S y n t h e t i c S t u d i e s o n O p t i c a l l y A c t i v e G i b b e r e l l i n A3, D i s c o v e r y a n d A p p l i c a t i o n o f C h r o m i c A c i d C a t a l y z e d O x i d a t i v e R e a r r a n g e m e n t o f T e r t i a r y A l l y l

(1)

A3 , . .

S y n t h e t i c S t u d i e s o n O p t i c a l l y A c t i v e G i b b e r e l l i n A3, D i s c o v e r y a n d A p p l i c a t i o n o f C h r o m i c A c i d C a t a l y z e d

O x i d a t i v e R e a r r a n g e m e n t o f T e r t i a r y A l l y l i c A l c o h o l s

2 4

( M a t s u n a g a , K a z u m a )

(2)

A₃ C D 1 6

. . 1 9

8 , C D

8 2 8

C D 3 1

G A3

6 3 4

3 8

S m I2 A B C 4 5

γ- C D 4 9

5 5 6 3 6 4 1 6 2

(3)

A c a c e t y l

A n a l . e l e m e n t a l a n a l y s i s

A Z A D O 2 - A z a a d a m a n t a n e N- o x y l

B n b e n z y l

B u b u t y l

c o n c . c o n c e n t r a t i o n

D B U 1 , 8 - d i a z a b i c y c l o [ 5 . 4 . 0 ] u n d e c - 7 - e n e

D I B A L d i i s o b u t y l a l u m i n u m h y d r i d e

D M A P d i m e t h y l a m i n o p y r i d i n e

D M F N,N- d i m e t h y l f o r m a m i d e

D M P D e s s - M a r t i n p e r i o d i n a n e

D M S O d i m e t h y l s u l f o x i d e

d r d i a s t e r e o m e r i c r a t i o

e e e n a n t i o m e r i c e x c e s s

E I e l e c t r o n i o n i z a t i o n

e q u i v e q u i v a l e n t

E t e t h y l

F A B f a s t a t o m b o m b a r d m e n t

H M P A h e x a m e t h y l p h o s p h o r a m i d e

H R h i g h r e s o l u t i o n

i- i s o-

I B X 2 - i o d o x y b e n z o i c a c i d

(4)

L D A l i t h i u m d i i s o p r o p y l a m i d e

L H M D S l i t h i u m b i s( t r i m e t h y l s i l y l ) a m i d e

M e m e t h y l

M O M m e t h o x y m e t h y l

M E M 2 - m e t h o x y e t h o x y m e t h y l

M s m e t h a n e s u l f o n y l

M S m a s s s p e c t r u m

M S m o l e c u l a r s i e v e s

m / z m a s s - t o - c h a r g e r a t i o

N M R n u c l e a r m a g n e t i c r e s o n a n c e

N O E n u c l e a r O v e r h a u s e r e f f e c t

N O E S Y N O E c o r r e l a t e d s p e c t r o s c o p y

o x . o x i d a t i o n

p- p a r a-

P C C p y r i d i n i u m c h l o r o c h r o m a t e

P D C p y r i d i n i u m d i c h r o m a t e

P h p h e n y l

P M B p- m e t h o x y b e n z y l

P M P p- m e t h o x y p h e n y l

P P T S p y r i d i n i u m p- t o l u e n e s u l f o n a t e

P r p r o p y l

P y p y r i d i n e

r t r o o m t e m p a r a t u r e

S E M 2 - ( t r i m e t h y l s i l y l ) e t h o x y m e t h y l

(5)

S M s t a r t i n g m a t e r i a l

t- t e r t i a r y

T B A B t e t r a -n- b u t y l a m m o n i u m b r o m i d e

T B A F t e t r a -n- b u t y l a m m o n i u m f l u o r i d e

T B S t- b u t y l d i m e t h y l s i l y l

t e m p . t e m p e r a t u r e

T E M P O 2 , 2 , 6 , 6 - t e t r a m e t h y l p i p e r i d i n e 1 - o x y l

T F A t r i f l u o r o a c e t i c a c i d

T H F t e t r a h y d r o f u r a n

T H P t e t r a h y d r o p y r a n

T L C t h i n l a y e r c h r o m a t o g r a p h y

T M S t r i m e t h y l s i l y l

T s t o l u e n e s u l f o n y l

(6)

( g i b b e r e l l i n s , G A s ) ,

, , ,

. .

, . . 1 8 9 8 ,

, ,

.^{1 )}1 9 2 6 , .^{2 )}

1 9 3 5 , G i b b e r e l l a f u j i k u r o i

,

( g i b b e r e l l i n , ) . 1 9 3 8 ,

, A . 1 9 5 4 , C u r t i s

G i b b e r e l l a f u j i k u r o i , ,

( g i b b e r e l l i n a c i d ) . 1 9 5 5 , A

, ,

A1, A2, A3 ( G A1, G A2, G A3) ,

A₃ ( F i g u r e

1 ) .^{3 )} G A3 , 1 9 5 9 , C r o s s G A3

,^{4 )} 1 9 6 2 , M c C a p r a X .^{5 )}

, , 1 3 0

CO₂H H

H O

HO

OC OH

CO₂H H

H O

HO

OC OH

gibberellin A₃ (GA₃) gibberellin A₁ (GA₁) Figure 1

1

3 6

9 15 7 10 8

11 19

16 18 17

13

(7)

. , 2 0 0 8 ,

G I D 1 .^{6 )}

,

C1 9 C2 0 , 6 , 5 , 6

5

. , ,

( I P P ) , ( G G P P )

, ,

W a g n e r - M e e r w e i n , 6 , 6 , 6 , 5 e n t-

HO₂C

CHO H

HO2C H

ent-kaur-16-ene

GA₁₂-aldehyde IPP

Scheme 1

CO2H H

H O

HO OC

GA₄

GA₁

GA₃ GGPP

OPP

H H⁺

H H

OPP

H H

H H OH

H H H HO2C

O H

H

H H

H H H

CO₂H H

HO2C H CHO

CO2H H

H O

OC OH

GA₂₀ GA₁₉

CO2H H

H O

OC OH

GA₅

PPO H

CO2H H

H O OC

GA₉

H

OH

ent-7α-hydroxykaur -16-en-19-oic acid

Fe⁴⁺ O Enz

CO2H H

H O

OC OH

HO

CO2H H

H O

OC OH

HO

(8)

, A1 2- .

C2 0 , C1 9 2 0

, ,

. , A_{1 2}- ,

, . . ( S c h e m e 1 ) .^{7 a )} ,

, G A .^{7 b )}

,

G A3 ., , 1 , 3 1 3

, γ- , .

, ,

4 .

(9)

1 , C o r e y ^{8 )}

G A3 C o r e y ( S c h e m e 2 ) .

V I I I ( ± ) -I X D i e l s - A l d e r

. , 2 A

, 4 , 5 A B , γ-

1 1 0 A

2 3 . I X

, ( + ) -I X .

( + ) -I X G A3 ,, ( + ) -I X G A3 , ,^{9 )}

, .

BnO O

O OMe

O

O OMe HO

H

OBn OH

Δ, benezene O

THPO H

CHO

THPO H

K, TiCl₃

OH OH OHC

OHC

THPO H

O OMEM

HO H

OMEM

O H

OMEM

O Cl

1) 160ºC epoxypropane benzene 2) LiN(i-Pr)C₆H₁₁ then MeI 3) ZnBr₂

(+)-GA₃

O H

OH

O H

(±)-IX (+)-IX optical resolution

Scheme 2 (Corey's Route)

I III

IV

V VI

VII

VIII

II

D 1) (PhCH₂)₂N⁺H₂•TFA^-

2) Ph₃P=CH₂, HMPA 3) AcOH

C

B

8 steps

4 steps

Cl COCl

8 steps 1 10

4

3 5

CO2H H

H O

OC OH

HO n-BuLi

(10)

I I I) , (I V V) , 6 5

(V V I V I I) . ,

, , .

S c h e m e 3 .^{1 0 )} X 2 -

D i e l s - A l d e r . X I , o x y - C o p e

B C . D

B u2C u L i .

Br

CO₂Me

OTMS

Br

H

BrOTMS CO₂Me

H

O BrO

Δ, benezene 1,2-epoxypropane CO₂Me

COMe , BF³·Et₂O 1)

2) Me₃SiOSO₂CF₃

H

O OH

Bu₂CuLi

X XI XII

XIII XIV

H

O OMEM

HO EtO

XV Scheme 3

5 steps

3 steps

2 steps

HO H

OMEM

VII

(11)

, C o r e y X I V , S t o r k

( S c h e m e 4 ) .^{1 1 )} 3 ,

C , 8

.

O

O O

O BrCN

O

O O

O CN

O O

H

O O O O

O O O

O O

OMe O

O OEt

H O

O O

O

H KHMDS

O O

1) NaOMe 2) NaCl wet DMSO

1) K, NH₃ (NH₄)₂SO₄ 2) AcOH H₂O

XVI XVII XVIII

XIX XX XXI XXV

XXII XXIII XXIV

1) C6H11NH2

Br OMe

KOH 2) LDA; EtOH

3) H₃O⁺

Scheme 4

H

O OH

XIV

8

(12)

M a n d e r , D (X X V I X X V I I) , W o l f f

B (X X V I I I X X I X) , M i c h a e l γ-

(X X X X X X I) , A

(X X X I I X X X I I I) ( S c h e m e 5 ) .

X X X I I I ( ± ) - X X X I V , G A₃ ,

( + ) - X X X I V . ( + ) - X X X I V 9 G A3

.

OMe O

N₂

OCOCCl₃

O

OCOCCl₃ O TFA

CO2Me

OH

O O EtOCO H

CO2Me

OH

O O O

OC

H

KH, DMF

CO₂Me

OH

O O O

OC

H

H O

CO₂Me

OH

O O O

OC

H

HO H

CO₂Me

OH

O O O

OC

H

(±)-XXXIV (+)-XXXIV optical resolution

CO2Me

OH

O O C

D

B

XXVI XXVII XXVIII

XXX XXXI

XXXII

1) Na₂CO₃ aq 2) (CH₂OH)₂, H⁺ 3) K-Selectride 4) i-Pr₃PhSO₂N₃

α : β = 1 : 1

XXXIII Scheme 5 (Mander's Route)

O

OH

O N₂ O

1) disiamylborane;

H₂O₂, Na₂HPO₄ 2) CrO3•2Py

1) PhSO₂Cl, Py 2) DBU, DMF Bu₃N⁺Br^-

9 steps 6 steps

K₂CO₃ MeOH

hν;

CH₂N₂

XXIX

(+)-GA₃

CO₂H H

H O

OC OH

HO

(13)

3 , , ^{1 3 )}

, , C , A

, B , D ( S c h e m e 6 ) . , D i e l s - A l d e r

A (X X X V X X X V I I) , F r i e d e l - C r a f t s B

(X X X V I I I X X X X I) , 8

(X L X L I) , ,

X L I I I G A3 .

OMe CN

CN CO2Et

OMe CN

CN EtO₂C

OMe O

O

OMe AlCl3

CH₂OMOM O SEMO H H

O SEMO H H

OMOM

• hν

1) O3, NaHCO3, MeOH then Me2S 2) K, NH₃, (NH₄)₂SO₄

SEMO H H

OH OH

XXXV

XXXVI

XXXVII XXXVIII

XXXXI XL

XLI

XLII

1) KOH

CO₂H H

OMOM

XLIII

OMOM

Scheme 6 (Nagaoka's Route)

MOMH₂C H

MOMH₂C HO₂C

MOMH2C H HO₂C H

H H

14 steps

15 steps 6 steps

2) Ac₂O

(±)-GA₃

CO₂H H

H O

OC OH

HO

(14)

D e C l e r c q ,

( S c h e m e 7 ) . , α,β- X L I V

M i c h a e l , 2 , 3 -

X L V , C o r e y D ( S c h e m e 7 ) .

X L V I X L V I I , D i e l s - A l d e r

, X L V I I I

, B W o l f f

. L I , G A3 ,

( + ) - L I 5 G A3 .

O MeO₂C

Br O

H

MeO₂C O

H

OH

OH OTBS H

O MeO₂C O

CO₂Me OH

OTBS

H H₂O, 65ºC

β-cyclodextrin

CO₂Et H

TBSO OTBS

MeO₂C

O OTBS

TBSO

H

N₂ CO₂Me

hν; CH3CHN2

MeO₂C OMe

O MgI then BrCH₂CBr=CH₂

HMPA

CO₂Et H

TBSO OTBS

MeO₂C

XLIV

H

XLV XLVI

XLVII XLVIII

L LI

XLIX

(n-Bu)₂CuLi

Scheme 7 ( De Clercq's Route)

4 steps

7 steps

RhCl₃ MeOH

5 steps

(+)-LI (+)-GA₃

(+)-GA₃

CO2H H

H O

OC OH

HO

(15)

, , , (Z) -α,β-

1 S m I2 , , D i e c k m a n n

, , γ- C1 9

A B 2 ,

( S c h e m e 8 ) .^{1 5 )}

MeO₂C

CO₂Me

O OMe

OSmI₂

I₂Sm

H

O H O OC

MeO O

O H

OSmI₂

O OR Dieckmann

condensation

reductive cyclization lactonization

SmI₂ THF

1 2

i ii

Scheme 8

O

, ( ± ) - G A1

.^{1 6 )} S c h e m e 9 . 1 0 1 1 S m I₂

. 9 , 3 4

, 5 ,

8 , S m I2 H M P A

.

(16)

O OMe

4 steps OMOM

H

OSEM

O H

OC O

OMOM H

MeO2C OSEM

MeO2C H TBSO

O O

O

9 steps

MeO₂C O TBSO

OH O

O H H

TBSO

O O

O

TMS

(±)-GA₁

H TBSO

OMe O

O

H TBSO

O O

O

TMS TMS

• hν

3 5 6

7 8

9

11

CHO O

1) LDA, O 2) TBSCl

SmI2

THF

MgBr

1) O3, MeOH 2) TBAF SmI₂

MeO₂C

then PPTS, H₂O

10

4

HMPA

CO₂H H

H O

OC OH

HO

G A3 .

G A3 G A1 A ,

, A . , G A₃

G A1 . , G A1

α,β- 1 2 3

( S c h e m e 1 0 ) .

GA₁

CO₂H H

H O

O

OC OH

1

3 reduction

CO₂H H

H O

HO

OC OH

Scheme 10

12 GA₃

(17)

, 1 2 1 3 1 4

, , S m I2

G A3 , ( F i g u r e 2 ) .

OMOM H

MeO₂C OSEM MeO₂C

O X

OMOM H

MeO₂C OSEM MeO₂C

O X

Figure 2

14 13

1 2

, S c h e m e 1 1 1 3

2 5 , 9 , , C D

2 4 . , G A₃

9 , D-

1 5 1 6 L-

. - 1 8

, P D C 2 0 , 8

2 1 .

, ,

, S m I2 C D .

(18)

TBSO H

O O

O

TBSO H

O O O

• hν (Pyrex^®)

α : β

= 13 : 1 80%

21

t-BuO₂C t-BuO₂C

TBSO H

O O O

18

t-BuOAc, LHMDS CeCl3, THF, -78ºC

20

O

CHO O O

HO O O

O H R S

15 17

L-proline (30 mol%) H₂O (5.0 equiv) DMSO, rt, 72 h 63%

(2.0 equiv)

9

75% (3 steps) 1) TBSCl, imidazole DMF, 0ºC to rt, 16 h 2) LDA, TMSCl, THF, -78ºC 3) Pd(OAc)2, O2, DMSO, rt, 48 h

dr. 10 : 1

OMOM H

MeO2C OSEM MeO2C

O OR'

SmI₂ OMOM

H

OSEM

O H

OC OR'O

(+)-GA₃

1

26 25

9 8

TBSO H

O O O

1) LiAlH₄, THF, reflux, 3 h 2) DMP, CH₂Cl₂, rt, 30 min

3) PPh₃, CBr₄, NEt₃, CH₂Cl₂, 0ºC, 10 min 4) BuLi, THF, -78°C, 1 h

44% (4 steps)

22 23

O H

O O

O

O MeOH

-70ºC, 6 h

24

O H O O

O OH

1) O₃, NaHCO₃ MeOH, -78°C

32% (2 steps)

SmI₂, HMPA

88%

16

2) TBAF, THF

rt, 30 min t-BuOH, THF

rt, 20 min PDC (2.0 epuiv)

MS4A

90%

CH2Cl2

rt, 20 h

TBSO H O O

19

OH t-BuO₂C 40%

, α

( S c h e m e 1 2 ) .

(19)

O

OTBS

H O OC

MeO₂C 1) SmI₂, THF

rt, 10 min 2) p-TsOH CH₂Cl₂ rt, 30 min

O

OTBSOH

CO₂Et H

+

α : β = 1 : 1

58% 39%

O EtO₂C

EtO₂C

OTBS

6 steps

27 28 29 30

Scheme 12

, 1

, ( S c h e m e 1 3 ) .

H

CO₂MOM O

MOMO OMOM OC

H OH

O

1) MsCl, Et₃N toluene rt, 30 min 2) DBU, toluene 85°C, 7 h

H

CO₂MOM O

MOMO OMOM OC

H O

21% (2 steps)

31 32

4 steps

GA₃ Scheme 13

1

, S c h e m e 1 1 2 4 , 2 5

, G A3 . , .

, . L-

, .

, . . C D ,

t- . ,

, .

, , t-

, [ 3 . 2 . 1 ]

, , ,

( S c h e m e 1 4 ) .

(20)

35

O H O O

O O OH

34

O H O O

O

CO₂t-Bu O

24

O H O O

O OH Ph₃P CH₂ O₃, NaHCO₃

MeOH, -78°C

TBSO H

O O

O

MeO₂C

CO₂t-Bu

33

SmI₂, HMPA t-BuOH, THF, rt

57%

TBAF, THF rt, 14 h 63%

TBSO H

O O

O

t-BuO₂C

21

, , . G A₃

.

, , , L-

, ,

. ,

C D , , γ- A B C D

.

(21)

A3 C D

3 4 t-

C D , t-

, 4 0

, S c h e m e 1 5 . ,

1 0 T B S , .

, T M S .

8

O H O O

OH O

H O O

TMSO H

O O

O

EtO2C

TMSO H

O O

O

EtO2C

37 38

8

Scheme 15

O H O O

OH

• hν

SmI2 Ph3P CH2

O

CHO O O

HO O O

O H R S

15 17

L-proline (30 mol%) H2O (5.0 equiv) DMSO, rt, 72 h

63%

(2.0 equiv)

9

dr. 10 : 1 36

1) TMSCl

TMSO H O O

EtO2C OH 2) Saegusa-Ito ox.

3) AcOEt, LDA

PDC

8

16

TMSO H

O O

O

EtO2C

39

8 O3, EtOH

then Ph3P CO2Et

TBAF

10

(22)

, 8

3 9 , α

, C D β

.

, 1 5 1 7

( T a b l e 1 ) . , 1 6

2 . 0 , 5 . 0 , D M S O ( 1 5 : 0 . 5 M ) ,

7 2 , 6 3 % , 1 0 : 1

1 7 ( e n t r y 1 ) . , ,

, , ( e n t r i e s 2 - 5 ) ,

Table 1

O

CHO O O

HO O O

O H R S

15 17

L-proline (30 mol%) H2O (5.0 equiv)

solvent

9

DMSO (0.5) rt

entry 16 (equiv) solvent (M)^a temp. time dr^b yield^c (%)

2.0 5.0 10 20 50 20 50 20

72 h 40 h 24 h 10 h 6 h 13 h 10 h DMSO (0.5)

DMSO (0.5) DMSO (0.5) DMSO (0.5)

- -

10 : 1 14 : 1 9 : 1

>20 : 1

85%

88%

91%

92%

97%

>20 : 1

63%

18 : 1 rt

rt rt rt rt rt

- 0ºC 30 h >20 : 1 64%

ee = >99%

1 2 3

5 4

7 6

8

16

a The ratio of 17 to the other diastereomers. The ratio was determined by ¹H-NMR.

b A concentration of 15 in DMSO

c Isolated yield.

(23)

5 0 , 1 7

( e n t r y 5 ) . , D M S O ,

, 9 7 %

( e n t r y 7 ) .

, 1 5 1 7 ,

, , 1 7 3 7

( S c h e m e 1 6 ) . 1 7 T M S ,

- 4 2 ,

3 6 . 3 6

, P D C 2 . 0 ,

3 7 , , 3 8 % . .

. , ( 1 : 1 ) , P D C 3 . 0

, 6 7 % ,

. ,

, .

HO O O

O H

17

TMSO H

O O O

TMSCl, Et₃N, DMAP THF, 0°C to rt, 1 h

AcOEt, LDA THF -78°C, 15 min

42

1) LDA, TMSCl THF, -78°C

PDC (2.0 equiv), MS4A CH₂Cl₂, rt, 3 h

TMSO H

O O

O

EtO₂C

TMSO H

O O O

80% (2 steps) 2) Pd(OAc)₂, O₂ DMSO, rt, 48 h

41 Scheme 16

TMSO H O O

EtO2C

90%

38%

or

PDC (3.0 equiv), MS4A

(24)

, ( S c h e m e 1 7 ) .

, i ,

i i . , i i

, . i i i

i v , .

, P D C , P C C , ,

, ,

. , ,

2 ~ 3 .

O O Cr X

O

X = Cl or OCrO₃H

R OH R O

R O

Cr O HO O

R O

Cr O HO O HO Cr OH

O PDC or PCC

i

ii iii

iv

H X

Scheme 17

,

( S c h e m e 1 8 ) . , I B X ( a )^{1 8 )}

T E M P O⁺X^- ( b )^{1 9 )} . T E M P O

, L e w i s ( c - e )2 0 - 2 3 )

(25)

, , I B S ( f )^{2 4 )} , P t b l a c k

( g )^{2 5 )} . , 3 6

, ,

.

Bu OH Bu O

43a 43b

a) IBX (2 equiv), pyridine (2 equiv), DMSO (0.2 M*), 55°C, 3.5 h, 80%.

b) TEMPO⁺BF₄^- (1.5 equiv), MeCN (0.2 M*), rt, 0.1 h, 94%.

c) TEMPO (0.01 equiv), NaIO₄ -SiO₂ (2 equiv), CH₂Cl₂ (0.15 M*), rt, 2 h, 92%.

d) TEMPO (0.1 equiv), PhIO (1.2 equiv), Bi(OTf)3 (0.08 equiv), MS4A, CH2Cl2 (0.2 M*), 0°C, 0.5 h, 84%.

e) TEMPO (0.1 equiv), CuCl2•2H2O (0.5 equiv), MS4A, O2, MeCN (0.2 M*), rt, 7 h, 90%.

f) IBS (0.05 equiv), Oxone (1 equiv), Bu₄NHSO₄ (0.01 equiv), K₂CO₃ (0.5 equiv), Na₂SO₄, AcOEt (0.2 M*), 60°C, 3 h, 84%.

g) Pt black (0.01 equiv), H₂O₂ (3 equiv), H₂O (1.0 M*), 90ºC, 3 h, 85%.

Scheme 18

* Concentration of 43a

, ,

, ,2 6 - 3 2 )

.

, 1 - - 2 - (4 3 a) , 0 . 0 1

P D C 3 . 0 P h I ( O A c )2 ,

(4 3 a : 0 . 2 M ) , ( T a b l e 2 ,

e n t r y 1 ) . , ( 2 4 ) ,

,, 3 - - 2 - (4 3 b) 8 4 %

, .

, 1 . 5 , 1

(26)

P h I ( O A c )2, (4 3 a : 0 . 5 M ) ,

, 9 4 % . ,

., . P h I ( O A c )2

, , ,

. 1 ,

, . P h I ( O A c )2 ,

P D C ,

, . . ,

, , ,

1 , 9 6 %

, . ,

Bu OH Bu O

PDC (cat.), PhI(OAc)₂ additive, CH₂Cl₂, rt

PDC (equiv)

PhI(OAc)₂ (equiv)

ambient gas conc.^a

(M) time

(h) yield^b (%) entry

1 2 3

5

7

43a 43b

6

additive (equiv)

8

0.01 3.0 0.2 24 84

0.01 3.0 0.2 1.5 88^c

0.01 3.0 0.2 1 88^c

Air O₂ 0.05

Ar

1.5 O₂ 0.5 0.25 94^d

0.05 1.5 O₂ 0.5 0.25 96

0.05 1.5 O₂ 0.5 0.25 86

- - -

- H₂O (1.0)

2.0 - 0.2 3 91

- 1.5 0.2 5 0^e

Air Air -

- 4

H₂O (1.0) MgSO₄ (1.0)

a Concentration of 43a. ^b Isolated yield.

c A small amount of 1a was recovered.

d Low reproducibility. ^e No reaction.

Table 2

(27)

, 7 ,

, . .

.

, P D C C r O3 ,

C r O₂ ,

( T a b l e 3 ) . , 4 3 a 0 . 1

C r O2 0 . 1 , 1 . 5 P h I ( O A c )2, (4 3 a

: 0 . 5 M ) , , , P D C

( e n t r y 1 ) . , 2 , 6 - , D M A P , N a H C O3, M S 4 A

( e n t r i e s 4 - 8 ) . P h I ( O A c )₂

Table 3

CrO₂, base oxidant (1.5 equiv) CH₂Cl₂ (0.5 M^a), O₂, rt

base (equiv) yield^b

(%)

- 0^c

pyridine (0.1) 94

2,6-lutidine (0.1) 0^c

DMAP (0.1) 0^c

0^c entry

3 4 5 6 7

MS4A 0^c

8

oxidant

PhI(OAc)₂ PhI(OAc)₂

time (h)

1 0.5

1 1 1

1 1 PhI(OAc)₂

NaHCO₃ (0.1)

PhI(OAc)₂

pyridine (0.1) 0^c

9 PhIO

Bu OH Bu O

43a 43b

2

- 1

1

10 NaIO₄

CrO₂ (equiv)

0.1 0.1

0.1 0.1 0.1 0.1 0.1 2.0

0.1

- 0^c

1

- 1

2.0

15

pyridine (0.1) 90

11 0.1 IBX

(28)

, I B X , 4 3 b 9 0 % ( e n t r y 1 1 ) .

T a b l e 2 , 3 , P D C C r O2 ,

P h I ( O A c )₂ ,

,

( T a b l e 4 ) . , , P D C

T a b l e 2 e n t r y 6 . , e n t r i e s 2 - 5

4 4 a-4 7 a . , T B S , M O M ,

, ., ,

4 4 b-4 7 b ( e n t r i e s 2 - 5 ) .

4 8 a 4 9 a

, 4 8 a ,

( 0 . 2 M ) , P h I ( O A c )2 3 . 0 , ,

4 8 b 8 4 % , ( e n t r y 6 ) .

4 9 a , ( 0 . 1 M ) , P h I ( O A c )₂ 3 . 0

, 4 9 b 6 9 % ( e n t r y 7 ) . 4

5 0 a . , 5 0 b ,

2 5 1 a ,

5 1 b ( e n t r i e s 8 a n d 9 ) . , 6

, ,

, 7 5 3 a 8 5 4 a, 5 5 a ,

, 5 5 2 a , 5 2 b

( e n t r i e s 1 0 - 1 3 ) .

(29)

Ph OH Ph O 1.5 84^c

OH O

EtO2C EtO2C 24 69^d

Bu OH Bu O 0.25 96

AcO OH AcO O

MOMO OH MOMO O

BnO OH BnO O

81 1

77 1

86 1

substrate product yield^b

(%) time

entry (h)

1

2

3

4

5

6

48a 48b

44a 44b

45a 45b

46a 46b

47a 47b

PDC (0.05 equiv), PhI(OAc)₂ (1.5 equiv) MgSO₄ (1.0 equiv), H₂O (1.0 equiv)

CH₂Cl₂ (0.5 M^a), O₂, rt R' R"

R OH

R' R"

R O

41 0.5

51 3

7

49a 49b

Bu OH Bu O

90 0.5

1 4

TBSO OH TBSO O 1 87

43a 43b

Table 4

a Concentration of substate. ^b Isolated yield.

8

50a 50b