16_Sharpless_Asymmetric_E 哈佛有机化学课件
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有机化学英文课件
+ C H 3 C H 2 -O -H + C H 3 C H 2 -O -H
SN 2
+ C H 3 C H 2 -O -C H 2 C H 3 + O -H
H
H
H
A new oxonium ion
11-11
Preparation of Ethers
Step 3: proton transfer to solvent completes the reaction
+
CH 3 CH 2 -O -CH 2 C H 3 + O -H
H
H
proton tran sf er
+ CH 3 CH 2 -O -CH 2 C H 3 + H O -H
H
11-12ቤተ መጻሕፍቲ ባይዱ
Preparation of Ethers
Acid-catalyzed addition of alcohols to alkenes
Acid-catalyzed dehydration of alcohols
• diethyl ether and several other ethers are made on an industrial scale this way
• a specific example of an SN2 reaction in which a poor leaving group (OH-) is converted to a better one (H2O)
CH 3 CH3C=CH2 + H
+ O CH3
H
CH3 C H 3 C+C H 3 +
有机化学英文课件chapter6-78页PPT精选文档
Energy Diagrams
u Energy diagram: a graph showing the changes in energy that occur during a chemical reaction
u Reaction coordinate: a measure in the change in positions of atoms during a reaction
• Markovnikov’s rule: in the addition of HX, H2O, or ROH to an alkene, H adds to the carbon of the double bond having the greater number of hydrogens
6-16
is n o t s u p p o r te d
• exergonic reaction: a reaction in which the Gibbs free energy of the products is lower than that of the reactants; the position of equilibrium for an exergonic reaction favors products
M a c in to s h P IC T im ag e fo rm at
is n o t su p p o rted
6-4
Reaction Mechanisms
u A reaction mechanism describes how a reaction occurs
• which bonds are broken and which new ones are formed
高等有机化学课件3-第三章 立体化学
联苯类化合物
NO2 CO2H
NO2 CO2H
有对称面（能同镜影分子重选），非手性。
NO2 CO2H
CO2H NO2
CO2H NO2
NO2 CO2H
手性分子
6
Br Br 6'
Br
Br
2' 2 Cl Cl
Cl
Cl
(R)-2,2’-二氯-6,6’-二溴联苯
(R)-2,2’-dibromo-6,6’-dichlorobiphenyl
构型异构： 顺反异构： H
Cl CH3 Cl H
COOH H OH CH3 HO
CH3 H
COOH H CH3
H
对映异构：
D-(-)-乳酸 mp: 52.8° 非对映异构： H
H COOH OH OH CH3
L-(＋)-乳酸
COOH H HO OH H CH3
构象异构：
H H
CH3 H H CH3
V U X
R R
V W Z W Z
S S
V
V W X W X
S R
U X
U Z
R S
U Z
Y (A)
Y ( B)
Y (C)
Y ( D)
A和B（C和D）为对映异构体，A和C或者D（B和 C或者D）为非对映异构体。
• 对映异构体之间有相同的性质（除了对偏 振光和手性环境），然而非对映异构体具 有不同的熔点、沸点、溶解度、反应性等 物理、化学及光谱性质。 • 多手性中心的分子最多具有2n个异构体（n ＝分子中手性中心数），但有时分子内存 在着对称面，这时异构体数减少。
今有两试管分别置入（－）乳酸和（＋）乳酸，我 们如何知道它们的构型？
NO2 CO2H
NO2 CO2H
有对称面（能同镜影分子重选），非手性。
NO2 CO2H
CO2H NO2
CO2H NO2
NO2 CO2H
手性分子
6
Br Br 6'
Br
Br
2' 2 Cl Cl
Cl
Cl
(R)-2,2’-二氯-6,6’-二溴联苯
(R)-2,2’-dibromo-6,6’-dichlorobiphenyl
构型异构： 顺反异构： H
Cl CH3 Cl H
COOH H OH CH3 HO
CH3 H
COOH H CH3
H
对映异构：
D-(-)-乳酸 mp: 52.8° 非对映异构： H
H COOH OH OH CH3
L-(＋)-乳酸
COOH H HO OH H CH3
构象异构：
H H
CH3 H H CH3
V U X
R R
V W Z W Z
S S
V
V W X W X
S R
U X
U Z
R S
U Z
Y (A)
Y ( B)
Y (C)
Y ( D)
A和B（C和D）为对映异构体，A和C或者D（B和 C或者D）为非对映异构体。
• 对映异构体之间有相同的性质（除了对偏 振光和手性环境），然而非对映异构体具 有不同的熔点、沸点、溶解度、反应性等 物理、化学及光谱性质。 • 多手性中心的分子最多具有2n个异构体（n ＝分子中手性中心数），但有时分子内存 在着对称面，这时异构体数减少。
今有两试管分别置入（－）乳酸和（＋）乳酸，我 们如何知道它们的构型？
哈佛大学D.A..Evans有机化学讲义29
OHC I
EtO2C EtO2C
10 mol%
Me N CO2H H
Et3N, -30ºC
OHC
EtO2C EtO2C
92% yield, 95% ee
List, B. JACS 2004, 126, 450-451.
D. A. Evans, J. F. Lawrence
Properties and Reactivity of Enamines
Lecture Number 29
Enamines and Imminium Ions in Organocatalysis
N R
N R
R
! Introduction and General Trends ! Historical Backgound - The Hajos-Parrish Reaction ! Direct Asymmetric Aldol and Mannich Reactions ! !-Amination and Oxidation Reactions ! Michael Reactions ! Cascade Reactions
O R C NR2
■ Nature uses enamines, "stabilized" enolates, and enol derivatives in C–C bond constructions extensively.
"Amino Acids and Peptides as Asymmetric Organocatalysts", Miller, Scott Tetrahedron, 58, 2481 (2002).
! Reading Assignment for this Week:
第六章氧化反应
第四节 醛、酮的氧化
• 一、醛的氧化 • 1.反应通式
• 2.应用特点 • （1）醛氧化制备羧酸
新制Ag2O、CuO氧化
（2）Dakin反应
当醛基的邻、对位有-OH等供电子基时，则 经过酸氧化，甲酸酯中间体生成羟基
当-CHO邻、对位有供电子基时，芳环电子云密度较 丰富，有利于“b式”重排；若无取代基或供电子 基在间位以及存在吸电子基时，则按“a式”重排， 形成酸。
• O3/H2O2; O3/Zn/H+; O3/DMS; O3/Ph3P
• NaIO4/KMnO4; NaIO4/OsO4替代方法
第六节 芳烃的氧化反应 一 芳环的氧化开裂 1. KMnO4氧化
即:芳环上有供电子基的优先被氧化
2. RuO4氧化
3 CuCl+Py氧化
二、氧化成醌 1.铬酸氧化剂
• M-CPBA
• OsO4 • Bromohydrin
• Prevost • Woodward
5. Asymmetric Dihydroxylation Reaction
Sharpless Catalytic Asymmetric Dihydroxylation (AD) Reaction
三、烯烃的氧化性断裂及还原性断裂
• 二、酮的氧化
• Baeyer-Villiger oxidation
反应机理
迁移能力：3>2>环己基>苄基>苯基>1>H 越富电子烷基越先迁移
第五节 含烯键化合物的氧化
一、烯键的环氧化 1.a、b-不饱和羰基化合物的环氧化
环氧化机理：
此键可旋转，最终生成比较稳定的E型环氧 化合物
如：
两个较大基团在环的两侧
有机化学英文课件chapter3共44页文档
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
M a c in to s h P IC T im a g e fo r m a t
is n o t s u p p o r te d
M acin to sh P IC T im ag e fo rm at
3-17
Enantiomers & Diastereomers
u 2,3,4-Trihydroxybutanal
Organic Chemistry
William H. Brown Christopher S. Foote Brent L. Iverson
3-1
M acintosh PICT M acintosh PICT im age form at im age form at
is not supported is not supported
u Enantiomers: stereoisomers that are nonsuperposable mirror images
• refers to the relationship between pairs of objects
3-7
Enantiomers
u 2-Butanol
• has one chiral center • here are four different representations for one
4. If the groups are read clockwise, the configuration is R; if they are read counterclockwise, the configuration is S
is n o t s u p p o rte d
M a c in to s h P IC T im a g e fo r m a t
is n o t s u p p o r te d
M acin to sh P IC T im ag e fo rm at
3-17
Enantiomers & Diastereomers
u 2,3,4-Trihydroxybutanal
Organic Chemistry
William H. Brown Christopher S. Foote Brent L. Iverson
3-1
M acintosh PICT M acintosh PICT im age form at im age form at
is not supported is not supported
u Enantiomers: stereoisomers that are nonsuperposable mirror images
• refers to the relationship between pairs of objects
3-7
Enantiomers
u 2-Butanol
• has one chiral center • here are four different representations for one
4. If the groups are read clockwise, the configuration is R; if they are read counterclockwise, the configuration is S
有机化学英文课件chapter7知识讲解共43页文档
、实际上，我们想要的不是针对犯 罪的法 律，而 是针对 疯狂的 法律。 ——马 克·吐温 42、法律的力量应当跟随着公民，就 像影子 跟随着 身体一 样。— —贝卡 利亚 43、法律和制度必须跟上人类思想进 步。— —杰弗 逊 44、人类受制于法律，法律受制于情 理。— —托·富 勒
45、法律的制定是为了保证每一个人 自由发 挥自己 的才能 ，而不 是为了 束缚他 的才能 。—— 罗伯斯 庇尔
66、节制使快乐增加并使享受加强。 ——德 谟克利 特 67、今天应做的事没有做，明天再早也 是耽误 了。——裴斯 泰洛齐 68、决定一个人的一生，以及整个命运 的，只 是一瞬 之间。 ——歌 德 69、懒人无法享受休息之乐。——拉布 克 70、浪费时间是一桩大罪过。——卢梭
45、法律的制定是为了保证每一个人 自由发 挥自己 的才能 ，而不 是为了 束缚他 的才能 。—— 罗伯斯 庇尔
66、节制使快乐增加并使享受加强。 ——德 谟克利 特 67、今天应做的事没有做，明天再早也 是耽误 了。——裴斯 泰洛齐 68、决定一个人的一生，以及整个命运 的，只 是一瞬 之间。 ——歌 德 69、懒人无法享受休息之乐。——拉布 克 70、浪费时间是一桩大罪过。——卢梭
17_Sharpless_Asymmetric_D
Cis-Disubstituted Olefins are generally poor substrates. With a modified catalyst, DHQD-IND, fair to good enantioselectivities can be obtained: ee at 0 °C
>99% yield, 98% ee
PYDZ =
O N N
O
(DHQD) 2 AQN
Ph O O
88% ee vs. 77% ee, (DHQD)2 PHAL
O O CH3O CH3
98% yield, 97% ee
78% ee vs. 44% ee, (DHQD)2 PHAL
O
96% yield, 91%ee Becker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1996, 3 5, 448-451.
Mnemonic:
(DHQD)2-PHAL
n-Bu RS RL RM H n-C5H11
n-Bu
*
97, R, R
93, S, S
CO2Et *
99, 2S, 3R
96, 2R, 3S
(DHQ)2-PHAL α
CO2Et *
97, 2S, 3R
95, 2R, 3S
Application of Mnemonic:
a few tetra-substituted olefins work well, see: Sharpless, K. B., et al. J. Am. Chem. Soc. 1993, 115, 8463-8464.
N N O Et O H N H OCH3
有机反应机理
Ph
(5). Tosylhydrazone reduction (Shapiro reaction): (modified Wolff-Kishner reduction):) TsNHNH2 // RED
Synthesis, 2001, 16, 2370. N N Ts H-
H H for acyclic, may C=C side product
R n-BuSn n-BuSnBr
H R n-BuSnH R
n-BuSn
1-c C-NH2
(1). RCH2NH2
C-H
p-TsCl BuLi LiAlH4 RCH2-H
ArSO2Cl RCH2NH2 Hinsberg's test
O
RCH2NH
SO2Ar
BuLi - BuH SO2Ar
RCH2N SO2Ar LiAlH4
Raney Nickel: Ni - Al alloy, suspension
HN N CH2Ph
(1). Raney Ni (2). Li / NH3
Raney Ni
burn filter paper if dry
mechanism uncertain, probably radical
(3). LiAlH4 / CuCl2 JCS Perkin Trans I, 1973, 654. NaBH4 / NiCl2 NaBHEt3 / FeCl2 (or CoCl2, VCl3) Chemistry: R-SH R-S-R R-SS-R remove: Hg+; Ni R2SO R2SO2
S C O Ph n-Bu3SnH CH 3
CH3 H CH3
via:
哈佛大学高等有机化学讲义Lecture19A
100% e.e. (R)
Li N
95% e.e. (S)
(S,S) dimer
(R,R) dimer
Bu N Et Zn O
Bu Me Me2 N Zn Me O Me2 N Zn Me O
N Li
90% e.e. (R)
Ph
90% e.e. (R)
90% e.e. (R)
+
(Results are cited for the reaction of benzaldehyde and Et2Zn)
Zn–Et O H
the catalyst
Et
90-98% ee
Et2Zn
Me
Me Me N Me O Zn Et H H
00 00 0000 0000 0000
Me
Me Me N O Me Zn O Et C H Et
Me
Me Me N Me Zn Zn Et O Et C H Et
Me
(DAIB-Zn)
O
(S) catalyst
H
Et2Zn
96% ee
OH
O
Lepicidin Application: The reaction functions in complex systems
C5H11 OR Bu Et Zn O Ph O Evans, Black, JACS 1993, 115, 44974513 H
Matthew D. Shair
Friday, November 1, 2002
D. A. Evans
Enantioselective C=O Addition: Noyori Catalyst
The Catalytic Cycle
有机化学英文课件chapter2-71页PPT精选文档
• alphabetize the names of substituents first and then insert these prefixes
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
2-15
Nomenclature - IUPAC
• indicate the number of times the substituent appears by a prefix di-, tri-, tetra-, etc.
• use commas to separate position numbers
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
2-13
Nomenclature - I UPAC
6. If there are two or more different substituents, • list them in alphabetical order • number from the end of the chain that gives the
u Structure and nomenclature
• to name, prefix the name of the corresponding openchain alkane with cyclo-, and name each substituent on the ring
• if only one substituent, no need to give it a number • if two substituents, number from the substituent of
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
2-15
Nomenclature - IUPAC
• indicate the number of times the substituent appears by a prefix di-, tri-, tetra-, etc.
• use commas to separate position numbers
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
2-13
Nomenclature - I UPAC
6. If there are two or more different substituents, • list them in alphabetical order • number from the end of the chain that gives the
u Structure and nomenclature
• to name, prefix the name of the corresponding openchain alkane with cyclo-, and name each substituent on the ring
• if only one substituent, no need to give it a number • if two substituents, number from the substituent of
4_Birch
• Loewenthal and co-workers first demonstrated single step reductive alkylation of aromatic compounds: CO2H 1. Na, NH3 2. CH3I 69% Bachi, M. D.; Epstein, J. W.; Herzberg-Minzly, Y.; Loewenthal, H. J. E. J. Org. Chem. 1969, 34, 126-135. HO2C CH3
–
H H
M
or RX
• Reduction in low molecular weight amines (in the absence of alcohol additives) furnishes more extensively reduced products than are obtained under Birch conditions (M, NH3, ROH). A Comparison of Methods Using Lithium/Amine and Birch Reduction Systems: Kaiser, E. M. Synthesis 1972, 391-415.
Asymmetric Birch Reduction: Reviews: Schultz, A. G. Acc. Chem. Res. 1990, 23, 207-213; Schultz, A. G. Chem. Commun. 1999, 1263–1271. O N H O M, NH3, THF N t-BuOH (1 equiv) (M = Li, Na, or K) H O (proposed convex attack) RX OM RX H –78 °C O R O N
有机化学英文课件chapter7共42页文档
7-2
Nomenclature
u IUPAC: use the infix -yn- to show the presence of a carbon-carbon triple bond
M a c in to s h P IC T im a g e fo r m a t
is n o t s u p p o r te d
u Common names: prefix the substituents on the triple bond to the word “acetylene”
IUPAC name:
2-Butyne
1-Buten-3-yne
Common name: Dimethylacetylene Vinylacetylene
which the alkyne and halogen acid are mixed
Br
Br
CH3 C CH HBr CH3 C= CH2 HBr CH3 CCH3
Propyne
Br 2-Bromopropene 2,2-Dibromopropane
7-17
Addition of HX
• the intermediate in addition of HX is a 2°vinylic carbocation
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
7-10
Preparation from Alkenes
• for a terminal alkene to a terminal alkyne, 3 moles of base are required
Nomenclature
u IUPAC: use the infix -yn- to show the presence of a carbon-carbon triple bond
M a c in to s h P IC T im a g e fo r m a t
is n o t s u p p o r te d
u Common names: prefix the substituents on the triple bond to the word “acetylene”
IUPAC name:
2-Butyne
1-Buten-3-yne
Common name: Dimethylacetylene Vinylacetylene
which the alkyne and halogen acid are mixed
Br
Br
CH3 C CH HBr CH3 C= CH2 HBr CH3 CCH3
Propyne
Br 2-Bromopropene 2,2-Dibromopropane
7-17
Addition of HX
• the intermediate in addition of HX is a 2°vinylic carbocation
M a c in to s h P IC T im a g e fo rm a t
is n o t s u p p o rte d
7-10
Preparation from Alkenes
• for a terminal alkene to a terminal alkyne, 3 moles of base are required
有机人名反应(3)
O R R'
NH3
O NH4OCH R
NH2
+ CO2
R'
HO R
NH2 R'
-H2O R
NH R'
HCO2H R
NH2 R' O
O H
Lieben Iodoform Reaction
Lieben Iodoform Reaction
O R CH3 1) NaIO 2) NaOH 3) HCl
I2 +
Sharpless Epoxidation
Ti(Oi-Pr)4, t-BuOOH
OH
(+)-DET, DCM, -20° C
O
OH
89% yield >98% ee
OH EtO2C CO2Et EtO2C
OH CO2Et
OH (-)-DET
OH (+)-DET
Sharpless Epoxidation
Mannich Reaction mechanism
O O + R
1
H HCl N R2
+
HCHO N R1
R2
OH
R1
H N
-H
R2 + HCl
O
OH
+ HCHO
R1 N R2
OH
+H
-H2O
R
1
N
R2
+H2O -H
N R2
R1
H
Milas Hydroxylation
紫外光照射或锇、钒、铬氧化物催化下，烯烃被过氧化氢 氧化为顺式邻二醇。N. A. Milas 在1930年代报道。 此反应在合成中已被 Upjohn 双羟基化反应和 Sharpless不 对称双羟基化反应所取代。
NH3
O NH4OCH R
NH2
+ CO2
R'
HO R
NH2 R'
-H2O R
NH R'
HCO2H R
NH2 R' O
O H
Lieben Iodoform Reaction
Lieben Iodoform Reaction
O R CH3 1) NaIO 2) NaOH 3) HCl
I2 +
Sharpless Epoxidation
Ti(Oi-Pr)4, t-BuOOH
OH
(+)-DET, DCM, -20° C
O
OH
89% yield >98% ee
OH EtO2C CO2Et EtO2C
OH CO2Et
OH (-)-DET
OH (+)-DET
Sharpless Epoxidation
Mannich Reaction mechanism
O O + R
1
H HCl N R2
+
HCHO N R1
R2
OH
R1
H N
-H
R2 + HCl
O
OH
+ HCHO
R1 N R2
OH
+H
-H2O
R
1
N
R2
+H2O -H
N R2
R1
H
Milas Hydroxylation
紫外光照射或锇、钒、铬氧化物催化下，烯烃被过氧化氢 氧化为顺式邻二醇。N. A. Milas 在1930年代报道。 此反应在合成中已被 Upjohn 双羟基化反应和 Sharpless不 对称双羟基化反应所取代。
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C2-Symmetric Substrates: Venustatriol:
• Any minor diastereomer that is produced is rapidly removed by bis-epoxidation.
Excercise: Why?
CH3 H3C CH3 H3 C OH H3 C O
Ko, S. Y.; Lee, A. W. M.; Masamune, S; Reed, L. A., III; Sharpless, K. B.; Walker, F. J. Tetrahedron 1990, 46, 245-264. OH H 3C (±)
(–)-DIPT 40% conversion H 3C
fast
• Products are diastereomeric. • Sense of induction is dominated by the catalyst. • The C4 center reinforces and erodes this in "MATCHED" and "MISMATCHED" cases, respectively, as shown.
Myers
Reviews: Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1-300.
Sharpless Asymmetric Epoxidation Reaction
Substitution patterns:
Chem 215
Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, Ojima, I., Ed.; VCH: New York, 1993, pp. 103-158. Johnson, R. A.; Sharpless, K. B. In Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I., Eds., Pergamon Press: New York, 1991, Vol. 7, pp. 389-436. Pfenninger, A. Synthesis 1986, 89-116.
Ti(Oi-Pr)4 (1.0 equiv) (+)-DET (1.2 equiv)
OH
O +
OH
O OH 10% 90%ee Excercise: What isomer would you have predicted using the Sharpless mnemonic? Takano, S.; Iwabuchi, Y.; Ogasawara J. Am. Chem. Soc. 1991, 113, 2786-2787. M. Movassaghi
Ti(Oi-Pr)4,(+)-DET t-BuOOH, 3Å-MS CH2Cl2, –20 °C
R2
O R1
• 5-10 mol% catalyst in the presence of 3 or 4 Å-MS. • 10-20 mol% excess tartarate vs. Ti(OiPr)4 required. • (+)- and (–)-DET are readily available and inexpensive.
O
97%, 86% ee
97%, 86% ee
Chiral Substrate: CH3 H3 C O O OH O syn Ratio (syn : anti)
R2 R3 R R1 HO H HO R R1 R2 R3
Kinetic Resolution: CH3 H3C O O OH O anti (+)-DET "O" (+)-DET "O" +
• (+)- and (–)-DIPT, diisopropyl tartarate, are also available and sometimes lead to higher selectivity. Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765-5780. Mnemonic for selectivity: L-(+)-DET "O"
70% yield >95% ee
• Disubstituted olefin is more reactive than monosubstituted olefin (krel ~100). • kfast/kslow for chiral E-propenylcarbinols is ~100. H3C O OH Excercise: Apply the Sharpless mnemonic to predict the stereochemistry of this product. Sharpless, K. B.; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.; Viti, S. M.; Walker, F. J.; Woodard, S. S. Pure Appl. Chem. 1983, 55, 589. • Allylic 1,2-diols do not follow the Sharpless mnemonic: OH H OH O H CH3 OH (+)-DIPT OH 71% 90% ee
H3C TBHP, –20 °C 1-4 d 50%, 41% ee
OH
Ti(Oi-Pr)4 (1.0 equiv) (+)-DET (1.2 equiv)
Rossiter, B. E.; Sharpless, K. B. J. Org. Chem. 1984, 49, 3707-3711.
CH3 TBHP, 0 °C 48 h 22%, 29% ee
OH
Hosokawa, T.; Kono, T.; Shinohara, T.; Murahashi, S.-I. J. Organometal. Chem. 1989, 370, C13-C16. For other examples see: Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, Ojima, I., Ed.; VCH: New York, 1993, pp. 103-158 and Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1-300.
OH O OBn CH3
OBn
meso
OBn
Schreiber, S. L.; Schreiber, T. S.; Smith, D. B. J. Am. Chem. Soc. 1987, 109, 1525-1529. Schreiber, S. L.; Goulet, M. T.; Schulte, G. J. Am. Chem. Soc. 1987, 109, 4718-4720.
With the exception of Z-disubstituted allylic alcohols, krel > 25. When krel = 25, the ee of unreacted alcohol is essentially 100% at 60% conversion. Allylic tertiary alcohols are not successfuly epoxidized under Sharpless conditions. Factors may combine for high selectivity:
OH
OH OH
OH
OH OH
OH
• Z-disubstituted olefins are least reactive and selective. Asymmetric Epoxidation of Allylic Alcohols: R3 R2 R1 OH R3 OH Examples of Sharpless Epoxidation: product O OH (+)-DET = EtO2C CO2Et OH O O C7H15 Ph R2 R1 HO H3 C D-(–)-DET "O" Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974-5976. Application of Mnemonic: CH3 O OH AE-(–)-DET CH3 OH AE-(+)-DET O CH3 OH Ph Ph From: Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765-5780 and Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, Ojima, I., Ed.; VCH: New York, 1993; pp. 103-158. M. Movassaghi CH3 O R3 O CH3 OH CH3 OH 100 BnO O CH3 CH3 OH 120 (–)-DET (150) –20 5 90 94 OH 5 (+)-DET (7.4) –20 0.75 95 91 (+)-DET (142) –20 14 80 80 5 (+)-DIPT (7.5) –35 2 79 >98 Pr OH OH 10 (+)-DET (14) –10 29 74 86 4.7 (+)-DET (5.9) –12 11 88 95 Ph O OH 5 (+)-DIPT (7.5) –20 3 89 >98 OH Ti(%) 5 tartarate (%) (+)-DIPT (6.0) °C 0 h 2 yield (%) ee (%) 65 90 OH