columbia大学有机化学课件14_11_15.html

Ph3P
Me
OMe
Me
Ph3P
Ph3P Me
Ph3P
Not stable; must be made in situ and used immediately
Ph3P
Wittig Olefination: Background and Principles
Stereoselectivity with non-stabilized ylides
+ Ph3P
Me
O
PPh3H O R HR
As the size of the R groups increases, selectivity for Z-alkene increases Nonpolar solvents favor initial addition Polar solvents favor the elimination
Ph3P H
O
H
Me
-[Ph3P=O] Me
Z-alkene
Wittig Olefination: Background and Principles
Stereoselectivity with stabilized ylides
Me
Ph3P
O
O
Ph3P
OEt
Ph3P
Me
semistabilized
Olefination Reactions
Lecture Notes
Key Reviews:
Wittig Reaction K. C. Nicolaou and co-workers, Ann. 1997, 1283. Horner-Wadsworth-Emmons and Tebbe Olefinations S. E. Kelly, Comprehensive Org. Synth. 1991, Vol. 1, 729.

Some important relationships in NMR
The frequency of absorbed electromagnetic radiation is proportional to
the energy difference between two nuclear spin states which is proportional to
Chapter 13 Spectroscopy
Infrared spectroscopy Ultraviolet-Visible spectroscopy Nuclear magnetic resonance spectroscopy
Mass Spectrometry
13.1 Principles of Molecular
align parallel and
antiparallel to applied
field.
+
+
H0
+ +
There is a slight excess of nuclear magnetic moments aligned parallel to the applied field.
+
+
+ +
the applied maFra biblioteknetic field
Some important relationships in NMR
The frequency of absorbed electromagnetic radiation is proportional to
Units Hz
the energy difference between two nuclear spin states which is proportional to

biotin
P. N. Confalone, J. Am. Chem. Soc. 1980, 102, 1954.
Nitrile Oxides: Applications in Total Synthesis
Me N O Cl N C O Et3N, toluene, 80 ° C Me N O
NO2
Zn, AcOH, (66%) 25 ° 4 h C,
O
Me OH
OTBDPS
vinblastine T. Fukuyama and co-workers, J. Am. Chem. Soc. 1999, 121, 3791 For a review, see Classics in Total Synthesis II, Chapter 18
H
CO2Me
N O 48 kcal
OH
J. Tufariello, Acc. Chem. Res. 1979, 12, 396.
Nitrones: Applications in Total Synthesis
CO2Me N O + OH Nitrone 1,3-dipolar cycloaddition
N O
CO2Me CO2Me Nitrone 1,3-dipolar cycloaddition N O
mCPBA N O H H O O O
CO2Me
N DBU = N Cl
Oxidative ring opening
N O MeO2C
CO2Me 1. MsCl, py 2. DBU MeO2C
CO2Me N O OH CO2Me Nitrone 1,3-dipolar cycloaddition [protection step] N O OH

HAc
N H 95 %
草绿碱
3 制备杂环化合物
eg 5 CH2 CH CH2 NCH3 C=O CH2 CH CH2
eg 6 CH3 N
O
4 制α,β-不饱和酮、α,β-不饱和酯
O R-C-CH2CH2NMe2 △ ，蒸馏
O R-C-CH=CH 2
CH3I
O R-C-CH2CH2NMe3
OH △
O
O + CH3CCH2CH2NR3I-
碱
G
O
OH O
G
G
O
G=H, R, Ar, COOR, OCR等
鲁宾逊增环反应实际上是分三步完成的：
O
CH3CCH2CH2NR3I-
碱 ①
O CH3CCH=CH 2
曼氏碱热消除
O
碱
G
② 麦克尔加成
OO 碱
③
G
分子内醇醛缩合
OH O
G
二 应用实例
eg 1. 选用合适的原料合成
O CH3C-CH2
H
OH CH3-C=CH 2
R CH2=N
O
R
R' CH3-C-CH2-CH2-N + H+
R'
三 氨甲基化反应实例
1 用来制备β-氨基酮
eg 1
O CH3CCH2CH3 + CH2O + Me2NH HCl
O
αβ
CH3CCHCH 2NMe2 HCl CH3
不对称酮反应时，亚甲基比甲基优先反应。
O R-C-CH=CH 2
实例
O
OH
O HO O
H2C=N+(CH3)2 ILDA