Relationship between Nucleophilic Reactions and Single-Electron

23

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Relationship between Nucleophilic Reactions and Single-Electron Transfer Application to Reactions of Radical Cations Addy Pross Department of Chemistry, Ben-Gurion University of the Negev, Beersheva, Israel,* and Department of Chemistry, Stanford University, Stanford, CA 94305

Nucleophilic reactions often compete with single-electron-transfer (SET) processes. The configuration mixing (CM) model, which builds up reaction profiles qualitatively, is utilized to provide simple experimental criteria for predicting the factors likely to encourage one pathway over the other pathway. The analysis suggests both nucleophilic and SET processes involve a single-electron shift. Factors that favor a SET process include (1) strong donor-acceptor pair ability of nucleophile and electrophile, (2) steric interactions in the transition state, (3) delocalization of the odd electrons that make up the nucleophile-substrate bond, and (4) the nucleophile-substrate bond strength. The apparent reluctance of aromatic radical cations to undergo direct nucleophilic attack is explained on the basis of the single-electron shift model for nucleophilic reactions.

TTHE CLASS O F SINGLE-ELECTRON-TRANSFER (SET) processes in organic chemistry (for a recent review on organic electron-transfer reactions, see reference 1) has expanded enormously over recent years so that organic reaction mechanisms may be broadly divided into two general classes: the polar reactions in which electrons seem "to move about in pairs" and the socalled one-electron processes in which electrons are transferred one at a time (2). Yet, strangely, the relationship between these two pathways is far from clear. For the specific case of nucleophilic reactivity, the question arises: * Where correspondence should be sent. 0065-2393/87/0215-0331$06.00/0 © 1987 American Chemical Society

In Nucleophilicity; Harris, J., et al.; Advances in Chemistry; American Chemical Society: Washington, DC, 1987.

NUCLEOPHILICITY

332

Why do nucleophiles at times follow a polar pathway, for example, the S 2 reaction or nucleophilic addition to the carbonyl group, whereas at other times these same nucleophiles might react via a S E T process? What is the relationship between these two general pathways and what factors influence which reaction pathway will be followed in any particular case? This chapter analyzes this problem using the configuration mixing (CM) model (3-5) by comparing both reaction processes. Finally, we will turn to the chemistry of odd electron species. The reaction of radical cations with nucleophiles has been extensively studied over recent years. In a detailed review, Parker (6) concluded that certain radical cations, which were previously thought to undergo direct nu cleophilic attack, actually react via a series of electron-transfer steps. Using the C M analysis, this chapter provides a simple explanation for the puzzling reactivity properties of odd-electron species and shows how their behavior fits into the polar-S E T mechanistic picture.


N

Discussion An S 2 reaction, depicted in equation 1, seems to come about by an electron pair on the nucleophile "displacing" a second electron pair—the R - X σ bond. Four valence electrons appear to be involved. The problem with this representation is that the electronic rearrangement seems radically different from that in a S E T process, such as the initiation step of the S 1 process (7), equation 2. Clearly, just a single electron has been transferred from the nucleophile to R X . As a consequence of these quite different descriptions, the relationship between the two processes becomes obscure. What factors encourage one pathway over the other is not clear. N

RN

N:" + R — X ^ N—R + :X"

N:~ + R — X —

N- + (R^X)-

(1)

(2)

Despite the fact that polar nucleophilic reactions are commonly termed "two-electron" processes, what the term really signifies must be understood. The term does not mean that during the course of the reaction, electron pairs relocate within the molecule two by two, in the way that the curly arrow convention implies. Two-electron processes merely indicate that all electrons that were spin-coupled in reactants remain spin-coupled in the products. Actually, the S 2 process and indeed all other polar nucleophilic reactions are really just single-electron-shift processes (2, 3). The approximate wave function that describes the reactants of the S 2 process (equation 1) is given by x , equation 3, and differs from the corresponding wave function describ ing products, x , equation 4, by just a single-electron shift. The singleN

N

R

P


23. PROSS

NucleophileSingle-Electron Transfer Reactions

333

electron-shift nature of the reaction becomes even more apparent when simple V B structures are used to represent χ and χ , as shown in I and II respectively. β


x

«

=

X*

=

yfc

Ρ

[ΦΝ(1)ΦΝ(2)Φ (3)ΦΧ(4) - φ (1)φ (2)φ (3)φ (4)] η

Ν

\ 7 Γ [ΦΝ(1)ΦΚ(2)ΦΧ(3)Φ (4) χ

N:"

R

Χ

Ν

κ

χ

φ (1)φ (2)φ (3)φ (4)] Ν

Ν

κ

R

I

χ

χ

(3)

(4)

:Χ"

II

To convert I to II all that is needed is to shift a single electron from N : ~ to · X . In other words, the barrier to an S 2 reaction may be thought of as coming about through the avoided crossing of χ and χ (3, 8-10) or, using the D (donor)-A (acceptor) terminology, by a D A - D A ~ - a v o i d e d crossing (9, 11). Consideration of the S 2 process in these terms provided a means of assess ing the factors governing reactivity in these systems (8, 11, 12). In the context of this chapter, we demonstrate that only by considering polar nucleophilic processes as S E T processes can the factors that govern the competition between polar and S E T processes as well as nucleophilic reac tions of radical cations be adequately understood. Consider the reaction of a carbonyl compound with a nucleophile, the hydroxide ion: N

κ

Ρ

+

N

HOr

+

\ = 0

—

HO—C—Or

/

(5)

I

For this reaction, reactant and product configurations are depicted by III and IV, respectively. Here again, we see that reaction comes about by a singleelectron shift. The product configuration has two spin-paired electrons on Ο and C that can form a bond once that electron shift has occurred. So we see that the différence between a nucleophilic addition process and S E T lies not in the number of electrons that are shifted but in whether two coupled electrons in close proximity are generated following the electron shift. This statement is the essence of the polar-S E T competition. In a S E T pathway D , A reacts to form D , A ~ , while in a polar process such as that in equation 5, +

HO:"

C—Ο III

HO

C—OIV


334

NUCLEOPHILICITY +

_

D , A react to form D - A . The difference is that in the polar pathway two odd electrons on D a n d Α · ~ , brought about by the single-electron shift, are paired into a single bond. In the case of the S E T process, no such interaction occurs. +


SET versus Polar Pathways Any factor that inhibits or disallows coupling of the two odd electrons after the single-electron shift will encourage S E T over a polar nucleophilic path way. This statement forms the basis for understanding the competition between these two routes. The following factors will have a bearing on the polar-S E T competition (2). Donor-Acceptor Pair Ability. The better the donor-acceptor pair, the earlier the avoided crossing between D A and D A configurations so that the degree of coupling between the two odd electrons is reduced. This relationship will lead to an increase in the likelihood of a S E T process, and numerous examples where this trend is observed exist (13-18). +

-

Steric Interactions between D and A . If D or A is sterically hindered, then coupling between D and A is impeded and a S E T pathway is encouraged (13, 19, 20). +

_

D - A Bond Strength. The stronger the D - A bond, the more likely D - A coupling will occur. If the D - A bond that is to form is weak, the S E T is encouraged. The tendency for iodide ion to act as an electron donor but fluoride ion as a nucleophile (21-22) may be explained in this manner. Radical Derealization. If the two radical centers on D and A are extensively delocalized, coupling is inhibited and a S E T pathway is encour aged. This actually represents a special case of D - A bond strength, because the coupling of delocalized radicals leads to weak bonds. Numerous exam ples of all of these predictions exist (2); these examples make the foregoing analysis a most useful one. We see therefore that only by viewing the polar process as a single-electron shift does the relationship between the polar and SET pathways become clear. Nucleophilic Attack on Radical Cations What is the mechanism of attack of nucleophiles on radical cation species such as anthracene or thianthrene radical cations? Extensive studies by a number of groups have been conducted on the reaction of radical cations with nucleophiles (6, 23, 24). Two main mechanisms have been proposed: the disproportionation pathway, equations 6 and 7, in which the nucleophile,


23. PROSS

Nucleophile—Single-Electron Transfer Reactions

335

Nu, attacks the dication formed by the disproportionation of the cation radical A ; and the half-regeneration mechanism, equations 8 and 9, in which nucleophilic attack takes place directly on the radical cation. A third mechanism, termed the complexation mechanism, is closely related to the disproportionation mechanism but differs from it in that one of the reacting radical cation molecules of equation 6 is complexed to a molecule of the nucleophile in a donor-acceptor charge-transfer ττ complex. The role of the nucleophile donor is to facilitate electron transfer to the second radical cation group. The disproportionation step of the complexation mechanism is indi cated in equation 10.


+

2A-+-+ A

2 +

+ A

(6)

2+

(7)

2

A + + Nu — (A-Nu) Α·

+

+ Nu;=± ( A - N u ) +

(A-Nu)-+ + Α · — ( A - N u ) +

+

2+

+

(8) + A

(9)

2 +

A - / N u + A - — A / N u 4- A

(10)

The actual mechanism that is followed in any given case has been a subject of considerable controversy. As Parker and co-workers noted (6, 24\ these reactions are exceedingly complex because they involve multistep pathways through a large number of intermediates. Despite the complexity, evidence for each of the three pathways has been presented (6, 24). Most recently, however, in an excellent review of the subject, Parker (6) reassessed the existing data and concluded that in certain cases the half-regeneration pathway is not operative, as was initially thought. Thus, for example, diphenylanthracene radical cation in its reaction with pyridine is now thought to react via the complexation pathway (6), and not via the half-regeneration pathway (25) (for a selection of papers on the reaction of radical cations with nucleophiles, see references 26-37; for a more extensive list of references, see references 6 and 24). Indeed, on the basis of Parkers analysis, we believe that the reaction of radical cations with nucleophiles proceeds predomi nantly, if not exclusively, via the disproportionation mechanism (or the closely related complexation mechanism). The question now arises: Why does a dication, whose formation is governed by an equilibrium constant of approximately 1 0 , appear to be the species that actually undergoes nucleophilic attack? What is the factor that inhibits direct attack of the nucleophile on the highly reactive radical cation itself? On the basis of the C M analysis, the likelihood of direct attack—the -9


336

NUCLEOPHILICITY

central feature of the half-regeneration pathway—is considered to be slight, as shown by comparing the reactions of normal cations, R , with their radical cation counterpart, A · . The direct attack of a nucleophile, N , on a cation, R , involves a single electron shift (3, 38). The reaction may be described by the avoided crossing of D A and D A " curves as indicated in Figure l a . A single-electron shift from N : to R in the R+ : N pair generates the R N radical pair, which can collapse to form an R - N σ bond. The case of a radical cation is, however, quite different. A n electron shift from N u : to a radical cation A merely regenerates A , the parent hydrocarbon; therefore, a simple nucleophilic +

+

+

+

+

+


+

REACTION

COORDINATE

REACTION

(a)

COORDINATE

(b)

Figure I. (a) Schematic energy diagram illustrating the way in which the reaction profile for nucleophilic attack on a normal cation may be built up from the avoided crossing of DA and D A~ configurations, (b) Corresponding diagram for nucleophilic attack on a radical cation, in which the product configuration is now D *A~. Because D *A~ is doubly excited with respect to DA, while D A~ is just singly excited, E* > E*,. +

+

3

+ 3

+

2


23. PROSS

Nucleophile-Single-Electron Transfer Reactions

addition process is precluded. In simple terms, after the electron shift no odd electron exists in the hydrocarbon moiety with which the nucleophile radical, N u , can couple. Thus, a D A - D A crossing for a radical cation-nucleophile pair does not describe a nucleophilic addition process but describes an electron transfer reaction from the nucleophile to the radical cation. A nucleophilic addition process on a radical cation is brought about by exciting the D A configuration to D * A (Figure lb). Only this doubly excited configuration is electronically set up to bring about the nucleophilic addition reaction: the shift of an electron from the nucleophile to the radical cation prepares the nucleophile for covalent bonding, while excitation of the hydrocarbon moiety to the triplet state uncouples an electron pair; therefore, the electron pair is also prepared for covalent bonding. However, as seen in Figure l b , a high-energy product configuration is likely to lead to a highenergy pathway, so that we believe direct nucleophilic attack on a radical cation is an unfavorable process. For this reason, competing pathways, which only involve singly excited D A product configuration (i.e., electron-trans fer reactions), are preferred for radical cations. This result is indeed what is observed (6). The disproportionation and complexation mechanisms involve the radical cation species in just electron-transfer steps. Only at the dication stage does direct nucleophilic attack occur. At this point, a D A - D + A crossing, that is, a single-electron shift, will lead to a nucleophilic addition. Formation of the radical cation species as a consequence of the electron shift from Ν to A leads to an A N radical pair, which can collapse to give A - N ; nucleophilic attack has occurred. The inexplicably slow protonation reaction of radical anions may be understood in similar terms and will be discussed elsewhere (A. Pross, to be published). +

+

+


337

+

3

_

_

-

-

2 +

+

+

+

+

Acknowledgmen t I am indebted to Sason Shaik, whose collaboration in the development of the C M model led to many of the ideas discussed. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Eberson, L. Adv. Phys. Org. Chem. 1982, 18, 79. Pross, A. Acc. Chem. Res. 1985, 18, 212. Pross, Α.; Shaik, S. S. Acc. Chem. Res. 1983, 16, 363. Pross, A. Adv. Phys. Org. Chem. 1985, 21, 99. Pross, Α.; Shaik, S. S. J. Am. Chem. Soc. 1982, 104, 187. Parker, V. D. Acc. Chem. Res. 1984, 17, 243. Bunnett, J. F. Acc. Chem. Res. 1978, 11, 413. Shaik, S. S.; Pross, A. J. Am. Chem. Soc. 1982, 104, 2708. Pross, Α.; Shaik, S. S. J. Am. Chem. Soc. 1982, 104, 1129. Pross, Α.; Shaik, S. S. Tetrahedron Lett. 1982, 5467. Shaik, S. S. J. Am. Chem. Soc. 1983, 105, 4359. Shaik, S. S. Prog. Phys. Org. Chem. 1985, 15, 197.


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13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38.

NUCLEOPHILICITY

Rollick, K. L . ; Kochi, J. Κ.J.Am. Chem. Soc. 1982, 104, 1319. House, H . O. Acc. Chem. Res. 1976, 9, 59. Evans, J. F.; Blount, Η. N . J. Am. Chem. Soc. 1978, 100, 4191. Troughton, E . B.; Molter, Κ. E.; Arnett, Ε. M .J.Am. Chem. Soc. 1984, 106, 6726. Russell, G. Α.; Jawdosiuk, M . ; Makosa, M .J.Am. Chem. Soc. 1979, 101, 2355. Zieger, H . E . ; Angres, I.; Mathisen, D.J.Am. Chem. Soc. 1976, 98, 2580. Ashby, E . C.; Goel, A. B.J.Am. Chem. Soc. 1981, 103, 4983. Ashby, E. C.; Goel, A. B.; DePriest, R. N . J. Org. Chem. 1981, 46, 2329. Evans, T. R.; Hurysz, L. F. Tetrahedron Lett. 1977, 3103. Rozhkov, I. N . ; Gambaryan, R. P.; Galpern, E. G. Tetrahedron Lett. 1976, 4819. Bard, A. J.; Ledwith, Α.; Shine, H . J. Adv. Phys. Org. Chem. 1976, 13, 156. Hammerich, O.; Parker, V. D. Adv. Phys. Org. Chem. 1984, 20, 55. Manning, G.; Parker, V. D.; Adams, R. N .J.Am. Chem. Soc. 1969, 91, 4584. Shine, H . J.; Murata, Y. J. Am. Chem. Soc. 1969, 91, 1872. Murata, Y.; Shine, H . J. J. Org. Chem. 1969, 34, 3368. Parker, V. D.; Eberson, L.J.Am. Chem. Soc. 1970, 92, 7488. Marcoux, L.J.Am. Chem. Soc. 1971, 93, 537. Svanholm, U.; Hammerich, O.; Parker, V. D.J.Am. Chem. Soc. 1975, 97, 101. Svanholm, U.; Parker, V. D.J.Am. Chem. Soc. 1976, 98, 997, 2942. Kim, K.; Hull, V. J.; Shine, H . J. J. Org. Chem. 1974, 39, 2534. Evans, J. F.; Blount, Η. N . J. Org. Chem. 1977, 42, 976. Evans, J. F.; Blount, Η. N . J. Am. Chem. Soc. 1978, 100, 4191. Evans, J. F.; Blount, Η. N . J. Phys. Chem. 1979, 83, 1970. Hammerich, O.; Parker, V. D. Acta Chem. Scand., Ser. Β 1981, 35, 341. Cheng, H . Y.; Sackett, P. H.; McCreery, R. L. J. Am. Chem. Soc. 1978, 100, 962. Hoz, S. J. Org. Chem. 1982, 47, 3545.

RECEIVED for review October 21, 1986. A C C E P T E D January 31, 1986.


Relationship between Nucleophilic Reactions and Single-Electron

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