
s2 s
R
p2s
No. (4q+2)s = 3
No. (4r)a
=0
Total
=3
ALLOWED
[1,2] Sigmatropic Rearrangements
•
[1,2]-C shift to cation: Wagner-Meerwein Rearrangement
R
R
2p Carbon radical
C
1 olefin
radical cation
+
H
OH
Suprafacial migration: ALLOWED
•
[1,2]-C shift to anion: Wittig Rearrangement
R
R
2p Carbon radical
2 olefin
radical anion
R
O
R
BuLi
C
O
Li
Suprafacial migration: FORBIDDEN
Must be stepwise
[2,3] Sigmatropic Rearrangements
R
R'
*
X
R
R'
X Y
Y
R
*
X
X, Y = C, N, O, S, Se, P
• FMO Analysis
2 vinyl radical
X Y
Suprafacial migration
ALLOWED
2 allyl radical
Y
R'
[2,3] Sigmatropic Rearrangements
•
X=O, Y=C Wittig Rearrangement1
[2,3]
BuLi
O
O
Li
Ph
•
+
LiO
Ph
X=S, Y=C Sulfonium Ylide Rearrangement2
[2,3]
BuLi
S
+
S
+
Li
S
1.
2.
Ph
Baldwin, JACS 1971, 93, 3556
Lythgoe, Chem. Comm. 1972, 757
S
+
S
S
[2,3] Sigmatropic Rearrangements
•
X=N, Y=C Ammonium Ylide Rearrangement3 (Stevens)
R
R
BuLi
+
[2,3]
+
N
N
Li
CN
•
R
Me2 N
+
CN
CN
X=C, Y=C All-carbon Rearrangement4
[2,3]
Cu(I)
ROH
-N2
O
O
N2
3.
4.
O
H
Buchi, J. Am. Chem. Soc. 1974, 96, 7573
Smith, J. Org. Chem. 1977, 42, 3165
O
OR
[2,3] Sigmatropic Rearrangements
•
X=N, Y=O Meisenheimer Rearrangement5
R
R
[2,3]
+
Et N
O
Et
•
R
Zn/HOAc
Et
N
O
OH
Et
X=S, Y=O Sulfoxide Rearrangement6
(MeO)3P
MeOH
Ph
S
+
O
[2,3]
S
Ph
5.
6.
Tanabe, Tet. Lett. 1975, 3005
Evans, Accts. Chem. Res. 1974, 7, 147
O
OH
BuLi
PhSCl
[2,3] Sigmatropic Rearrangements
•
X=Se, Y=N Related Rearrangement7
Ph
Ph
Ph
Se
+
Se
N
N
Ts
X=S, Y=N Related Rearrangement8
TsO
TsO
TsO
NaN(Cl)Ts
SPh
7.
8.
NHTs
Ph
Ts
•
Ph
MeOH
[2,3]
(MeO)3P
MeOH
Ph
S
Hopkins, Tet. Lett. 1984, 25, 15
Dolle, Tet. Lett. 1989, 30, 4723
[2,3]
+
N
Ts
N
PhS
N
Ts
Ts
[2,3] Sigmatropic Rearrangements
•
Olefin Selectivity from starting olefin
–
1,2-Disubstitution(E)
R
X
Y
R'
R
X
R'
H
X
H
Y
R'
H
H
R
R'
X
Y
R and R’ prefer to sit in pseudo-equatorial positions9
2 LDA
(E) selectivity: 75%
O
CO2 H
9.
Y
R
Y
X
–
R'
R
Nakai, Tet. Lett. 1981, 22, 69
HO
CO2H
[2,3] Sigmatropic Rearrangements
•
Olefin Selectivity from starting olefin
–
1,2-Disubstitution(Z)
R
X
Y
R
H
H
Y
R'
X
Y
R
R'
R'
H
Y
R
H
X
Y
Generally, higher levels of 1,3 induction seen with Z olefins10
R
Bu3Sn
10.
X
R'
X
–
R'
R
BuLi
O
Still, J. Am. Chem. Soc. 1978, 100, 1927
R
OH
Only E isomer
obtained
[2,3] Sigmatropic Rearrangements
•
Olefin Selectivity from starting olefin
–
(E)-Trisubstituted
R
X
Y
R'
R
X
R'
H
X
H
Y
R
Y
X
Y
–
R'
R
R'
H
H
R
R'
X
Y
E transition state still generally preferred but R-Me interaction
may cause significant destabilisation10
n-Bu
Bu3Sn
BuLi
O
>96% Z isomer
n-Bu
OH
[2,3] Sigmatropic Rearrangements
•
Olefin Selectivity from starting olefin
–
(Z)-Trisubstituted
R
X
Y
R
H
H
X
R'
X
Y
R'
X
Y
–
R'
R
Y
R
R'
R'
H
H
R
X
Y
Again, generally higher levels of 1,3 induction seen with Z
olefins due to highly destabilising R-R’ interaction
[2,3] Sigmatropic Rearrangements
•
Olefin Selectivity from allylic position
R
X
Y
R'
R
X
H
Y
X
R'
R'
H
R
R > R'
–
R
R'
H
Y
X
Y
R'
H
R
X
Y
May expect selectivity dependent on size difference of R vs. R’11
SLi
BuLi
S
11.
R
Rautenstrauch, Helv. Chim. Acta 1971, 54, 739
R
(E):(Z) = 3:2
[2,3] Sigmatropic Rearrangements
•
Chiral Auxiliaries12
O
O
CH2OR
O
CH2OR
Li
BuLi
O
N
ROCH2
–
HO
N
ROCH2
O
N
ROCH2
96% de
Via:
O
M
O
ROCH2
12.
CH2OR
N
Katsuki, Tet. Lett. 1986, 27, 4577
CH2OR
[2,3] Sigmatropic Rearrangements
•
Internal Relay of Stereochemistry13
O
O
O
O
O
BuLi
O
O
HO
SnBu3
–
HO
ratio 79:6
Via: (Felkin-Ahn)
C
O H
H
O
O
13.
Bruckner, Angew. Chem. Int. Ed. 1988, 27, 278
[2,3] Sigmatropic Rearrangements
•
Steric Effects
Y
X
t-Bu
t-Bu
–
t-Bu
Y
X
Y
t-Bu
Pseudo-equatorial attack generally favoured14
N2
S
+
Ph
Cu(I)
CO2 Et
SPh
t-Bu
CO2 Et
selectivity 91:9
14.
Evans, J. Am. Chem. Soc. 1972, 94, 3672
X
[2,3] Sigmatropic Rearrangements
•
Ring Expansion15
Cu(I)
S
•
CO2 Et
[2,3]
S
N2CHCO2Et
+
S
CO2 Et
Ring Contraction16
O
Br
Ph
MeO
O
+
N
Ph
MeOH
O
N
Ph
N
"
15.
16.
Vedejs, Accts. Chem. Res. 1984, 17, 358
Stevenson, Tet. Lett. 1990, 31, 4351
O
"
+
N
Ph
O
N
Ph
[3,3] Sigmatropic Rearrangements
• FMO Analysis
X
X
X
Y
Y
Y
2 allyl radical
Chair geometry
ALLOWED
• Dewar-Zimmerman
Zero Phase Inversions
Hückel Topology
Six electrons
THERMALLY ALLOWED
Boat geometry
ALLOWED
[3,3] Sigmatropic Rearrangements
X
X
X
Y
Y
Y
X, Y = C, O, N, etc
X
•
Cope
X
O
O
Cope Rearrangement: Boat vs. Chair Transition State17
trans-trans
17.
Claisen
Doering, Roth, Tetrahedron 1962, 18, 67
trans-cis
cis-cis
[3,3] Sigmatropic Rearrangements
•
Cope Rearrangement: Boat vs. Chair Transition State
H
H
Me
Me
H
Me
Me
H
Me
Me
Me
Me
H
Me
H
H
H
Me
Me
H
10%
trans-cis
<1%
trans-cis
99.7%
H
H
Me
Me
H
cis-cis
H Me
H
Me
Me
H
90%
Me
H
H
trans-trans
H
Me
H
H
Me
Me trans-trans
0.3%
[3,3] Sigmatropic Rearrangements
•
Cope Rearrangement: Use of ring strain18
H
5-20°C
H
–
•
Relief of ring strain upon rearrangement
Oxy-Cope Rearrangement19
H
keq ~ 105
220°C
OH
–
18.
19.
OH
Tautomerism shifts equilibrium to right
Brown, Chem. Comm. 1973, 319
Marvell, Tet. Lett. 1970, 509
O
[3,3] Sigmatropic Rearrangements
•
Oxy-Cope Rearrangement
HO
k1
O
–
–
k2
HO
O
O
1010 < k2 < 1017
k1
Significant rate acceleration for anionic Oxy-Cope.20
Counter-ion also important
OX
OX
66°C
THF
H
H
MeO
20.
Golob, J. Am. Chem. Soc. 1975, 97, 4765
OMe
OX
Half-life
T/°
C
OH
OLi
ONa
OK
(66 yrs)
No rxn
1.2 hrs
1.4 min
66
OK
O- K+
11 hrs
4.4 min
10
[3,3] Sigmatropic Rearrangements
•
X
X
Claisen Rearrangement
O
O
X = C, H, O, N
Thermodynamic driving force: (C-O) p-bond and (C-C) s-bond
formation
X=Heteroatom leads to higher exothermicity and reaction rate
–
–
H
OR
~30
O
O
~20
H
~20 kcal/mol
OR
O
~30 kcal/mol
O
[3,3] Sigmatropic Rearrangements
•
Synthesis of allyl vinyl ethers21,22
OH
Hg(OAc)2
O
AcOHg
OEt
O
OEt
O
Ph
Ph
O
Cp2Ti
21.
22.
Cl
AlMe2
Watanabe, Conlon, J. Am. Chem. Soc. 1957, 79, 2828
Evans, Grubbs, J. Am. Chem. Soc. 1980, 102, 3272
O
[3,3] Sigmatropic Rearrangements
•
Endocyclic Olefins23
Et
O
Via Chair intermediate:
O
144°C
Et
O
t-Bu
t-Bu
diastereoselection >87:13
t-Bu
•
Exocyclic Olefins24
O
EtO
O
OEt
O
OEt
t-Bu
t-Bu
–
23.
24.
t-Bu
ratio 52:48
Overlap equally good from either face
Ireland, J. Org. Chem. 1983, 48, 1829
House, J. Org. Chem. 1975, 40, 86
[3,3] Sigmatropic Rearrangements
•
Olefin Selectivity
CHO
Me
O
O
H
CHO
Me
H
R group prefers to sit in pseudo-equatorial position25
–
CHO
O
110°C
R'
CHO
R'
R'
R
25.
O
R
(E)
Faulkner, J. Am. Chem. Soc. 1973, 95, 553
R
(Z)
R
R’
(E):(Z)
Me
Et
90:10
Me
i-Pr
93:7
Et
Et
90:10
[3,3] Sigmatropic Rearrangements
•
Olefin Selectivity
O
Et
Me
X
O
X
H
Et
X
O
Me
Et
O
Et
Me
H
X
X
Et
O
Me
Me
–
Extra substituents lead to
enhanced diastereoselection25
Larger X => better
selectivity
X
(E):(Z)
H
90:10
Me
>99:1
MeO
>99:1
Me2N
>98:2
[3,3] Sigmatropic Rearrangements
•
Claisen Variants: Johnson Orthoester Claisen26
EtO
OH
MeC(OEt)3
OEt
OEt
O
O
OEt
O
+
H
•
Claisen Variants: Eschenmoser Claisen27
MeO
OH
NEt2
MeO
MeO
O
NEt2
NEt2
O
Xylene
150°C
26.
27.
Johnson, Faulkner, Peterson, J. Am. Chem. Soc. 1970, 92, 741
Eschenmoser, Helv. Chim. Acta 1964, 47, 2425
NEt2
O
[3,3] Sigmatropic Rearrangements
•
Claisen Variants: Ireland Enolate Claisen28
O
OTMS
OH
LDA
O
–
TMSCl
O
O
Substituted enolates afford an additional stereocentre29
R
R'
R'
R
R
O
R'
O
O
H H
OTBS
H R
R
R'
O
OTBS
Ireland, J. Am. Chem. Soc. 1976, 98, 2868
Ireland, J. Org. Chem. 1991, 56, 650
OTBS
R'
R
O
R'
O
H
28.
29.
OTBS
OTBS
OTBS
[3,3] Sigmatropic Rearrangements
•
Lewis Acid catalysed Claisen rearrangement
LA
O
LA
LA
+
O
+
O
O
LA
Presence of Lewis Acid can influence rearrangement30
–
R
R
O
LA
X
R
X
R
O
O
30.
O
Yamamoto, J. Am. Chem. Soc. 1990, 112, 316
X
Lewis
Acid
X
R
X
LA O
[3,3] Sigmatropic Rearrangements
•
Chiral Lewis Acid promoted Claisen rearrangement31
Ph
(R)-1
1.1 - 2 eq
Si(t-Bu)Ph2
Ph
O
88% ee
Al
O
DCM, -20°C
O
SiMe3
Me
O
SiMe3
Si(t-Bu)Ph2
(R)-1
•
Enantioselective Claisen Rearrangements32
OBL2
O
L2BBr
i-Pr2NEt
DCM
31.
-20°C
O
>97% ee
O
Ph
ArO2S
O
OBL2
L2BBr
Et3N
PhMe
OH
OH
O
Yamamoto, J. Am. Chem. Soc. 1990, 112, 7791
N
N
B
SO2Ar
Br
-20°C
O
Ph
L2BBr
96% ee
32. Corey, J. Am. Chem. Soc. 1991, 113, 4026
[m,n] Sigmatropic Rearrangements
•
[4,5] shift
NMe2
Ph
–
•
NMe2
Ph
MeONa
NMe2
Ph
[4,5]
[2,3] possible but [4,5] favoured. [2,5] and [3,4] forbidden
[3,4] shift
OMe
MeO
MeO
O
OH
OH
Key Retrons
R
• C=C + X: 1-6
Cope rearrangement
R'
X
R
R'
R
XH
H
X
Retro-ene reaction
R'
• C=C + X: 1-5
R
R
R'
Claisen rearrangement
X
X
R'
R
• C=C + X: 1-4
X
R
[2,3] rearrangement
Wittig X=O
X
H
R'
R'
R'
Ene reaction
H
X
R'