Synthesis of Î²-Lactams from Unsaturated Sugars and Isocyanates

Chapter 4

Synthesis of ß-Lactams from Unsaturated Sugars and Isocyanates Marek Chmielewski, Zbigniew Kałuża, Jacek Grodner, and Romuald Urbański

Downloaded by COLUMBIA UNIV on August 2, 2012 | http://pubs.acs.org Publication Date: June 2, 1992 | doi: 10.1021/bk-1992-0494.ch004

Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland

Cycloaddition of trichloroacetyl isocyanate to glycals proceeds satisfactorily at room temperature to give a mixture of [2+2] and [4+2]cycloadducts. The isocyanate attacks the glycal stereospecifically anti with respect to the C-3 substituent. Glycolic cleavage of the vic-diol present in 2-C:1-N-carbonyl-2-deoxy-glycopyranosylamines with sodium meta-periodate provides useful starting materials for the synthesis of 1-oxabicyclic β-lactams.

Owing t o t h e importance o f β-lactam a n t i b i o t i c s , t h e [ 2 + 2 ] c y c l o a d d i t i o n s o f ketenes t o imines and i s o c y a n a t e s t o o l e f i n s p l a y a s p e c i a l role

because

four-membered

both

reactions

azetidinone-2

lead

ring.

to direct

The f i r s t

formation

u s i n g a l a r g e v a r i e t y o f ketenes and ketene e q u i v a l e n t s , the

second

one l e a d s

chlorosulfonyl and d i e n e s .

5

to useful

isocyanate

compounds

and v i n y l

acetates,

of a

one c a n be performed only 3

1 , 2

whereas

i n t h e case o f

vinyl

silyl

ethers,

4

One example o f t h e a d d i t i o n o f an i s o c y a n a t e t o a v i n y l

e t h e r has been r e p o r t e d (Scheme

OZZCITN^

l).

6

c

so ci 2

R' = OAc, CH=CH0Ac, CH=CH

2

Scheme 1

0097-6156/92/0494-0050$06.00/0 © 1992 American Chemical Society

In Cycloaddition Reactions in Carbohydrate Chemistry; Giuliano, R.; ACS Symposium Series; American Chemical Society: Washington, DC, 1992.

4.

CHMIELEWSKI ET AL.

51

Synthesis of β-Lactams

I t i s known t h a t n u c l e o p h i l i c o l e f i n s , such as v i n y l e t h e r s , a c e t a t e s o r enamines, and h i g h l y e l e c t r o p h i l i c s u l f o n y l o r a c y l i s o c y a n a t e s , g i v e c y c l o a d d u c t s i n good y i e l d s , but o n l y i n a few cases a r e t h e adducts s t a b l e enough t o be i s o l a t e d . The electron-donating substituent (X) in the olefin and the e l e c t r o n - w i t h d r a w i n g s u b s t i t u e n t (Ζ) i n the i s o c y a n a t e , n e c e s s a r y f o r c y c l o a d d i t i o n t o o c c u r , a r e r e s p o n s i b l e a l s o f o r t h e low s t a b i l i t y o f the c y c l o a d d u c t , i n d u c i n g h e t e r o l y t i c cleavage o f t h e N-C-4 bond and f o r m a t i o n o f α,β-unsaturated amides via a z w i t t e r i o n i c i n t e r m e d i a t e (Scheme 2 ) . T h e r e f o r e , i n o r d e r t o o b t a i n a s t a b l e s t r u c t u r e , i t i s n e c e s s a r y t o remove t h e e l e c t r o n - w i t h d r a w i n g s u b s t i t u e n t from t h e n i t r o g e n atom p r i o r t o p u r i f i c a t i o n o r t o any o t h e r t r a n s f o r m a t i o n of the [2+2]cycloadduct. T h i s , so f a r , g e n e r a l l y has been a c c o m p l i s h e d s u c c e s s f u l l y i n the case of the c h l o r o s u l f o n y l g r o u p .


7

7

X

X: - OAcyl, O A l k y l , N R R

2

3

Ζ = S0 R , Acyl 2

Scheme 2

S e v e r a l years ago, we i n i t i a t e d a s y n t h e t i c p r o j e c t l e a d i n g from sugars t o 1 - o x a b i c y c l i c β-lactams (Scheme 3 ) . T h i s has prompted us t o i n v e s t i g a t e t h e [ 2 + 2 ] c y c l o a d d i t i o n o f i s o c y a n a t e s t o g l y c a l s and t o the r e l a t e d d i h y d r o - 2 H - p y r a n d e r i v a t i v e s . The d i r e c t f o r m a t i o n o f a β-lactam r i n g was t h e c r u c i a l step i n t h e planned s y n t h e s i s .

III

Scheme 3


CYCLOADDITION REACTIONS IN CARBOHYDRATE CHEMISTRY

52 The

7 and c h l o r o s u l f o n y l

r e a c t i o n between t r i - O - a c e t y l - D - g l u c a l

i s o c y a n a t e has been s t u d i e d cycloadduct

nor

of

a

i n t h e p a s t , but n e i t h e r

rearranged

product

has

formation of a

been

observed.

I s o c y a n a t e a c t e d o n l y as a c i d c a t a l y s t c a u s i n g d e c o m p o s i t i o n m a t e r i a l . On t h e o t h e r hand, [ 2 + 2 ] c y c l o a d d i t i o n of a c t i v e to

dihydro-2H-pyran

investigated,

and

9 , 1 0 , 1 1 , 1 2

to

i t s derivatives

to the formation

cyclization

of b i c y c l i c

temperature

resulted

been The

widely reaction

β-lactam

2.

in

rearrangement

the

9

Elevation

(0°)

of the of

the

amide 3 (Scheme 4 ) .

four-membered r i n g t o t h e open-chain


o f sugar

isocyanates

1 a t low temperature

of t o s y l i s o c y a n a t e w i t h dihydro-2H-pyran led

has

under a v a r i e t y o f c o n d i t i o n s .

8

R=Ts,CC1 CH 0S0 ,CC1 CH S0 ,CF3CO 3

2

2

3

2

2

Scheme 4

Recently ethylsulfonyl,

Barrett

at

a l .

1

0

found

that

2 ,2 , 2 - t r i c h l o r o e t h o x y s u l f o n y l ,

2 ,2 , 2 - t r i c h l o r o and

trifluoroacetyl

isocyanate reacted w i t h 1 to give the respective

u n s a t u r a t e d amide

no β-lactam b e i n g

S i m i l a r r e s u l t s were

i s o l a t e d i n a l l t h r e e cases.

r e p o r t e d by Chan and H a l l

1 1

f o r monosubstituted

dihydro-2H-pyrans.

Scheme 5


3,

4.

CHMIELEWSKI ET AL.

53


Chitwood, G o t t , and M a r t i n found t h a t when 1 was t r e a t e d t r i c h l o r o a c e t y l i s o c y a n a t e , t h e u n s a t u r a t e d amide 6 was o b t a i n e d the u n s t a b l e β-lactam 4 and t h e [4+2] c y c l o a d d u c t 5 (Scheme 5 ) . observed t h a t t h e r e a c t i o n performed i n a c e t o n i t r i l e proceeded times f a s t e r than i n c h l o r o f o r m . Owing t o t h e i r low s t a b i l i t y , by-products 4 and 5 were d e t e c t e d o n l y by NMR. 1 2

with via They ten both


8 - 1 2

I n f e r e n c e s drawn from l i t e r a t u r e d a t a prompted us t o a p p l y the h i g h - p r e s s u r e t e c h n i q u e t o the [ 2 + 2 ] c y c l o a d d i t i o n of i s o c y a n a t e s to glycals. The l a c k of r e a c t i v i t y a t room temperature and atmospheric pressure, the e x c e p t i o n a l s e n s i t i v i t y of cycloadducts t o temperature, and the large negative activation volume of [2+2]cycloadditions, i n c o n t r a s t t o t h e u s u a l l y low s e n s i t i v i t y of i n t r a m o l e c u l a r rearrangements t o t h i s p a r a m e t e r , s t r o n g l y supported the use of h i g h p r e s s u r e f o r t h i s r e a c t i o n . 1 3

1 4

0 7

8

Scheme 6

A p p l i c a t i o n of p r e s s u r e s of 10-11 Kbar g r e a t l y f a c i l i t a t e s the [ 2 + 2 ] c y c l o a d d i t i o n of t o s y l i s o c y a n a t e t o a c e t y l a t e d g l y c a l s (Scheme 6 ) . The r e a c t i o n s were performed o v e r n i g h t i n e t h y l e t h e r a t room temperature o r a t 50°C. U s u a l l y a c r y s t a l l i n e p r o d u c t was o b t a i n e d . The r e a c t i o n showed h i g h s t e r e o s e l e c t i v i t y , a f f o r d i n g p r o d u c t s w i t h the four-membered r i n g anti w i t h r e s p e c t t o the a c e t o x y group a t C-3. Upon h e a t i n g , o r even a t room t e m p e r a t u r e , t h e adducts (Scheme 6) underwent r e t r o a d d i t i o n t o a f f o r d t h e g l y c a l . ' The r a t e of r e t r o a d d i t i o n i n c r e a s e d w i t h a r i s e of temperature and p o l a r i t y o f the s o l v e n t . T h i s unexpected tendency o f c y c l o a d d u c t s f o r r e t r o a d d i t i o n e x p l a i n s why β-lactams c o u l d not be o b t a i n e d from 1 5 , 1 6

1 6

8 , 1 7

1 7

g l y c a l s and i s o c y a n a t e s under thermal c o n d i t i o n s . High pressure not o n l y a c c e l e r a t e s t h e r e a c t i o n r a t e but a l s o a f f o r d s c y c l o a d d u c t s that are thermodynamically u n s t a b l e a t normal p r e s s u r e . Moreover, demonstration, f o r the f i r s t t i m e , of the r e v e r s i b i l i t y of the i s o c y a n a t e c y c l o a d d i t i o n t o o l e f i n s puts a new l i g h t on the mechanism


54


of t h i s r e a c t i o n and on t h e p o t e n t i a l f o r t h e p r e p a r a t i o n o f cycloadducts under conditions of normal pressure. The d i a s t e r e o s e l e c t i v i t y o f the [ 2 + 2 ] c y c l o a d d i t i o n o f t o s y l i s o c y a n a t e t o 3-deoxyglycals was r e l a t i v e l y low. The i s o c y a n a t e entered p r e f e r e n t i a l l y anti w i t h r e s p e c t t o the t e r m i n a l C-6 carbon atom. The r e a c t i o n o f g l u c a l 7 w i t h 2 , 2 , 2 - t r i c h l o r o e t h o x y s u l f o n y l i s o cyanate under 10 Kbar p r e s s u r e a t room temperature i n e t h e r s o l u t i o n a f f o r d e d a m i x t u r e o f β-lactam 9, u n s a t u r a t e d amide 10 and u n r e a c t e d s u b s t r a t e (Scheme 7 ) . The c o n t e n t s o f 7 , c y c l o a d d u c t 9, and amide 10 depended on t h e r e a c t i o n t i m e , as shown. When t r e a t e d w i t h a l c o h o l s o r water a t room temperature, a l l β-lactam-adducts underwent a r a p i d opening o f t h e f our-membered r i n g t o g i v e t h e r e s p e c t i v e g l y c o s i d e s o r c y c l i c h e m i a c e t a l s (Scheme 8 ) . The opening o f t h e β-lactam r i n g proceeded s t e r e o s p e c i f i c a l l y w i t h i n v e r s i o n o f t h e c o n f i g u r a t i o n a t the C - l carbon atom. 1 6


1 8

1

6

,

1

8

:H OAC 2

3Ac/ AcCT

AcO S0 0CH CC1

AcO

2

2

3

C0NHS0 0CH CCI, 2

10 l h 2 7.3% 5h 1 7 . 2 % 8 h 16.7%

18.2% 34 . 5 % 48.7%

54 . 5 % 48.3% 34 . 9%

Scheme 7

The found

r e v e r s i b i l i t y and thermodynamic c o n t r o l o f p r o d u c t

f o r the high-pressure

isocyanate glycals

1 6

reaction

i n d i c a t e d t h a t the including

an excess

glycals

formation and t o s y l

[2+2]'cycloaddition o f i s o c y a n a t e s t o

c o u l d o c c u r a t atmospheric

conditions

between

p r e s s u r e under s p e c i f i c r e a c t i o n

of isocyanate,

as w e l l

as

proper

s e l e c t i o n o f s o l v e n t and s u b s t r a t e s . A c y l i s o c y a n a t e s a r e g e n e r a l l y less

reactive

isocyanates, .

1 0 , 1 2

in

except

[2+2]cycloaddition for

In addition, acyl

competitive

formation

thermodynamically

trichloro-

reactions

i s o c y a n a t e s are p r o b l e m a t i c

of

[4+2]cycloadducts,

p r e f e r r e d over the

than

and t r i f l u o r o a c e t y l

sulfonyl isocyanate

because o f t h e

which

[2+2]cycloadducts.

are usually 12


4.

CHMIELEWSKIETAL

55



Scheme 8

The reaction between di-O-acetyl-L-rhamnal 11 and t r i c h l o r o a c e t y l i s o c y a n a t e was i n v e s t i g a t e d under v a r i o u s c o n d i t i o n s , under h i g h and atmospheric p r e s s u r e . The r e s u l t s c o n f i r m e d t h e e x p e c t a t i o n s based on the p r e v i o u s experiments u s i n g t o s y l i s o c y a n a t e and a c e t y l a t e d g l y c a l s under h i g h p r e s s u r e . The i s o c y a n a t e approached rhamnal 11 p r e f e r e n t i a l l y anti w i t h respect to the 3 - 0 - a c e t y l group (Scheme 9 ) . The percentages o f t h e s u b s t r a t e and p r o d u c t s as a f u n c t i o n o f t h e s o l v e n t , p r e s s u r e , t e m p e r a t u r e , and i n i t i a l p r o p o r t i o n o f s u b s t r a t e s were s t u d i e d . The f o r m a t i o n o f s u b s t a n t i a l amounts o f t h e β-manno c y c l o a d d u c t 14 i s n o t e w o r t h y , and can be a t t r i b u t e d t o t h e c o m p l e x a t i o n o f the i s o c y a n a t e by t h e 3 - 0 - a c e t y l group. 1 5 , 1 6

1 8

12

13

14

15

Scheme 9


56



Consistent w i t h reported data, free energies of a c t i v a t i o n of the c y c l o a d d i t i o n , o f t h e r e v e r s e r e a c t i o n , and o f t h e rearrangement t o t h e a,β-unsaturated amide, do n o t d i f f e r c o n s i d e r a b l y . Hence, a s l i g h t m o d i f i c a t i o n o f t h e g l y c a l m o i e t y , o r even a change i n t h e s o l v e n t c o u l d s h i f t t h e r e a c t i o n towards t h e d e s i r e d c y c l o a d d u c t , o r s u b s e q u e n t l y towards t h e u n s a t u r a t e d amide. P o l a r s o l v e n t s , such as a c e t o n i t r i l e , a c t e d i n a d u a l manner, c a u s i n g a c c e l e r a t i o n o f t h e reaction rate and a s h i f t o f t h e e q u i l i b r i u m towards t h e cycloadducts. The a d d i t i o n o f t r i c h l o r o a c e t y l i s o c y a n a t e t o rhamnal 11 i n e t h y l e t h e r under 10 Kbar p r e s s u r e was used f o r t h e p r e p a r a t i o n o f the [4+2]cycloaddition product 12 (Scheme 9). During the h i g h - p r e s s u r e experiment, compound 12 c r y s t a l l i z e d i n good y i e l d and i n n e a r l y pure form . C y c l o a d d u c t 12 was o b t a i n e d s t e r e o s p e c i f i c a l l y , as a r e s u l t o f i s o c y a n a t e a d d i t i o n anti w i t h r e s p e c t t o t h e C-3 a c e t o x y group. The s t e r e o s p e c i f i c i t y o f t h e f o r m a t i o n o f 12 c o u l d be a t t r i b u t e d t o t h e k i n e t i c c o n t r o l o f a d d i t i o n by t h e C-3 s u b s t i t u e n t ; n e v e r t h e l e s s , a s h i f t o f t h e e q u i l i b r i u m : β-manno [4+2] β-manno [ 2 + 2 ] c y c l o a d d u c t , e n t i r e l y towards t h e β-lactam s h o u l d a l s o be t a k e n i n t o c o n s i d e r a t i o n . The l a c k o f s t a b i l i z i n g anomeric e f f e c t o f t h e i m i d a t e f u n c t i o n as w e l l as a x i a l l o c a t i o n o f t h e c a r b o n y l group a t the C-2 carbon atom i n the pyranoid ring o f t h e β-manno [4+2]cycloadduct support t h i s assumption. Attempts a t i s o l a t i o n o f c y c l o a d d u c t s 13 and 14 from t h e r e a c t i o n m i x t u r e f a i l e d owing t o t h e i r h i g h r e a c t i v i t y . T h e r e f o r e , JV-deprotection was n e c e s s a r y p r i o r to isolation o r chemical transformation of 13 and 14. JV-Unsubstituted β-lactam 16 was o b t a i n e d by p a s s i n g a m i x t u r e o f 12 15 t h r o u g h a F l o r i s i l column. Compound 16 was accompanied by amide 17 and a,β-unsaturated amide 18. The low s t a b i l i t y o f t h e β-manno adduct 14, manifesting itself by the absence of the respective JV-unsubstituted β-lactam, was noteworthy. The m i x t u r e of 13 and 14, o b t a i n e d a f t e r s e p a r a t i o n o f 12, t r e a t e d w i t h methanol a f f o r d e d a m i x t u r e o f g l y c o s i d e s 19 and 20 w i t h t h e α-L-gluco and β-L-manno c o n f i g u r a t i o n , r e s p e c t i v e l y . Traces o f β-lactam 16 and amide 18 were also i s o l a t e d . 1 8

1 8

1 8

1 8

The r e s u l t s o f t h e h i g h - p r e s s u r e experiments aided i n the s e l e c t i o n o f t h e most e f f e c t i v e s u b s t r a t e s and c o n d i t i o n s f o r performing c y c l o a d d i t i o n s of isocyanates t o g l y c a l s a t atmospheric p r e s s u r e . T r i c h l o r o a c e t y l i s o c y a n a t e and g l y c a l s h a v i n g nonpolar p r o t e c t i n g groups were found t o be the most s u i t a b l e s u b s t r a t e s f o r c y c l o a d d i t i o n , p r o v i d i n g r e l a t i v e l y s t a b l e c y c l o a d d u c t s , and o f f e r i n g an i s o c y a n a t e - a c t i v a t i n g s u b s t i t u e n t r e a d i l y removable from t h e c y c l o a d d u c t s under m i l d c o n d i t i o n s . 1 9 , 2 0 , 2 1 , 2 2



4.

CHMIELEWSKI ET AL.

57


23

24

25

R - ^ T M S , Bn 2

R »H,

C H

, C H ^ R

3

1

Scheme 10

Glycals pressure

21

with

were

found

2-3-molar

to

react

equiv.

of

readily tosyl

under

or

atmospheric

trichloroacetyl

i s o c y a n a t e . The r a t e o f a d d i t i o n and the p r o p o r t i o n o f t h e s u b s t r a t e and

products

differed

i n dependence on t h e s o l v e n t s and s u b s t r a t e s

used. The r e a c t i o n s c a r r i e d out under atmospheric with high s t e r e o s e l e c t i v i t y

to afford

which

place

addition

substituent in

had

taken

anti

(Scheme 10). T h i s h i g h

pressure

cis-fused b i c y c l i c with

respect

stereoselectivity

proceeded systems i n

to

the

C-3

i s noteworthy,

c o n t r a s t t o t h a t found f o r the c y c l o a d d i t i o n of t r i c h l o r o a c e t y l

isocyanate to l l .

1 8

T o s y l i s o c y a n a t e gave the r e s p e c t i v e β-lactams 22

a f t e r 6-40 h. Subsequently

slow rearrangement of t h e adduct i n t o t h e

respective

amide was o b s e r v e d .

α,β-unsaturated

2 1

Attempts t o c l e a v e

the t o s y l s u b s t i t u e n t from the n i t r o g e n atom o f 22 i n o r d e r t o o b t a i n stable

JV-unsubstituted

β-lactam

ring,

were

compounds, unsuccessful

without and

decomposition this

reaction

of

the

was

not

i n v e s t i g a t e d any f u r t h e r . Trichloroacetyl [2+2]cycloadducts The

initial

resulting

isocyanate

reacted

23, [4+2]adducts

proportion

of the adducts

i n t h e predominance

intermediates s l o w l y rearranged

with

glycals

21

producing

24 and the o p e n - c h a i n amide 25. 23 and 24 changed

of 24. I n a l l c a s e s ,

both

t o amide 25.


slowly, bicyclic


58


P o l a r s o l v e n t s , such as a c e t o n i t i l e o r n i t r o m e t h a n e a c c e l e r a t e d the r e a c t i o n r a t e , more so t h e c y c l o a d d i t i o n than t h e rearrangement t o t h e amides. An i n c r e a s e i n p o l a r i t y of t h e s o l v e n t promoted f o r m a t i o n o f t h e [2+2] c y c l o a d d u c t as a k i n e t i c p r o d u c t . The r a t e of c y c l o a d d i t i o n depends on t h e c o n c e n t r a t i o n o f b o t h components, whereas t h e i n t r a m o l e c u l a r rearrangement o f c y c l o a d d u c t s t o 25 does not. The h i g h e s t c o n t e n t o f [2+2]cycloadduct i n the r e a c t i o n m i x t u r e c o u l d be a c h i e v e d when the c y c l o a d d i t i o n was performed w i t h more concentrated s o l u t i o n s of b e n z y l a t e d g l y c a l s i n a p o l a r s o l v e n t . For example, t r i - O - b e n z y l a l l a i 26 (30 mg/ml) p l u s 3 m o l a r e q u i v . o f trichloroacetyl isocyanate i n n i t r o m e t h a n e produced 42% o f the r e s p e c t i v e β-lactam 27 a f t e r 10 h r s , whereas a t a g l y c a l - c o n c e n t r a t i o n o f 400 mg/ml, 27 was formed i n a 60% y i e l d a f t e r 5 h r s . (Scheme 11)

2 2

2 2

Scheme 12


4.

CHMIELEWSKI ET AL.

59


A d d i t i o n of a p r i m a r y amine t o a m i x t u r e of 23 and 24 quenched the

reaction

formation

progress,

of s t a b l e

stable b i c y c l i c

t o removal

β-lactams.


afforded

leading

β-lactams. F u r t h e r

o f JV-protection

deprotection

and t o

of oxygen atoms

20-23

Scheme 13

This

i s illustrated

β-lactam 2 8 . and

glycals

procedure isocyanate the

same

2 0

i n Scheme 12 by the example o f t h e s y n t h e s i s of

U n t i l now 14 s t r u c t u r e s d e r i v e d from dihydro-2H-pyrans

were

could

obtained,

be a p p l i e d

and a r e shown i n Scheme t o the c y c l o a d d i t i o n

t o the f u r a n o i d g l y c a l 2 9 . high

[4+2] c y c l o a d d u c t s

2 3

stereoselectivity having

the oc-D-gluco

JV-Deprotection l e d t o the f o r m a t i o n

13. The

same

of t r i c h l o r o a c e t y l

The r e a c t i o n proceeded

with

to

and

produce

configuration

[2+2]

(Scheme 14).

of s t a b l e compound 30.


60


•HOCH CH NH


2

2

2

0 30 Scheme 14 P e r i o d a t e o x i d a t i o n of compound standard

28 l a c k i n g

^ - p r o t e c t i o n , under

1 7

c o n d i t i o n s , l e d t o the f o r m a t i o n of complex m i x t u r e s

of

p r o d u c t s w h i c h were not i n v e s t i g a t e d . I n o r d e r t o o b t a i n more s t a b l e compounds, sugar

β-lactams

t h r e e - s t e p procedure β-lactam

31

could

were b e n z y l a t e d a t the n i t r o g e n atom i n a

to a f f o r d also

be

compounds 31 (Scheme 15). obtained

using

another

2 4

JV-Benzyl

sequence

of

r e a c t i o n s , w h i c h was found t o be p a r t i c u l a r i l y a t t r a c t i v e i n t h e case of c y c l o a d d u c t s content

of

galactal

32

[2+2]cycloadduct

and

trichloroacetyl

nitromethane containing Compound

o b t a i n e d from b e n z y l a t e d

the

solution up

33,

reacted

was

isocyanate

to afford

t o 75% of the d e s i r e d thus

obtained,

a c c o r d i n g t o the procedure

was

glycals,

observed.

f o r which a high

2 2 , 2 4

i n an

For

a mixture

[2+2]cycloadduct

benzylated

at

example,

acetonitrile of

or

cyloadducts (Scheme 1 6 ) .

the n i t r o g e n

d e s c r i b e d f o r s i l y l a t e d compounds

atom

(Scheme

16), and s u b s e q u e n t l y was s u b j e c t e d t o h y d r o g e n o l y s i s i n t h e presence of

a

palladium

catalyst

a f f o r d i n g 34;

JV-benzyl group was observed.

no

hydrogenolysis

2 4

Scheme 15


o f the

4.

CHMIELEWSKI ET AL.


61

G l y c o l i c c l e a v a g e o f t h e v i c - d i o l g r o u p i n g p r e s e n t i n sugar β-lactams i s e x e m p l i f i e d i n Scheme 17 w h i c h shows t h e o x i d a t i o n o f the β-arabino compound 35. P e r i o d a t e o x i d a t i o n o f 35 under s t a n d a r d c o n d i t i o n s l e d t o t h e f o r m a t i o n o f r e a c t i v e d i a l d e h y d e 36, w h i c h epimerized t o t h e trans compound 37, depending on t h e pH o f t h e reaction mixture. Upon p r o l o n g a t i o n o f t h e r e a c t i o n t i m e , an i n t r a m o l e c u l a r a l d o l r e a c t i o n a f f o r d e d t h e b i c y c l i c a l d e h y d e 40. I n o r d e r t o o b t a i n t h e d e s i r e d p r o d u c t , c o n t r o l o f t h e r e a c t i o n time and pH was n e c e s s a r y . The p r o g r e s s o f t h e r e a c t i o n c o u l d be stopped a t the stage o f 3 , 4 - d i s u b s t i t u t e d a z e t i d i n o n e s by t h e r e d u c t i o n o f t h e aldehyde f u n c t i o n s i n 36 o r 37 t o t h e r e s p e c t i v e h y d r o x y m e t h y l groups (Scheme 1 7 ) . A l t e r n a t i v e l y , d i a l d e h y d e 36 c o u l d be o x i d i z e d i n a one-pot r e a c t i o n w i t h sodium c h l o r i t e , i n t h e presence o f hydrogen p e r o x i d e as a c h l o r i n e s c a v a n g e r , t o a f f o r d t h e d i c a r b o x y l i c a c i d 41. Owing t o t h e m a l o n y l g r o u p i n g p r e s e n t i n 4 1 , e p i m e r i z a t i o n a t the a z e t i d i n o n e o c c u r r e d r e a d i l y . A t -5°C, t h e cis c o n f i g u r a t i o n was preserved, whereas o x i d a t i o n a t room temperature l e d o n l y t o t h e trans isomer 42 (Scheme 1 8 ) . 2 4


2 4

2 5

2 6

2 6

The u s e f u l n e s s o f t h e above-presented r e s u l t s f o r t h e s y n t h e s i s of 1 - o x a b i c y c l i c β-lactam a n t i b i o t i c s can be w e l l e x e m p l i f i e d by t h e


62


2 7


p r e p a r a t i o n o f t h e clavam compound 4 3 . F o r m a t i o n o f t h e clavam s k e l e t o n 44 was a c h i e v e d a c c o r d i n g t o t h e r e a c t i o n sequence shown i n Scheme 19. T h i s s t r a t e g y l e f t , however, t h e unnecessary a c e t o x y m e t h y l group a t t h e C-6 carbon atom.

Scheme 17

42

36

41

Scheme 18


4.

CHMIELEWSKI ET A L

Synthesis of

β-Lactams

63

H


43

We have shown t h a t c o n s i d e r a t i o n of the thermodynamic and k i n e t i c p r o p e r t i e s of the c y c l o a d d i t i o n r e a c t i o n s of i s o c y a n a t e s w i t h g l y c a l s a i d e d i n s e l e c t i o n of the most e f f e c t i v e s u b s t r a t e s and r e a c t i o n c o n d i t i o n s . The g l y c o l c l e a v a g e of the v i c - d i o l group p r e s e n t i n 2-C: 1 - N - c a r b o n y l - 2 - d e o x y g l y c o p y r a n o s y l a m i n e s p r o v i d e s a f u l l y s t e r e o c o n t r o l l e d route to the 1 - o x a b i c y c l i c β-lactams h a v i n g d e s i r e d c o n f i g u r a t i o n at the carbon atoms connected to the n i t r o g e n and oxygen atoms. Thus, owing to the s t e r e o s p e c i f i c i t y of c y c l o a d d i t i o n , D - g l u c a l , D - g a l a c t a l , L - a r a b i n a l , and D - x y l a l gave 3 , 4 - d i s u b s t i t u t e d a z e t i d i n o n e s w i t h the S-configurâtion at the C-4 c a r b o n atom, whereas D - a r a b i n a l , L - x y l a l , L-rhamnal, and L - f u c a l a f f o r d e d those of the a l t e r n a t i v e R-configuration. C o n s t r u c t i o n of a second r i n g can be a c h i e v e d i n many d i f f e r e n t ways, one of w h i c h , l e a d i n g to the clavam 44, i s shown (Scheme 1 9 ) .

2 8

Scheme 19


64

C Y C L O A D D m O N REACTIONS IN CARBOHYDRATE CHEMISTRY

Literature Cited


1.

Staudinger, H. Liebigs Ann. Chem. 1907, 356, 51; Bose, A. K.; Spiegelman, G.; Manhas, M. S. J: Am. Chem. Soc. 1968, 90, 4506; Wagle, D. R.; Garai, C.; Chiang, J.; Monteleone, M. G.; Kurys, B. E . ; Strohmeger, T. W.; Hegde, V. R.; Manhas, M. S.; Bose, A. K. J. Org. Chem. 1883, 53, 4277; Ghosez, L . ; Haveaux, B.; Viehe, H. G. Angev. Chem., Int. Ed. Engl. 1969, 6, 454; Rogalska, E . ; Beizecki C. J. Org. Chem. 1984, 49, 1397; Gilman, H.; Spencer, M. J. Am. Chem. Soc. 1943, 65, 2255; Giuchowski, G.; Cooper, L.; Bergbreiter, D. E.; Newcomb, M. J . J. Org. Chem. 1980, 45, 3413; Ojima, I.; Inoba, S. Tetrahedron Lett. 1980, 21, 2077; 2081. 2. Koopel, G. A. in "The Chemisty of Heterocyclic Compounds. Small Ring Heterocycles" Ed. Hassner, Α.; Wiley, J . & Sons Inc., New York 1983, Vol. 42 Part II, p. 219. 3. Clauss, K.; Grimm, D.; Prossel G. Liebigs Ann. Chem. 1974, 539; Kametani, T.; Honda, T.; Nakayama, Α.; Fukumoto, K. Heterocycles 1980, 14, 1967; Cecchi, R.; Favara, D.; Omodei-Sale, Α.; Depaoli, Α.; Consonni, P. Gazz. Chim. It. 1984, 114, 225; Buynak, J . D.; Narayama, Rao M.; Pajouhesh, H.; Yegna Chandrasekaran, R.; Finn, K.; Meester, P.; Chen, S. C. J. Org. Chem. 1985, 50, 4245. 4. Ohashi, T.; Kan, K.; Sada, I.; Miyama, Α.; Watanabe, K. Eur. Pat. Appl. 1986, 167,154; 167,155; Sada, I.; Kan, K.; Ueyama, H.; Matsunobu, S.; Ohashi, T.; Watanabe, K. Eur. Pat. Appl. 1988, 280,962; Ishiguro, M.; Iwata, K.; Nakatsuka, T.; Tanaka, T.; Maeda, Y. ; Nishibara, T.; Noguchi, T. J. Antibiot. 1988, 51, 1685 5. Moriconi, E. J.; Meyer, W. C. J. Org. Chem. 1971, 36, 2871. 6. Hungerbühler, E . ; Bioloz, M.; Ernest, I.; Kalvoda, J.; Langa, M.; Schneider, P.; Sedelmeier, G. in Yoshida, Z . ; Shiba, T.; Ohshiro Y. Ed. "New Aspects of Organic Chemistry" VCh, New York, 1989, p. 419. 7. Graf, R. Liebigs Ann. Chem. 1963 661, 111; Moriconi, E. J.; Crawford, W. C. J. Org. Chem. 1968, 33, 370; Graf, R. Org. Synth. 1966 46, 51. 8. Hall, R. H.; Jordaan, Α.; Lourens, G. J . J. Chem. Soc., Perkin I 1973, 38; Hall, R. H.; Jordaan, Α.; de V i l l i e r s , O. G. ibid. 1975, 626. 9. Effenberger, F.; Gleiter, R. Chem. Ber. 1964, 97, 1576. 10. Barrett, A. G. M.; Fenwick, A. and Betts, M. J. J. Chem. Soc., Chem. Commun. 1983, 299. 11. Chan, J . H.; Hall, S. S. J. Org. Chem. 1984, 49, 195.



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12. Chitwood, J . L . ; Gott, P. G.; Martin, J . C. ibid. 1971, 36, 2228. 13. Isaacs, N. S.; Rannola, Ε. J. Chem. Soc., Perkin II, 1975, 1555; Swieton, G.; von Jouanne, J.; Keim, H . ; Huisgen, R. i b i d . , 1983, 37; Wiering, P. G.; Steinberg, H. Recl. J. Roy. Neth. Chem. Soc. 1981, 100, 13. 14. Jenner, G. in "Organic High PressureChemistry";Ed. Le Noble, W. J . Elsevier, Amsterdam 1988, p. 143, and references cited therein. 15 Chmielewski, M.; Kałuża, Z . ; Bełżecki, C . ; Sałański, P.; Jurczak, J . Tetrahedron Lett. 1984, 25, 4797. 16. Chmielewski, M.; Kałuża, Z . ; Bełżecki, C.; Sałański, P.; Jurczak, J.; Adamowicz, H. Tetrahedron 1985, 41, 2441. 17. Chmielewski, M.; Kałuża, Z. unpublished results. 18. Chmielewski, M.; Kałuża, Z . ; Mostowicz, D.; Bełżecki, C . ; Baranowska, E . ; Jacobsen, J . P . ; Sałański, P.; Jurczak, J. Tetrahedron 1987, 43, 4563. 19. Chmielewski, M.; Kałuża, Z. J. Org. Chem. 1986, 51, 2395. 20. Chmielewski, M.; Kałuża, Z. Carbohydr. Res. 1987, 167, 143. 21. Chmielewski, M.; Kałuża, Z . ; Abramski, W.; Mostowicz, D.; Hintze, B.; Bełżecki C. Bull. Acad. Pol. Sci. 1987, 35, 245. 22. Bełżecki, C.; Grodner, J.; Urbański, R.; Chmielewski, M. unpublished results. 23. Chmielewski, M.; Badowska-Rosłonek, K. unpublished results. 24. Chmielewski, M.; Kałuża, Z . ; Abramski, W.; Grodner, J.; Bełżecki, C.; Sedmera, P. Tetrahedron 1989, 45, 227. 25. Dalcanale E.; Montanari F. J. Org. Chem. 1986, 51, 567. 26. Chmielewski, M.; Grodner, J.; Fudong Wang unpublished results. 27. Brown, D.; Evans, J . R.; Fletton, R. A. J. Chem.Soc.,Chem. Commun. 1979, 282. 28. Chmielewski, M.; Grodner, J. unpublished results. RECEIVED December2,1991


Synthesis of Î²-Lactams from Unsaturated Sugars and Isocyanates

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