Anomeric Effect - American Chemical Society

5 Aspects of Conformational Analysis of Pentopyranosyl Acetates, Benzoates, and Halides HANS PAULSEN, PETER LUGER, and FRED R. HEIKER

Downloaded by CORNELL UNIV on September 23, 2016 | http://pubs.acs.org Publication Date: January 25, 1979 | doi: 10.1021/bk-1979-0087.ch005

Institute of Organic Chemistry and Biochemistry, University of Hamburg, 2000 Hamburg 13, West Germany

At the beginning of this article, some X-ray data of glycopyranosyl halides will be discussed that refer to the bond lengths at the anomeric center and which are of great importance for discussion of the anomeric effect. As is well known, acylated derivatives of ß-xylosyl halides exhibit rather interesting conformational effects because in solution all of them adopt the unusual tetraaxial conformation predominantly or totally (1—6). By means of X-ray structure-analysis, we were able to determine the conformation and arrangement in the crystalline state both of the benzoates and the acetates. It was demonstrated that the tribenzoates favor the tetraaxial conformation, whereas the triacetates crystallize favorably in the tetraequatorial form, even though the tetraaxial form predominates in solution (4). Figures 1 and 2 show the aforementioned compounds in the conformations which they adopt in the crystalline state. Of particular interest are the various bond-lengths at the anomeric center. These may be supposed to indicate the amount of back donation that occurs with the halide in the axial disposition and hence strengthens the anomeric effect. V e r y i n t e r e s t i n g a r e t h e t w o f l u o r o compounds d e p i c t e d i n t h e t o p l i n e o f F i g u r e 1, where t h e b e n z o a t e c r y s t a l l i z e s a l l a x i a l l y , a n d t h e a c e t a t e a l l e q u a t o r i a l l y ( T ) . The b e n z o a t e i s o b s e r v e d a s two i n d e p e n d e n t m o l e c u l e s i n t h e s y m m e t r i c a l u n i t ; t h e i n t e r e s t i n g d i s t a n c e s i n b o t h compounds a r e shown i n F i g u r e 1. O b v i o u s l y , t h e s h o r t e n i n g o f t h e d i s t a n c e s between C - l a n d t h e r i n g - o x y g e n atom, t o 1.5^—1.36 A, i s q u i t e c o n s i d e r a b l e . Some c r y s t a l l o g r a p h i c p r o b l e m s w e r e e n c o u n t e r e d w i t h t h i s compound. The s t r u c t u r e was d e t e r m i n e d c e n t r o s y m m e t r i c a l l y and s u b s e q u e n t l y r e f i n e d a s y m m e t r i c a l l y t o an R - v a l u e o f 3«9#. M i n o r u n d e r t a i n t i e s i n t h e bond l e n g t h s c a n n o t be e n t i r e l y

0-8412-0470-5/79/36-087-063$05.00/0 © 1979 A m e r i c a n C h e m i c a l Society

Szarek and Horton; Anomeric Effect ACS Symposium Series; American Chemical Society: Washington, DC, 1979.

ANOMERIC EFFECT


US2 (1>47)

V365 (U39)

1.38S (! 390;

>.40£ \,U7

e

Solution 90*100% exist

(.451

1,383

Solution

\,859

80-90*/. axial

1,417

1,428

1,754

OBz P D-xyJo Solution 90-100% sxial

ff-P-gyio (4)

S e s s i o n 7 5 - 8 5 % sxiel ( l , * 0

1,443 1,366 1,6S§

David t t Qi. 1976 (9J

Figure 1



5.

PAULSEN E T A L .

Conformational

Analysis

P-D-xylo

p-D-arablno

Solution 90-100% a s i a l

1,420

65

U9«

Norton etf ol. 1972 (fl)

\,443

r

Tetraacetate

3z0

P- -«Xi£

OBz

D

P-D-xylo Solution

Solution ~28*A a x i a l

~ 50% axial

1429

Durotto, Norton 1971(13)

1 395

1*22

0

1*09

1,409

AcO B-D-orabino J a m a s , Stevens

oi-D-^rabjno 1974 (|5)

J a m u , Stevens

1974

(Ifi)

Figure 2


66

ANOMERIC E F F E C T

excluded. I n the a l l - e q u a t o r ! a l l y a c e t y l a t e d f l u o r o compound ( F i g u r e l ) , the d i s t a n c e s approach normal values ( T ) . In the c h l o r i d e s e r i e s , the benzoate ( F i g u r e 1, c e n t e r ) , c r y s t a l l i z e s i n a skew conformation S Q ( 8 ) . However, the arrangement around the anomeric center corresponds t o a t e t r a a x i a l conformation, and thus a comparison o f d i s t a n c e data should be p e r m i s s i b l e . In a d d i t i o n , the a-mannopyranosyl c h l o r i d e r e c e n t l y determined by David e t a l . (9) i s shown i n F i g u r e 1. Obviously, the d i s t a n c e s between C - l and the r i n g oxygen atom are about 1. 37—1. 38 l , and only s l i g h t l y l a r g e r as compared with the f l u o r o compound. The t e t r a e q u a t o r i a l , a c e t y l a t e d c h l o r o compound e x h i b i t s almost "normal" data (10). F i g u r e 2 shows the bromo d e r i v a t i v e s (6). In the t e t r a a x i a l benzoate, a C - l - r i n g oxygen d i s t a n c e of 1. 37 I i s observed, which corresponds t o a c o n s i d e r a b l e shortening of almost the same magnitude 8s i n the f l u o r o and c h l o r o derivatives. The C - l — b r o m i n e bond i s c o n c u r r e n t l y s t r e t c h e d t o 2.003 I. Other i n t e r e s t i n g molecules are the p-tetrabenzoate and the p - t e t r a a c e t a t e o f xylopyranose. According t o Durette and Horton (12, P5), 50$ of the benzoate and 28$ of the acetate adopt the t e t r a a x i a l conformation i n s o l u t i o n . This c l e a r l y demonstrates t h a t benzoate groups, i n c o n t r a s t t o acetate groups, f a v o r the a x i a l d i s p o s i t i o n . In the c r y s t a l l i n e s t a t e , the benzoate again shews the t e t r a a x i a l conformation (Ik). The data i n F i g u r e 2 demonstrate n o t a b l y that, i n t h i s case, the shortening of the bond ( t o 1. 39 I) i s comparatively small, as might have been expected f o r an oxygen-bound s u b s t i t u e n t at C - l . Quite s i m i l a r d i s t a n c e s have been observed by Stevens i n the p-Darabino d e r i v a t i v e s (15), and again the corresponding a-Darabino d e r i v a t i v e ( l 5 ) shows normal bond-lengths. (See F i g u r e 2T. By comparison, i t may be noted t h a t the v a r i a t i o n of bond d i s t a n c e s i s minor i n these cases. A l t o g e t h e r , the bond-distance data g i v e evidence that, i n the case of a x i a l anomeric s u b s t i t u e n t s , a back-donation e f f e c t occurs, with the f l u o r o compound behaving s i m i l a r l y t o the c h l o r o and bromo d e r i v a t i v e s . The same proves t r u e with oxygenbound s u b s t i t u e n t s , although here the enhanced bond-distances p o i n t t o a s u b s t a n t i a l l y smaller e f f e c t . We were s u r p r i s e d t h a t , of a l l the compounds studied, the benzoates, as compared w i t h the acetates, favored the a x i a l arrangement. T h i s i s e s p e c i a l l y obvious when the p-xylopyranose tetrabenzoates and t e t r a a c e t a t e s are compared i n s o l u t i o n . We supposed as a working hypothesis t h a t the 1 , 3 - d i a x i a l i n t e r a c t i o n of two benzoates should be even smaller than t h a t of the


2



5.

PAULSEN E T A L .

Conformational Analysis

67

corresponding two acetates. I f t h i s were so, a s i m i l a r e f f e c t should g e n e r a l l y occur i n the manifold a c y l a t e d pentopyranoses s t u d i e d by Durette and Horton (13). Here, the s p l e n d i d and most accurate n. m. r. data of Durette and Horton (I3O are at hand. As shown i n F i g u r e 3, an i n t e r a c t i o n of the phenyl r i n g s i n the t e t r a a x i a l conformation o f 1,2,3,4-tetra-Obenzoyl-p-D-xylopyranose i s r a t h e r u n l i k e l y . In the c r y s t a l , the phenyl r i n g s are arranged at random angles t o each other. There would be a f u r t h e r p o s s i b i l i t y f o r e x p l a i n i n g the d i f f e r e n c e between benzoates and acetates i f t h e r e were an a d d i t i o n a l o b s t r u c t i o n i n the e q u a t o r i a l d i s p o s i t i o n , but o n l v f o r the benzoates, which would then l e a d t o a l a r g e r gauche interaction. As key compounds f o r f u r t h e r s t u d i e s of t h i s problem, the three 1,5-anhydropentitols shown i n F i g u r e k are w e l l s u i t e d , because here the i n f l u e n c e of anomeric e f f e c t i s eliminated. We prepared the t r i a c e t a t e s and the t r i b e n z o a t e s of these compounds and s t u d i e d the conformational e q u i l i b r i a i n d e t a i l by n. m. r. spectroscopy (IT). For determination o f standard coupling-constants i n t h i s s e r i e s of compounds, as the b a s i s f o r c a l c u l a t i o n o f the d i s t r i b u t i o n of conformers, the D-arabino compound i n F i g u r e 5 turned out t o be p a r t i c u l a r l y s u i t a b l e . The arrangement of C - l and C-2 o f the one and C-5 and C-4 of the other conformation correspond t o each other. Thus by a simple c a l c u l a t i o n , t a k i n g i n t o account an average value of the coupling-constants involved, standard coupling-constants are obtained ( J 1. 5 10.6 f o r acetates and 10. k Hz f o r benzoates. ; The d e r i v a t i v e s i n the r i b o s e r i e s are v e r v i n t e r e s t i n g . F i g u r e 6 shows the e q u i l i b r i a of 1 , 5 - a n h y d r o r i b i t o l s . In t h i s case, 2k% of the a c e t a t e and 46$ of the benzoate are found to adopt the d i a x i a l ^ conformation ( l e f t ) . Again, the moref a v o r a b l e a x i a l arrangement of benzoate groups i s observed i n t h i s compound. Acetone was used as solvent throughout. In both conformations ( r i g h t and l e f t ) , two gauche i n t e r a c t i o n s between e q u a t o r i a l and a x i a l s u b s t i t u e n t s may be observed. As these should be of comparable magnitude i n the d i f f e r e n t conformers, they were not considered i n the energy evaluation. Furthermore, i n the l e f t i ^) form, a 1 , 3 - d i a x i a l i n t e r a c t i o n has t o be taken i n t o account. This i s the one having an e q u a t o r i a l s u b s t i t u e n t i n the middle, and i n which the a x i a l groups are opposed by the ring-oxygen atom. The symbols i n F i g u r e 6 demonstrate t h i s f a c t . r(e)0Ac//QAc/0r denotes two s y n - 1 , 3 - d i a x i a l a c e t o x y l groups (QAc//0Ac), opposed by a r i n g oxygen atom (/Or) with an e q u a t o r i a l s u b s t i t u e n t (e) between them]. For the form on the r i g h t , only the A-value of the ecyloxy group has t o be considered. Thus, by means of the experimentally determined magnitude o f AG and an A-value o f 0. 7 kcal/mol, e

e

1

1



ANOMERIC EFFECT

O-orgpino

Figure 5


Conformational


PAULSEN E T A L .

RO

Acotato

Analysis

OR

~24%

B«nzoat« ~ 4 6 %

OR

76% *£

4

54%

4

Q,

A O ° -0.7 K c a l / m o l

*£,

A 0 ° - 0 . 1 Kcal/mot

AG° * C»yn-1,3-diaxiaN(«)OR#OR/Or(•) OAc4fOAc/Or ~ U (•)

OBz#OBz/Or

A - V a l u o OR

Kcal/mol

- 0 . 8 Kcal/mol

Figure 6


ANOMERIC

70

EFFECT

the s i z e of the 1 , 3 - d i a x i a l i n t e r a c t i o n may be c a l c u l a t e d . As a r e s u l t , f o r two a c e t o x y l groups, 1.U, and f o r two benzoylcocy groups 0. b kcal/mol, are determined. As had been expected, a c o n s i d e r a b l y lower value r e s u l t e d f o r the benzcylcocy groups. I t i s remarkable f o r t h i s system that, even i n i n s t a n c e s of p o s s i b l e a n g l e - d i s t o r t i o n s , the gauche i n t e r a c t i o n s i n both conformers should correspond t o each other and thus need not be considered. It i s quite interesting that 2 , 3 , ^ - t r i - 2 - b e n z o y l r i b i t o l which, as a l r e a d y mentioned, adopts t o the extent of 50$ i n s o l u t i o n the d i a x i a l ^ conformation, i n the c r y s t a l l i n e s t a t e f a v o r s the d i e q u a t o r i a l C i form. 2,3,U-Tri-O-benzoylxylitol a l s o adopts the t r i e q u a t o r i a l form i n the c r y s t a l l i n e s t a t e , i n c o n t r a s t t o the xylopyranose d e r i v a t i v e i n F i g u r e 3. Both c r y s t a l s t r u c t u r e s are shown i n F i g u r e 7. Both p e n t i t o l d e r i v a t i v e s l a c k the anomeric e f f e c t , which would otherwise l e a d t o h i g h p r o p o r t i o n s of the i n v e r s e (^C^) forms f o r the p-anomers. From the r i n g - t o r s i o n a l angles of the r i b o and x y l o compounds i n F i g u r e 7, we may conclude t h a t , i n both i n s t a n c e s , there are o n l y s m a l l d e v i a t i o n s from the i d e a l i z e d c h a i r conformations. The t o r s i g n a l angles o f the benzcylcocy groups i n the r i b o compound (~ 55 ) and the x y l o compound (—65 ), a l s o d i f f e r only s l i g h t l y (see F i g u r e 7). A v a l i d assumption should be that the gauche i n t e r a c t i o n o f two s u b s t i t u e n t s i n a x i a l — e q u a t o r i a l and e q u a t o r i a l — e q u a t o r i a l d i s p o s i t i o n i s of s i m i l a r order.


4

F i g u r e 8 shows the a-D-ribo compounds, where i n both acetates and benzoates, the p r o p o r t i o n of the C conformer i s s i m i l a r ( l ^ ) . T h i s was t o be expected, because the 1,3" d i a x i a l i n t e r a c t i o n i n both conformers should be s i m i l a r . Again, i n these d e r i v a t i v e s , both conformers e x h i b i t t h r e e gauche i n t e r a c t i o n s , which need not be considered. Because of t h i s — i n a d d i t i o n t o the 1 , 3 - d i a x i a l i n t e r a c t i o n s — only the anomeric e f f e c t i n the l e f t ( G ) form has t o be taken i n t o account. Thus, by c a l c u l a t i o n u s i n g the formerly determined values, the magnitude of the 1 , 3 - d i a x i a l i n t e r a c t i o n with a c e n t r a l e q u a t o r i a l s u b s t i t u e n t and an a x i a l hydrogen atom opposing the a x i a l groups i s obtained. In t h i s i n s t a n c e , s l i g h t l y i n c r e a s e d values should r e s u l t , i n c o n t r a s t t o the former case w i t h the ring-oxygen atom opposing the two a x i a l groups. T h i s presumption i s , i n f a c t , supported by the c a l c u l a t e d v a l u e s , which are found to be 1.9 kcal/mol f o r the acetcocy, and 1. 5 kcal/mol f o r the benzoylcocy group. As before, a c h a r a c t e r i s t i c d i f f e r e n c e between the two groups may be observed. I t should be mentioned that, f o r both the acetcocy and the benzoylcocy group, the same anomeric e f f e c t (1. 3 kcal/mol) served as the b a s i s of the c a l c u l a t i o n . T h i s value may be concluded from the measurements of Durette and Horton (18) on mixed a c y l a t e d pentopyranoses. When the s i t u a t i o n i s examined f o r the g - r i b o compound (Figure 9 ) , the C i form on the r i g h t shows three, and the ^"C^ form on the l e f t , o n l y two gauche i n t e r a c t i o n s . The 1 , 3 - d i a x i a l 1

4

X

4

4



PAULSEN E T A L .

Conformational Analysis

2,3,4-Tri-g-b«nzoyl-ribitol 01- 02 — 03-04 02- 0 3 — 0 4 - 0 5 03- G 4 — 05-05 04- C 5 - 05-01 05- 0 5 - 01-02 05-C1 — 02-03

-51.9 52.7 -58.4 64.0 -63.3 57.2

021-02-03-031 031-G3— 04-041

2,3,4-Tri-fi-btnzoyl-xylitol 01 - 0 2 — 0 3 - 0 4 02- 0 3 - 04-05 03- 0 4 - 05-O5 04- 0 5 - 05-01 05- 0 5 - 01-02 05-01 - 02-03

-56.3 56.2 -60.3 63.9 -63.1 59.8

O21-02—03-031 031-03- G4-041

Figure 7




RO

Acotott

OR

~ 23%

1

RO

C

77% *£,

4

Bonzoato ~ 2 7 % *C

A 6 ° -0.74 K c o l / m o l

73V. * C ,

4

A G ° • (•)OR//OR/Or • anom. Eff. (•)OAc//OAc/H

- 1 9 Kcal/mol

(•) O B z l O B z / H

-w 15 Kcal/mol

OR

A©•

-0.60Kcol/mol

-(olOIMfOR/H

Figure 8

OR

'C

p-D-ribo

4

Acttatt

- 57%

Bonzoato

^77%

1

£

4

Cj

4

4 3 % *£,

A O ° •0.18

Kcal/mol

^4

2 3 % ^1

A G ° • 0.72

Kcal/mol

A G * »(•)OR//OR/Or - g a u c h * OR /OR - anom. Eff. gauch*

OAc/OAc

~ 0 . 3 Kcal/mol

gauche

OBz/ OBz

—0.2 K c a l / m o l

Figure 9



5.

Conformational

PAULSEN E T A L .

73

Analysis

i n t e r a c t i o n f o r the l e f t (^C^form i s known from the 1,5-anhydro r i b i t o l as shown before, the anomgric e f f e c t has t o be considered, and thus w i t h the experimental AG -value, the gauche i n t e r a c t i o n s may be c a l c u l a t e d . The gauche i n t e r a c t i o n of two acetoxv groups amounts t o 0. 3 kcal/mol, and t h a t f o r the benzoyloxy groups t o 0. 2 kcal/mol. These values are not s u b s t a n t i a l l y d i f f e r e n t , and are of the same magnitude as c a l c u l a t e d by Angyal (19, 20) and Z e f i r o v (21) by t h e i r methods. Thus f a r , these three model corapounds i n v e s t i g a t e d form the b a s i s f o r determination of t h r e e values of nonbonding i n t e r a c t i o n s . In 1 , 5 - a n h y d r o x y l i t o l ( F i g u r e 10), the conformational e q u i l i b r i u m i s s h i f t e d t o the e q u a t o r i a l form ( r i g h t s i d e ) . By accurate measurements, data c o u l d be obtained f o r determining the e q u i l i b r i u m , according t o which the t r i a x i a l form amounts t o about 13$ f o r the acetate and t o about 17$ f o r the benzoate. The two gauche i n t e r a c t i o n s i n the C i form on the r i g h t , and one 1 , 3 - d i a x i a l i n t e r a c t i o n p l u s one A-value i n the form on the l e f t , have t o be taken i n t o account. The c a l c u l a t i o n s f o r the 1 , 3 - d i a x i a l i n t e r a c t i o n o f two groups having a middle a x i a l group and an opposing ring-oxygen atom g i v e r i s e t o a smaller v a l u e than i n the former instance having a middle e q u a t o r i a l group, a f a c t that was t o be expected. For two acetoxy groups, 1.1 kcal/mol and f o r two benzoyloxy groups 0.6 kcal/mol, were determined. Again, the d i f f e r e n c e between the two s u b s t i t u e n t s i s n e a r l y the same, as observed before. However, because the e q u i l i b r i u m i s c o n s i d e r a b l y s h i f t e d toward one. conformation, these values have a l a r g e r margin f o r e r r o r . 4

The f o u r t h p o s s i b l e 1 , 3 - d i a x i a l i n t e r a c t i o n may be c a l c u l a t e d from the g-xylo compound shown i n F i g u r e H . As mentioned before, 28$ o f the t e t r a a c e t a t e and 50$ o f the benzoate adopt the C conformation shown on the l e f t (13). In the C i form on the r i g h t , t h r e e gauche i n t e r a c t i o n s and the anomeric e f f e c t have t o be considered, whereas i n the C form on the l e f t , two 1 , 3 - d i a x i a l i n t e r a c t i o n s of d i f f e r e n t types occur. The c a l c u l a t i o n f o r the 1 , 3 - d i a x i a l i n t e r a c t i o n t o two groups having a middle a x i a l group and opposing hydrogen atoms r e s u l t s i n 1. 7 kcal/mol f o r two acetoxy groups and 1.3 kcal/mol f o r two benzoyloxy groups. 1

4

4

1

4

These data correspond w e l l w i t h the r e s u l t s i n r e g a r d t o the other model compound, and are s l i g h t l y smaller than the comparable i n t e r a c t i o n i n the case of a middle e q u a t o r i a l group. Thus, by t h i s approach, we were able t o determine a l l four d i f f e r e n t 1 , 3 - d i a x i a l interactions. In a l l of these instances, comparable and c h a r a c t e r i s t i c d i f f e r e n c e s are observed between acetoxy and benzoyloxy groups. Now the c a l c u l a t e d values may be a p p l i e d t o a d d i t i o n a l , isomeric pentose d e r i v a t i v e s . In the a-D-xylopyranose d e r i v a t i v e ^ the e q u i l i b r i u m i s p r a c t i c a l l y t o t a l l y on the side of the C i form (13). S i m i l a r l y , the g-D-arabinopyranose d e r i v a t i v e t o t a l l y adopts the C conformation ( l j ) . Consequently, n e i t h e r 4

1

4




RO

OR

Acttatt

~13%

Bonzoato

-19%

^ !

87%

£

81%

4

*C, *Cj

A G ° • (a) OR//OR/Or • A - V a l u o (a)

0Ac//OAc/Or

-

la) OBz//OBz/Or

AG°-I.2 AG°-0.9

Kcal/mol Kcal/mol

OR - 2 g a u c h « OR/OR

1.1 K c a l / m o l

- 0.6 K c a l / m o l

Figure 10

RO

RO-WÂÂÔR OR

OR 'C*

p-O-zyip

Acttatt

- 2 8 % 'C

Btnzoatt

-50%

AG (a)

4

4

'C*

7 2 % *£,

AG°

5 0 % *C,

A G °- 0

- 0.58 K c a l / m o l Kcal/mol

» (a)OR//OR/Or • (a) OR//OR/H - anom. E f f - 3 g a u c h t

OAc//OAc/H

- 1.7

Kcal/mol

(a) OBz//OBz/H

- 1.3

Kcal/mol

OR/OR

Figure 11



5.

PAULSEN E T AL.

Conformational

Analysis

75

of these compounds are s u i t a b l e f o r f u r t h e r considerations. In 1,5-anhydro-D-arabinitol (Figure 12), c l o s e l y corresponding data are obtained f o r the conformational e q u i l i b r i a of the acetate and benzoate, i f these are c a l c u l a t e d by use of the determined energies of i n t e r a c t i o n . However, with a-D-arabino and a l s o a- and p-D-lvxo d e r i v a t i v e s , a s p e c i a l e f f e c t i s observed. In these three compounds a new i n t e r a c t i o n i s at hand, which has not yet been discussed. T h i s i s an i n t e r a c t i o n of an a x i a l acyloxy group with a 1 , 3 - d i a x i a l hydrogen atom and the opposing ring-oxygen atom. Such an i n t e r a c t i o n i s shown i n F i g u r e 13 w i t h the acyloxy group at C-4 i n the l e f t column and the acyloxy group at C-2 i n the r i g h t column. C a l c u l a t i o n s of the e q u i l i b r i a w i l l g i v e i n c o r r e c t r e s u l t s i f the i n t e r a c t i o n of both the acyloxy group at C-4 and that at C-2 are considered t o be o f the same magnitude. I f , f o r t h i s i n t e r a c t i o n , 8 d i f f e r e n c e of 0 . 7 — 0 . 9 kcal/mol i s considered, which r e l a t e d t o the enhanced i n t e r a c t i o n of the 2-acyloxy group, the c a l c u l a t i o n of a l l of these e q u i l i b r i a according t o the energies of i n t e r a c t i o n determined gives mostly s a t i s f a c t o r y r e s u l t s . Obviously, i n the conformation t o the r i g h t , which shows the c h a r a c t e r i s t i c arrangement of an a x i a l 2-acyloxy group with a 1 , 3 - d i a x i a l i n t e r a c t i o n towards a hydrogen atom and the r i n g oxygen atom, an a d d i t i o n a l d e s t a b i l i z i n g f a c t o r of 0 . 7 — 0 . 9 kcal/mol has t o be taken i n t o account. A reason f o r t h i s a d d i t i o n a l d e s t a b i l i z i n g e f f e c t cannot be given s t r a i g h t f o r w a r d l y , although there seems t o be a c e r t a i n s i m i l a r i t y t o the formerly discussed A 2 - e f f e c t (20, 22). In general, most authors tend t o i n c o r p o r a t e t h i s f a c t o r i n t o the anomeric e f f e c t ; however, i t seems t o be j u s t i f i e d i n the pentopyranose s e r i e s t o consider t h i s e f f e c t separately. A H of the r e s u l t s are compiled i n F i g u r e 14. For the four d i f f e r e n t p o s s i b l e 1 , 3 - d i a x i a l i n t e r a c t i o n s , s l i g h t l v d i f f e r e n t values have been determined. As might have been expected, the i n t e r a c t i o n s are smaller i f the ring-oxygen atom opposes the d i a x i a l substituents, i n contrast t o hydrogen atoms i n 1 , 3 - d i a x i a l d i s p o s i t i o n . Furthermore, the i n t e r a c t i o n i s a l i t t l e smaller i f the middle substituent between the two d i a x i a l groups adopts the a x i a l r a t h e r than the e q u a t o r i a l d i s p o s i t i o n . The data show c l e a r l y th8t, i n a l l instances f o r two benzoyloxy groups, the energy of i n t e r a c t i o n i s 0 . 4 — 0 . 6 k c a l / mol smaller than f o r two acetoxy groups. The gauche i n t e r a c t i o n between two acetoxy and two benzoyloxy groups seems t o be of s i m i l a r magnitude. The d i f f e r e n c e i n the 1 , 3 - d i a x i a l i n t e r a c t i o n s cannot be explained by taking i n t o account an enhanced gauche i n t e r a c t i o n between two benzoyloxy groups. For the s p e c i a l arrangement of an a x i a l acetoxy group at C-2 with hydrogen and the ring-oxygen atom i n 1 , 3 - d i a x i a l d i s p o s i t i o n , an a d d i t i o n a l d e s t a b i l i z i n g e f f e c t has t o be considered, as shown i n the formula a t the bottom of F i g u r e 14.



RO

RO ^

oroblno


Acotato Bonzoato

caic. 34% *C calc. 30% *C|

4

£i

found 29% found 25%

t

Figure 12

H

RO

H

OR

1p, 4-OR

4.-0-arabino

0R#H/0r-f- 2-OR OR//H/Or

/ S R ^ O ^ O R

RO

OR "1

difforonco ~0.9 Kcal/mol

R O - V ^ ^ v

0OR 1

H

Anomeric Effect - American Chemical Society

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