Highly Selective Synthesis with Novel Metallic Reagents - American

7 Highly Selective Synthesis with Novel Metallic Reagents HITOSI NOZAKI, TAMEJIRO HIYAMA, KOICHIRO OSHIMA, and KAZUHIKO TAKAI

Downloaded by UNIV OF LEEDS on October 17, 2016 | http://pubs.acs.org Publication Date: April 28, 1982 | doi: 10.1021/bk-1982-0185.ch007

Kyoto University, Department of Industrial Chemistry, Kyoto, 606, Japan

Allylchromium reagents as produced from allylic bromides and Cr(II) salts in anhydrous THF or DMF react with carbonyl components to form homo allylic alcohols. The aldehyde adducts, RCH(OH) -CHMeCH=CH, are oxidized with various recently described reagents to produce epoxy alcohols with different ways of steric control.--Alkylation of cyclopropane derivatives with R Al proceeds from preliminary heterolysis in one case, whereas the reaction introduces alkyl carbanions with S 2like inversion in other cases.--Catalysis with Pd(O) makes possible the substitution of an -ΟΡΟ(OR) group on an sp carbon and finds a number of synthetic applications.--Finally, the aliphatic Claisen rearrangement is smoothly per formed at room temperature by means of R2AlX reagents (where X = R, H, or SPh etc.) involving "combined acid-base" attack. 2

3

N

2

2

T h i s paper w i l l d e a l with f o u r t o p i c s : t h e f i r s t one i s r e l a t e d t o allylchromium reagents, while the l a t t e r three r e f e r t o the behavior o f t r i a l k y l a l u m i n u m o r r e l a t e d species i n d i f f e r e n t s i t u a t i o n s . The authors' main concern here i s t o d e s c r i b e new reactions useful for selective synthesis. Allylchromium Reagents i n Homoallyl A l c o h o l Synthesis Organochromium compounds prepared from h a l i d e s and C r ( I I ) species i n anhydrous, a p r o t i c , p o l a r s o l v e n t s provide means o f s e l e c t i v e s y n t h e s i s as has been d e s c r i b e d p r e v i o u s l y U , 2 ) . In p a r t i c u l a r , the Grignard type carbonyl a d d i t i o n o f allylchromium reagents proceeds much more slowly and s e l e c t i v e l y than t h a t o f organomagnesium compounds. Scheme 1 i n d i c a t e s threo s e l e c t i v i t y i n the r e a c t i o n o f

0097-6156/82/0185-0099$05.00/0 © 1982 American Chemical Society

Eliel and Otsuka; Asymmetric Reactions and Processes in Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1982.

ASYMMETRIC

100

REACTIONS

AND

PROCESSES

IN

CHEMISTRY

Scheme 1 . RCHO + M e ^ ^ B r ι1 mol ™i mni 29 mol R

Solvent

Ph Downloaded by UNIV OF LEEDS on October 17, 2016 | http://pubs.acs.org Publication Date: April 28, 1982 | doi: 10.1021/bk-1982-0185.ch007

Ph

b

Ph

CrCl (4mol) LAH ( 2 m o l )

R Y

3

1

. V

I 0 H

3

Y i e l d (%)

L V

R +

V I 0 H

t h r e o (%) 0

THF

96

100

THF

87

100

0

92

75

25 7

DMF

D-Pr

THF

59

93

i-Pr

THF

55

95

5

i-Pr

DMF

78

66

34

û-Am

THF

70

97

3

η-Am

DMF

77

68

32

a

T h e r e a c t i o n was c a r r i e d o u t a t room temp f o r 2 h . The c i s - i s o m e r o f c r o t y l bromide was u s e d .

Scheme 2 P h

J L

^

Ph

OH

t-Bu00H/Al(0Bu-t) mCPBA

.

Y i e l d (%) 2

3

52

I

Ph

OH

Oxidant $-Bu00H/V0(acac)

I

.

OH Isomer R a t i o (%) 76 : 2 4

51

1 8 : 82

69

55 : 45


7.

NOZAKI

ET

AL.

Metallic

Reagents

101

c r o t y l bromide (3) as reported a l s o by Heathcock (4). Tetrahydrofuran (THF) as s o l v e n t gives higher s e l e c t i v i t i e s but somewhat poorer y i e l d s than dimethylformamide (DMF). Epoxidation o f the r e s u l t i n g h o m o a l l y l i c a l c o h o l s has been i n v e s t i g a t e d (Scheme 2 ) . The Sharpless and r e l a t e d epoxidation techniques (5_,6) provide a way to c o n t r o l the stereochemistry o f three neighboring carbons. The C r ( I I ) mediated r e a c t i o n has been extended f u r t h e r t o systems i n v o l v i n g aldehydes and 2,2-diiodopropane (with HI l o s s ) as w e l l as v i n y l i o d i d e s and bromides, a l l a f f o r d i n g a l l y l i c a l c o h o l s (7).


A l k y l a t i o n o f an sp3 Carbon with Trialkylaluminum The r e a c t i o n o f d i e t h y l geranyl phosphate with R3AI produces q u a n t i t a t i v e l y a mixture of geranyl-R and l i n a l y l - R products i n 9:1 r a t i o , while the corresponding n e r y l phosphate a f f o r d s 4-RCMe2~ s u b s t i t u t e d 1-methylcyclohexenes e x c l u s i v e l y (8). Evidence f o r the intermediacy o f a c a r b o c a t i o n species i n the r e l a t e d r e a c t i o n shown i n Scheme 3 i s d e r i v e d from the f a c t t h a t the o p t i c a l act i v i t y o f the s t a r t i n g acetate substrate i s completely l o s t i n the r i n g cleavage r e a c t i o n product (9,10). A p o s s i b l e e x p l a n a t i o n i s given i n Scheme 4. Throughout these and subsequent r e a c t i o n s we use no l e s s than a 2:1 mol r a t i o o f aluminum reagents which are mostly d i m e r i c . We p o s t u l a t e t h a t the l e a v i n g acetate group i s s u b s t a n t i a l l y reduced i n n u c l e o p h i l i c i t y by double complexation with R 3 A I , so t h a t the c a t i o n i c p a r t i s almost naked even i n the e a r l y i o n - p a i r stage. The cyclopropylmethyl c a t i o n i s isomerized to the more s t a b l e b e n z y l i c one which i s then slowly a l k y l a t e d by the complex anion p a r t . I t should be noted t h a t the a n i o n i c comp l e x , but not the Lewis a c i d i t s e l f , p a r t i c i p a t e s i n t h i s key step. Thus the R3AI reagent may be c a l l e d a "combined acid-base." In sharp c o n t r a s t , however, Scheme 5 gives an instance o f a methyl carbanion being introduced l a r g e l y i n an SN2-type i n v e r s i o n stereochemistry. Note t h a t the substrate c a r r i e s a cyclopropane carbon doubly a c t i v a t e d by 1,3-dicarbonyl groups. A p o s s i b l e exp l a n a t i o n i s given i n Scheme 6. The r e a c t i o n can be u t i l i z e d i n the s e l e c t i v e s y n t h e s i s o f dl-neonepetalactone and i t s epimer. The sequence i n v o l v e s (1) e n o l i z a t i o n (NaH) and p h o s p h o r y l a t i o n ( C l P O ( 0 E t ) ) , (2) methylation (Me2CuLi), (3) o z o n o l y s i s (MeOH, -78°) and r e d u c t i o n , and (4) the f i n a l l a c t o n i z a t i o n (PyH.OTs). 2

2 A l k y l a t i o n o f an sp

Carbon with the R3A1-Pd(0) System

The methylation [step (2)] i n the above sequence proceeds smoothly due to the presence o f an ethoxycarbonyl a c t i v a t i n g group. A new technique (11) i s based on the c a t a l y s i s by a Pd(0) complex and provides a methodology o f a l k y l s u b s t i t u t i o n o f an enol phosphate moiety i n the absence o f such an a c t i v a t i n g group. The r e s u l t s are given i n Table 1. As the e n o l i z a t i o n o f ketones can be performed regi©selectively, the technique f u r n i s h e s an approach t o r e g i o s e l e c t i v e o l e f i n formation from ketones.


ASYMMETRIC

REACTIONS

AND

PROCESSES

IN

CHEMISTRY


102

Scheme 6


NOZAKI


7.

ET

AL.

Metallic

103

Reagents

T a b l e 1. C o u p l i n g on an s p ^ C a r b o n Product Substrate

Reagent

Time ( h )

Y (%)

Me Al

2

91

Et Al

3

71

3

47

b

2

82

b

(Ej-l-heptenylAIBu ^

4

66

C

Me Al Et Al

2

94

d

2

80

3

67

5

72

6

70

Me(CH ) C(=CH )-0P0(0Ph) 2

a

9

2

2

3

3

Me(CH2)4C=CAlEt2 PhC=CAlEt 2

1

PhC(=CH )-0P0(0Ph) 2

2

3

3

PhC=CAlEt 4-t-Bu-l-cyclohexenyl< >2 0 P 0

a

Me;jAl PhC=CAlEt

0 P h

Pd(PPh ) 3

4

0.1/C1CH CH C1 a t 2 5 ° . 2

2

2

Enyne p r o d u c t e x c l u s i v e l y .

2

C

(E)-Diene G.l.p.c.

product yield.


b

b

only.

104

ASYMMETRIC

REACTIONS

A N D PROCESSES

IN

CHEMISTRY


2

In c o n t r a s t t o the analogous s p carbon a l k y l a t i o n procedures (12,13), the present method does not a f f e c t c o e x i s t i n g v i n y l s u l f i d e groups as shown i n Scheme 7 (14). T h i s r e a c t i o n p r o v i d e s ac cess t o ketones R'C^COR s t a r t i n g from R'O^COOH. Y i e l d s i n pa rentheses i n d i c a t e the formation o f e t h y l a t e d (R = Et) p l u s hydrogenated (R = H) products i n the r e a c t i o n o f E t 3 A l . In benzene s o l v e n t the r a t i o o f these two products i s roughly 2:1. In hexane the hydrogenated products are predominant. Scheme 8 shows the s y n t h e s i s o f 1 , 3 - d i a l k y l a t e d cyclohexenes from 2-cyclohexenones c o n s i s t i n g o f 1,4-addition o f organocuprates, enol phosphorylation, and the f i n a l a l k y l a t i o n o f the sp2 carbon. Scheme 9 provides a novel a d d i t i o n t o the technique o f 1 , 2 - t r a n s p o s i t i o n o f a carbonyl moiety accompanied by a l k y l a t i o n i n tandem (15) . The d e s u l f u r i z a t i o n i s best performed by Mukaiyama's T1CI4 method (16). Treatment o f an enone, PhCOCH=CHMe, with RSLi (R = Ph, Et) and subsequent phosphorylation with ClPO(OPh) give PhC[OPO(OPh)2]=CH-CHSR-Me. The phosphate group i s s u b s t i t u t e d by methyl by means o f the present technique t o produce PhCMe=CH-CHSR-Me, the transformation o f which i n t o PhCMe=CHCOMe i s known (17). In e f f e c t the sequence f u r n i s h e s a new route o f 1.3- carbonyl t r a n s p o s i t i o n cum a l k y l a t i o n . 2

A l i p h a t i c C l a i s e n Rearrangement a t Room Temperature Sigmatropic rearrangement o f a l l y l v i n y l ether substrates u s u a l l y r e q u i r e s heating a t around 200°. A l l y l phenyl ether rearranges a t room temperature i n the presence o f Lewis a c i d r e a gents, which have, however, turned out to be i n e f f e c t i v e with a l i p h a t i c e t h e r s . The concept o f "combined acid-base a t t a c k " pre v i o u s l y mentioned (18,19) has motivated s e v e r a l s u c c e s s f u l e x p e r i ments as shown i n Schemes 10 through 12 (20). A s o l u t i o n o f ΜββΑΐ i n hexane (1 M, 4.0 mmol) was added t o a s o l u t i o n o f l - b u t y l - 2 - p r o p e n y l v i n y l e t h e r (2.0 mmol, Scheme 10) i n 1,2-dichloroethane (15 ml) a t 25° under an A r atmosphere and the mixture was s t i r r e d f o r 15 min. Workup and TLC (S1O2) p u r i f i c a t i o n gave the o l e f i n i c a l c o h o l (0.28 g, 91% y i e l d ) , the E/Z r a t i o being almost 1:1. As shown i n Scheme 10 (b,c) an a l k y n y l o r a l k e n y l group i s introduced i n preference t o an a l k y l group. Examples o f r e d u c t i v e rearrangement are found i n Scheme 11. With exception o f a s i n g l e instance producing a 2-phenylethenyl system, the r e s u l t i n g o l e f i n i c l i n k a g e has shown p r a c t i c a l l y no s t e r e o s e l e c t i v i t y . The r e g u l a r C l a i s e n products, o r γ,6-unsaturated aldehydes, have been produced i n the r e a c t i o n with R2AlSPh as summarized i n Scheme 12. A combination o f a c i d (Et2AlCl) and base (PPh ) has turned out t o be e f f e c t i v e . I t i s i n t r i g u i n g t o note that the rearrangement o f 3.4- dihydro-2-vinyl-2H-pyran a f f o r d i n g 3-cyclonexenecarbaldenyde (60% y i e l d ) takes p l a c e i n the presence o f t h i s couple a t room temperature w i t h i n one hour. The p y r o l y t i c procedure without 3


7.

Metallic Reagents

NOZAKi E T A L .

105

Scheme 7 0P0(0Ph)

R

2

R'CH=C

>R'CH=C


N

N

SPh

SPh

R'

R

Ph

Me

1

64

Et

2

(55)

n-Pr

Time ( h ) Y (%)

Me

1

83

Et

2

(82)

PhC=C-

2

83

a

a

A mixture o f e t h y l a t i o n and hydrogénation product ( s e e t e x t ) .

Scheme 8 0 D

1. B u C u L i , 2

2. C l P 0 ( 0 P h ) 0P0(0Ph)

.à Q

Bu

2

à

^ Pd(PPh ) °Bu 82% 3

84%

2

2 5 0 j

3

4

h


106

ASYMMETRIC

REACTIONS

AND

PROCESSES

IN

CHEMISTRY

a) 1. LDA/PhSSPh ( Y 7 8 Î Î , 2. NaH, C l P 0 ( 0 P h ) ( Y 8 2 X ) . 2

b) M e A l , P d ( P P h ) Downloaded by UNIV OF LEEDS on October 17, 2016 | http://pubs.acs.org Publication Date: April 28, 1982 | doi: 10.1021/bk-1982-0185.ch007

3

3

4

(Y80X).

c) T i C l , aq, CH C1 4

2

(Y78X).

2

Scheme 10 . 0 ^

BiA ^

ί y

^0H ^ B i r

^ \ j f

-

m

4 7 / 5 3

Ph C H 6

c k

] 3

J

_

3

b) Et AlC=CPh ( Y 8 2 * ) . c ) ^ A l C H - C H C g H j - ( E ) 2

3

Scheme 11

Scheme 12

1

O^R

H0>

R '}

R

Bu

Η

Reagent A

R

38/62

Bu

Η

Β

81

43/57

Bu

Me

A

77

52/48

Ph H

Η Ph

A

67

100/0

A

86

AD

A

78

— —

40/60

°Bu

Me

A

89

45/55

D

Ph

Η

A

93

100/0

H

Ph

A

91

—

A

90

...

Β: B u A l H ( 2 . 5 ) . 2

Υ ( ί ) E/Z 39/61

80

]

Reagent

84

Β

(2.6).

R

A

Η

Ί

R 2

Η

Bu

Α : -Βιι,Α1

1

1

-Bu a

( ° Ό

U O / R

R

Y ( % ) E/Z 82

1

/O^R

J$

R 2

^ OH

a) M e A l ( Υ 9 Ί % ) .

D

^

OH OH

^

D

b

A: E t A l S P h ( 2 . 5 ) 2

B: E t A l C l (2) + P P h 2

3

(2.2).


7.

NOZAKi E T A L .

Metallic

Reagents

107

such a reagent r e q u i r e s h e a t i n g a t 410°. The Et2AlCl/PPh3 system can be compared with Mukaiyama's R2BOSO2CF3/NR'3 system (21) o r with T s u j i ' s R A10R /NR 3 system (22) . The p o s s i b i l i t y o f an Et2AlP Ph3 species being the a c t i v e reagent i n our r e a c t i o n w i l l be i n v e s t i g a t e d . ,

,,

2


+

Acknowledgments Thanks are given f o r h e l p f u l d i s c u s sions with P r o f . E . L. E l i e l on h i s occasion o f v i s i t i n g Japan i n 1978 as w e l l as f o r v a l u a b l e c o n t r i b u t i o n s by e n t h u s i a s t i c students o f t h i s research group, whose names are found i n the r e f e r e n c e s . F i n a n c i a l support by the M i n i s t r y o f Education, Sciences, and C u l t u r e , Japanese Government, through S c i e n t i f i c Research Grants (510202, 56430027 etc.) i s g r a t e f u l l y acknow ledged .

Literature Cited 1. Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3175. 2. Okude, Y.; Hiyama, T.; Nozaki, H. Tetrahedron Lett. 1977, 3829. 3. Hiyama, T.; Kimura, K.; Nozaki, H. ibid. 1981, 22, 1037. 4. Buse, C.T.; Heathcock, C. H. ibid. 1978, 1635. 5. Takai, K.; Oshima, K.; Nozaki, H. ibid. 1980, 21, 1657. 6. Tomioka, H.; Takai, K.; Oshima, K.; Nozaki, H. ibid. 1980, 21, 4843. 7. Hiyama, T.; Kimura, K.; Takai, K.; Nozaki, H. The 44th Fall Meeting of Chem. Soc. Jpn. at Okayama, 2D12, Oct. 13, 1981. 8. Yamamoto, H.; Nozaki, H. Angew. Chem. Int. Ed. Engl. 1978, 17, 169. 9. Itoh, Α.; Ozawa, S.; Oshima, K.; Sasaki, S.; Yamamoto, H.; Hiyama, T.; Nozaki, H. Bull. Chem. Soc. Jpn. 1980, 53, 2367. 10. Hiyama, T.; Morizawa, T.; Yamamoto, H.; Nozaki, H. ibid. in press. 11. Takai, K.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1980, 21, 2531. 12. Hayashi, T.; Katsuro, Y.; Kumada, M. ibid. 1980, 21, 3915. 13. Okamura, H.; Miura, M.; Takei, H. ibid. 1979, 43. 14. Sato, M.; Takai, K.; Oshima, K.; Nozaki, H. ibid. 1981, 22, 1609. 15. Fristad, W. E.; Bailey, T. R.; Paquette, L. A. J . Org. Chem. 1980, 45, 3028 and ref. cited. 16. Mukaiyama, T.; Kamio, K.; Kobayashi, S.; Takei, H. Bull. Chem. Soc. Jpn. 1972, 45, 3723. 17. Trost, Β. M.; Stanton, J. L. J. Am. Chem. Soc. 1975, 97, 4018. 18. Trost, Β. M.; Hutchinson, C. R. (ed.); "Organic Synthesis Today and Tomorrow (IUPAC)"; Pergamon Press: Oxford, New York, 1981; p. 241.


108

ASYMMETRIC REACTIONS AND PROCESSES IN CHEMISTRY

19. Oshima, K.; Nozaki, H. Yuki-Gosei-Kagaku (J. Synth. Org. Chem. Jpn.) 1980, 38, 460. 20. Takai, K.; Mori, I.; Oshima, K.; Nozaki, H. Tetrahedron Lett. in press. 21. Inoue, T.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1980, 53, 174. 22. Tsuji, J . ; Yamada, T.; Kaito, M.; Mandai, T. Tetrahedron Lett. 1979, 2257; Bull. Chem. Soc. Jpn. 1980, 53, 1417.


RECEIVED December 14, 1981.


Highly Selective Synthesis with Novel Metallic Reagents - American

Recommend Documents