284
J . Am. Chem. Sot. 1990, 112, 284-291
Quantitation of Proximity Effects on Rate. A Case Study Involving Dyotropic Hydrogen Migration within syn-Sesquinorbornene Disulfones Carrying Central Substituents Having Different Spatial Demands Leo A. Paquette,* Mark A. Kesselmayer, and Robin D. Rogers Contribution from the Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 4321 0,and the Department of Chemistry, Northern Illinois University, DeKalb, Illinois 601 15. Received May 30, 1989
Abstract: The syn-sesquinorbornadiene that is produced upon Diels-Alder reaction of (2)1,2-bis(phenylsulfonyI)ethylene with tricycle[ 5.2.1 .02.6]deca-2,5,8-trienehas been regiospecifically reduced at its central double bond with diimide. Allied reactions take a parallel course, thereby allowing for the fusion of oxirane, aziridine, cyclopropane, and methylcyclopropane subunits in the central region of this molecule. All of these products undergo clean dyotropic migration of their endo a-sulfonyl protons to the proximal double bond. The distances involved have been quantified by X-ray crystallographic analysis in each case. Following up on this, the kinetics of these isomerizations were measured in order to establish a relative reactivity scale. A very good correlation is seen between reaction rate and the average intracavity distance. These extensive data are in agreement with the notion that reactivity is primarily dependent upon distance in a series where gross structural modifications need not operate at the transition-state level. In the present investigation, modulation of the intracavity distance to an extent slightly in excess of 0.3 A is reflected in a rate spread greater than lo4.
Intramolecular reactions often exhibit remarkably enhanced rates. Considerable interest has arisen in these processes because of the belief that the consequences of intramolecularity can be utilized to better understand mechanisms of enzyme action.’ However, rate accelerations stemming from covalently enforced proximity have proven difficult to analyze from the mechanistic vantage point. As a result, the area has been fraught with controversy. Koshland’s early proposal2 that high rates are a direct consequence of optimal orbital alignment within a reactant, the so-called “orbital steering theory”, met almost immediately with The need to imply force cunstants for partly formed bonds that exceed those of covalent bonds is viewed as particularly ~nrealistic.~The Milstein-Cohen “stereopopulation control” proposal for lactonization* was subsequently counteracted by calculations showing that nucleophilic attack by methanol on formic acid has very loose angular requirements.Im Other evidence has subsequently been gained to show that neither phenomenon can be a major contributor to overall kinetic a~celeration.’~J~ In fact, scant information exists on the precise manner in which geometric disposition affects reactivity. The critical importance of distance to rate has been championed by both Bruice” and Menger.I6 As matters have turned out, Menger’s “spatiotemporal hypothesis” has been criticized by Houk who has claimed that no necessary relationship exists between the distance separating the reacting atoms in the starting material and the reaction rate.17 However, Houk‘s “transition-state modeling’’ approach has more recently also come under This exasperating state of affairs has arisen because of the necessary interplay of several ancillary factors during intramolecular reaction, depending on the precise nature of the chemical event. Certainly there are known cases where the freezing of a single rotation has led to substantitive (ca. lo4) rate enhancements8*IbbHowever, without accompanying kinetically relevant structural changes, only a 5-fold increase in k can be anticipated from this type of favorable energy contrib~tion.’~*’~ Nonetheless, calculations do exist that predict the possibility for attaining accelerations as high as IO7 under the proper circumstances.20 These do not include examples where a decrease in distance would be accompanied by a substantial strain increase elsewhere in the reactant. As Houk points out, there is need to give serious thought to the ease of achieving transition-state geometries in addition to the geometric details in the substrate molecule.17 Failure to *Address correspondence to this author at The Ohio State University.
0002-7863/90/1512-284$02.50/0
do so may ignore the adverse energetic effects associated with precompression. In light of the above, it occurred to us that definitive information concerning proximity effects on rates could be acquired if the systems under study were inherently free of as many assumptions (1) Czarnik, A. W. In Mechanistic Principles of Enzyme Activity; Liebman, J. F., Greenberg, A., Eds.; VCH Publishers, Inc.: New York, 1986. (2) (a) Storm, D. R.; Koshland, D. W., Jr. Proc. Nafl.Acad. Sci. U.S.A. 1970,66,445. (b) Koshland, D. E., Jr.; Carraway, K. W.; Dafforn, G. A.; G a s , J. D.; Storm, D. R. Cold Spring Harbor Symp. Quanr. Biol. 1971,36, 13. (c) Storm, D. R.; Tjian, R.; Koshland, D. E., Jr. J. Chem. Soc. D 1971, 15,854. (d) Storm, D. R.; Koshland, D. E., Jr. J . Am. Chem. Soc. 1972,94, 5805, 5815. (e) Dafforn, A,; Koshland, D. E., Jr. Biochem. Biophys. Res. Commun. 1973, 52, 779. (3) (a) Bruice, T. C. In Annual Review ofbiochemistry; Annual Reviews, Inc.: Palo Alto, CA, 1976, Vol. 45, pp 352-357. (b) Bruice, T. C. In The Enzymes; Boyer, P. D., Ed.; Academic Press: 1970; Vol. 11, Chapter 4. (c) Bruice, T. C.; Benkovic, S. J. In Bioorganic Mechanisms; W. A. Benjamin, 1970; Chapter 4. (4) (a) Bruice, T. C.; Brown, A.; Harris, D. 0. Proc. Natl. Acad. Sci. U.S.A. 1971,68,658. (b) Bruice, T. C. Cold Spring Harbor Symp. Quant. Biol. 1971, 36, 21. (c) Bruice, T. C. Nature (London) 1972, 237, 335. ( 5 ) Jencks, W. P.; Page, M. I. Biochem. Biophys. Res. Commun. 1974,57, 887. (6) Capon, B. J. Chem. SOC.B 1971, 1207. (7) Hoare, D. G. Nature (London) 1972, 236, 437. (8) Milstien, S.; Cohen, L. A. J . Am. Chem. SOC.1972, 94, 9158. (9) Herschfield, R.; Schmir, G. L. J . Am. Chem. SOC.1972, 94, 6788. (10) (a) Halgren, T. A.; Lipscomb, W. N. J . Chem. Phys. 1973,58, 1569. (b) Schemer, S.; Lipscomb, W. N.; Kleier, D. A. J . Am. Chem. SOC.1976, 98, 4770. (1 1) Moriarty, R. M.; Adams, T. J . Am. Chem. Soc. 1973,95,4070,4071. (12) Mihel, I.; Knipe, J. 0.;Coward, J. K.; Schowen, R. L. J . Am. Chem. SOC.1979. 101.4349. (13) Menger, F. M.; Chow, J. F.; Kaiserman, H.; Vasquez, P. C. J . Am. Chem. SOC.1983, 105, 4996. (14) Gandour, R. D. In Transition States of Biochemical Processes; Gandour, R. D., Schowen, R. L., Eds.; Plenum Press: New York, 1978; pp
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529-557
(15) Bruice, T. C. Ann. Rev. Biochem. 1976, 45, 331. (16) (a) Menger, F. M.; Venkataram, U. V. J . Am. Chem. Soc. 1985,107, 4706. (b) Menger, F. M. Acc. Chem. Res. 1985.18, 128. (c) Menger, F. M. Adu. Mol. Model. 1988, I , 189. (d) Sherrod, M. J.; Menger, F. M. J. Am. Chem. SOC.1989, 111, 2611. (17) (a) Dorigo, A. E.; Houk, K. N. J . Am. Chem. SOC.1987, 109, 3698. (b) Dorigo, A. E.; Houk, K. N. Ado. Mol. Model. 1988, I , 135. (18) Page, M. I.; Jencks, W. P. Proc. Nafl. Acad. Sei. U.S.A. 1971, 68, 1678. (19) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95. (20) Delisi, C.; Crothers, D. M. Biopolymers 1973, 12, 1689.
0 1990 American Chemical Society
J . Am. Chem. SOC.,Vol. 112, No. I, 1990 285
Quantitation of Proximity Effects on Rate Scheme I
H
10 MCPBA, CH2CIz O'C
/
PhN38
CH2C12
\ Ph'
\\
H
11
Ph
/N
N
so*Ph
12
as possible. A detailed appreciation of all relevant structural and mechanistic issues is especially necessary. Also, since the "spatiotemporal hypothesis" necessitates that activation energy be a very steep sigmoidal function of distance, the critical distance must not be exceeded or E, will no longer decrease with decreasing interatomic distance. The other criteria alluded to above must also be met. syn-Seaquinorbomenesand Hydrogen Dyotropy. Although the least-motion transfer of two hydrogen atoms from eclipsed ethane to ethylene is symmetry-allowed if concerted, a surprisingly large barrier (7 1 kcal/mol) has been calculated for this process.22 The analogous reaction involving diimide and ethylene, which profits from a very large energy lowering due to nitrogen evolution:3 has an estimated activation energy of approximately 27 kcal/m01.*~ In related fashion, development of a sizable proportion of the resonance energy of naphthalene ( 6 1 kcal/mol) at the transition state forms the basis for the ability of cis-9,lO-dihydronaphthalene to transfer its two central hydrogen atoms.25 When the suprafacial dyotropic reactionz6is made intramolecular as in 1,27advantage can continue to be taken of aromatic ring formation. Furthermore, the rigid positioning of the two migrating hydrogens in close proximity to the double bond facilitates the 2-fold migration still m ~ r e . ~ * In - ~ 1981, ~ Vogel
"
13
recorded the important observation that these processes need not depend on the formation of aromatic compounds for their opera t i ~ n . Thus, ~ ~ 3 undergoes reversible pericyclic isomerization to give 4 at 130 OC. The equilibrium constant for 4:3 in C6D6 solution at this temperature is 1.1-1.2.
fi H
H H
HE
E
130'C
E = COOCH,
3
2
(21) Woodward, R. B.;Hoffmann, R. The Conservation of Orbital Symmetry; Verlag Chemie: Weinheim, 1971; pp 141-144. (22) Feller, D. F.; Schmidt, M. W.; Ruedenberg, K. J . Am. Chem. SOC. 1982, 104,960. As noted by a referee, the differences between experimental and calculated values would undoubtedly decrease with the use of high-level basis sets and post-Hartrees-Fock calculations that can be accomplished today with the use of supercomputers. (23) Hunig, S. Angew. Chem., Int. Ed. Engl. 1965, 4. 271. (24) Pasto, D. J.; Chipman, D. M. J . Am. Chem. Soc. 1979, 101, 2290. (25) Doering, W. von E.; Rosentahl, J. W. J. Am. Chem. Soc. 1967, 89, 4534. (26) (a) Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1972.11, 129, 131. (b) Reetz. M. T. Tetrahedron 1973, 29,2189. (c) Reetz, M. T. Ado. &gunomet. Chem. 1977, 16, 33. (27) (a) Mackenzie, K. J . Chem. SOC.1965,4646. (b) Mackenzie, K. J . Chem. Soc. C 1969, 1784. (c) Mackenzie, K.; Adam, C. H. M. Ibid. 1969, 480. (28) For a related example, consult the following: Chow, T. J.; Ding, M..F. Angew. Chem., Int. Ed. Engl. 1986, 25, 1121. (29) Heterocyclic analogues of 1 have been prepared and studied: (a) Mackenzie, K.;Proctor, 0. J.; Woodnutt, D. J. Tetrahedron Lett. 1984, 25, 977. (b) Mackenzie, K.; Proctor, G. J.; Woodnutt, D.J. Tetrahedron 1987, 43, 5981.
E
4
These uncatalyzed intramolecular hydrogen migrations are seen to involve the synchronous translocation of two C-H u bonds. A totally symmetrical transfer mode is, as usual, not strictly required. In principle, the distances involved are ascertainable by X-ray crystallographic analysis of starting material and product. In 3 and 4, the compressed molecular topographies guarantee that the traversed distance is short. However, precise structural information is not available. Herein we describe the synthesis of syn-sesquinorbornene disulfones of general type 5, where the distance separating the pair X
Y
1
e H
of a-sulfonyl protons and the double bond is progressively altered by the introduction of suitable structural subunits across the C(4)
