Organic Synthesis

13504327907
Emailyekq@jlu.edu.cn


1.
2.
3.

1.
2.
3.

(10%)
(20%)

(70%)

R. B. Woodward1965

;
;
.

:,;
:.


H.Koble1845
FeS2
C

Cl2

heat
CCl4

CS2

hv

Cl

Cl

Cl

Cl

Cl3CCO2H
H2O

electrolysis
CH3COOH

1856W.H.Perkin
H3C
O
NH2

H OH

19 E.Fischer

OH
H

HO

HO
HO

H
H

OH
OH

(+)-

Robinson1917

H3C

E.Fischer Robinson19021947

R. B. Woodward
Woodward

R. B. Woodward 1965
1973EschemmoserB12

C63H88CoN14O14P

J.C. Sheehan1957
V
H

PhH2COCHN
N
O
HOOC

S
H

Corey
Corey

1990


B. Merrifield
B

A- B

A- B- C

A- B- C

B. Merrifield1984

Kishi1989
Palytixin

Palytoxin
C131H227N3O53
Mr=2692.26
64 asymmetric
6 Olefin centers
270=1.2x1021
isomers

2090
Nicolaou

W. S. KnowlesR. NoyoriB. M. Sharpless

2001


1902

Emil Fisher

1968

H. G. Khorana

1905

Adolf von Baeyer

1969

Dereck H. Barton
Odd Hassel

1910

Otta Wallach

1975

Vincert Prelog
John W. Cornforth

1912

Victor Grignard
Paul Sabatier

1979

Herbert C. Brown
Georg Wittig

1928

Adolf Windaus

1981

Roald Hoffman
Kenichi Fukui

1930

Hans Fischer

1984

R. B. Merrifield

1937

Walter Haworth
Paul Karrer

1987

D. J. Cram,
J.-M. Lehn,
C. J. Pedersen

1939

Leopold Ruzicka

1990

Elias J. Corey

1947

Robert Robinson

1994

George A. Olah

1950

Otta Diels
Kurt Alder

2001

William S. Knowles
K. Barry Sharpless
Ryji Noyori

1955

Vincent du Vigneaud

2005

Yves Chauvin
Richard R. Schroch
Robert H. Grubbs

1963

Karl Ziegler Giulio

Natta

2010

Richard F. Heck
Ei-ichi Negishi
Akira Suzuki

1965

Robert B. Woodward

2004

2006
Greene /Wuts Protective Groups in Organic
Synthesis, 3rd Ed. 1999)
()

2003


Organic Synthesis
Organic Reactions
Reagents for Organic Synthesis
Compendium of Organic Synthesis Methods
Chemical Abstract (CA)
Beilsteins Handbuch der Organischen Chemie
Present scientific periods:
J. Am. Chem. Soc.;
J. Org.Chem.; Organic letter
J. Chem. Soc.; Tetrahedron ; Tetrahedron letter;
Angew. Chem. Int. Ed. etc
,
,


SciFinder
SciFinder ScholarACS
CASChemical
Abstract ServiceChemical
Abstract
CA 1907

CA
Reaxys

Retrosynthetic
(or antithetic) analysis

Contents
1.
2.
3.
4.

1.

Retrosynthetic analysis is a
problem-solving technique for
transforming the structure of a
synthetic target (TGT)
molecule to a sequence of
progressively simpler structures
along a pathway which
ultimately leads to simple or
commercially available starting
materials for a chemical
synthesis.

LOGO
www.themegallery.com


(Transforms, Synthon)


1.
Synthon

TM

2.
Synthetic
equivalent
R

CN

R'

OH

R'

CN-

O
NaCN, KCN, TMSCN. etc.

OH

R
O

R1
R2

H+

CO2

R-

RMgX

O
O

R1

H+

R2-

R2MgX

H O

H+
O

O
O

TM
OH

OH

MgBr

OH

OH
O

MgBr

Et2O
NH4Cl

2.

FGI)

Rearrangement)

FGA)


Functional Group Interchange (FGI)
OH
O

O
Ph

Ph
OH

FGI

PhMgBr

FGI
H
OAc
9

OH

MgBr


(Rearrangement)
O

Pinacol
Rearrangement

OH
2

HO

10

OH

O
Ph

COOH

Ph

Ph

PhMgBr


Functional Group Addition (FGA)
NH2
I

FGA

MeO2C

MeO2C
FGA

11

O
N Ph

N Ph
H

NH2

CO2Me

O
N Ph

COOH

COOH FGA

O
OMe

OMe O

OMe

OMe

FGA

FGA
O
12

a.
COOH

13

NaOH aq.
reflux

COOH

b.
CCl3

COOH
+ H2O

Ca(OH)2

c.
CH3(CH2)5CH3

CH2N2
hv

CH3(CH2)6CH3 + CH3CH(CH2)4CH3
CH3

+ CH CH CH(CH ) CH
2
2 3
3
3
CH3
14

+ (CH3CH2CH2)2CHCH3

d.
H+
OH

15

2-
C-C-C

C-

OH

+ Br
FGI
FGI
CH3COOEt +
16

Br

EtOOC

OH

3)
TM

O
O

O
O

FGI

FGI

FGI

FGI

O
17

Br

Cl

HO

FGA
O
+
O

18

+
O

CH3I

TM
TM
OH

OH

OH
OH
FGI
OH
19

OH

H
O

H
O

O
FGA

O
O

O
+

20

6
O
FGI

+
Br

CHO
NMe

NH2Me
CHO

21

3.
1C-C
(1)
(2)
+
MgX

HO
NMe2

NMe2

NMe2

+ HNMe2

O
Ph
22

Ph

OH

+ PhMgX

RCH2CH2OH
O

RCH2OH

CHOH
R

HCHO

HCO2R'
R'CHO

RMgX

RX
R'COR''

R'CO2R''
R'
R''
23

R
CHOH

R'

R'

OH

R
OH

R'
R

R'
OH

OH
Ph

Ph

PhMgBr

O
Ph

MgBr

MgBr

Ph

Ph

Ph

Ph

Br

OH

Ph

O
Ph

MgBr

OH

?
Ph
Ph
24

OH

Ph

2-

OH

HO

+
O

,
O

FGI

OH

O
H

25

3
1,3-ClaisenReformasky
Knovevenagel

O
O

O
OEt

O
O

O
OEt

26

CN

O
CH3
O

O
CH3

CH3

OH

OH

O
CH3

+
OH

27

HCO2Et

OH

CH3
H
O

O
OEt
Ph
OEt
O

OEt
Ph

Ph
OEt
O

28

(COOEt)2

+
EtO

O
EtO

OEt

1,5- Michael
a

O
+

R'

O
R

O
R C

R'

O
+
R'

O O
OEt

+
O
29

O OEt

O
O

CO2Et
+

CH2O +

O
EtOOC(CH2)5COOEt

30

O
+ EtOCOEt

1,6-

O
R

O
Ph

31

COOH


Ph

Ph

FGI

Ph

OH
PhMgBr

O
COOH

HO2C
HO2C

CO2H

CO2H

CO2H
HOOC

HO2C

COOH

Diels-Alder

O
+

HO2C
CO2H
32

CX
R NH Me

R NH2

RNH2

MeI

RNHMe

MeI

MeI

RNMe2

MeI

RN+Me3I-

1MeIMeI
33

FGI
O
RNH2

R' COCl

RNH

R'

R1
RNH2 +

34

O
R2

LiAlH4

R1
RN
R2

RNHCH2R'

LiAlH4
NaB(CN)H3

RNH

R1
R2

NMe2

FGI

NMe2

COCl +

HNMe2

O
N

35

FGI

Cl

C-N
O

H
N

ArNH2

Ph

36

1) HONO
2) CuCN

Cl

CN-

ArCN

Ph

CN

H2, Pd-C
+

LiAlH4

ArCH2NH2

Ph

NH2

O
NHEt

NH2

NH

FGI

Ar

Ar
F3C
FGI

NOH
Ar

Ar

37

3
R'CH2NO2

MeO

R2X

NH2

R3X

R1
R2
R3

NO2

MeO

CN

FGI
MeO

MeO

R1
R2
R3

H2

NH2

MeO

Cl

MeO

MeO
+

CH2O + HCl

MeO

MeO
MeO
38

NO2

MeO

CHO
+

MeO

MeNO2

6DA
Z

Z
D-A

Z = COR, CO2Et

(Z)

CN, NO2, etc.

(Z)

COOEt
COOEt
O
COOEt

39

D-A

O +
COOEt

Diels-Alder

carbo-Diels-Alder Transform

MeO2C

MeO2C

N Ph

N Ph
H
40

CO2Me

O
N Ph

Ph

Ph

FGI

NH2

Ph

FGI

NO2

D-A

NO2

Ph
+
NO2

PhCHO + O2NCH3

CO2Me

O
O
H

41

H
HO

H
CO2Me

CO2Me D-A

FGI

HO
H

COOMe
+

O
+

MeO

MeO

MeO

O
O
+

MeO

42

OH

FGI

II

CH3

CH3

NHAc FGR
NO2

43

CH3

NO2

NHAc


I C-X
II
A
B
C

44

O
O

CH3

O
O

CH3

O
O

CH3
O

O
O

O
O

O
H

O
O

Michael addition
45

CH3
O

Br
HC CH

46

Br

FGI

NaNH2
NH3

HgSO4
H2SO4

HC CH

TM

Ph

COOMe

Ph
O

47

14-
O

O
O

-
OH

O
R
48

O
R

Br

MeOOC

+
MeOOC

COOMe

Br
O

49

 umpolung

d/a

50

R+

R X
Nu
Mg

RMgX

Nu

+ MgX +
E

51

O
CH3C

1.
O
R C H
OH
R C
B

OH
R C H
CN

CN
H+
O

+H

Ph

OH
R C
CN

B-

OH
R C
CN

O
Ph
H

H+
H2O

O
Ph

Ph

OH

O
R

OH
R C
CN

52

2.
1,3-
O

S
S

BuLi

HS
HS

C O
H

S
Li
S

S
S

RI

S
R

H3O+
RCHO

dC
53

(CH3)2NH +

OH
H2C
N(CH3)2

H2C O

(CH3)2N CH2
Mannich Base

O(CH3)2N CH2

N
54

O
NH


1.
Cr(CO)6
Cr(CO)3
> 80%
R
H

+R
Cr(CO)3

[O]

Cr(CO)3

55

2.
ROH

H
CH2 C CN

H2S
RNH2

H
CH2 C CF3 + ROH

ROCH2CH2CN
HSCH2CH2CN
RNHCH2CH2CN

ROCH2CH2CF3

56


Formation of Carbon- Carbon
bond

Contents
-
1.
2.
3.()


1.

2.
3.

3.1

(RM)

M
+

M: LiNaKMgAlZnCuHg

RK > RNa > RLi > RMg > RAl > RZn > RCu > RHg
0.82 0.93 0.98 1.31 1.61 1.65 1.90 2.00

3.1.1
Grignard , RMgX
1. RX Mg
+

RX

Et2O or THF

Mg

RMgX

RXRI > RBr > RCl1o > 2o > 3o RX

Cl

Br

Mg

+
Cl

Et2O

Mg*

Cl

MgBr

THF
MgCl

2. -
RH

R'MgX

RMgX

R'H

HC

CH +

EtMgBr

HC

CMgBr

C2H6


1. RX Li

RX

CH3CH2CH2CH2Cl

RLi

2 Li
+

Br

2 Li

n-C6H14

Li

Et2O

LiX

CH3CH2CH2CH2Li

LiCl

Li

CH2=CHCH2XPhCH2X
( )

2. -
RH

RLi + R'H

R'Li

n-BuLi
Li
n-C4H9

CH

n-BuLi

n-C4H9

CLi

3.1.2
Wurtz
R Li

R' X

R R'

LiX

R MgX

R' X

R R'

MgX2

SN2

PhCH2Li

+
H3C

CH2CH3

CH2CH3

Li
Et2O
Br

Br

PhH2C

+
H

CH3

n-C8H17I
Li

THF, 0 oC

C8H17-n

LiBr

MgBr
+

Cl
Cl

Cl

Li
S

+ Br

RMgBr
or

C O

Et2O or THF

H3O+

R C OH

RLi


1.
O
R' C OR''

(1) 2 RMgBr
+
(2) H3O

OH
R' C R
R

2.
1
R1

O
C

r
OMe (1) RMgB

N
Me

MLn

O
R'

+
(2) H3O

R1

O
C

Weinreb

N CHO

(1)PhCH2CH2MgCl
+

(2) H3O

PhCH2CH2CHO

2
R'

C N

(1) RMgBr

R'

C NMgX
R

+
(2) H3O

R'

3
OEt
EtO C OEt
H

RMgBr

OEt
O
H3O+
R C OEt
C
R
H
H

CO2
RMgBr + CO2

H3O+

RCOOH


Ph
H

PhCH2MgX
N
CH3

Ph

H3O

Ph
H

NH
CH3

C=NC=O
-H
O

MgBr

OMe

THF

O
N

OMe

H3O+

CHO
OMe


RMgX +

H3O+

OH

H3O+

O
RMgX +
R'

OH

R
R'

3.1.3

1. RXZn

RX + Zn

RZnX

2.

RLi + ZnX2
RMgX + ZnX2

RZnX + LiX
RZnX + MgX2


Reformatsky
(H)R'

OH
C O + Zn .+ Br

C COOEt

H3O+

(H)R'

C COOEt

-
O
H + Br

COOEt

Zn, Et2O

H3O

OH
COOEt

3.1.4
Gilman

1. RLi CuX

2 RLi

CuX

R2CuLi

2.
HC

CH + R2CuLi

Li
Cu


1.
R R' + RCu + LiX

R2CuLi + R'X

1RXCH3X, 1o, 2o, C=CX, ArX (XBr, I)

2RXCOOEt
CN>CO
CuLi

Br

THF

3
SN2

Ph

CH3(CH2)6CH2I +

Br Me2CuLi

H3C
H

H
2

CuLi

Me
Ph

H3C
H

H
CH2(CH2)6CH3

2.
Me2CuLi

H3O+

OH

R2CuLi

H3O+

OH
R

SN2

3.
R'COCl + R2CuLi
O
O
CH3(CH2)4C(CH2)4CCl + Me2CuLi

R'COR
-78C

O
O
CH3(CH2)4C(CH2)4CCH3

4.
O

O
Me2CuLi

H3O+
98 %

R2CuLi

O
R'HC CHCR''

OLi
R'HC CH=CR''
CuIIIR2

1,4-

CuR2
Li+
O
R'HC CHCR''
OLi
R'HC CH=CR''
R

RCuI

R2CuLi

O- M+

O
R'

R'

R'
E

E = H3O+, R-X, RCHO etc.

O-

O
Me2CuLi

O
MeI

O-

O
Me2CuLi

O
I2

3.2
3.2.1
1.
C
A

B-

C-

B-H

( A)

2.
1C-
O-

O
-

CH2

CH2

2(Ylide)
P, S, As
R2CH PPh3

R2CH S(CH3)2

3) d
SPSid C-
S

n-BuLi
THF

H H

S
H

H H

4)
Huckel

n-BuLi
THF

O
H

3.
1
C R + X-

C- + R X
A

O
C- +R C L
A

OC C L
A R

O
C C R +LA

2
OC C

O
C- + C
A

BH

-H2O

C C
A

O-

O
C- +
A

H OH
C C
A

O
A

Michael 1,4-

3.2.2
1.
O

B-

1
O-

O
R2CH

CH2R

R2C

OCH2R +

R2CH

CHR

( LDA/DME,0C)
( NaH/Et2O,0C)

74

26

O
1) LDA, THF, -78C
2) MeI, -78C~25C

EtO

>90%
EtO

O
+

TiCl3

TiCl4 (cat.)

r.t.,

OH

TiCl3

2.
1

OLi

LDA, THF
-78 oC

O
H3O+

OH

,-
O

LDA, THF
o
OEt - 78 C

OH O

OEt

OEt

(1) LDA
COOEt
(2) Me3SiCl

OSiMe3
OEt

Ph
O
TiCl4

Ph

COOEt
OH

2 Mukaiyama

OTMS

OTMS
DMF, reflux
78

OTMS

22
O

OLi
LiNH2
liq. ammonia

n-Bu-I

Bu

f raction

Et3N, TMSCl

Lewis

Me3SiO

O
+

Ph

Ph

TiCl4 (cat.)
H2O
CH2Cl2, -78 oC

Ph

Cl
Cl
Cl
Ti
O
O

SiMe3

Cl
O TiCl3

-Me3SiCl
Ph

Lewis TiCl4SnCl4AlCl3ZnCl2

OH

OH

O
H

OSiMe3

TiCl4 (cat.)

H2O

CH2Cl2
O

Cl
O

1) LDA, THF, -78C

2) TMSCl

OTMS
ZnBr2, DCM

-ar
( )

3.
1Mannich
O

O
R2

R1
R3

R4

R7
R5

N
H

R6

OR

base or acid
protic solvent

R1
R2 R3

R5
N
R7

R6

1- 1o
2o
2
3 Mannich

Mannich
R4

H+

R4

R5

R5

OH

O
R2

R1

R2

R1
R3

R3

R5
R4

R7
N
R6

R1

H2N CH3

O
COOH

R4

OR

-H2O

R2

R5
N
R3 R
7

CH3
N
COOH

HOOC

R5

-HOH

COOH
H
H

H R4 R7
N
O
H R5 R6

R7
HN
R6

R6

R7
N
R6

R4

OR

-H+

R5

R2 R3

N
R7

R1

-CO2

R7
N
R6

R5

CH3
N

R6

4 Knoevenagel

(H)R'
R

X
C O + H2C
Y

(H)R'
C C
R

XY: -COOR-COOH-OR-CN-NO2
PKa16

CHO +

COOC2H5

NH ,

COOC2H5

COOC2H5

CHO

COOC2H5

COOC2H5

NH
+ CH2(COOC2H5)2

OH

80~90 %

3.3 C=C
3.3.1 Wittig
+ Ph3P C + C O

C C

+ Ph3P=O

Wittig

Ph3P+ OC C

Ph3P

 C=C
O

H
Ph3P=CH2

OMe H3O+

Ph3P=CHOMe

H
C Br

PPh3

Ph3P

H
C

CHO

Ph3P

C-

HWE(HornerWadsworthEmmons Reaction):
O

O
P(OC2H5)2

C2H5O

(1) NaH, THF

O
OC2H5

(2) RCHO R

+ (H5C2O)2P

ONa

NaH
DME() THF

HWE:
O

P(OC2H5)2

C2H5O

- H2

NaH

P(OC2H5)2 Na

C2H5O

O Na
RCHO

(C2H5O)2P

C2H5O2C H

O
OC2H5

(H5C2O)2P

ONa

HWE:

-
O,O-
ER1

Example :
O

O
OR1

P(

R2O

(1) (CH3)3COK, -78 C

)2

BnO

OR2

(2) BnO

CHO

R1 = Me,

R2 = Me

R1 = i - Pr, R2 = Et

OEt

(EtO)2P
O

(Z) : (E) = 3 : 1
(Z) : (E) = 5 : 95

(1) NaH , THF

(2)

CHO , THF

OEt
(E) =100%

3.4

3.4.1
BIIIA

R3 B

R3R B-M+ R2BOH

R2BOR

RB(OH)2 RB(OR)2

O
B2H6

HB

B
R

O
B
O
R

Br

RBr

Mg

Mg

RMgBr

MgBr

BF3

B(OCH3)3

R3B

B(OCH3)2

H+

B(OH)2


LewisLewisCO

R3B
NaBH4

H2O
100C
125C

C O

R
R B C O
R

R
H
OH
R B C OH
R
R R
H2O2
R B C OH
OHR
R
H2O2
O B C R
R

RCH2OH
R
R
R
R

O
R
OH

C-B

BH3

CO
B

THF

100C

H2O2
OH

BH

OH
B
C OH

CO
Cl

B O

Cl

H2B

H2O
Cl

H2O2
C O

OH
Cl

>>

C OH
3

3.4.2

SiCSiH

3d2p
--

Si-O532kJ/molSi-F808kJ/mol

OSiMe3

SiMe3

SiMe3

SiMe3

-- -

1.
O SiMe3

OH O
(n-Bu)4NF

PhCHO

Ph

2.
MgBr

Me3SiCl

SiMe3
H

H
SiMe3

AlCl3
Cl

3.
MgBr

Me3SiCl

SiMe3

n-C6H13CHO

SiMe3
OH

TiCl4
n-C6H13

CH2Cl2

PhCOCl

SiMe3

SiMe3
Ph

AlCl3

TiCl4
CH2Cl2

1,4-
Ph

4. Peterson-
--,

SiMe3
SiMe3
R1

Me3Si
N
O

Ph

1) LDA
(2) R1COR2

R2
N
O

Ph

Wittig
.

Li

LDA

3.4.3
Sn
SiSn-HSn-C
SnSn-HSn-C

1. Sn-H
n-Bu3Sn
C-C

2.
NaBH3CNn-Bu3SnH

-
Lewis
EZ
Sn(n-Bu)3

PhCHO
BF3, -78C

Sn(n-Bu)3

OH
Ph

3.4.4
C-C

Heck
Stille
Suzuki
Sonogashira

Heck

PdII
Br
Pd(OAc)2
B-, Ligand
OTf
OAc
NHcbz

Pb(OAc)2, PPh3
K2CO3, Bu4NCl

OAc
NHcbz

Heck

Pd(OAc)2
Pd0

I>Br~OTf>>Cl

Stille

Pd0

SnBu3
H3CO

NO2

NO2 PdCl (PPh )

2
3 2

TfO

LiCl, DMF
H3CO

SnBu3

OH

PdCl2

OH

Stille
---

Cl
H3CO

Bu3Sn

Pd2(dba)3, P(t-Bu)3
CsF
O

dba

H3CO

Suzuki
Pd

ArX
or

RBL2

R'HC CHX

Pd(0) (cat.)
Base, ligand

ArR
or
R'HC CHR

X-BL2

Suzuki
R
R

BX2

R'

R'

BX2

(Ph3P)4Pd

H
H

H
H

(Ph3P)4Pd

H
H

X = OH, OR, R; Y = Cl, Br, I

Pd(PPh3)4
I>Br~OTf>>Cl

R'

R'

Sonogashira
Pd(PPh3)4
CuI
I

Pd(PPh3)4
CuI

I~OTf>Br>Cl
Sp2>>>


-
:
O

O
Ph

O
Ph

hv

O
O

N N
NC

hv
CN

2 Ph

N2
CN

N-
RON=O
OR Cl

RO

NO

RO

Cl


H
C

N N
NC

H Sn(Bu-n)3

2 NC
h

CN

NC

Sn(Bu-n)3

Sn(Bu-n)3

R R
(n-Bu)3Sn Sn(Bu-n)3

Sn(Bu-n)3

R
R

X Sn(Bu-n)3

H Sn(Bu-n)3

Y
R

Sn(Bu-n)3

R X

Sn(Bu-n)3

Br

AIBN, (n-Bu)3SnH
CN

SePh
N

COOBn

CN 80%

SnBu3
AIBN, 73%

COOBn

AIBN
PhS, PhSe
H

H
O

AcO

MeOH2C

R OH

AIBN
Bu3SnH

NaH, CS2
CH3I

O
AcO
MeOH2C

S
R O

H
O
H

AIBN
SMe

Bu3SnH

R H


CuCl2
Cu2+
Cu2+

-H+
R

2R

R
R


Cycloadddition Reactions

Contents
1.
2.
3.

+
-

+
-

Ph
NC

Ph
O

LDA, THF
-78C

NC

Br

NHBn

OH MsCl/Et3N
CH2Cl2

NC

Br

OH
Me

Ph

OH

OH
Me

OMs
NHBn

77%

Me
N
Bn

OMe

OMe

OMe

Me

Me

MeSO3H
P2O5
MeOOC

H
Me

MeOOC

H
Me

MeOOC

H
Me

N
H

Et3N
MeCN
Reflux
n
OB

O
Et3N

N
H

OBn

N
H

OBn


OTBDMS
O

O
O

AgOSO2CF3

4
N

80%
O

OTBDMS

O
O

n-Bu3SnH

ArO2S N

AIBN

ArO2S N

ArO2S N

n-Bu3SnH

H
ArO2S N

Br

COSePh

n-Bu3SnH

CO2Me AIBN

CO

88%
CO2Me

Co2Me

Baldwin

n3-8
endoexo

Ysp3(tet) sp2(trig)
sp(dig
X

exo
Y

endo

Baldwin

n3-8
endoexo

Ysp3(tet) sp2(trig)
sp(dig
X

exo
Y

endo

Baldwin

Tet(sp3)
Trig(sp2)
Dig(sp)

exo

endo
exo

endo

exo

endo

5-exo-trig
MeOOC

N
H

COOMe

COOMe 5-end o-trig

MeOOC
NH2

Baldwin

5-exo-trig
5-endo-trig

MeOOC

N
H

MeOOC

MeOOC
Pd(OAc)2
PPh3, K2CO3

Br
OTBDMS

OTBDMS

Heck
O

O
Pd(dba)3, AsPh3
I
Bu3Sn

NMP, 70C,96%

Stille

,:,
,,

R1

R2
+

R1

R2

R1
R1

R2
R2

R1

R1

R2

R2

R2

R2

+
R1

R1

ROMP

RCM
R1HC CHR1

CHR1
CHR2

R2HC CR2

R2
R1

R2

R1

CHR1
CHR2

ROM


D Cl
Ru
Cl
D1 R

D =

Ru


CHR

-CH2=CH2

MLn
-MLn=

CHR
MLn

-CH2=CH2
MLn

MLn

0.1%Cat.
xylene, 25C

O
O

O
N

OH

Cl PCy3
Ru
Cl
PCy3

N
(F3C)2MeCO Mo
(F3C)2MeCO
Cat.
Ph

H
O

O
N

CH2Cl2
Ph
Ph

Ph

OH

+
+


Diels-Alder/[4+2]
R2

R2
R1

R1
R3

R3

HOMOLUMO
D-A
HOMO
LUMO
D-ALUMO
HOMO


a.
b.
c.
d.
COOC2H5

COOC2H5

COOC2H5

COOC2H5

COOC2H5
+
C2H5OOC

COOC2H5
COOC2H5

COOMe

25oC

COOMe

H
74%
COOMe
+

H 26%

rt

+
COOMe

COOMe
Ph

Ph

CHO
+

Ph
CHO

 Diels-Alder
H
O

,
210 oC

42 %

O
H O

O
H
160 oC
95 %
H

ci s:t rans = 9:1

COOCH3

COOCH3

O +

COOCH3

COOCH3
OMe
+
Me3SiO

OMe
O
H

ZnCl2
R CH2Cl2

Me3SiO
Lewis D-A
COOCH3
N
25 oC
N
COOCH3

H3O+

O
R

O
O

R
N

COOCH3

N
COOCH3


1,3-/[3+2]
41, 32

1, 3-D-A

b
b

b
a

c
d


1,3-
1,3-

N
RC

CR2

N
N

CR2

RC

CR2

N
O

RC

NR

NR

RC

CR2

R2C

R
N

R
N

R2C


HOMOLUMO

O
O

O N

CO2Me

H
H

CO2Me

1,3-
CO2Me

MeO2C

Me

Me

N O

1,3-
Ph

N N
RO2C

CO2R

RO2C

N
N
CO2R

1,3-
O

O
O

O N

CO2Me

H
H

CO2Me


[2+2]
1
2CH2CH2 R2CCO
RNC=O
3)
O

O
h , -70 C
o

+
Me

CH2Cl2
Me

~90%


H
O
Me

Et3N
Cl

O
C
CH2

O
C
N

R
+

O
C

N
R

R
+

N
R


[1+2]
1[1+2]

/(HCX3 H2CX2/B:),
/R1R2CN2/cat.
/CH2I2/Zn-Cu

/(HCX3 H2CX2/B:),
NaOH(50%)
+

CHCl3

Cl
Cl

TEBA

/IIIIR1R2CN2/cat.

CuSO4
N2

/CH2I2/Zn-CuSimmons-Smith

+
O

CH2I2

Zn/Cu
O

,-

Oxidative Reactions

Contents
1.
2. -
3.
4.

5.1
1

CC

?
?
:

5.1.1 Cr(VI)
1.
2.
3.
4.
()

HOCrO3HH2CrO4HCrO4-CrO42-,
Cr2O72-,HCr2O7-H2Cr2O7


R
R
H

OH

O
Cr OH
R
O
O
H

H2CrO4

O
Cr OH
R
O
O
H

R
R

+
O

HCrO3- + H3O+

H2O

O
Cr OH
R
O
O
H

R
R

+
O

H2CrO3

Ha

t-Bu
H

OH

t-Bu
H

H
OH

3:1

H
Hb
OH
t-Bu

Ha
t-Bu
H

Hb

OH

5:1

1 H2CrO4 CrO3
2Jones H2CrO4H2SO4 (CC)

(3)Sarett CrO3Py
(4)Collins CrO3Py2

(5) PCC (CrO3PyHClCH2Cl2)

(6) PDC(H2CrO4Py2)

1. H2CrO4 CrO3
()

RCHO

OH O
Cr OH
R
O
O
H

OH
R C O CrO3H
H

HCrO4
R
HO

+
O

HCrO3- + H3O+

H2O
OH O
Cr OH
R
O
O
H

R
HO

+
O

H2CrO3

2Jones (H2CrO4, H2Cr2O7, K2Cr2O7)

CrO3+H2SO4+
Cr(VI)
Cr(III)
(black)
(green)
(1)2o

R
R

(2) 1o

Jones
OH
acetone

O
R

OH

OH
H3C(H2C)3C C C CH3
H

Jone reagent
acetone,H2O
15-20oC
Jone reagent
acetone,H2O
15-20oC

O
H3C(H2C)3C C C CH3

3Sarett CrO3Py

H
C
OH

CrO3-C5H5N

4Collins (CrO32pyridine)
Collins
CH2Cl2,
1o
2o

O
2

+ CrO3

+
N ) Cr O
2
_
O

Collins
CrO3-Py2

CH2Cl2

OH
AcO

O
O

AcO

O
O

5. PCC(Pyridinium Chlorochromate)
-

N
H

CrO3Cl-

CH3(CH2)5CH2OH

N
H

CrO3Cl

CH2Cl2

CH3(CH2)5CHO

6. PDC (Pyridinium Dichromate )

N
H

Cr2O722

DMF

PDC

PDC
CHO

OH DMF

CH2Cl2

OH

PDC
DMF

COOH

5.1.2
1. KMnO4
1
KMnO4

RCH=CR'R"

RCH-CR'R"
OH OH

RCH=CR'R"
RCH2OH RCHO
Ar(CH2)nCH3

RCOOH R'R"CO
RCOOH
ArCOOH

2. MnO2

KMnO4

CH3
MnO2
HC C CH C CH2OH CH COCH
3
3
HO

CH3
HC C CH C CHO

HO

>>

MnO2

OH

H3CO
H3CO

OH

MnO2,
OH acetone

H3CO

H3CO

OH

MnO

2
CH2=CHCH2OH
,

CH2=CHCHO

5.1.3
Moffatt
(DMSO) + (DCC+
1 :
H O

H OH
H

DMSO, DCC
H

H3PO4

H
O

Moffatt

N C N
H

N C N

H
H2C
H3C

CH2 H
R1
S
R2
H3C
O

H
N

N
O

H O H
N C N

R1

O
R2
O
R1

R2

H3C

CH3
S
CH3

CH2 H

H3C
S CH3
O H
N C N

R1
HO
R2

Swern
(DMSO) + (TFAA
1 :
2
H

DMSO, (COCl)2
OH

100%

OH

O
H

DMSO

(CF3CO)2O
O

COOMe

COOMe

HO
I

5.1.4 DMP

IBX =

O
O

HO
I
COOH

KBrO3
H2SO4

Ac2O, AcOH

AcO OAc
I OAc
O

IBX
OH
DMP

AcO O
I OAc
O

CH2Cl2
O

DMP
O

CH2OH
O

RO
O
NH2 O
AcO

O
O

Ph
DMP, DMSO, r.t.

RO
O

NHAC

NH2 O

OAc
OAc

AcO

CH
O
O

NHAC
OAc
OAc

Ph

5.1.5 Oppenauer
(, )+()


: :

CH3

CH3
Al(OC4H9-n)3
CH3COCH3

HO

Al

Al
CH3

O
C
CH3

O
C R
H R

CH3

O
C H
CH3

+
R

O
C

5.1.5
1.

CH2OH
OH
HO
H
OH

H
O
OH
H
CH2

COOH
OH
O2,Pt

HO
H
OH

H
O
OH
H
CH2

2.2
OH OH

O
(Bu3Sn)O, Br2
CH2Cl2

OH

5.2 -

5.2.1

O
F3C

OOH

>

>

CO3H

CO3H

CO3H

>

>
H3C

Cl

OOH

> HO OH > t -BuO OH

NO2

H2C CH2

RHC CH2

RHC CHR

R2C CH2

R2C CHR

R2C CR2

24

500

500

6500

>>6500

H
C
C

O
O C R

O +
O

O
C

CH3CO3H

CHCl3,

mCPBA
CHCl3

H
H
O

H
H
99%

1%


OH
HO

OH

m-CPBA
O

CH2Cl2,0C

:
92
8

OAc
OAc
AcO

m-CPBA
CH2Cl2,0C

60

40

5.2.2 -
1.

H
H

O
Mn
O
O

R
R

MnO4
Mn()

OH
H2O

H
[Mn( ) ]

R
R

H
OH H2O R
R
O

OMnO2
O
Mn()

R
R

O
MnO2
O

H
H2O

R
R

OH
2OMnO3

H
[Mn()]

_
MnO4
H

[Mn( ) ]

H2O

H
R
R

OH
OH
H

HO

COOH

COOH

HOOC

COOH

COOH

COOH

HO

HOOC

H
OH

H
COOH
HO

2.
H
L
O
O
Os
O O
L
H

Et2O

O O
Os
O O

OH

H2O

OsO3
OH

L
Me

H
CO2Et
Me

Me
OsO4

H
HO
HO

CO2Et
Me

5.2.3 -
+
O _
O
O

+
_ O
O
O

_ O +
O
O

+ O _
O
O

1,3-
R'
R

R'

O
R

R'

R
R

O
O

R
O

R'
O
O

O
R'

O
R'
R

R'
R

O
R

O
R'

R O O R
R

R'
O

R'

O O R'

O
R3
R1
R2 O O H

O
R3
R1
R2 OH OHH
R1

R2

R3

R1
R2

R3

HO

ZnCH3SCH3,
H2O2
O3

O
O

HCOOH
H2O2

O
O
HO C CH2CH2CH2CH2 C OH
85%

5.3 -
5.3.1
1) KMnO4-NaIO4
KMnO4 NaIO4
KMnO4 MnO2 NaIO4 KMnO4
KMnO4 :

KMnO4(cat.)
HIO4

COOH
COOH

2OsO4-NaIO4 (OsO4)

MeO

OMe

MeO
OsO4(cat.)
NaIO4

OAc

OMe

HCHO
O
OAc

5.3.2 Baeyer-Villiger
Baeyer-VilligerH2SO5

COCH3

OCOCH3

OH

C6H5CO3H
CHCl3
O

O
m-ClC6H4CO3H
CHCl3

LiAlH4

HOH2C
OH


>>>
->>-

O
C

NO2

O
C O

CH3CO3H
AcOH, H2SO4

NO2

95%

OH

O
CHO

H2O2, NaOH

O OH
O

OH

OH

OCHO

~100%

5.4 -
5.4.1

O
O
Ph

CH3
H

SeO2

Ph

CHO

R
O

O
CH2Ph

SeO2

OH

SeO2

R
Ph

Ph

C
O

Ph

H
R
O

R
R

Se

OH

OSeOH
R

Se
OH

H2SeO3

(SeO2 + H2O)

Se
O

R'

R
R

C
C

OH

OH

O
Se

R
O

C
C

O
O

5.4.2
20-45

CH3

CHO

CrO2Cl2,CS2
H2O

90%
O

KMnO4
R4NCl

Na2Cr2O4
Ac2O/AcOH

~100%

80%

CH3

CH3
CH3

CHO

MnO2
H2SO4, H2O
O

CH3
MnO2
H2SO4, H2O

CH3

Reductive Reactions

Contents
1.
2.
3.
4.

6.1

6.1.1

H-------H

1.
R
R
C
C H
H

R
H

R
C

C H

2.
H

R
H

R
C H

1)

3.

HH H H

1.
1

RCH=CH2 > RCH=CHR'~ R'RC=CH2

> R'RC=CHR''> R2C=CR2

H2

(1)

H2

(2)

(3)


> > >
H
H

OH
OH
OH

OH

86%

CH3
CH3

CH3

H2, PtO2

CH3

CH3CO2H

CH3

82%

CH3

18%

O 5%Pd/C, 1%Na2CO3
348K, 4h, H2
>96%

CO2Et
H

CO2Et

H2/Cat.
H
HO

H
HO
98%

2)

Raney Ni
H2 (4MPa) /Ni
170~230C
O

O
HO

OH
H2/Pd-C

O
HO

OH

OH

H2/Rh-Al2O3

Pd/C

3)

O
CH3

CH2OH

H2/PtO2

H2

FeCl3,EtOH

Pd-BaSO4

-Raney Ni-Cr

CH3CH=CHCHO

CHO

H2, 5% Os-C,
100C, 7 MPa

H2 (0.35MPa) r.t.
PtO2 (FeCl2)

CH3CH=CHCH2OH
90%

CH2OH

2.

OH

Ph
H2, Pd/C

COOH
COOH
H
R N

S
N

O
O

CH3
CH3

H2, Pd/C

COOH
COOH
H
R N

EtOH

S
N

O
Ph

CH3
CH3
OH

6.1.2

: RhRu
Ir :
(Ph3P)3RhCl (Ph3P)3RuCl(Ph3P)3IrH
PPh3 +H2

Ph3P
Rh
Ph3P

Cl

-PPh3

Ph3P
Rh
Ph3P
Cl

H
H

Ph3P H
Rh
Ph3P
Cl

+PPh3

Ph3P H
Rh
Ph3P
H
Cl

PPh3

Ph3P

H H

Rh
Ph3P

Cl

OH

OH
H2, (Ph3P)3RhCl
C6H6

NO2

CH2=CHCH2SPh

H2, (Ph3P)3RhCl

H2, (Ph3P)3RhCl

NO2

C3H7SPh

6.2

LiAlH4
(NaBH4)

C=CCC

C=C

6.2.1 LiAlH4

C=OCN, N=O,S=O

H H
H Al Li O
H
R
R

Al
H
H

Li+

O
H
R

H
H

Al O Li+ R
H
H
R
R
O

O
H
Al
H

Al

R
R
O
H

R
R
H

Li

Li+

H3+O

H Al

R
R
O
H

Li+ R

R
OH
H


C=O > COOR> CN> CONR2> C-NO2> CHBr >
CH2OSO2Ar
THPO

Me

THPO
O
O

1) LiAlH4/THF
2) H3+O
H
HO

O
H

H3C
O

Me

1) LiAlH4/THF
2) H3+O

H3C
OH

OH

O
LiAlH4
Me

Me
98%

C=C


COOEt

OH

LiAlH4
N

O
N

LiAlH4

CH3

CH3
CN

LiAlH4

NH2

Cl
n-C8H17

n-C8H17
N

Cl

O S
O2

1) LiAlH4, THF, reflux, 26h

2) H3+O

1) LiAlH4, ether, reflux, 1.5h

2) H3+O

O
S
O
O

TsO-

6.2.2
LiAlH(Ot-Bu)3 LiAlH(OEt)3

1) LiAl(OEt)3
N

C N

2) H3+O
1) LiAl(OEt)3

2) H3+O

O
O

CHO

1) LiAl(Ot -Bu)3

CH2OH

+
COOCH3 2) H3 O

COOCH3
O

H
Me OMs

H
Me OMs

1) LiAl(Ot -Bu)3
2) H3+O

O
Me

HO
Me

6.2.3 NaBH4

O2N

NC

CHO

NaBH4,
EtOH

NaBH4
H2O

CH2OH

O2N

NC

OH

NaBH4
O
HO2C

OH
HO2C


Cl

a
COOCH3 N BH4

N
Me
O

COOC2H5 NaBH4

Cl

OH

N
Me
O

O
OH

NaBH4 / CeCl3 Luche Reduction

,-12
O

OH
NaBH4/CeCl3

R
R

NaBH4

R
R

OH

OH

NaBH4/CeCl3

R
R

OH

6.2.4

O
O

KBH(OAc)3
O

OH

LiBHEt3

Ph

Ph
CH3

OMs

Na (CN)BH3

O
Ph

NaBH3(CN)
Br

HMPA

O
Ph

O O O t-Bu
NaBH3(CN)
pH = 4, 79%
COOMe
COOMe

N
S
MeO
N
O

O O O t-Bu
N
S
MeO
HN
O

COOMe
COOMe

6.2.4
26

Lewis

>>>>>>
>

O + BH3

C O BH2

C O BH2

COOH

CH2OH

O
B2H6
O

O
O

H2O

C OH
H

6.2.5 (iBu)2AlH
DIBAL DIBAL-H

Al
H
CO2Et

BnO

DIBAL, -78C

OH

BnO

CO2Me
H

CO2Me

DIBAL, CuMe

Me
H

Me
H

,C=C

6.3

6.3.1
R

eO

R
R

H+
OH

R
H
R

OH

Me

Me

OH

OH

Na-EtOH

99%

1%

NaBH4

69%

31%

Al(i-Pr)3

42%

58%

7-35%

65-93%

OH
R

Me

R
e-

H+

OH
Me

Me

O
1) Li0, NH3, ether

O
H
O

2) MeI

OH
Me

Me

Me
Me
O

,C=C

Clemmensen
Na-Hg, Zn-Hg
()

O +

2 Na-Hg

HO

H2O

COCH3

CHOH + 2 NaOH + 2 Hg

Zn-Hg, HCl

HO

OH

CH2CH3
OH

MeO

MeO
Zn-Hg, HCl

HO

CHO

HO

CH3

6.3.2

e-

H+

R
R
R

H+

e-

CH3CH2C C (CH2)3CH3

CH3(CH2)7C C(CH2)7CO2H

Na, NH3

Li, NH3

(CH2)3CH3

Et

97%~99%

(CH2)7CO2H

H
CH3(CH2)7

6.3.3

(Birch )
H

L i ,

L i ,

CH3OH
H

OCH3

Na+
H

OCH3
H

OCH3
H

OCH3

CH3OH
H

Na+

2 EtOH
H
H

+ 2
NaOEt

OH

OH

MeO

Li, NH3

MeO

1--1,4-

Na, NH3
CO2H
EtOH

CO2H

2,4-

6.4
6.4 .1

Et3SiH, TFA

H
O

(EtO)2SiHMe
KF, 95%

OH

6.4.2 Wolff-Kishner-

(DMSO),

R
R

CH=N NH2

C=O + H2NNH2

R
H
R

N NH

B-

R
H
R

B-

N N

HB

R
CH=N NH
R

R
H
R

N N

NH2NH2, NaOH
(HOCH2CH2)2

NHNH2

Protecting Groups in Organic

Synthesis

Protecting Groups

Contents
1.
2.
3.

4.

5.

7.1

12-13-

7.1.1
1. , MeOR
I.
1Me2SO4, MeOH, Bu4N+I-,
6090%
2MeI,
3CH2N2 /HBF4

O
O

OH
O

O
O

t-BuOK, MeI,THF
100%

OCH3
O

O
O

II.
pH= 1-14

(1) Me3SiI/CHCl3
(2) LewisBBr3 CH2Cl2
(3) HI

(CH3)3Si

CH3

CH3I + ROSi(CH3)3

H2O

ROH + (CH3)3SiOH

2. BnOR, PhCH2OR
I.

BnBr
OH

O
Me

Me

KH

OBn

O
Me

Me

II.
pH= 1-14,

III.

3. TrOR, Ph3COR

I.

II.

1 80% HOAc
2 20%CF3COOHCH2Cl2
3HCOOHEt2O
O

NH

NH
(p-MeOC6H4)n(Ph)mCO

N
O

HO
80%HOAc

OH OH

(p-MeOC6H4)n(Ph)mOR
n = 0, m = 3, 48 h
n = 1, m = 2, 2h
n = 2, m = 1, 15min
n = 3, m = 0, 1 min

N
O
OH OH

4. MeOCH2ORMOMOR

II.
pH = 4-12

III.
HCl/MeOH; HCl/THF; H2SO4/HOAc

5. R3SiOR

ROH>ArOH>COOH>NH>CONH>SH

>
>

COOSiR3>NHSiR3>CONHSiR3>SSiR3

1Me3SiORTMSOR

Me3SiCl, (Me3Si)2NH, (Me3Si)2O, (NHSiMe3)2C=O

1.

2.
3.

II.

III.

-
/THF

TMSO
H3CO

OTMS
OTMS
O

K2CO3/MeOH
OTMS 0C, 45 min, 100%

OH
HO
H3CO

OH
O

OH

(2)TIPSOR
I.
(i-Pr)3SiCl
II.

III.

3TBDMSOR
I.
t-BuMe2SiClt-BuMe2SiOTf

II.
PH=4-12

III.
:TBAF
OH

TBAF
THF

OH

OTBS
OTBS

OTBS

HF.Py
THF

95%

TBS = TBDMS= t-BuMe2Si-

OH
90%

7.1.2
2,4,6-

pH=1-8

AcOR

//

PhCOOR

BzCl,TEA

Ph
HO

COOMe
NH2.HCl

Ph
BnO

COOMe
NH2.HCl

7.1.3

-
CrO3/py NaIO4, Pb(OAc)4, KMO4
/ TFA/
OHOH
NC

COOC2H5

O O

(CH3)2C(OCH3)2
TsOH

NC

COOC2H5

7.2

7.2.1
,

pH=4-12

/THF

12-13-

-
pH = 1-12


N-I2/DMSO
O

O O
O

R
SHSH

S O
O

S
OH

1) PDC
2) MeOCH=PPh3

LiAlH4

Zn(OTf )2
O

CH3

O
CH3

S
S

O CH
3

CH3

OBn
HgO, BF3-Et2O

1) HCl/H2O
2) NaBH4
3) PhCH2Br
O

CH3

OBn

O
CH3

CH3

7.3
1.
2.
1.
2.

7.3.1 N-N-

Pd-C/
O
H2N
Ph

OH

O
OH

BnCl
K2CO3, H2O

Bn2N
Ph

OBn

Bn2N
Ph

NH2
Ph

1) Pd-C, HCO2NH4 H N
2
Ph

OH

NH2
Ph

N-SiR3

OSiMe3
MeO2C

CO2Me
NHSiMe3

MeO2C

OH

OSiMe3

NHSiMe3

NH

OH

7.3.2 N-
Ac +
DCC
pH= 1-12

NH2

NH

NH

con. H2SO4

Ac2O

SO3H
O

NH

O
NO2

H2SO4
HNO3
HO3S

H+

NH
NO2

CF3CO+
/
O
HN

CH3
OH

H3C

OEt

F3CCO
1) (CF3CO)2O, K2CO3
2) HBr, AcOH, Ac2O

HN

H3C

CH3

OH
H3C

F3CCO

Me C8H17

R=

Me
H

H
H

CH3
OH

ROH

Br

CH3
OH

7% K2CO3

H3C

 PhCO + +
6N

pH= 1-14

7.3.3 (CH3)3OC(O)NR2, R2NBoc

,
pH = 1-12

HClTFA

OH
CO2Me
TBDMSO

86%

N3

OH

NHBoc

RHN
Ph

Pd-C, EtOAc
H2,(BOC)2O

Ph

HCl/AcOEt

OH
CO2Me
TBDMSO

NHBOC

OH

NH2

RHN
Ph

Ph

7.4

1.
2.
3.
4.DCC
1.
2.
3.
4.

7.4
1.

(Me3Si-Et3Si-)
MgBr

Me3SiCl

SiMe3

SiMe3

Mg

1.CO2
2.H+

Br

Br
SiMe3

1.AgNO3 OH2. H+
COOH

COOH

MgBr

Asymmetric Synthesis

Contents
1.
2.
3.
4.

8. 1

2001
20
HO
H
HO

L-

COOH HO
NH2
HO

D-

COOH
NH2

O H

O
NH

H
O

O
O

(S)

(R)

NH

8. 2

ee
enantiomeric excess
de,
diastereomeric excess
(ee) =

[R]-[S]
[R]+[S]

(de) =

[RS]-[SS]
[RS]+[SS]

ee98%
99%1%


(),

,
,

,
,,

8. 3

8.3.1

S - G*
O
R2N

P*- G*
O

OH
O

Zn(BH4)2
-78C

OH OH
O

R2N
>98% d e

8.3.2

S A* S-A* R
O

P*-A*
+

O
N
NH2
O

H3O+

O 1) LDA, 0C
2) n-C3H7I, -110C

O
H

P* + A*

N
NH2

8.3.3
SR*
P*
S R* P*
H Me

Me

(B H3)2
,
0
Me

(-)-

Me

C
Me

Me
2R ( ) -
ee 87%

Me
H
H

HO
H

H2O2/OH

P*2 BH

Me

BH

(+) H2O2/OH

H
H

Me
2S- ( +) -
Me

Me

BH
HO
H

OH
H

H
H

Me
2R ( ) -

H
H

OH
H

Me
2S ( +) -
ee 86%

8.3.4
L*SR

P*

L*(cat.)
MeO

COOH

(R,R)-DIPAMP-Rh(I) MeO

NHAc

AcO

H2

COOH
NHAc

AcO

>95% ee
Ph
HO

COOH

MeO

Ph
OMe

NHAc

HO
L-dopa

(R,R)-DIPAMP

2001William S. Knowles, K. Barry Sharpless, Ryji Noyori

8. 4

8.4.1
1.
OH

COOPri
O
B
O

RCHO

R
COOPri
R = alkyl, ~86% ee

O
R

R'2Zn
H

L*

OH
*
R
R'
NHSO2CF3

NMe2

OH
But

ee

S 99%

NHSO2CF3

OH

R 98%

S 90%

N,O-

2.

O
R

OM
R

R1

R2CHO
R1

R1

OH
R2

R1

Me

OB(Ipc)2

1
Me

DIPEA

R1

O
R1

Et

R2

Me

Et

Et

Et

R2

R1
R
anti

R
sy n

M = Li, Mg, Sn, Ti, Si, B, etc.

OH

OH O
R2CHO
H2O2
i Pr

R2

R1
Me

Me

i BuCh
2

Pr 2-Furyl

ee/%

82

80

yield%

91

92

80
84

Me
91
78

88
99

86
79

Me
1

O
BOSCH3F3
O
2

Lewis

O
N

N
Cu

O X
Ti
X
O

O
N
Ph

Ph
2

3
X = Cl, OPri

O
BnO

OSiMe3
H

OSiMe3

O
MeO

Me
O

SBut

SBut

2(0.5% eq.)
-78C

2(0.5% eq.)
-78C

OH O
BnO

SBut
100%, 99% ee
HO Me O

BnO
Me
96%, 99% ee

SBut

3.
Ts
N
BH
O
N O 0.05 eq.
H
-78C

H
Br

H
N
O

Br

CHO
Br

O
O
B
N
H
O S O
Tol

98%
exo : end o = 97:3
ee(exo) = 96%

OMe

O
H

(R)-BINOL-TiCl2(0.1 eq.)

CO2Me

CO2Me
O
TBSO

Ar

OMe

(R)-BINOL-BOPh
Bn

Ar

N
Bn

8.4.2
1.
OCH3

H CH P Ph
)2 Ph2P
2 (

O
O

(-)-

H3C P

Ph
P CH2

OMe

CH2 P

Ph

H CH2P(Ph)2

H3CO
*
LA

*
LB

Ph C C
H
H3COCHN

( Z)

- -

HO

COOH

*
LC

* *
H2/Rh LDLDCl
2
25C,4atm,4h,50%MeOH

HO
* *
H2/Rh LDLDCl
2
NHCOCH3
COOH

Ph CH2CHCOOH
NHCOCH3

- ( S) ( +) N .

.
95 7%e e

OH

*
LD

OH
NHCOCH3
COOH
H
94%e.e

L* :

2.

OH

/ THF

C6H5 C CH3 + BH3

25C,2min

O
C6H5 CH
3

H Ph

Ph

BH
2

C6H5

- 1-
R
( )
.
99% %e e>97%

O
N

B H
H

R
O
Ph

Me

CH3

H Ph
Ph
N

O
B
CH3

8.4.3
1. Sharpless
:

:O:
R2

R1
OH

R3

:O:

R2
R,R-(+)-DET
t-BuOOH,Ti(OPr-i)4
R3
CH2Cl2,-20C
R2

S,S-(-)-DET
t-BuOOH,Ti(OPr-i)4
R3
CH2Cl2,-20C

R1
O
OH
R1
O
OH

DET: DI PT

O
H
CH2OH
CH2OH R R- + -DET t -Bu
OOH
, ( )
,
Ti(OPr-i)4, CH2Cl2
H
CH3(CH2)9 H
CH3(CH2)9

.
97% 95%e e
H

2.
O

5%
NaClO,aq,CH2Cl2

72%,
L

R'

R'
N

N
t-Bu

Mn
Cl

t-Bu
t-Bu

Mn -S a len-C omplexe

t-Bu

O
.
98%e e

9.1
9.1.1
phase transfer catalystPTC

20%

9.1.2

+X-

M+Nu-

RX

RNu + M+X-

M+

u-

+
Q Nu

+X-

RNu

PTC

M+X-

+
Q Nu

RX

9.1.3
1

PhCH2CN + C2H5Br

NaOH/H2O
TEBA

PhCHCN
C2H5
88%

NC-CH2COOR + CH2ClCH2Cl

NaOH
TEBA

CN
COOH

2
NaOH
Cl3C-N+R4
Cl3C- N+R4
H

Cl

NaOH/H2O/CHCl3

C C
Ph

Ph

+ -

R4N X

Cl2C

H
Ph

R4N+ClO

Cl
H

H2O

Ph

Ph

CH=CH2
CH2CH2Br

NaOH

2h

1%
Bu4N+Bro
90 C,2h

CH CH2
100%

H
Ph

KMnO4K2Cr2O7NaOClH2O2NaBH4

CH3(CH2)7CH=CH2

K2Cr2O7 + H2SO4

KMnO4
R4N+Cl-

TBAB/H2O/CH2Cl2CHCl3
-5~0C

CH3(CH2)7COOH
100

+ H .r - RCH2OH
TBA
C O4 ]
[

RCHO

4
O

+ R4N+X-

X-CH2CH2O- N+R4

O
XCH2CH2O- + R C R'

X CH2 CH2

R
O C R'
O

O
O

R'
R

CHO
2

+ KCN

O
Bu4N+ClH2O,r.t

CH C
OH
70%

20h1h

5
CH2Br
Pd(PPh3)4,(C6H13)4N+HSO4+ CO
,
CH2Cl2,NaOH,

CH2COOH

1atm

OH
Br

Co2(CO)8,Bu4N+Br-, C6H6,NaOH
+ CO

6C,1atm, h

O
O

9.2
Microwave Irradiation Organic Synthesis
300MHz-300GHz,100cm
1mm(100cm-0.1cm)

(1) :

9. 2. 2

245MHz

2.45109

9.2.1
1.
S

CO CH
COOH
HCl
2
3
S
+ H2O
L
+ CH3OH
MWI
NH
NH
MWI=Microwave Irradiation

20
HOOC
H

H
COOH

+ CH3OH

H2SO4
MWI

H
H3CO2C

CO2CH3
H

50min480min

2Diels-Alder
COOEt

EtOOC
COOEt
MWI

+
COOEt

87%

1072h
O
+ EtOOC C C COOEt
O

COOEt
COOEt

10 min7

1Claisen

OH

O
DMF
MWI

1072h
2Pinacol

CH3 CH3
H3C C C CH3
OH OH

n+

M /
MWI,15min

CH3 CH3
H3C C C CH3
CH3 O

15h

4.
MeSiCl2H

CuCl,TMEDA

SiMeCl2

360
N C O + ArNH2

MWI
Solide-State

NO2

N C

S +H2NAr

MWI2
X
Solid State

NH C HNAr
O
NO2
80%~89%

NH C

NHAr

S
82%~95%

XCl, Br, EtO

9.3

1963 Merrifield

1984

9.3.1
Solid-phase Synthesis

:
3:
(1)

;
(2)

(3)

:
(1)
;
(2)
;

(3)

(4) (
)

(5)

(1)
(2)
(3)

(4)
(5)
(6)
(7)

1
1)
NH2-CHRCOOH

HCOOH

OHCNH-CHRCOOH,

CH3OH

NH2-CHR'COOH

NH2-CHR'COOMe

2)
DCC
OHC-NHCHRCOOH + NH2CHR'COOMe

OHC-NHCHRCONHCHR'COOMe

3)
0.5M HCl

NH2CHRCOHNCHR'COOMe

OHC-NHCHRCONHCHR'COOMe
1N NaOH

OHC-HNCHRCONHCHR'COO

2
R

CPh2Cl + HO(CH2)10OH

CPh2O(CH2)10OSO2CH3

HCl
H2O

OHC

CH2OCH2CH(CH2OH)OH

CHO

O
O

CH3SO2Cl
Py

CPh2O(CH2)10 C CC2H5

CPh2OH + HO(CH2)10 C CC2H5

LiC CC2H5

CPh2O(CH2)10OH

CH2OCH2CH(CH2OH)OH

OHC

CHO

CH2P+Ph3BrO
, n-C4H9Li,
O
+
H

9. 3. 2

Combinatorial Chemistry

building
blocks,

A + B

AB

A1

B1

A2

B2

A3

B3

A4

B4

An

Bn

A1~nB1~n

CH3CH2CH2COOH

CH3OH
CH3CH2OH
CH3CH2CH2OH
CH3CH2CH2CH2OH

CH3CH2CH2COOCH3
CH3CH2CH2COOCH2CH3
CH3CH2CH2COOCH2CH2CH3
CH3CH2CH2COOCH2CH2CH2CH3

R1
R2
S

R3
R4

SR1
SR2
SR3
SR4

9.4
9. 4. 1

R CH2NO2 +

Al2O3

R2

CHO

R2

NO2
CH C R1
O
70%~93%

Al2O3

9.4.2
(ultrasound, US)
16KHz5MHz500MHz
20KHz10MHz

Ba(OH)2,EtOH
CHO
PhCH2OH + PhCOOH
U.S.
O 2N
I
NO2

Cu,DMF
60,U.S.,15min

NO2
70%

9. 4. 3

AlCl3AlCl3

BF4-PF6-OTf(CF3SO3)NTf2-[N(CF3SO2)2-]CP3COO-CTf3[C(CF3SO2)3]
-C H COO-PO -
3 7
4
F
F B F
F

F
F
F
P
F
F
F

F O
F C S OF O

BF4-

PF6-

CF3SO3-

F
F

O
C

S
F

N
OO

O
S

N(CF3SO2)2

2.
*
*
*
*
*
*

Me N

n-BuCl

Me N
Cl

X
N R

MW
RX

KPF6
N Bu-n
HPF6/NaOH

Me N

N Bu-n
BF6

MW
X-R-X

4
X
R1

HN

[bmim]PF6

R2

R2
O

R1

R : NO2, CN

R : NO2, F,

X: F, Cl, Br

Y: N, O

O
,

O, MeC(CO2Et)2

X
N

- - Eudesmol
Me
Me OH

Me
Me OH

Me
Me OH

Me
Me O

H
OH

COOEt

Me
Me OH

Br

O
O


O EtONa

NaBH4

BzCl
O

OBz

1) Mg
2) CO2

PBr3

3 CH N
Br ) 2 2

OH
1) BH3/THF
2) H2O2, OHMe 3) CrO3
Me OH

COOMe

1) MeMgI
2)H3O+

Ph3=CH2Br

Me
Me OH

Me
Me OH


(Artemisinin)

C15H22O5 ,282.3,
156158
[]=+66.3()

C
DP388

ene