2-aza-Cope N R N R
2-aza-Cope Rearrangement
t-BuO H N HO NR2 (CH2O)n, NaSO4 MeCN, 80 C
o
t-BuO
t-BuO
N CH2 HO NR2 aza-Cope HO
N CH2 NR2
t-BuO
Mannich O
N CH2 NR2
41
42
Ireland -Claisen rearrangement
43
44
O O O LDA, TBSCl THF, -78 oC then ; AcOH TMS TMS OH TMS O O H H O Oi-Pr
45
46
47
Aza-Cope Rearrangement
1-aza-Cope N R N R R N R 3-aza-Cope N
a) FMO (Frontier Molecular Orbital theory)
HOMO orbitals controls the course of reactions 4 electrons
6
6 electrons
b) Orbital Correlation diagrams The orbital symmetries of both reactants and products are considered The orbitals of the S. M. should must be smoothly transformed into orbitals of products having the same symmetry.
*
A S A S A S
S A S A S A
3
Symmetry-allowed Disrotatory
Symmetry-forbidden Conrotatory
12
c) The aromaticity or antiaromaticity of transition state Hückel type or the Möbius type T.S The basis set of orbitals, i.e. the total set of 2p orbitals are considered Aromatic transition state, low activation energy, allowed; anitaromatic transition state, high activation energy, forbidden. Hückel system zero (or any even number) of phase change aromatic when there are 4n+2 electrons Möbius system one (or any odd number) of phase change aromatic when there are 4n electrons
1
处理周环反应的方法：
轨道对称性守恒原理
（The Conservation of Orbital Symmetry）
在反应过程中，反应物的具有特定对称性的轨道可以被顺利地转化成 产物的具有相同对称性的轨道。
轨道相关图和态相关图
（Orbital Correlation diagrams）
前线轨道理论（FMO） 芳香性过渡态理论 （The aromaticity or antiaromaticity of transition state）
15
x HOMO vacant for EWG occupied for EDG
x LUMO vacant for EWG occupied for EDG
outward
inward
outward
inward
16
17
Examples of electrocyclic reactions:
34
major
35
Examples of Cope rearrangement:
Very rapid
36
b a g f h i
c e
b g f
c d
d j
a
e j i
h
At room temperature, only on signal in 1H NMR and 13C NMR
37
Oxy-Cope rearrangement
o
H
H
H
H
4 electrons
Conrotatory rotating
H H3C H3C H H H
H H3C H3C H3C H H3C
H H 400 oC
H3C H3C
conrotation
4
6 electrons
Disrotatory rotating
5
Mechanistic Treatment
98 %
48
7. 2. 3 [2,3] Sigmatropic rearrangements
The reaction is most facile in systems where X and Y bear charges
49
50
A Allylic sulfoxide, selenoixde and amine oxide
13
4 electrons Conrotatory rotating,
,Möbius aromaticity disrotatory rotating,
Hückel antiaromaticity
6 electrons
Conrotatory Möbius antiaromaticity
Disrotatory Hückel aromaticity
Suprafacial (inversion at M. C)
Suprafacial (retention at M. C)
26
*, LUMO
*, LUMO
HOMO HOMO
27
The aromaticity or antiaromaticity of transition state
14
The substitutents at the C3 might rotate inward or outward
Steric effect: larger group move outward Donor substituents such as O¯¯ and NH2rotate outward; accepter substituents such as CH=O andCH =NH2+ rotate inward.
Endo T. S. is preferred
51
B Sulfonium and ammonium ylides
52
C. Anionic Wittig Rearrangement
Driving force — formation of the carbonyl compounds
Greatly accelerated
38
Pd2+ could catalyze Cope rearrangement:
39
Claisen Rearrangement
40
Ortho-ester-Claisen rearrangement
周环反应特点 Concerted process with no reaction intermediates detected during the reaction. Cyclic transition states Stereospecificity and regioselectivity Reaction mechanism is rationalized with symmetry properties of orbitals that are directly involved.
28
29
30
Examples of [1, n] sigmatropic rearrangements:
31
32
7. 2. 2 [3,3] Sigmatropic rearrangements
33
Cope Rearrangement
Cope rearrangement usually proceeds though a chair-like transition state But the boat-like transition state is allowed. If steric factors make a boatlike transition state more favorable, the reaction will proceed through a boat.
18
Very rapid process Valence tautomerism
19
Electrocyclic Reactions of Charged Species
X H
-X slow H fast
or concerted
2 electrons
Sterically favorable
20
2×10６more rapidly
2
7.1 Electrocyclic Reactions
两种转动方式
Conrotatory rotating
Disrotatory rotating
3
CH3 H CH3 H 175 C
o
CH3 H H CH3 H H
CH3 H H CH3 175 C