chapter 10 pericyclic reactions (周环反应)
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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) - PowerPoint PPT PresentationTRANSCRIPT
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 -bond across a conjugated -system
• [m,n] shift when the -bond migrates across m atoms of one system and n of another
R R
R R
[1,3]-shift1
2
3 1
2
3
1
2
3
1'2'
3'
1
2
3
1'2'
3'
[3,3]-shift
1' 1'
Conjugated π Systems
nonbonding
4
3
3
2
2
1
1 Bonding
Antibonding
2 p-orbitals 3 p-orbitals 4 p-orbitals
Suprafacial/Antarafacial• Suprafacial migration: Group moves across same face
• Antarafacial migration: Group moves from one face to the other
R'R
R R'
R R'
R'R
R'R
R R'
R'
R
R
R'
R'
RR
R'
R R'R'R
FMO Analysis• [1,3] Sigmatropic Rearrangements: H migration
R R'
H
R R'
H
R R'
H+
R R'
H
R R'H
Suprafacial migration Antarafacial migration
FORBIDDEN ORBITALLY ALLOWED BUTH CANNOT BRIDGE DISTANCE
2 allyl anion HOMO
1s proton LUMO
FMO Analysis• [1,3] Sigmatropic Rearrangements: C migration
R R'
CH3
R R'
CH3
R R'
CH3
+
R R'
C HH
H
R R'
C
H
HH
Suprafacial migrationRetention at carbon
Suprafacial migrationInversion at carbon
FORBIDDEN
2 allyl anion HOMO
ALLOWED
2p Carbon LUMO
FMO Analysis• [1,5] Sigmatropic Rearrangements
R R'
X
R R'
X
R R'
X+
H
C
C
3 pentadienyl anion HOMO
1s proton LUMO
Suprafacial migrationALLOWED
3 pentadienyl anion HOMO
2p carbon LUMO
Suprafacial migrationRetention at Carbon
ALLOWED
Antarafacial migrationInversion at Carbon
ALLOWED
Antarafacial migrationFORBIDDEN
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:
– Aromatic = Thermally allowed (Photochemically forbidden)– Antiaromatic = Thermally forbidden (Photochemically allowed)
System Aromatic Antiaromatic
Hückel 4n + 2 4n
Möbius 4n 4n + 2
Dewar-Zimmerman• [1,3]-H shift
• [1,5]-H shift
R R'
H
R R'
H
H H
Suprafacial:Two Phase InversionsHückel TopologyFour electronsFORBIDDEN
H
R R'
H
R R'
H H
Suprafacial:Zero Phase InversionsHückel TopologySix electronsTHERMALLY ALLOWED
Antarafacial:Three Phase InversionsMöbius TopologyFour electronsALLOWED
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
• [1,5]-H shift – antarafacial
H HH 4s
2s
No. (4q+2)s = 1No. (4r)a = 0Total = 1ALLOWED
No. (4q+2)s = 1No. (4r)a = 1Total = 2FORBIDDEN
H
H
H 4a
2s
Woodward-Hoffman• [1,7]-H shift – antarafacial
• [3,3] rearrangement
Chair Boat
RR
HH H
2s
6a
No. (4q+2)s = 1No. (4r)a = 0Total = 1ALLOWED
R
2s
2s
2s
R
2s
2s
2s
No. (4q+2)s = 3No. (4r)a = 0Total = 3ALLOWED
No. (4q+2)s = 3No. (4r)a = 0Total = 3ALLOWED
[1,2] Sigmatropic Rearrangements• [1,2]-C shift to cation: Wagner-Meerwein Rearrangement
• [1,2]-C shift to anion: Wittig Rearrangement
R RC
1 olefin radical cation
2p Carbon radical
Suprafacial migration: ALLOWED
R RC
2 olefin radical anion
2p Carbon radical
Suprafacial migration: FORBIDDENMust be stepwise
OR BuLi O
R
Li
OHH
+
[2,3] Sigmatropic Rearrangements
R'R
XY
R R'
YX X Y
R R'
X, Y = C, N, O, S, Se, P
* *
• FMO Analysis
X Y
2 allyl radical
2 vinyl radicalSuprafacial migration
ALLOWED
[2,3] Sigmatropic Rearrangements
O
Ph
LiO PhO
Ph
Li+
BuLi [2,3]
• X=O, Y=C Wittig Rearrangement1
• X=S, Y=C Sulfonium Ylide Rearrangement2
1. Baldwin, JACS 1971, 93, 3556
2. Lythgoe, Chem. Comm. 1972, 757
S+
S
S SS
+
SLi
+
BuLi [2,3]
[2,3] Sigmatropic Rearrangements
R
N+
CN
R
CN
Me2N
R
N+
CN
Li+
BuLi [2,3]
• X=N, Y=C Ammonium Ylide Rearrangement3 (Stevens)
• X=C, Y=C All-carbon Rearrangement4
3. Buchi, J. Am. Chem. Soc. 1974, 96, 7573
4. Smith, J. Org. Chem. 1977, 42, 3165
O
N2O
O
H
O
OR
Cu(I)
-N2
ROH[2,3]
[2,3] Sigmatropic Rearrangements
R
N+
EtEt O OH
R
ON
Et
Et
R
[2,3] Zn/HOAc
• X=N, Y=O Meisenheimer Rearrangement5
• X=S, Y=O Sulfoxide Rearrangement6
5. Tanabe, Tet. Lett. 1975, 3005
6. Evans, Accts. Chem. Res. 1974, 7, 147
S+
OPh
OS
Ph
OH[2,3]
(MeO)3PMeOH
BuLiPhSCl
[2,3] Sigmatropic Rearrangements
Se+
NPh
Ph
NHTs
PhN
Se
Ph
Ph
[2,3]
Ts
Ts
MeOH
• X=Se, Y=N Related Rearrangement7
• X=S, Y=N Related Rearrangement8
7. Hopkins, Tet. Lett. 1984, 25, 15
8. Dolle, Tet. Lett. 1989, 30, 4723
SPh
TsO
[2,3]NaN(Cl)Ts
S+
TsO
NPh
TsO
NPhS
N
TsTs
Ts(MeO)3PMeOH
[2,3] Sigmatropic Rearrangements
R'R
XY
X
Y R'
H
R
H
Y
X H
R
R'
H
R'R
YX
R'
R YX
• Olefin Selectivity from starting olefin– 1,2-Disubstitution(E)
– R and R’ prefer to sit in pseudo-equatorial positions9
9. Nakai, Tet. Lett. 1981, 22, 69
O
CO2HOH CO2H
(E) selectivity: 75%2 LDA
[2,3] Sigmatropic Rearrangements
R
XY
R'
X
Y H
R'
R
H
Y
X H
R
H
R'
R'R
YX
R'
R YX
• Olefin Selectivity from starting olefin– 1,2-Disubstitution(Z)
– Generally, higher levels of 1,3 induction seen with Z olefins10
10. Still, J. Am. Chem. Soc. 1978, 100, 1927
R
OBu3Sn
ROH Only E isomer
obtained
BuLi
[2,3] Sigmatropic Rearrangements
R
XY
R'
X
Y R'
H
R
H
Y
X H
R
R'
H
R'R
YX
R'
R YX
• Olefin Selectivity from starting olefin– (E)-Trisubstituted
– E transition state still generally preferred but R-Me interaction may cause significant destabilisation10
n-Bu
OBu3Sn n-BuOH
>96% Z isomerBuLi
[2,3] Sigmatropic Rearrangements
R
XY
R'
X
Y H
R'
R
H
Y
X H
R
H
R'
R'R
YX
R'
R YX
• Olefin Selectivity from starting olefin– (Z)-Trisubstituted
– Again, generally higher levels of 1,3 induction seen with Z olefins due to highly destabilising R-R’ interaction
[2,3] Sigmatropic Rearrangements
R
XY
R'
X
Y H
H
R
R'
Y
X R'
R
H
H
R
YX
R'
R YX
R'
R > R'
• Olefin Selectivity from allylic position
– May expect selectivity dependent on size difference of R vs. R’11
11. Rautenstrauch, Helv. Chim. Acta 1971, 54, 739
S RR
SLi
BuLi (E):(Z) = 3:2
[2,3] Sigmatropic Rearrangements
N
O
O
CH2OR
ROCH2
N
OH
O
CH2OR
ROCH2
BuLi
N
O
O
CH2OR
ROCH2
Li
96% de
• Chiral Auxiliaries12
– Via:
12. Katsuki, Tet. Lett. 1986, 27, 4577
O
MO
N CH2ORROCH2
[2,3] Sigmatropic Rearrangements
OO
O
SnBu3
BuLi OO
OH
OO
OH
ratio 79:6
• Internal Relay of Stereochemistry13
– Via: (Felkin-Ahn)
13. Bruckner, Angew. Chem. Int. Ed. 1988, 27, 278
OO
OH
CH
[2,3] Sigmatropic Rearrangements
t-Bu XY t-Bu
YX
t-Bu
YX
• Steric Effects
– Pseudo-equatorial attack generally favoured14
14. Evans, J. Am. Chem. Soc. 1972, 94, 3672
t-BuSPh
CO2Et
t-Bu S+
CO2Et
PhN2Cu(I)
selectivity 91:9
[2,3] Sigmatropic Rearrangements
S S
CO2Et
S+
CO2Et
Cu(I)
N2CHCO2Et
[2,3]
• Ring Expansion15
• Ring Contraction16
15. Vedejs, Accts. Chem. Res. 1984, 17, 358
16. Stevenson, Tet. Lett. 1990, 31, 4351
N
N+
O
Ph
N+
O
Ph
N
O
Ph
N
O
Ph
Br
O
Ph
"
MeO
MeOH
"
[3,3] Sigmatropic Rearrangements• FMO Analysis
• Dewar-Zimmerman
2 allyl radical
Chair geometryALLOWED
Boat geometryALLOWED
X
Y Y
X
Y
X
Zero Phase InversionsHückel TopologySix electronsTHERMALLY ALLOWED
[3,3] Sigmatropic Rearrangements
• Cope Rearrangement: Boat vs. Chair Transition State17
17. Doering, Roth, Tetrahedron 1962, 18, 67
trans-trans trans-cis cis-cis
X
Y Y
X
Y
X
X XO O
X, Y = C, O, N, etc
Cope Claisen
[3,3] Sigmatropic Rearrangements• Cope Rearrangement: Boat vs. Chair Transition State
H
Me
H
Me
Me
MeH
H
H
Me H
Me
HMe
H
Me
Me
HMe
H
HMe HMe
Me
HH
Me
H
Me Me
H
Me
HH
Me
HMe MeH
trans-trans
cis-cis
trans-cis
trans-cis
trans-trans
90%
10%
<1%
99.7%
0.3%
[3,3] Sigmatropic Rearrangements• Cope Rearrangement: Use of ring strain18
– Relief of ring strain upon rearrangement
• Oxy-Cope Rearrangement19
– Tautomerism shifts equilibrium to right
18. Brown, Chem. Comm. 1973, 319
19. Marvell, Tet. Lett. 1970, 509
H
H
5-20°C
OH
H
OH O
220°C keq ~ 105
[3,3] Sigmatropic Rearrangements• Oxy-Cope Rearrangement
– Significant rate acceleration for anionic Oxy-Cope.20
– Counter-ion also important
20. Golob, J. Am. Chem. Soc. 1975, 97, 4765
OH OH O
O O 1010 < k2 < 1017
k1
k1
k2
MeO
OX
OX
OMe
H
H
66°C
THF
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 min10
[3,3] Sigmatropic Rearrangements• Claisen Rearrangement
– Thermodynamic driving force: (C-O) -bond and (C-C) -bond formation
– X=Heteroatom leads to higher exothermicity and reaction rate
O
X
O
X
X = C, H, O, N
O
H
O
OR
O
H
O
OR~20 kcal/mol
~30
~30 kcal/mol
~20
[3,3] Sigmatropic Rearrangements• Synthesis of allyl vinyl ethers21,22
21. Watanabe, Conlon, J. Am. Chem. Soc. 1957, 79, 2828
22. Evans, Grubbs, J. Am. Chem. Soc. 1980, 102, 3272
OH
OEtO
AcOHg
OEt
O
O
O
Ph OPhCp2Ti
ClAlMe2
Hg(OAc)2
[3,3] Sigmatropic Rearrangements• Endocyclic Olefins23
• Exocyclic Olefins24
– Overlap equally good from either face
23. Ireland, J. Org. Chem. 1983, 48, 1829
24. House, J. Org. Chem. 1975, 40, 86
t-Bu
O
Et
t-Bu
Et
O
O
t-Bu
144°C
diastereoselection >87:13
Via Chair intermediate:
t-Bu
O
OEtt-Bu
O
OEt
t-Bu
O
EtO
ratio 52:48
[3,3] Sigmatropic Rearrangements• Olefin Selectivity
– R group prefers to sit in pseudo-equatorial position25
25. Faulkner, J. Am. Chem. Soc. 1973, 95, 553
O
H
Me
O
CHO
CHO
Me
H
O
R'
R
O
R'
R
CHO
R
CHOR'
(E) (Z)
110°C
R R’ (E):(Z)
Me Et 90:10
Me i-Pr 93:7
Et Et 90:10
[3,3] Sigmatropic Rearrangements• Olefin Selectivity
– Extra substituents lead to
enhanced diastereoselection25
Larger X => better
selectivity
Et
O
Me
XEt
Me
O
X
Et X
O
Me
Et
H
MeO
X
H
Et
Me
OX
X (E):(Z)
H 90:10
Me >99:1
MeO >99:1
Me2N >98:2
[3,3] Sigmatropic Rearrangements• Claisen Variants: Johnson Orthoester Claisen26
• Claisen Variants: Eschenmoser Claisen27
26. Johnson, Faulkner, Peterson, J. Am. Chem. Soc. 1970, 92, 741
27. Eschenmoser, Helv. Chim. Acta 1964, 47, 2425
O
OEt
O
OEtEtO
O
OEtOH
H+
MeC(OEt)3
O
NEt2
O
NEt2MeO
O
NEt2OH
NEt2
MeO
MeO
Xylene150°C
[3,3] Sigmatropic Rearrangements• Claisen Variants: Ireland Enolate Claisen28
– Substituted enolates afford an additional stereocentre29
28. Ireland, J. Am. Chem. Soc. 1976, 98, 2868
29. Ireland, J. Org. Chem. 1991, 56, 650
O
O
O
OTMS
O
OH
LDA
TMSCl
R'
O
R
OTBS
R'
O
R
OTBS
R
H
R'O
OTBSH
O
R
OTBS
R'
R
H
R'O
OTBS
H
O
R
OTBS
R'
[3,3] Sigmatropic Rearrangements• Lewis Acid catalysed Claisen rearrangement
– Presence of Lewis Acid can influence rearrangement30
30. Yamamoto, J. Am. Chem. Soc. 1990, 112, 316
O+LA
O+LA
O OLA
LA
R O XR
O
X
O
X
R O
X
R
LA
R
O
X
LA
LewisAcid
[3,3] Sigmatropic Rearrangements• Chiral Lewis Acid promoted Claisen rearrangement31
• Enantioselective Claisen Rearrangements32
31. Yamamoto, J. Am. Chem. Soc. 1990, 112, 7791 32. Corey, J. Am. Chem. Soc. 1991, 113, 4026
O
OO
OBL2
O
OH
O
OBL2
O
OH
>97% ee
96% ee
L2BBri-Pr2NEt
DCM
-20°C
-20°CL2BBrEt3N
PhMe
O SiMe3
Ph
O SiMe3
Ph(R)-1
1.1 - 2 eq
DCM, -20°C
88% eeO
O
Al Me
Si(t-Bu)Ph2
Si(t-Bu)Ph2
(R)-1
NB
N
Br
ArO2S SO2Ar
Ph Ph
L2BBr
[m,n] Sigmatropic Rearrangements• [4,5] shift
– [2,3] possible but [4,5] favoured. [2,5] and [3,4] forbidden
• [3,4] shift
Ph NMe2
NMe2PhPh NMe2
MeONa [4,5]
OMeO OH
OMe
OHMeO
Key Retrons• C=C + X: 1-6
• C=C + X: 1-5
• C=C + X: 1-4
RR'
X
R
R'XH
XH
R'
R
R R'
X
R
X
R'
RR'
XH
R
X
R'R'
HX R'
Cope rearrangement
Retro-ene reaction
Claisen rearrangement
[2,3] rearrangementWittig X=O
Ene reaction