Stereoelectronic Effects in Phosphate Esters - ACS Publications

14 Stereoelectronic Effects in Phosphate Esters D. G. GORENSTEIN, R. ROWELL, and K. TAIRA Downloaded by QUEENSLAND UNIV OF TECHNOLOGY on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch014

University of Illinois, Chemistry Department, P.O. Box 4348, Chicago, IL 60680

The role of orbital orientation in organic and enzymatic reactions has been of considerable current interest. Deslongchamps and coworkers(1) in studying tetracovalent carbon species have recently demonstrated selective cleavage of bonds which are trans, antiperiplanar (app) to lone pairs on directly bonded oxygen and nitrogen atoms. Molecular orbital calculations have also provided theoretical justification for these stereoelectronic effects in tetracovalent and pentacovalent phosphorus species (2-7). As has been shown in molecular orbital calculations on the X -P-X (X = O,N) structural fragments, the X -P bond is strengthened (as indicated by an i n crease in the Mulliken overlap population) while the P-X bond is weakened when the X atom lone pair is app to the P-X bond. Thus, in the g,t conformation of dimethyl phosphate (Structure 1) the overlap population for the trans P-O bond is .017 electron lower than the overlap population for the gauche P-O bond. As shown for g,t dimethyl phosphate one lone pair (shaded in 1) on the gauche bond oxygen is app to the trans bond, while no lone pairs on the trans bond oxygen are app to the gauche bond. Thus, the weakest X -P bond has one app lone pair and no lone pairs on X app to the P-X bond. Further ab initio molecular orbital calculations on the reaction profile for the base-catalyzed hydrolysis of dimethyl phosphate in various ester conformations have provided support for this theory (5,6): (CH 0) P0~- + OH + (CH 0) PO H (CH^PC^H + Cl^O Typically, for the methoxide elimination step the transition state which has an antiperiplanar lone pair to the methoxide leaving group is ca. 11 kcal/mol lower in energy than the transition state without this app lone pair (Fig.1). In order to experimentally assess the magnitude of the stereoelectronic effect at phosphorus, we have prepared and studied the reactions of the six-membered ring cyclic esters such as 1

2

1

2

1

2

1

1

2

3

?

2

3

2

Configurâtional and conformational analysis of these isomeric 2-aryloxy-2-oxo-trans-5,6-tetramethylene-l,3,2-dioxaphosphorinanes 0097-6156/81/0171-0069$05.00/ 0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

Downloaded by QUEENSLAND UNIV OF TECHNOLOGY on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch014

70

Ο R E A C T I O N C O O R D I N A T E (A) Figure 1. Reaction profilesfor hydroxide-catalyzed hydrolysis ofdimethyl phosphate (5). Torsional angles about the Ρ- Ο Me bonds for the phosphorane intermediates are defined by the Me ΟΡΟ Me structuralfragment, and the torsional angle about the P-OH bond is defined by the MeOePOH fragment. Conformers are defined by the following order for the torsional angles: apical ester, equatorial ester, and apical P- OH bonds. The reaction coordinate is defined by the P- OH distance (ÛPOH) and P- Ofa)CHj distance (d POCHJ)for the attack and displacement steps, respectively. Solid line represents profilefor OH~ attack on g,g DM Ρ to yield g,g, -g DM Panes (Ώ) andfor OH~ attack on g,t DM Ρ to yielding DM Panes (·). Dashed line represents profile for OH~ attack on g,t DM Ρ to yield g,t,t DM Panes (A).

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.


GORENSTEIN E T A L .

Stereoelectronic Effects in Phosphate

Esters

R 2 a - 5 a (R=H); 6 a ( R = C H ) 3

O I!

R 2 b - 5 b (R=H); 6 b ( R = C H ) 3



72

PHOSPHORUS CHEMISTRY

2~5 (ArO = p-methoxyphenoxy, p-nitrophenoxy, phenoxy, and 2,4-dinitrophenoxy, r e s p e c t i v e l y ) and isomeric 2-p-nitrophenoxy-2-oxo-5methyl ( c i s and trans)-5,6-tetramethylene-l,3,2-dioxaphosphorinanes, 6 and 1 have been determined by NMR c o u p l i n g data and P-31 and C-13 NMR and IR s p e c t r a . The a x i a l a r y l o x y isomers 2a6a. of these trans d e c a l i n - t y p e six-membered r i n g phosphorinanes (and c i s - d e c a l i n Zâ) are i n c h a i r conformations. However, NMR and IR data support the assignment of a twist boat conformation f o r the " e q u a t o r i a l " isomer of the 2,4-dinitrophenoxy e s t e r §fc« Mixed c h a i r and twist boat conformations are found f o r the other a r y l o x y e s t e r s 2b-4b. A pure c h a i r conformation i s found f o r the other e q u a t o r i a l p-nitrophenoxy e s t e r , 6b (R = CH3) presumably due to the s t e r i c i n t e r a c t i o n of the a x i a l methyl group with the phosphate i n any twist conformation. The a x i a l isomers 2â~6â are 1.52 kcal/mole lower energy and hydrolyze i n base 4-17 times slower than t h e i r epimers. Only the twist boat isomer of 2,4-dinitrophenoxy e s t e r , 5b, r e a c t s with 100% i n v e r s i o n of c o n f i g u r a t i o n with methoxide. A l l other compounds r e a c t with 4-83% i n v e r s i o n of conf i g u r a t i o n with the most r e t e n t i o n obtained f o r the poorest l e a v ing groups. An 0-18 i s o t o p i c s h i f t on P-31 chemical s h i f t s of epimeric 1, 3,2-dioxaphosphorinane e s t e r s (10) has been used to i n v e s t i g a t e the stereochemistry of hydroxide c a t a l y z e d h y d r o l y s i s i n these a r y l phosphorinane t r i e s t e r s . As shown i n Scheme I the a x i a l epimer of 2-(2,4-dinitrophenoxy)-2-oxo-trans-5,6-tetramethylene-l,3,2-dioxaphosphorinane) 5a, was hydrolyzed i n 0-18 enriched hydroxide. The c y c l i c d i e s t e r , 8, was methylated with diazomethane i n methanol. The P-31 NMR spectrum of the 0-18 l a b e l e d a x i a l methyl p h o s p o r i nane product, 2, showed three s i g n a l s r e p r e s e n t i n g the unlabeled phosphate, the Ρ 0—18-CH^ ( e s t e r oxygen) labeled phosphate, and the ρ m 0-18 (phosphoryl) l a b e l e d phosphate. A n a l y s i s of the 0-18 d i s t r i b u t i o n by d i r e c t i n t e g r a t i o n of the three s i g n a l s gave 100% P-0 a r y l bond cleavage and 82% i n v e r s i o n of c o n f i g u r a t i o n at phos phorus . The hydroxide c a t a l y z e d h y d r o l y s i s of the e q u a t o r i a l e p i mer of the p-methoxyphenoxy-1,3-2-dioxaphosphorinane y i e l d e d 59% inversion. The epimeric s u b s t i t u t e d a r y l o x y phosphorinanes 2-§ were hy dro lyzed i n 30% dioxane/water at 70 C with a v a r i e t y of nucleo p h i l e s (11). The r e a c t i v i t i e s were s e n s i t i v e to changes i n both the n u c l e o p h i l e and l e a v i n g group. The Bronsted β s f o r the e q u a t o r i a l l e a v i n g groups 2,4-DNP, PNP, and Ph are 0.48, 0.64, and 0.75 r e s p e c t i v e l y . The Bronsted β s are -0.96, -1.04, -0.85, -0.66, -0.64, -0.57, -0.46, and -0.§5 f o r n u c l e o p h i l e s water, methoxyacetate, a c e t a t e , phosphate, h e x a f l u o r o i s o p r o p o x i d e , c a r bonate, t r i f l u o r e t h o x i d e , and hydroxide r e s p e c t i v e l y . These r e s u l t s suggest a concerted S^2(P) mechanism e s p e c i a l l y i n r e a c t i o n s where ^ g r e a t e r than 0.6. However, the hydroxide c a t a l y z e d h y d r o l y s i s of 5a. and Zb y i e l d e d s u b s t a n t i a l r e t e n t i o n product at phosphorus. Thus an intermediate i s r e q u i r e d f o r a t t a c k by very b a s i c n u c l e o p h i l e s i n c o n t r a s t to the Bronsted r e l a t i o n s h i p r e sults. Together, the stereochemical data, m u l t i p l e s t r u c t u r e r e a c t i v i t y r e l a t i o n s h i p s , and epimer r a t e r a t i o s may be r e c o n c i l e d 1

1

s



14.

GORENSTEiN E T A L .

Stereoelectronic

Effects in Phosphate

Esters

Scheme I. OAr I "OAr

INVERSION

RETENTION

Ο

0

0,

0

CH N ,DME

CH OH

CH OH

3

1 8

1 6

CH N ,DME 2

9(AXIAL

1 8

8( 0, 0)

1 6

0)

2

2

2

3

9 (EQUATORIAL

1 8

0,

16

Q)


73


74 PHOSPHORUS CHEMISTRY

Scheme II.



14.

GORENSTEiN E T A L .

Stereoelectronic Effects in Phosphate Esters

75

by a s s u m i n g a c o n t i n u u m o f mechanisms f o r r e a c t i o n s o f p h o s p h a t e t r i e s t e r s , from a d d i t i o n / e l i m i n a t i o n t o concerted S 2 ( P ) . Unfortunately the unusual conformational f l e x i b i l i t y of the e s t e r s 2-6 p r e c l u d e a d e f i n i t i v e e s t i m a t e o f t h e m a g n i t u d e o f t h e s t e r e o e l e c t r o n i c e f f e c t i n phosphate e s t e r r e a c t i v i t y . However, we^have e g r l i e r p r o p o s e d ( 4 ) t h a t a s i g n i f i c a n t f r a c t i o n o f t h e 10 t o 10 - f o l d r a t e a c c e l e r a t i o n i n t h e h y d r o l y s i s o f s t r a i n e d c y c l i c five-membered-ring phosphate e s t e r s r e l a t i v e t o t h e i r acyc l i c c o u n t e r p a r t s (12) was due t o a s t e r e o e l e c t r o n i c e f f e c t . I n a d d i t i o n , t h e d r a m a t i c d i f f e r e n c e i n P-0 bond c l e a v a g e (13) i n 10 and 11 c o u l d a r i s e f r o m a s t e r e o e l e c t r o n i c e f f e c t . T h u s , a s shown i n Scheme I I t h e p h o s p h o r a n e f o r m e d b y h y d r o x i d e a t t a c k o p p o s i t e t h e r i n g o x y g e n i n 10 h a s two app l o n e p a i r s on t h e b a s a l o x y g e n w h i c h f a c i l i t a t e r i n g P-0 bond c l e a v a g e . The p h o s p h o r a n e f o r m e d f r o m h y d r o x i d e a t t a c k on 11 h a s o n l y one app l o n e p a i r o p p o s i t e t h e a p i c a l r i n g oxygen (the n i t r o g e n l o n e p a i r w i l l l i e i n t h e b a s a l p l a n e ) a n d P-0 bond c l e a v a g e i s n o t f a v o r e d . Pseudorotation c o n c o m i t a n t w i t h p r o t o n r e o r g a n i z a t i o n y i e l d s a new p h o s p h o r a n e i n w h i c h t h e a p i c a l n i t r o g e n i s app t o two o x y g e n l o n e p a i r s , p o s s i b l y p r o v i d i n g a n e x p l a n a t i o n f o r t h e 1 0 0 % P-N c l e a v a g e i n 1 1 .

LITERATURE CITED 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Deslongchamps, P. Tetrahedron 1975, 31, 2463. Lehn, J.M.; Wipff, G. J . Chem. Soc. Chem. Comm. 1975, 800. Gorenstein, D.G.; Findlay, J.B.; Luxon, B.A.; Kar, D. J . Am. Chem. Soc. 1977, 99, 3473. Gorenstein, D.G.; Luxon, B.A.; Findlay, J.B.; Momii, R. J . Am. Chem. Soc. 1977, 99, 4170. Gorenstein, D.G.; Luxon, B.A.; Findlay, J.B. J . Am. Chem. Soc. 1977, 99, 8048. Gorenstein, D.G.; Luxon, B.A.; Findlay, J.B. J . Am. Chem. Soc. 1979, 101, 5869. Gorenstein, D.G.; Luxon, B.A.; Goldfield, E. J . Am. Chem. Soc. 1980, 102, 1759. Gorenstein, D.G.; Rowell, R. J . Am. Chem. Soc. 1979, 101, 4929 and refs therein to related studies by other authors. Gorenstein, D.G.; Rowell, R.: Findlay, J.B. J . Am. Chem. Soc. 1980, 102, 5077. Gorenstein, D.G.; Rowell, R. J . Am. Chem. Soc. 1980, 102 6165. Gorenstein, D.D.; Rowell, R. J . Am. Chem. Soc., accepted for publication. Westheimer, F.H. Acc. Chem. Res. 1968, 1, 70. Boudreau, J.Α.; Brown, C.; Hudson, R.F. J. Chem. Soc. Chem. Comm. 1975, 679.

RECEIVED September 10, 1981.


Stereoelectronic Effects in Phosphate Esters - ACS Publications

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