Alkylation by Asymmetric Phase-TransferCatalysis张文全

Keiji Maruoka, Professor

Keiji Maruoka was born in 1953 in Mie, Japan. He graduated from Kyoto University (1976) and received his Ph.D. (1980) from University of Hawaii(Thesis Director: Prof. H. Yamamoto). He became an assistant professor of Nagoya University (1980) and was promoted to a lecturer (1985) and an associate professor (1990) there. He moved to Hokkaido University as a full professor (1995-2001), and he currently is a professor of chemistry in Kyoto University since 2000. (2007/2008). He is a board member of Chem. Commun. and is a member of the international advisory editorial board of Org. Biomol. Chem. And Chem. Asian J. His current research interests include bidentate Lewisacids in organic synthesis and practical asymmetric synthesis with chiral C2-symmetric phase-transfer catalysts and chiral bifunctional organocatalysts..

• Design of Chiral Phase Transfer Catalysts for Practical Amino Acid Synthesis

• Design of Chiral Organocatalysts for Practical Asymmetric Synthesis Bronsted Acid Catalysts

• Development of Bidentate Lewis Acid Chemistry and Application to Selective Organic Synthesis

Alkylation

Michael Addition

Aldol and Related Reactions

Darzens Reaction

Neber Rearrangement

Horner¨CWadsworth¨CEmmons Reaction

Cyclopropanation

Epoxidation

Aziridination

Oxidation

Reduction

FluorinationSulfenylationCyanation

phase transfer catalysts

Alkylation

NPh

Ph

O

OR PTC cat. (xmol%)

PTC condition NPh

Ph

O

OR

HR'

R'X

N

HO

N

Cl

NPh

Ph

O

OtBu

Cl

Br cat 10mol%

50% Aq. NaOHCH2Cl2, 25oC

NPh

Ph

O

OtBu

Cl64 ee%95 yield%

Pioneering work

O’Donnell J. Am. Chem. Soc. 1989, 111, 2353.

cinchoninium

N

O

N

Br

cinchonidinium

Corey, E. J J. Am. Chem. Soc. 1997, 119, 12414.

NPh

Ph

O

OtBucat 10mol%

CsOH H2OCH2Cl2low temperture

NPh

Ph

O

OtBu

RX

R

99 >ee%

Lygo, B. Tetrahedron Lett. 1997, 38, 8595.

N

HO

N

R condition: cat 10mol%, RT, toluene, KOH/NaOH

almost all of the elaborated chiral phase-transfer catalysts reported so far have been restricted to cinchona alkaloid derivatives, which unfortunately constitutes a major difficulty in rationally designing and fine-tuning catalysts to attain sufficient reactivity and selectivity for various chemical transformationsunder phase-transfer catalyzed conditions

Design new PTC catalyst which contain C2-Symmetry

N

Br

R

R

NAr

ArBr

NPh

Ph

O

OtBucat 1mol%, 0oC

toluene-50% aq KOHNPh

Ph

O

OtBu

RXHR

J. Am. Chem. Soc. 1999, 121, 6519.

N

Br

N

Br

Ph

PhPh

Ph

SYNLETT 2003, 12, 1931

N

Br

R

R

R2

R2

Angew. Chem. Int. Ed. 2002, 41, 1551

N

Ar

Ar

Ar'

Ar'

Ar

Ar

Ar'

Ar'

T. A. 2003, 14, 1599

N

(C8F17H2CH2C)Me2Si

(C8F17H2CH2C)Me2Si

SiMe2(CH2CH2C8F17)

SiMe2(CH2CH2C8F17)

(F17C8CH2CH2)Me2Si SiMe2(CH2CH2C8F17)

SiMe2(CH2CH2C8F17)(F17C8CH2CH2)Me2Si

O.L. 2004, 6, 1429

NN

NNnBrBr

Tetrahedron: Asymmetry 2004, 15, 1243

OMe

OMe

MeO

MeO

MeO

MeO

OMe

OMe

N+Bu

BuBr-

T.L. 2005, 46, 8555

NPh

Ph

O

OR cat. (xmol%)

toluene-base NPh

Ph

O

OR

HR'

R'X

R= tBu, Me, Et, etc.

R'= Bn, Alk, etc.

N

O

OtBu

Cl

T. A. 2006, 17, 603

classical reaction：

NPh

Ph

O

OtBuBr

cat. (xmol%)

toluene-base0oC

NPh

Ph

O

OtBu

HN

p

p

Adv. Synth. Catal. 2002, No. 3+4, 344,

NPh

Ph

O

OtBu 1)R1X,2)R2X 0.5M citric acidH2N

O

OtBu

CsOH H2O/toluene-10oC-0oC

THFR1 R2

R1X= Br

R2X= PhCH2Br

J. Am. Chem. Soc. 2000, 122, 5228.

Anaerobic Conditions is needed Synlett 2001, 7, 1185

61yield%, 87ee%80yield%, 98ee%

NPh

Ph

O

OtBu R1

OBn

Br Chiral PTC (1mol%)

toluene-50% KOH aq 0oC, 1-2h

1M citric acid

THF, r.t. 10h

H2NO

OtBu

R1

OBn

10%Pd/C, H2

THF, r.t %h

H2NO

OtBu

R1

OH

Facile synthesis of L-Dopa tert-butyl ester

Tetrahedron Lett. 2000, 41, 8339.

For two chiral binaphthyl catalysts are difficult for their fruitful modificationsThey design more flexible one.

NPh

Ph

O

OtBucat 1mol%, 0oC

toluene-50% aq KOHNPh

Ph

O

OtBu

RXHR

>90 yield%>90 ee%

N

Br

R

R

R2

R2

flexible

Angew. Chem. Int. Ed. 2002, 41, 1551

N

(C8F17H2CH2C)Me2Si

(C8F17H2CH2C)Me2Si

SiMe2(CH2CH2C8F17)

SiMe2(CH2CH2C8F17)

(F17C8CH2CH2)Me2Si SiMe2(CH2CH2C8F17)

SiMe2(CH2CH2C8F17)(F17C8CH2CH2)Me2Si

NPh

Ph

O

OtBucat 1mol%, 0oC

toluene-50% aq KOHNPh

Ph

O

OtBu

RXHR

O.L. 2004, 6, 1429

NPh

Ph

O

OtBu chiral PTCachiral PTC

toluene-50% aq KOH 0oC

NPh

Ph

O

OtBu

RXHR

Angew. Chem. Int. Ed. 2005, 44, 625

3,4,5_F3C6H2

3,4,5_F3C6H2

N+Bu

Bu

NPh

Ph

O

OtBucat xmol%, 0oC

toluene-50% aq KOHNPh

Ph

O

OtBu

RXHR

x=0.1-0.01mol%

Angew. Chem. Int. Ed. 2005, 44, 1549

81-98 yield%97-99 ee%

OMe

OMe

MeO

MeO

MeO

MeO

OMe

OMe

N+Bu

BuBr-

>90 yield%>95 ee%

T.L. 2005, 46, 8555

Chem. Asian J. 2008, 3, 1702

O

CO2tBu

cat(1mol%)PhCH2Br(1.2eq)

toluene-base

O

CO2tBu

N

Br

Ar

ArAr=

CF3

CF3

Angew. Chem. Int. Ed. 2003, 42, 3796

O

CO2tBu

O

CO2tBuO

CO2tBu

96 yield%85 ee%

88 yield%92 ee%

94 yield%97 ee%

90 yield%95 ee%

Other Alkylation

N

HN

O

O

OtBu

cat(2mol%)RX(1.1eq)

toluene/50% base aq.0oC

N

HN

O

O

OtBu

R

N

Br

Ar

Ar Ar=

But tBu

tBu

tBu

97 yield%97 ee%

Angew. Chem. Int. Ed. 2003, 5, 42

N

O

N

N

O

NH

N

O

N

R

OMe

PG

NH

PG

H2N

R1

O

R3H2N

R2

OH

R3H2N

R2

R4

J. AM. CHEM. SOC. 2005, 127, 5073

N

O

CO2tBu

Bocn

n=1,2

cat (1mol%)R1Br(1.2eq)

sat. K2CO3, o-xylene0oC

N

O

CO2tBu

Bocn

n=1,2

R1

84-99 yield%87-95 ee%

N

Ar

Ar

Br-Ar=

CF3

CF3

O.L. 2004, 7, 191

N

Ar

Ar

Br- Ar=

CF3

CF3

O

OO

R1 R2Brcat. (1mol%)

toluene, CsCO3

0oCO

OO

R1

R2

91 yield%91 ee%

Adv. Synth. Catal. 2006, 348, 1539

NO

O

O

Ar2 Ar1cat (1mol%)RBr (1.2eq)

25% KOH aq TBME-20oC-0oC

NO

O

O

Ar2 Ar1

R

70-87 yield%87-99 ee%

>90 ee%

Angew. Chem. Int. Ed. 2006, 45, 3839

Ph2CN CO2tBu

cat. (1mol%)

18-crown-6 (1mol%)toluene-KOH aq 0oC

R1 Br

Me kinetic resolution

R

fast

S

slow

R1 CO2tBu

Me

NCPh2

syn

R1 CO2tBu

Me

NCPh2

ant

N

Ar

Ar

Br-Ar=

F3C CF3

CF3

CF3

>95:5 syn/ant90 de%

O.L. 2007, 9, 3945

O

N CO2tBu

RXcat (1mol%)

CsOH, toluenelow temperture

O

N CO2tBu

R

3,5_F2C6H3

3,5_F2C6H3

N+Bu

Bu

T.L. 2008, 49, 5461

For pioneering work :Jew, S.-s. Org. Lett. 2005, 7, 1557. Angew. Chem., Int. Ed. 2004, 43, 2383

N

O

N

R

R1R2

R1

R2

CO2tBuR3Br

PTC (2mol%)

base, mesitylene -20oC

R1

R2

CO2tBuR3

R1= TMS, Ar, aliphatic, olefin

R2=Et, Me

R3=ArCH2OtBu

O

3,4,5_F2C6H3

3,4,5_F2C6H3

N+Bu

Bu

Angew. Chem. Int. Ed. 2009, 48, 5014

conclusion

• design new powerful PTC catalyst which contain C2-Symmetry which is different from the cinchona skeleton

• expand the application of the PTC in varieties of chemcal reaction

Thank you for your attention!