哈佛大学高等有机化学讲义Lecture12
合集下载
高等有机化学-Lecture 11
R H C C OH
+
R C C OH2+
R C C
2. Formation of a Nitrene
R
C O
N
N
N
R
C O
N
+
N2
Step II. Migration
Step III. The migration origin (A) acquires an octet Rearrangement with substitution (combinations with a nucleophile) Rearrangement with elimination (loss of H+)
O2N
COOH PhNH2 Br
O2N
Ph N OH Br PCl5
O2N
O2N NHCOPh H2O
Br
NH2 PhCOOH Br
The shift will keep the stereostructure of chiral center
CH3 C N HO C2H5 C CH2C2H5 H H2SO4 Et2O
-
Ph
PhCH2 CH2COOR
Intramolecular SN2 attack(structure maintaining):
Me COCH3 H Cl
Me Cl H
Me H
KOH
O
HO
-
Me H
O
OH H+
Me COOH H Me
CH2
-
Me
Me
KOH
H
HO
O
CH2
O OH
H
H+
+
R C C OH2+
R C C
2. Formation of a Nitrene
R
C O
N
N
N
R
C O
N
+
N2
Step II. Migration
Step III. The migration origin (A) acquires an octet Rearrangement with substitution (combinations with a nucleophile) Rearrangement with elimination (loss of H+)
O2N
COOH PhNH2 Br
O2N
Ph N OH Br PCl5
O2N
O2N NHCOPh H2O
Br
NH2 PhCOOH Br
The shift will keep the stereostructure of chiral center
CH3 C N HO C2H5 C CH2C2H5 H H2SO4 Et2O
-
Ph
PhCH2 CH2COOR
Intramolecular SN2 attack(structure maintaining):
Me COCH3 H Cl
Me Cl H
Me H
KOH
O
HO
-
Me H
O
OH H+
Me COOH H Me
CH2
-
Me
Me
KOH
H
HO
O
CH2
O OH
H
H+
第四章.哈工大大学化学精品课讲义
(5) 缓冲溶液的缓冲范围
ca pH pK lg c盐
a
弱酸及其强碱盐 缓冲溶液的pH值计算式
缓冲液的pH值与 pK a 及ca/c盐比值有关。 缓冲能力的大小取决于ca与c盐的大小及其比值的大小。 当ca/c盐=1时，（一般缓冲溶液的ca/c盐在0.1与10之间） 缓冲能力最大，因而： 缓冲溶液的缓冲范围为：
溶液中始终存在着解离产生的正、负离子和未解离的 分子之间的平衡，此称为解离平衡。
HAc (aq) H+ (aq) +Ac- (aq)
[ c ( H ) c ] [ c ( Ac ) c ] Ka 解离常数 c( HAc) c
K
对于不同的一元弱酸，既表示其解离程度，又代表其酸性的强弱。
将 (2) 代入 (1) 式, 得:
K
ca
表示一元弱酸浓度、 解离度和解离常数 12 之间的关系。
2. 一元弱酸和一元弱碱的离解平衡
(4) 与 K
b 的关系
K
a
ca
H2O(aq) 对于一元弱碱 HN3·
同样方法可得
c(OH ) c cb Kb
NH4+(aq) + OH-(aq)
K sp G RT ln K 可由实验测得，亦可由 r m sp计算，
20
附录列出了的值。
4.5.2 沉淀-溶解平衡
2. 溶度积规则
在第二章中, 通过比较反应商(J )和标准平衡常数( K )来判 断反应自发进行的方向，这一规律同样适用于难溶电解质的溶 解平衡。显然，J 在这里为离子积， 为溶度积，因此 K sp
化学工作者所考虑的溶液一般是气体、液体或固体等溶 本章主要研究液体溶于液体中形成的液体溶液。液体溶
ca pH pK lg c盐
a
弱酸及其强碱盐 缓冲溶液的pH值计算式
缓冲液的pH值与 pK a 及ca/c盐比值有关。 缓冲能力的大小取决于ca与c盐的大小及其比值的大小。 当ca/c盐=1时，（一般缓冲溶液的ca/c盐在0.1与10之间） 缓冲能力最大，因而： 缓冲溶液的缓冲范围为：
溶液中始终存在着解离产生的正、负离子和未解离的 分子之间的平衡，此称为解离平衡。
HAc (aq) H+ (aq) +Ac- (aq)
[ c ( H ) c ] [ c ( Ac ) c ] Ka 解离常数 c( HAc) c
K
对于不同的一元弱酸，既表示其解离程度，又代表其酸性的强弱。
将 (2) 代入 (1) 式, 得:
K
ca
表示一元弱酸浓度、 解离度和解离常数 12 之间的关系。
2. 一元弱酸和一元弱碱的离解平衡
(4) 与 K
b 的关系
K
a
ca
H2O(aq) 对于一元弱碱 HN3·
同样方法可得
c(OH ) c cb Kb
NH4+(aq) + OH-(aq)
K sp G RT ln K 可由实验测得，亦可由 r m sp计算，
20
附录列出了的值。
4.5.2 沉淀-溶解平衡
2. 溶度积规则
在第二章中, 通过比较反应商(J )和标准平衡常数( K )来判 断反应自发进行的方向，这一规律同样适用于难溶电解质的溶 解平衡。显然，J 在这里为离子积， 为溶度积，因此 K sp
化学工作者所考虑的溶液一般是气体、液体或固体等溶 本章主要研究液体溶于液体中形成的液体溶液。液体溶
哈佛大学高等有机化学讲义Lecture34
Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part B Chapter 9, " C–C Bond Forming Rxns of Boron, Silicon & Tin", 595–680. Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part B Chapter 10, "Reactions Involving Highly Reactive Electron-Deficient Intermediates", 595–680. Lecture 09A Simmons-Smith Reaction: Enantioselective Variants Lecture 26B Synthetic Applications of α-Diazocarbonyl Compounds
s the History of the Singlet-Triplet Gap
Year 1932 Method Qual. Thermochem Qual. QM Ab initio Kinetics SCF MINDO Expt An Initio Expt Expt Author Muliken Walsh Gallup Harrison Hase Pople Dewar Lineberger Schaeffer Zare Haydon HCH Angle Grnd State 90-100° 180° 160° 138° –– 132° 134° 138° ––– ––– ––– singlet triplet triplet triplet triplet triplet triplet triplet triplet triplet triplet S–T Splitting kcal/mol –– small 30 >33 8–9 19 8.7 19.5 19.7 8.1 8.5
s the History of the Singlet-Triplet Gap
Year 1932 Method Qual. Thermochem Qual. QM Ab initio Kinetics SCF MINDO Expt An Initio Expt Expt Author Muliken Walsh Gallup Harrison Hase Pople Dewar Lineberger Schaeffer Zare Haydon HCH Angle Grnd State 90-100° 180° 160° 138° –– 132° 134° 138° ––– ––– ––– singlet triplet triplet triplet triplet triplet triplet triplet triplet triplet triplet S–T Splitting kcal/mol –– small 30 >33 8–9 19 8.7 19.5 19.7 8.1 8.5
哈佛大学高等有机化学讲义Lecture33A
33A-06 3/14/96 11:22 PM
Shea, K. J.; Zandi, K. S.; Staab, A. J.; Carr. R. Tetrahedron Lett. 1990, 31, 5885.
CO2Et
R=H 90
R = Me >99
: :
t-Bu t-Bu
Si
OO
10
<1
R
CO2Et
Note: Intermolecular variant gives 1:1 ratio with opposite regiochemistry.
Gillard, J. W.; Fortin, R.; Grimm, E. L.; Maillard, M.; Tjepkema, M.; Bernstein, M. A.; Glasser, R. Tetrahedron Lett. 1991, 32, 1145.
- Function of tether length and steric bulk of alkyl substituents on silicon
❏ Functional Group Protection
- Serves as protecting group before and after reaction ❏ Facile Refunctionalization
- Protodesilylation, Tamao oxidation, allylsilane additions, and transmetallations are possible
Diels-Alder To Form 5-Atom Tether Ring:
OH SiR2Cl
哈佛大学高等有机
k1 kA kB k2
To relate this quantity to !G values, recall that !Go = -RT ln Keq or Keq = e-!G°/RT, k1 = e-!G1/RT, and k2 = e-!G2/RT. Substituting this into the above equation:
K. A. Beaver, D. A. Evans
Leading References:
Conformational Analysis and Reactivity: Curtin-Hammett Principle
Case 1: "Kinetic Quench"
Chem 206
J. I. Seeman, J. Chem. Ed. 1986, 63, 42-48. J. I. Seeman, Chem Rev. 1983, 83, 83-134. See also Eliel, pp. 647-655
H. Yamamoto et.al, Angew. Chem. Int. Ed. 2005, 44, 4389-4391 (pdf)
TIPSO
H Me H
Me H H O
Al(t-BuO)3
R H Me H O H
" "
Me H O R
t-BuOOH
4 sieves toluene, -20C
HO
Olefin Addition Reactions–2
! ! Sharpless Epoxidation continued..... Hydrogenation
Problem 579. The following publication (J. Org. Chem. 1991, 56, 5553) reported the surprisingly selective olefin epoxidation illustrated below. In this reaction, olefin B in 1 was found to be much less reactive than olefin A. Using your knowlege of stereoelectronic effects, provide an explanation for the reduced reactivity of olefin B in diene 1.
To relate this quantity to !G values, recall that !Go = -RT ln Keq or Keq = e-!G°/RT, k1 = e-!G1/RT, and k2 = e-!G2/RT. Substituting this into the above equation:
K. A. Beaver, D. A. Evans
Leading References:
Conformational Analysis and Reactivity: Curtin-Hammett Principle
Case 1: "Kinetic Quench"
Chem 206
J. I. Seeman, J. Chem. Ed. 1986, 63, 42-48. J. I. Seeman, Chem Rev. 1983, 83, 83-134. See also Eliel, pp. 647-655
H. Yamamoto et.al, Angew. Chem. Int. Ed. 2005, 44, 4389-4391 (pdf)
TIPSO
H Me H
Me H H O
Al(t-BuO)3
R H Me H O H
" "
Me H O R
t-BuOOH
4 sieves toluene, -20C
HO
Olefin Addition Reactions–2
! ! Sharpless Epoxidation continued..... Hydrogenation
Problem 579. The following publication (J. Org. Chem. 1991, 56, 5553) reported the surprisingly selective olefin epoxidation illustrated below. In this reaction, olefin B in 1 was found to be much less reactive than olefin A. Using your knowlege of stereoelectronic effects, provide an explanation for the reduced reactivity of olefin B in diene 1.
哈佛大学高等有机化学讲义Lecture15
Paterson, Tet Lett 1991, 32, 7601
favored O R Me disfavored R
H N R
O Li H
‡ Me R
OLi
Me
Me
Me
Me
Me
Me
Me
Me
Me R
OH
O
OH
Me O
O
O
O O
LDA, TMSCl Et3N
Me
LM–NR2
O Me H Li R H N R
OMe OMe
O NEt2
O Et2N Me Me Et 92% (E:Z = 98:2) OH Me
CH3C(NMe2)(OMe)2
O NEt2
H H
s Compare the two variants:
Me S OH
60% Hg(OAc)2, EVE
OEt
CH3C(OEt)3 CH3CH2CO2H (cat) 138oC
O O O O O
+ π2s]
π*
light
π*
new HOMO
C C
bonding
X
[2+2]
O O
[4+2]
O O
bonding
C T
s The related reaction of 2 ethylenes is nonconcerted: [2 + 2] cycloaddition
Y Y Y
批注本地保存成功开通会员云端永久保存去开通
D. A. Evans
Cycloaddition Reactions: Part–1
s Other Reading Material:
favored O R Me disfavored R
H N R
O Li H
‡ Me R
OLi
Me
Me
Me
Me
Me
Me
Me
Me
Me R
OH
O
OH
Me O
O
O
O O
LDA, TMSCl Et3N
Me
LM–NR2
O Me H Li R H N R
OMe OMe
O NEt2
O Et2N Me Me Et 92% (E:Z = 98:2) OH Me
CH3C(NMe2)(OMe)2
O NEt2
H H
s Compare the two variants:
Me S OH
60% Hg(OAc)2, EVE
OEt
CH3C(OEt)3 CH3CH2CO2H (cat) 138oC
O O O O O
+ π2s]
π*
light
π*
new HOMO
C C
bonding
X
[2+2]
O O
[4+2]
O O
bonding
C T
s The related reaction of 2 ethylenes is nonconcerted: [2 + 2] cycloaddition
Y Y Y
批注本地保存成功开通会员云端永久保存去开通
D. A. Evans
Cycloaddition Reactions: Part–1
s Other Reading Material:
高等有机化学--lecture 14
Here are some estimates of the strain based on "homodesmotic reactions" (agrees with experiments for carbon skeletons): theoretical strain energy (kcal/mol) cyclopropane (C3H6) 26.8 25.7 34.9 15.2
E. Kwan
Lecture 14: Small Ring Conformational Analysis
Chem 106
Geminal Hyperconjugations The effect of the D-C-A bond angle is illustrated by the relatively small hyperconjugations in propane vs. cyclopropane: Propane (CC to *CC = 0.52 kcal/mol)
D A D A
vicinal interaction
D
A
D
A
gemin normally talk about geminal interactions? It turns out that their strength depends a lot on the D-C-A angle. In a small ring, the angle is small, the overlap is good, and therefore the interaction is strong.
E. Kwan
Lecture 14: Small Ring Conformational Analysis Small Ring Conformational Analysis
高等有机化学精品讲义：2 (英文精品)
The standard approach is to use computations to predict bond lengths, transition state energies, vibrational frequencies, etc. These calculations correlate well with experimental observations. Therefore, it is reasonable to think that other useful information might be contained in the wavefunctions produced by these calculations. However, the canonical molecular orbitals (CMOs) are relatively delocalized entities that are hard to interpret chemically.
The NBO algorithim converts the wavefunctions/CMOs into other basis sets that are mathematically equivalent (span the same space), but easier to understand:
amide resonance
anomeric effect
hyperconjugation
non-Lewis corrections to Lewis structures
Helpful References
1. Coulson's Valence, 3rd ed. McWeeny, R. Oxford: Oxford University Press, 1979.
2024年中科院高等有机化学60讲
26
06
生物活性有机化合物
Chapter
2024/2/29
27
生物碱
2024/2/29
生物碱的定义与分类
生物碱是一类含氮的碱性有机化合物，在生物界分布广泛 。根据其化学结构，可分为吡啶类、嘌呤类、异喹啉类等 。
生物碱的生物活性
生物碱具有多种生物活性，如镇痛、抗菌、抗癌等。例如 ，吗啡是一种具有强镇痛作用的生物碱，而奎宁则具有抗 疟疾活性。
包括胺、酰胺、硝 基化合物、重氮化 合物等。
元素有机化合物
包括有机硅、有机 磷、有机硫等。
5
有机化学的发展历史
2024/2/29
萌芽阶段
18世纪末至19世纪初，有机化学处于萌芽阶段，人们开始从天然产物中分离出有机化合 物并进行研究。
发展阶段
19世纪中期至20世纪初，有机化学得到迅速发展，人们合成了大量新的有机化合物，并 发现了许多重要的反应类型和反应机理。
2024/2/29
周环反应在有机合成中的应用
周环反应在有机合成中具有广泛的应用，可用于构建复杂的碳环和杂环化合物，以及实 现官能团的转化和重排。
23
电环化反应
2024/2/29
电环化反应定义
电环化反应是指在光照或加热条件下，共轭体系中的π电子 发生环状流动，从而形成环状化合物的反应。
电环化反应机理
成熟阶段
20世纪中期至今，有机化学进入成熟阶段，研究重点转向合成具有特定功能或性能的有 机材料或药物等应用方面。同时，随着计算机技术的发展和应用，计算化学在有机化学中 也发挥着越来越重要的作用。
6
02
基础知识
Chapter
2024/2/29
7
原子结构与化学键
大学有机化学学习方法3篇
大学有机化学学习方法3篇在学习中我们可以根据有机化学自身的特点,掌握一定的学习方法,从而提高教学效率,达到事半功倍的效果今天店铺就与大家分享：大学有机化学学习方法，希望对大家的学习有帮助!大学有机化学学习方法一1、找本国内教科书，学习好基本反应，不懂的地方不要死扣，主要加强印象，对于一些基本概念掌握好，如共振、octet rule、molecular orbital、Sn1、Sn2、E1等基本概念。
推荐邢其毅的有机化学。
2.找本国外的有机化学原版书，如mcmurry或carey等人编的organic chemistry。
熟悉外文专业词汇的同时，加深理解，老外写的书都深入浅出，并不难理解(除了英文讨厌以外)。
推荐多看老外写的有机化学方面的讲稿(Lecture notes)，非常棒，可到国外大学的化学系上查找。
3、正式入门先看两本书grossman的The art of writing reasonable organic reaction mechanisms或miller的writing reaction mechanisms in organic chemistry。
还有一本pushing electrons(author Daniel P Weeks)也非常好的介绍了共振和机理，对于初学者可结合中文有机课本学习，很好。
如果你看完上面这三本书(其实搞懂一本即可)，就会对反应机理的分析和写法有个科学认识以及深入了解电子转移的内涵。
不用记住里面的机理，主要学习从反应如何合理的推导机理。
大学有机化学学习方法二1、阅读专题小册子，如国内超星上的亲核加成反应、饱和碳原子上的亲核取代反应历程、重排反应、周环反应等等按照基础反应特点介绍的小册子。
不要选择系统论述某类反应的长篇大作，你会很累的，并且不懂的地方很多，对自己的热情和自信会造成打击。
也有一些外文小册子书籍(推荐最好阅读此类外文书，写的生动)，书目我就不列举了。
哈佛大学高等有机课件32
NaBH3CN
N N CO2R MeO N MeO
3
+
NH2
CO2R
H
MeO
N OMe Me
1
MeO MeO
N Me
H
Me
Matthew D. Shair
Monday, December 9 , 2002
M. Shair, D. Evans
R1 R3 N R2 R4
Stabilized Cations: Iminium-Ions 1
(E)
TFA
N Me3Si Ph
Overman et al. TL 1984, 25, 5739.
H+, -ROH
Ph H N H SiMe3 N H H H
N
or Lewis Acid
R1 H
Oxidation of Amines
N Me X– H HgX2
Hg X N H Me rds
Hg(0) Me N H HX
A
B
PhCHO
Equilibrium between A and B driven towards B by conjugation of iminium double bond to the aromatic ring in B. Application to Yohimbine Analog Synthesis: Winterfeldt Chem. ber. 1968, 101, 2938. N H H CO2Me H Yohimbine OH H OMe N H
D. A. Evans
Iminium Ions and Their Transformations
CHO OHC
高等有机化学--lecture 8
The classic Doering-Roth experiments established that the Cope rearrangement proceeds via a chair transition state. Goldstein and Benzon later performed similar experiments with deuterated olefins. (Doering, Roth Tetrahedron 1962 18 67; Goldstein, Benzon JACS 1972 94 7147)
Me Me
Me Me
favored (>99%) E,Z-diene
Me Me
H
Me
disfavored (<1%)
Me
E,E-diene
If the hexadiene is fused into rings, then matched/mismatched effects can be observed:
E. Kwபைடு நூலகம்n
Lecture 8: Pericyclic Reactions II
Chem 106
Pericyclic Reactions II Eugene E. Kwan
Key Questions (1) Mechanism?
September 19, 2011
Scope of Lecture
Cope rearrangement
2. Fleming, I. Molecular Orbitals and Organic Chemical Reactions (Student Edition). Wiley, 2009. (Chapter 6 Thermal Pericyclic Reactions)
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
Con
HOMO
disrotatory
Examples
Ground State Conrotatory
Excited State Disrotatory
Con
LUMO
HOMO
Disrotatory
Conrotatory
Activation Energy (kcal/mol) for electrocyclic ring opening
dis-out
favorable H Me R A
Three-Atom Electrocyclizations (4 electrons)
H H A H A Dis?? R C H A Con?? R H A A H
relative rate
1
4
40,000
Ψ3
Ring-fused Cyclopropyl Systems When the cis substiltutents on the cyclopropyl ring are tied together in a ring the following observsations have been made
D. A. Evans
Pericyclic Reactions: Part–2
s Other Reading Material:
Chem 206
/~chem206/
Chemistry 206 Advanced Organic Chemistry
Electrocyclic Processes-1
Chem 206
Controtation and on to the indicated bonding and anti-bonding orbitals of cyclobutene:
LUMO
Excited State (Photochemical Process) disrotatory conrotatory
A H R A H Dis?? R C H A
Does solvolysis proceed via cation 1 followed by rearrangement to 2 (Case 1), or does it proceed directly to 2 (Case 2)?
Ψ3 fast +X– 2 Me H H Case 2 Ψ2 nonbonding X
The Nazarov Reaction
O OH +H+ A A A A f f A –H+ A O R Con?? A A
p
Chem 206
R
p
R Dis?? A A
p
A
A
Denmark, S. E. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5; pp 751. O O +H
Predict the stereochemical outcome of this reaction.
Ph O O O Ph
h
O O
s Reading Assignment for week: Carey & Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Fleming: Chapter 4 Thermal Pericyclic Reactions
Evans, Breit
Electrocyclic Processes-2: Torquoselectivity
How do we explain?
R R R
Chem 206
Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode
Torquoselectivilty is defined as the predisposition of a given R substituent for a given conrotatory motion Houk et al. Acc. Chem. Res 1996, 29, 471
R
con in
Houk, et. al. Acc. Chem. Res. 1996, 29, 471-477. Houk, et. al. JOC. 1996, 61, 2813-2825. Monday, Columbus Day, October 14, 2002
Ph
heat
h
Huisgen, TL, 1964, 3381.
View the 2 conrotatory modes by looking at the breaking sigma bond from this perspective
H
con
H
out
R R H H
Examples:
Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode
HOMO Dis
C
Note that there are two disrotatory modes
R R X Dis R X R R Dis R Sterically favored R Favored for R = ring R R LUMO
X
Me H Me C C H
HOMO Dis
+
H
R
+
+X–
X
TsO Ψ1 cation anion H
TsO H
Me
TsO H
H Me
H Me
relative rate 1
LUMO
4
DePuy, Accts. Chem. Res. 1967, 1, 33
40,000
+
R
H A H A
R Dis
+
H A C H C A
HOMO
X
LUMO
H Me H C Me Me
Ph
O
Suggest a mechanism for the following reaction.
H CO2Me MeO2C CO2Me H
heat
H CO2Me
Matthew D. Shair
H
Bloomfield, TL, 1969, 3719.
Evans, Breit
Electrocyclic Reaction - Selection Rules Ground State (Thermal process) 4n π e(n = 1,2...) 4n+2 π e(n = 0,1,2...) conrotatory
27
Disrotatory
O Ph
Conrotatory
Disrotatory
Ph O
O
O O
Disrotatory
Conrotatory
Ph Ph O O O
R Con R R R R
R
Con
R
Ph O
O
O
Ph
R Sterically favored
Ph Huisgen, TL, 1964, 3381. Ph O
O Cl base O– Cl –Cl– 3-exo-tet disallowed O– O
dis-in
•• Ar N
H CO2Me
MeO2C products
•• (–)
Evans, Breit
Five-Atom Electrocyclizations (4 electrons)
Electrocyclic Processes-3
Activation Energy (kcal/mol) for electrocyclic ring opening
Conrotatory
Disrotatory
42
45
Disrotatory Conrotatory
Conrotatory
H
29
H Criegee, Chem. Ber. 1968, 101, 102.
s Woodward-Hoffmann Theory R. B. Woodward and R. Hoffmann, The Conservation of Orbital Symmetry, Verlag Chemie, Weinheim, 1970. s Frontier Molecular Orbital Theory I. Fleming, Frontier Orbitals and Organic Chemical Reactions, John-Wiley and Sons, New York, 1976. s Dewar-Zimmerman Theory T. H. Lowry and K. S. Richardson, Mechanism and Theory in Organic Chemistry, 3rd Ed., Harper & Row, New York, 1987. s General Reference R. E. Lehr and A. P. Marchand, Orbital Symmetry: A Problem Solving Approach, Academic Press, New York, 1972.
Me H
R
R
H H
Me Me
Evans, Breit
HOMO
disrotatory
Examples
Ground State Conrotatory
Excited State Disrotatory
Con
LUMO
HOMO
Disrotatory
Conrotatory
Activation Energy (kcal/mol) for electrocyclic ring opening
dis-out
favorable H Me R A
Three-Atom Electrocyclizations (4 electrons)
H H A H A Dis?? R C H A Con?? R H A A H
relative rate
1
4
40,000
Ψ3
Ring-fused Cyclopropyl Systems When the cis substiltutents on the cyclopropyl ring are tied together in a ring the following observsations have been made
D. A. Evans
Pericyclic Reactions: Part–2
s Other Reading Material:
Chem 206
/~chem206/
Chemistry 206 Advanced Organic Chemistry
Electrocyclic Processes-1
Chem 206
Controtation and on to the indicated bonding and anti-bonding orbitals of cyclobutene:
LUMO
Excited State (Photochemical Process) disrotatory conrotatory
A H R A H Dis?? R C H A
Does solvolysis proceed via cation 1 followed by rearrangement to 2 (Case 1), or does it proceed directly to 2 (Case 2)?
Ψ3 fast +X– 2 Me H H Case 2 Ψ2 nonbonding X
The Nazarov Reaction
O OH +H+ A A A A f f A –H+ A O R Con?? A A
p
Chem 206
R
p
R Dis?? A A
p
A
A
Denmark, S. E. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5; pp 751. O O +H
Predict the stereochemical outcome of this reaction.
Ph O O O Ph
h
O O
s Reading Assignment for week: Carey & Sundberg: Part A; Chapter 11 Concerted Pericyclic Reactions Fleming: Chapter 4 Thermal Pericyclic Reactions
Evans, Breit
Electrocyclic Processes-2: Torquoselectivity
How do we explain?
R R R
Chem 206
Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode
Torquoselectivilty is defined as the predisposition of a given R substituent for a given conrotatory motion Houk et al. Acc. Chem. Res 1996, 29, 471
R
con in
Houk, et. al. Acc. Chem. Res. 1996, 29, 471-477. Houk, et. al. JOC. 1996, 61, 2813-2825. Monday, Columbus Day, October 14, 2002
Ph
heat
h
Huisgen, TL, 1964, 3381.
View the 2 conrotatory modes by looking at the breaking sigma bond from this perspective
H
con
H
out
R R H H
Examples:
Donor substituents prefer con–out mode Pi acceptor substituents prefer con–in mode
HOMO Dis
C
Note that there are two disrotatory modes
R R X Dis R X R R Dis R Sterically favored R Favored for R = ring R R LUMO
X
Me H Me C C H
HOMO Dis
+
H
R
+
+X–
X
TsO Ψ1 cation anion H
TsO H
Me
TsO H
H Me
H Me
relative rate 1
LUMO
4
DePuy, Accts. Chem. Res. 1967, 1, 33
40,000
+
R
H A H A
R Dis
+
H A C H C A
HOMO
X
LUMO
H Me H C Me Me
Ph
O
Suggest a mechanism for the following reaction.
H CO2Me MeO2C CO2Me H
heat
H CO2Me
Matthew D. Shair
H
Bloomfield, TL, 1969, 3719.
Evans, Breit
Electrocyclic Reaction - Selection Rules Ground State (Thermal process) 4n π e(n = 1,2...) 4n+2 π e(n = 0,1,2...) conrotatory
27
Disrotatory
O Ph
Conrotatory
Disrotatory
Ph O
O
O O
Disrotatory
Conrotatory
Ph Ph O O O
R Con R R R R
R
Con
R
Ph O
O
O
Ph
R Sterically favored
Ph Huisgen, TL, 1964, 3381. Ph O
O Cl base O– Cl –Cl– 3-exo-tet disallowed O– O
dis-in
•• Ar N
H CO2Me
MeO2C products
•• (–)
Evans, Breit
Five-Atom Electrocyclizations (4 electrons)
Electrocyclic Processes-3
Activation Energy (kcal/mol) for electrocyclic ring opening
Conrotatory
Disrotatory
42
45
Disrotatory Conrotatory
Conrotatory
H
29
H Criegee, Chem. Ber. 1968, 101, 102.
s Woodward-Hoffmann Theory R. B. Woodward and R. Hoffmann, The Conservation of Orbital Symmetry, Verlag Chemie, Weinheim, 1970. s Frontier Molecular Orbital Theory I. Fleming, Frontier Orbitals and Organic Chemical Reactions, John-Wiley and Sons, New York, 1976. s Dewar-Zimmerman Theory T. H. Lowry and K. S. Richardson, Mechanism and Theory in Organic Chemistry, 3rd Ed., Harper & Row, New York, 1987. s General Reference R. E. Lehr and A. P. Marchand, Orbital Symmetry: A Problem Solving Approach, Academic Press, New York, 1972.
Me H
R
R
H H
Me Me
Evans, Breit