Çáè ³ãït É @» R S w C · NaN(SiMe3)2 18-crown-6, THF-80 ¡C, 20 min O TBSO O R OH N C O PhO2S H NO2 R SiMe3 SiMe2Ph SiMe2But i-Pr t-Bu 1 52 59 49 39 40!-Hydroxylation and

多元素含有多環縮合中員環形成反応の開発

SiR3

R

O

O

OM

+

OR3SiO

CO2Me

R CHO

SiR3

OOM

+

R3SiO

CO2Me

CHO

(X)n

(X)n

[3 + 4] アニュレーションによる含酸素八員環形成反応の開発

( )

( )

[3 + 4] Annulation Using the Reaction of Acryloylsilaneswith the Lithium Enolates of Alkenyl Methyl Ketones

O

TBSO R

XE

XZ

5

6

SiMe2But

X

O

O

O

R3Si

X

R

R3SiO

O

X

ROLi

R

XE

XZ R

OO

R3Si

O

TBSO

XE

XZ

R

(E,Z)

+

EZ

5,6-cis5,6-trans

anionic oxy-Coperearrangement

X = SiMe3, SnBun3, alkyl

H

Takeda, K.; Takeda, M.; Nakajima, A.; Yoshii, E. J. Am. Chem. Soc.1995, 117, 6400-6401.Takeda, K.; Nakajima, A.; Takeda, M.; Okamoto, Y.; Sato, T.; Yoshii, E.; Koizumi, T. J. Am. Chem. Soc. 1998, 120, 4947-4959.Takeda, K.; Nakajima, A.; Takeda, M.; Yoshii, E. Org. Synth. 1999, 76, 199-211.

O

TBSO

( )n

X

2

6

R3SiO

O

R'

R3SiO

R' Y

X

OLi

SiR3O

R'

OLi

8

O

X

SiR3

O

R3SiO

R'

+

Formation of Eight-Membered Carbocycles by [3 + 4] Annulation

TBSOO

R

R

OR'3Si OSiMe2But

O

R

OMTHF

R

SiMe3

SiMe2But

i-Pr

t-Bu

c-C6H11

R

HOR'3Si

O

H

LiO

TBSO

H

R

H

conditions

-80 °C, 30 min

-80 ° to 0 °C

-80 °C, 30 min

-80 ° to 0 °C

-80 ° to 0 °C

yield (%)

66

65

45

84

45

+

O

LDA orNaN(SiMe3)2

Synthesis of Eight-Membered Carbocycles by [3 + 4] Annulation

TBSOO

R

TBSOO

R

OHH

TBSO

OM

R

N

O

PhSO2 Ar

R

SiMe3

SiMe3

t-Bu

t-Bu

base

LDA

NaN(SiMe3)2LDA

NaN(SiMe3)2

Vedejs !

52

66

Davis !

76

71

base MoOPH

or

yield (%)

!-Hydroxylation of Bicyclo[2.2.2]decenones

TBSOO

R

TBSOOM

R

SiMe2But

O

R

NO

PhSO2 Ar

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

base

NaN(SiMe3)2

NaN(SiMe3)2

NaN(SiMe3)2

LDA

LDA

OM

O

NaN(SiMe3)2

+

yield (%)

48

72

58

50

62

THF

-80 °C to rt

base

OH

Tandem [3 + 4] Annulation /!-Hydroxylation

TBSOO

R

OH

TBSO

CO2Me

CHOR

3 4

8Pb(OAc)4

Benzene-MeOH0 °C

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

yield (%)

95

96

95

97

93

Oxidative Cleavage of !-Hydroxyketones

R3SiOO

R'

R3SiO

R' CHO

CO2Me

OLi

SiR3O

R'

OLi

8

(X)

(X)(X)

(X)

X = O, NR, SO

(X)

Formation of Eight-Membered Heterocycles by [3 + 4] Annulation

O

O

Cossy, J.; Taillier, C.; Bellosta, V. Tetrahedron Lett. 2002, 43, 7263-7266.

Preparation of 6-Oxa-2-cycloheptenone

PPh3Cl

O

aq HCHO

NaH, DMFrt, 1.5 h

Et2Ort, 10 min

71 % (2 steps)

Grubbs'cat.II (1.0 mol%)

CH2Cl2, reflux, 4 h

85 %

O

O

O

O

O

O

PPh3

HO

SiMe2But

O

RO

ONa OButMe2SiO

O

R

+

NaN(SiMe3)2-98 °C, 10 min

CPME

-98 ° to -70 °C

O

O

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

CPME: OCH3

conditions

-98 °C to -50 °C

-98 °C to -70 °C

-98 °C to -50 °C

-98 °C to rt

-98 °C to rt

yield (%)

75

69

72

65

57

Formation of Eight-Membered Heterocycles by [3 + 4] Annulation (I)

OTBSO

O

R

OH

OTBSO

O

R

NaN(SiMe3)2

18-crown-6THF

N CO

HPhO2S

THF-80 °C, 30 min

OTBSO

OM

R

NO2

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

yield (%)

56

86

76

66

86

!-Hydroxylation of 2-Oxabicyclo[2.2.2]decene Derivatives

OTBSO

O

R

OH

OTBSO

CO2Me

CHOR

3 4

8Pb(OAc)4

Benzene-MeOHrt

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

yield (%)

93

99

100

100

97

Oxidative Cleavage of !-Hydroxyketones

O

BrMg

CuI, THF-Et2O-80 ° to rt

HO

93%

Cl

O

PPh3

NaH, DMF, rt

aq HCHO

Et2O, rt CH2Cl2, !

60% (two steps)

O

O

O

O

PPh3

O

O

N N

Ru

MesMes

Cl

Cl

PCy3

Ph

60%

Synthesis of 2-Oxabicyclo[5.4.0]undec-5-en-4-one

OTBSO

O

R

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

O

NaO

SiMe2But

O

R

+

CPME

-98 °to -50 °C

yield (%)

89

85

82

70

83

[3 + 4] Annulation Using 2-Oxabicyclo[5.4.0]undec-5-en-4-one

OTBSO

O

R

NaN(SiMe3)218-crown-6, THF

-80 °C, 20 min

OTBSO

O

R

OH

N C

O

HPhO2S

NO2

R

SiMe3

SiMe2Ph

SiMe2But

i-Pr

t-Bu

1

52

59

49

39

40

!-Hydroxylation and Oxidative Cleavage of 2-Oxatricyclo-[7.3.2.03,8]tetradec-4-en-13-one derivative

Pb(OAc)4

Benzene-MeOHrt

OTBSO

R

CO2Me

CHO

1

2

2

93

100

83

80

99

yield (%)