The Nonclassical Ion Problem - C&EN Global Enterprise (ACS

Nov 6, 2010 - Chem. Eng. News , 1967, 45 (7), pp 86–99. DOI: 10.1021/cen-v045n007.p086. Publication Date: February 13, 1967. Copyright © 1967 ...
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Nonclassical Ion Problem C&EN feature

A SYMPOSIUM-IN-PRINT

DR. HERBERT C. B R O W N , Department of Chemistry, Purdue University, Lafayette, Ind.

To someone not expert in carbonium ion chemistry, the nonclassical ion problem may seem largely one of notation. Should the norbornyl cation, for example, be repre­ sented by a classical (black solid bond lines) structure; by a nonclassical structure (pur­ ple dotted lines); or by equilibrating struc­ tures (gray lines)? When the nonclassical ion concept first became popular, some chemists even ques­ tioned whether the name was appropriate. "After protesting for years against the in­ appropriate name 'nonclassical ions,' " Dr. Paul D. Bartlett of Harvard, in his preface to a book on the subject, goes on to define an ion as nonclassical " i f its ground state has delocalized bonding σ electrons." But the root of the problem goes deeper than notation and nomenclature, or the topic could surely not have absorbed so much of the energies of some of the leading physical organic chemists for more than 15 years. Part of the problem is the interpretation of data. In 1961, Dr. Brown questioned the nonclassical concept, saying that many of the proposed nonclassical structures for car­ bonium ions rest on "exceedingly fragile ex­ perimental foundations." Many chemists, however, accept the same data as satis­ factory proof of the structures. The editors of C&EN have invited four prominent chemists to present some of their arguments in a symposium-in-print. In this first article, Dr. Brown presents his case for the classical ion concept. In subsequent is­ sues, Dr. George A. Olah of Case-Western Reserve will discuss direct observations of stable carbonium ion intermediates. Dr. Paul von R. Schleyer of Princeton will write about the use of kinetic data in this area. Finally, Dr. Saul Winstein of UCLA will dis­ cuss neighboring group participation and nonclassical ions. In this symposium-in-print, C&EN hopes to contribute to open discussion of this sig­ nificant scientific issue. The published arti­ cles will be available as a combined reprint.

T

he study of the rearrangement of camphene hydro­ chloride into isobornyl chloride has had major con­ sequences for the development of carbonium ion theory.

/£$ - ^ ckt Meerwein's proposal in 1922 that this rearrangement in­ volves the prior formation of a carbonium ion [Ber., B55, 2500 (1922)] appears to be the first application of car­ bonium ion intermediates to account for such a molecular transformation. In 1939 C. L. Wilson and his associates suggested that such a rapidly equilibrating pair of ions

Coffinl

οσΖ&Λ,

might be considered to be a mesomeric species [/. Soc, 1188 ( 1 9 3 9 ) ] :

Chem.

The problem Wilson's proposal proved to be highly popular. Indeed, with the possible exception of the methyl cation, nonclassi­ cal structures apparently have been considered for every known aliphatic, alicyclic, and bicyclic carbonium ion [P. D. Bartlett, "Nonclassical Ions," W. A. Benjamin, Inc., New York, 1965]. Representative systems for which nonclassical structures have been considered are shown at the top of the following page. In those cases for which nonclassical structures have been considered, it is also possible to represent the inter­ mediate as an equilibrating pair of cations. On this basis the nonclassical structures would represent the transition states for the equilibrating systems. Chemists are thus faced with the problem of deciding, in individual systems, whether the structure is best represented in its classical form, or as an equilibrating pair (or set) of cations, or as a resonance hybrid so stable that these prior alterna­ tive structures need not be considered. By using isotopic tags, it is possible to demonstrate in a large number of systems that the carbonium ion can be generated and transformed into products without the equilibration of the carbon atoms required by the bridged structure. For such cations (ethyl, 2-butyl, cyclodecyl, pentamethylethyl, β-phenylethyl) the static classical strucFEB. 13, 1967 C&EN

87

+ CH3CH2

ri

C~cf s.

c-

,Ο "~"°* w

+

CH,

H

y

κ y.

Electron-deficient nonclassical structures have been considered for these carbonium ions

J^i

/

•¥

•f

Normal or electron-sufficient nonclassical structures have been considered for these carbonium ions

ture appears to best represent the structure. However, in other cases (such as norbornyl, cyclopropylcarbinyl, 3-phenyl-2-butyl) equilibration of the tag approaches that predicted by the nonclassical structure. Accordingly, these systems cannot be represented as a static classical structure. Rather, they must involve either bridged ions or their kinetic equivalent, a rapidly equilibrating pair (or set) of ions. At this point I believe it is appropriate to call attention to two apparent anomalies in the current treatment of carbonium ions [/. Am. Chem. Soc, 87, 2137 (1965)]. Systematic lowering of the potential barrier separating two equivalent cations R

would be expected to lead to three distinct classes of such cations: • Essentially static classical cations that can be formed and transformed into products without significant equili­ bration. • Equilibrating cations that undergo rapid equilibration in the time interval between formation and conversion into products. 88 C&EN FEB. 13, 1967

• Static bridged species wherein the potential barrier has disappeared so that resonance now occurs involving the two structures. The first anomaly is that current interpretations assign practically all systems that have been examined to the first and third of these classes, leaving the intermediate class almost unpopulated. The second anomaly deals with the observed rates of solvolyses which lead to the formation of these ions. A valued and highly useful principle in organic chem­ istry is that a decrease in the free energy of formation of the product or first intermediate in a reaction will be ac­ companied by a corresponding decrease in the free energy of formation of the transition state leading to that in­ termediate. Yet in the area of nonclassical ions the formation of stable bridged species is frequently postu­ lated in the absence of significant rate accelerations. My coworkers and I therefore suggested that the anom­ alies may have their origin in the failure of current theory to give adequate consideration to Winstein's proposal that the stereochemical results corresponding to the formation and opening of a bridged ion might be simulated by a dy­ namic pair of isomeric cations [/. Am. Chem. Soc, 74, 1133 (1952)]. It appears that the formation of stable bridged species should be accompanied both by large rate en-

hancements and retained stereochemistry of substitution. In cases involving such stereochemistry without sig­ nificant rate enhancements, it is possible that the system involves rapidly equilibrating cations or ion pairs and not a resonance-stabilized bridged cation. Steric assistance vs. nonclassical

resonance

OTS

It might be of interest to indicate how my own atten­ tion was attracted to the problem. In 1946 I suggested that the accumulation of bulky alkyl groups around a central carbon atom would constitute a center of strain that should assist unimolecular ionizations involving the formation of a planar, less strained, carbonium ion [Science, 103,385 (1946)]. R ι -C-Cl

+ or

ι R

A number of systems of this kind were investigated. The results, such as the following, appeared to support the proposal [/. Am. Chem. Soc, 75, 10 (1953)]. ι

CM L C ( C H 3 } 3

ù

H^C-C-Cl 0

CH2C(CH3)3

H3C-C-Cl

ι CH 3

H3C-C-CI

CH3 CHZC(CH3)3

z\ 580

The concept was generally accepted. Accordingly, my as­ sociates and I abandoned work in this field for new areas. At this time, however, a new concept appeared on the scene, and it was used with increasing frequency to ac­ count for rate acceleration which seemed to me to be adequately accounted for by relief of steric strain. Thus, Ingold and his coworkers reported [Nature, 168, 65 (1951)] that camphene hydrochloride undergoes ethanolysis at a rate 6000 times greater than tert-butyl chloride. This enhanced rate was attributed not to relief of steric strain accompanying the separation of chloride ion from its highly crowded environment, but to the driving force provided by the formation of a nonclassical (synartetic, mesomeric) cation.

+ cr Similarly, Bartlett suggested that the formation of a methylbridged tri-ferf-butylcarbinyl cation might provide driving force for the observed fast rates of solvolysis of tritof-butvlcarbinvl derivatives [/. Chem. Educ, 30, 22 (1953)]. Ç(CH3)3

C(CH 3 ) 3

(cH3)3C-ç-v< C(CH 3 ) 3

_

3

Likewise, R. Heck and V. Prelog suggested that the high rate of solvolysis of cyclodecyl tosylate might be due to the formation of a stabilized bridged cyclodecyl cation [Helv. Chim. Acta, 38, 1541 (1955)], rather than to the decrease in internal strain as we had suggested [/. Am. Chem. Soc, 73, 212 (1951)].

|;+>CH 3

+ X'

+ "ors Originally I had no reason to question these proposals. However, it was interesting that the phenomenon appeared to be significant only for structures where my coworkers and I had anticipated that relief of steric strain would be an important factor. Accordingly, we began to examine a representative number of systems in order to establish how much of the observed rate enhancement might be due to relief of steric strain and how much to this new phenomenon of bridging by saturated carbon. Our experiments forced us to the conclusion that in those systems we had selected for study essentially all of the observed rate enhancements could be accounted for in terms of relief of steric strain—with no significant contribution possible for the proposed σ-bridges. At this point I was faced with one of those agonizing de­ cisions. The nonclassical concept had proved to be an ex­ ceedingly popular one. A large fraction of the physical or­ ganic chemists in the U.S. were engaged in research in this area. The subject had entered the textbooks and thou­ sands of graduate students were being taught and ex­ amined annually on the subject matter and approved interpretation. In the meantime the theory was going on to even more elaborate structures, including Dewar's formulation as 7r-complexes [Ann. Rev. Phys. Chem., 16, 321 (1965)]. (This might be considered the rococo period of carbonium ion structures. ) Obviously, to challenge the theory at this point would lead to severe repercussions. However, to re­ main silent might subject future generations of students to needless study of erroneous concepts. "The Emperor is naked" There comes a time when one cannot remain on the sidelines. It becomes necessary to stand forth and de­ clare, "But the Emperor is naked!" Accordingly, in March 1961, at the Symposium on Carbonium Ions held at the St. Louis meeting of the American Chemical Society, I pointed out that, in my opinion, many of the proposed nonclassical structures for carbonium ions rested on ex­ ceedingly fragile experimental foundations, and I sug­ gested the desirability for further experimental work to test and reaffirm these foundations. I had hoped that my cautious comments ["The Tran­ sition State," Special Publication No. 16, pp. 140-158, 174-178, The Chemical Society, London, 1962] would set into motion a critical, objective re-examination of the field. Instead, my remarks were considered to be in the FEB. 13. 1967 C&EN

89

Rather elaborate nonclassical structures have been proposed; typical examples of the rococo period of carbonium ion structures are:

OCH*

+

'Or

I H

nature of a heresy, and they appeared to initiate a "Holy War" to prove me wrong. Consequently, it seemed necessary to undertake our own program of research in this area. Four systems were se­ lected for a critical study: • The β-phenylethyl cation and its derivatives [/. Am. Chem. Soc, 87, 2137 (1965)]. • The cyclopropylcarbinyl cation. • The norbornyl cation [Chemistry in Britain, 199 (1966)]. • The 5-dehydronorbornyl cation. Actually, my associates and I have devoted major atten­ tion to the norbornyl cation. Not only was it the first such ion to be proposed, but its rigid structure is associated with highly interesting characteristics which it is important to understand even apart from the nonclassical ion problem. Space does not permit a detailed discussion of our efforts with these four representative systems. Accordingly, I am 90 C&EN FEB. 13, 1967

restricting my discussion here to a consideration of the norbornyl cation. Even with this restriction, only a small portion of the available evidence can be considered. Relationship to neighboring group

phenomena

The brilliant research work of Winstein and his co­ workers in the forties [A. Streitwieser, Jr., "Solvolytic Dis­ placement Reactions," McGraw-Hill Book Co., Inc., New York, 1962; B. Capon, Quart. Rev. (London), 18, 45 (1964)] established that donor atoms in the /^-position could greatly enhance the rates of solvolytic reactions and simultaneously control the stereochemistry of substitution.

At this point, it was believed by those working in the field that the observation of a large rate enhancement was essen­ tial to postulate the formation of a stabilized bridged inter­ mediate. For example, the fourfold rate enhancement ob­ served for iran«s-2-chlorocyclohexyl brosylate, compared with the cis isomer, was not considered significant by Winstein and his coworkers, and the formation of a chloronium intermediate was not proposed [/. Am. Chem. Soc, 70, 821, 828 (1948); /. Am. Chem. Soc, 73, 5458 (1951)]. But the corresponding large factors of 800 for the bromine and 10 6 for the iodine derivatives were believed to reflect the driving force accompanying the formation of the bridged intermediates.

4

8θΟ

"λ,ΊΟΟ,ΟΟΌ

It is important to note that even with the excellent donors embodied in the η-subdivision of neighboring groups there is a transition from groups such as thioalkoxy and iodide, which participate strongly, to groups such as methoxy and chloride, which participate very weakly or not at all. Somehow, in extending the theory to include participa­ tion by neighboring aryl groups (ττ-subdivision), the re­ quirement for a considerable rate enhancement to postulate the formation of a stabilized arylonium intermediate dis­ appeared. Thus in current theory, the formolysis of 2-phenylethyl tosylate, with a rate enhancement over ethyl of 2.1, the formolysis of 2-p-anisylethyl tosylate, with a rate enhancement of 160, and the ethanolysis of the conjugate base from 2-p-hydroxyphenylethyl bromide, with a rate enhancement of 10 8 , are all treated similarly. ocrii

160

\oO,oqofQOO

Clearly, there is a major inconsistency here which re­ quires resolution. Strong Lewis acid acceptors, such as aluminum bromide and gallium chloride, form relatively stable addition com­ pounds with donors of the η-class. Although the inter­ action is weaker, members of the ττ-class, such as benzene and mesitylene, also form complexes with aluminum bromide [/. Am. Chem. Soc., 88, 903 (1966)]. However, to my knowledge similar donor-acceptor interaction has never been demonstrated for saturated alkanes or cycloalkanes, such as would be involved in the extension of

participation to the proposed σ-class. Although this should make us cautious in postulating such participation by neighboring alkyl and cycloalkyl groups, it does not pro­ vide any basis for ruling out such participation. The in­ teraction of a neighboring group with a developing elec­ tron-deficient center may be subject to far different physical laws than the interaction of a donor molecule with a strong Lewis acid. We should examine the experi­ mental data critically and objectively to see whether these data require such participation by neighboring alkyl and cycloalkyl groups with its attendant formation of relatively stable intermediates containing carbon bonded to five atoms. Before proceeding to the norbornyl case, I believe it is appropriate to turn our attention to definitions. Surpris­ ing as it may seem, despite the vast literature on the sub­ ject, apparently no attempt was made to define the term "nonclassical ion" until very recently. I believe Roberts first used the term when he proposed the tricyclobutonium structure for the cyclopropylcarbinyl cation [/. Am. Chem. Soc., 73, 3542 (1951)]. The structure proposed was clearly different from the classical structure for the inter­ mediate discussed. The second appearance is due to Winstein, who refers to the "nonclassical structures" of norbornyl, choiesteryl, and 3-phenyl-2-butyl cations [J. Am. Chem. Soc, 74, 1154 (1952)]. The third reference I have located is Roberts' statement: "Recent interest in the structures of carbonium ions has led to speculation as to whether the ethyl cation is most appropriately formu­ lated as a simple solvated electron-deficient entity, C H 3 C H 2 + , a 'nonclassicaF bridged ethyleneprotonium ion,

S + \

or possibly as an equilibrium mixture of

the two ions" [/. Am. Chem. Soc, 74, 5943 (1952)]. It is clear from these references that the emphasis is on struc­ tures that differ markedly from the usual classical structures. Consequently, my coworkers and I suggested the fol­ lowing definition [/. Am. Chem. Soc, 87, 2137 ( 1 9 6 5 ) ] : A nonclassical ion is a carbonium ion in which the position in the structure of one or more atoms is markedly different from that predicted on the basis of classical structural principles. We also proposed two subclasses. First, ions, such as β-phenylethyl in its bridged phenonium form, which pos­ sess sufficient electron-pairs for all of the required bonds. It requires no extension of generally accepted bonding concepts to account for these structures. We suggested that such structures be termed "normal" or "electronsufficient" nonclassical ions. The second subclass consists of ions such as the bicyclobutonium and the norbornyl cation in its σ-bridged form, which do not possess suffi­ cient electrons to provide a pair for all of the bonds re­ quired by the proposed structures. A new bonding con­ cept not yet established in carbon structures is required. We suggested that such structures be termed "electrondeficient" nonclassical ions. More recently, Bartlett and Sargent urged that the term nonclassical be restricted to σ-bridged cations, that is, the electron-deficient group ["Nonclassical Ions"; Quart. FEB. 13, 1967 C&EN

91

Solvolysis exhibits the same pattern of reactivity observed in other reactions of norbornyl derivatives, but is treated by current theory as involving a totally different physical basis for this same reactivity pattern

Rev. (London), 20, 301 (1966)]. My only objection to this restriction is that the term has been frequently ap­ plied in the literature to the phenonium ion and similar "electron-sufficient" intermediates. I want to make one further point to clarify the pro­ posed definition of the term nonclassical ion. There is no doubt that the presence of the cyclopropyl ring greatly stabilizes the cyclopropylcarbinyl cation. If this stabiliza­ tion is the result of bonding through space between the carbonium center and one of the ring atoms, as is proposed in the bicyclobutonium ion, then this species would possess a nonclassical structure according to our definition. How­ ever, if the structure is that of the cyclopropylcarbinyl cation, with the stabilization provided by electron supply from the strained cyclopropyl ring primarily through the σ-bond system, the resulting cation would not be consid­ ered to possess a nonclassical structure. In a similar man­ ner, I would not consider the ieri-butyl cation to possess a nonclassical structure simply because it is greatly stabilized over the methyl cation by electron supply from the three alkyl substituents through its σ-bond system. This approach provides a consistent extension of neigh­ boring group participation from the η-groups, to the ττ-groups and, finally, to the σ-groups now undergoing criti­ cal re-examination. It is, of course, highly desirable to have one clear-cut case of σ-participation. The norbornyl system was there­ fore subjected to careful study to ascertain whether it provided that case. The norbornyl

system

The σ-bridged norbornyl cation was not only the first nonclassical ion to be suggested [C. L. Wilson, et αϊ., J. Chem. Soc, 1188 (1939)], but it has been the subject of innumerable studies. In Sargent's own words, it is "the most carefully scrutinized, if not the most spectacular, flower of the [nonclassical] garden . . ." [Quart. Rev. (London), 20, 301 (1966)]. Consequently, it appeared that here, if anywhere, there would be the data to set our fears at rest. The norbornane molecule possesses a rigid structure with unusual steric characteristics.

Carbon atoms 1 through 6 constitute a cyclohexane struc­ ture in the higher energy boat conformation. More­ over, the C-7-methylene group not only locks this ring 92 C&EN FEB. 13. 1Qfi7

system, but the constraint so produced accentuates the steric crowding within the boat structure. Much of the chemistry of norbornane is dominated by the far greater steric accessibility of the exo, as compared to the endo, position. For example, in many free radical substitution reactions the exo product is produced pref­ erentially [E. C. Kooyman, Record Chem. Progr. (KresgeHooker Sci. Lib.), 24, 93 ( 1963) ].

Similarly, many additions to norbornene proceed pre­ dominantly from the exo direction. For example, the hydroboration-oxidation of norbornene produces 99.5% of βχο-norborneol, with only 0.5% of the endo isomer ["Hydroboration," p. 126, W. A. Benjamin, Inc., New York, 1962; research in progress with J. Kawakami].

£t>»!LEW£tXH •

φ OK

99.57o

0.5%

Recently Stille reported that exo-norbornyl derivatives undergo cis E2 elimination, whereas endo-norbornyl de­ rivatives undergo trans E2 elimination [Tetrahedron Letters, 38, 4587 (1966)]. In each case it is the exo hy­ drogen that participates in the elimination. Thus, in this system the elimination appears to be controlled primarily by the greater steric availability of the exo hydrogen than by any stereoelectronic preference of the reaction mech­ anism for either cis or trans elimination.

There seems to be general agreement that this marked preference for reaction in the exo position is a simple con­ sequence of the greater steric availability of the exo posi­ tion as contrasted to the severe steric crowding within the concave, U-shaped environment of the endo portion of the structure [G. D. Sargent, Quart. Rev. (London), 20, 301 (1966)]. A similar marked stereochemical preference for the solvolysis of exo-norbornyl derivatives, as compared to the endo isomers, is also observed. Moreover, the ions formed

in the solvolysis undergo substitution predominantly from the exo direction.

Although this behavior is remarkably similar to the marked steric preference for the exo position exhibited by many other reactions, as discussed above, current theory treats this solvolysis reaction as a distinct class, with a totally different nonsteric explanation advanced for its interpreta­ tion. Winstein and Trifan proposed that the slow rate of the endo is normal, and the fast rate of the exo is the result of the σ-participation by the C-6 atom of the norbornane system [J. Am. Chem. Soc, 74, 1147, 1154 (1952)].

£tx^-£fc

chloride is not a suitable model. Foote and Schleyer have suggested that the carbonyl frequency in the infrared spectrum should provide a measure of angle strain and correlate the reactivity toward solvolysis [/. Am. Chem. Soc, 86, 1853, 1854 (1964)]. Consequently, cyclopentyl derivatives (v c o 1748 cm. - 1 ) appear to be much better models for norbornyl derivatives (vco 1751 cm. - 1 ) than cyclohexyl (Vco 1716 cm. - 1 ) or aliphatic (v c o 1718 c m . - 1 ) . On this basis, the rates for norbornyl derivatives (tertbutyl = 1.00, 25°C.) do not appear to be exceptional [/. Am. Chem. Soc, 85, 2322 ( 1963 ) ].

cl 2380

I36oo

Cl

355

+ *-

We are therefore faced with the unusual situation that solvolysis exhibits the same pattern of reactivity observed in other reactions of norbornyl derivatives, but is treated by current theory as· involving a totally different physical basis for this same reactivity pattern. A detailed examination of the literature revealed three main foundations for the proposal of a nonclassical struc­ ture for the norbornyl cation and its derivatives: • Unusually fast rates of solvolysis for the exo deriva­ tives. • High exo/endo rate ratios. • Predominant exo substitution in the cation, especially in the derivatives containing 7,7-dimethyl substituents. We first attempted to answer the question whether exo rates are unusually fast. As I have pointed out earlier, it had been proposed by Ingold and his coworkers that the fast rate of camphene hydrochloride (6000 times greater than tert-butyl chloride) requires the formation of a synartetically stabilized intermediate [Nature, 168, 65 (1951)]. It is true that the rate for camphene hydro­ chloride is quite fast. However, perhaps tert-buty\

Dr. HERBERT C. BROWN is the R. B.

Wetherill Research Professor at Purdue University. He has made numerous con­ tributions to organic chemistry. Among these are his highly original approach to the study of steric effects, his develop­ ment of a quantitative theory of directive effects in aromatic substitution, and his discovery of the rapid addition of diborane to olefins which provides a simple route to the organoboranes and their de­ rivatives. Also, he has devised procedures for synthesizing aliphatic and aromatic aldehydes from acid chlorides, from acid amides, and from nitriles. Dr. Brown is the codiscoverer, along with Prof. H. I. Schlesinger, of the borohydrides. He has served on the editorial hoards of the Journal of Organic Chemis­ try and the Canadian Journal of Chemistry, and is now a member of the editorial boards of Tetrahedron, Tetrahedron

t-Jlribfi*

\>oo ot 2-5 ° C ,

Quite clearly the results are in accord with the postu­ lated effect of steric strain in facilitating the rates of solvolysis of highly branched tertiary chlorides. It is important to recognize that these results do not dis­ prove the formation of a mesomeric cation in the solvolysis of camphene hydrochloride. However, they do remove the original basis for concluding that the rate of solvolysis of camphene hydrochloride is too fast to be explained on any basis other than the formation of mesomeric cations. Following my submission of this work as a Communica­ tion to the Editor (J. Am. Chem. Soc) it was returned with a very helpful comment by one of the referees. This referee cited Bunton ["Nucleophilic Substitution at a Saturated Carbon Atom," Elsevier Publishing Co., New York, 1963] as the authority for the position that tertiary norbornyl cations should be classical, since the stabilized tertiary carbonium center should not require participation by the 1,6-bonding pair. The referee believed, therefore, that the Communication was devoted to disproving a point

Letters, Journal of Inorganic b- Nuclear Chemistry, and Journal of Organometallic Chemistry. Born in London, England, in 1912, Dr. Brown did his under­ graduate work in the U.S.—at Chicago City Junior College (Assoc. Set. 1935) and the University of Chicago (B.S. 1936). He received his Ph.D. in organic chemistry under Prof. Schles­ inger in 1938 from the University of Chicago. After another year there, with Prof. M. S. Kharasch as a postdoctorate fel­ low, he was appointed an instructor at the university. He went to Wayne State University in 1943 and transferred to Purdue University as professor in 1947. He became Wetherill Professor at Purdue in 1959. Dr. Brown was the Centenary Lecturer of The Chemical Society (London) in 1955 and the Nichols Medalist of the New York Section of the American Chemical Society in 1959. In 1960 he received the ACS Award for Creative Work in Synthetic Organic Chemistry. Dr. Brown was elected to the National Academy of Sciences in 1957 and the American Academy of Arts and Sciences in 1966. FEB. 13, 1967 C&EN 93

We should expect to find a marked decrease associated with participation as we move along the series to more and more which should have been obvious to anyone expert in the field. Indeed, Bunton had pointed out that the resonance postulated for the norbornyl cation

should be unimportant in a tertiary derivative, where the structures differ so greatly in energy.

ά% *^ φ (Bunton's argument, although reasonable, is evidently not generally accepted by proponents of the nonclassical inter­ pretation, as indicated by the recent statement by Winstein: "Except for possible extreme tertiary systems, the available evidence seems to us to favor preferred bridged structures for typical secondary and tertiary cations" [/. Am. Chem. Soc, 87, 381 (1965)]. By contrast, Sargent [Quart. Rev. (London), 20, 301 (1966)] has come to the conclusion that participation is unimportant in such tertiary derivatives.) The referee's criticism suggested a new line of investi­ gation. It is a basic tenet of the nonclassical theory that the more stable the cationic center, the less stabilization that center will require from the rest of the molecule and the less important participation should be [S. Winstein, et al, J. Am. Chem. Soc, 74, 1113 (1952)]. (One comes to the same conclusion with Bunton's approach by considering the decrease in resonance between structures involving greater and greater differences in energy.) Consequently, we should expect to find a marked decrease in those char­ acteristics associated with participation as we move along the series to more and more stable cations.

(±3 φ OCH3

Consequently, my coworkers and I examined the exo/ endo rate ratios and the stereochemistry of substitution for a number of such derivatives. However, we observed no major change in these characteristics with increasing stability of the cationic center [see Chemistry in Britain, 199 (1966) for a review of the data with literature refer­ ences]. Sargent argues that this must be merely a fortuitous cancellation of decreased participation with increased re­ lief of steric strain [Quart. Rev. (London), 20, 301 ( 1 9 6 6 ) ] . However, my coworker Rei and I have equil­ 94

C&EN FEB. 13, 1967

ibrated exo- and enTS s t r a i n ) and steric hindrance to ioni­ zation ( G S s t r a i n < T S s t r a i n ) . However, in actual practice, both in the six model compounds used to fix the correla­ tion line and in all of the published examples, including encfo-norbornyl, TS s t e r i c s t r a i n was assumed to be negligible. Schleyer justified this assumption empirically on the ground that, "Steric deceleration, in fact, is but rarely encountered, evidently because leaving groups are generally able to find a propitious avenue for departure" [J. Am. Chem. Soc. 86,1854 (1964)]. Accordingly, it was desirable to test the generality of the assumption that GS s t e r i c s t r a i n involving the leaving group can be assumed to vanish in the transition state. The 6,6-dimethylnorbornane and the endo-trimethylenenorbornane systems exaggerate the U-shaped structural feature of the endo side of the norbornane molecule. Con­ sequently, the following tosylates were selected for study [H. C. Brown, P. v. R. Schleyer, et al, Troc. Natl Acad. Sci. U.S., 56, 1653 (1966)]:

3

Gj β -VW^&MMI-

-^u/o-^uyJjxyKA^ji

ihwSj&C

FEB. 13, 1967 C&EN

95

The carbonyl frequency in the ketone corresponding to endo-2 is 1743 cm." 1 , as compared to 1751 c m r 1 for 2According to both Foote and norbornanone itself. Schleyer a shift of this magnitude should correspond to a 10-fold increase in rate of acetolysis of endo-2- over endonorbornyl. Differences in torsional and inductive effects in the two systems are negligible. In the ground state, the strain in endo-norbornyl tosylate involving the leaving group is estimated as 1.3 kcal. per mole and that in endo-2 is estimated as 4.0 kcal. per mole. If the usual assumption is made that steric strain is largely relieved in the transi­ tion state, this will lead to another factor of 100 favoring endo-2 over endo-norbornyl tosylate. Consequently, the Schleyer correlation, with the provisional assumption that TS s t r a i n « 0 for the leaving group, suggests that endo-2 will solvolyze at a rate 1000 times that of endo-norbornyl tosylate. The observed relative rate is actually 0.1 [K. Takeuchi, et al, Bull. Chem. Soc. Japan, 38, 1318 (1965)]. Thus, there is a discrepancy of 10,000 between the rate observed and that calculated in this manner. In the case of endo-S the discrepancy between the ob­ served rate and that calculated in this manner is even larger [Proc. Natl Acad. Set. U.S., 56, 1653 (1966)]. In the 6,6-dimethyl derivative GS s t e r i c s t r a i n involving the leaving group is likewise estimated to be 4.0 kcal. per mole. Again, the assumption that this strain is relieved in the transition state leads to an estimated increase over endonorbornyl by a factor of 100. The carbonyl frequency difference, Av c o — 5 cm. - 1 , introduces another factor of 4.2. Thus the rate predicted on the basis of the Schleyer correlation, with the provisional assumption, TS s t e r i c s t r a i n « 0 , is 420. The observed rate is 1 / 1 9 that of endo-norbornyl [P. v. R. Schleyer, et al, J. Am. Chem. Soc, 87, 375 (1965)], which gives a discrepancy between the predicted and observed rates of 8000. Clearly, such a comparison of the observed and calculated rates provides a better assessment of the magnitude of steric hindrance to ioniza­ tion than does a mere comparison of the two actual rates, a procedure which ignores the potential driving force of the large ground strain energy present in 6,6-dimethylendo-norbornyl tosylate [S. Winstein, J. Am. Chem. Soc., 8 7 , 3 8 1 (1965)]. These results point to an important conclusion. Despite the large ground-state strain present in the U-shaped struc­ tures examined, relative to the model substances used for comparison, solvolysis involves not a decrease, but an actual increase in strain in proceeding to the transition state [/. Am. Chem. Soc, 88, 2811 (1966)], resulting not in an increase, but in an actual decrease in rate. Clearly it will be necessary in future studies to give careful con­ sideration to the precise model for the departure of the leaving group. Moreover, it is not warranted to assume that strain involving the leaving group is negligible in all cases. Consequently, the Foote-Schleyer correlations in their present stage of development cannot be relied upon to provide a definitive answer to the question as to whether the difference in energy of the two transition states, as re­ vealed by the Goering-Schewene diagram, is the result of 96 C&EN FEB. 13, 1967

stabilization of the exo transition state by nonclassical res­ onance, involving σ-participation, or is the result of steric strain in the endo transition state, or both [H. C. Brown, P. v. R. Schleyer, et al, Proc. Natl Acad. Sci. U.S., 56,1653 (1966)]. If the exo/endo rate ratio for the solvolysis of norbornyl tosylate is due to σ-participation in the exo, with accom­ panying charge derealization from the 2- to the 1- and 6-positions, it should be possible to use the well-tried tool of the organic chemist, the introduction of suitable substituents, to test for such charge derealization. My co­ workers and I, as well as Prof. Schleyer and his associates, have completed a number of tests of this kind, but every one has failed [see Chemistry in Britain, 199 (1966) for a summary of the data with literature references]. I know of no experimental data presently available that provide independent confirmation for the postulated presence of σ-participation, with accompanying charge delocalization, in a norbornyl system not undergoing rearrangement to a more stable structure. On the other hand, the results of a number of experi­ ments do provide strong support for the conclusion that steric inhibition of ionization must be a factor to be con­ sidered in rigid bicyclic systems [research with I. Rothberg, W. J. Hammar, and D. L. Vanderjagt]. Finally, we must consider the argument that almost ex­ clusive exo-substitution in the solvolysis of 7,7-dimethylnorbornyl brosylate requires a bridged ion [J. A. Berson, in "Molecular Rearrangements" Vol. 1, Chap. 3, Interscience Publishers, New York, 1963]. In the reaction of sodium borohydride with norcamphor and apocamphor, the pres­ ence of the 7,7-dimethyl substituents causes a change in the direction of preferential attack from the exo direction for the norcamphor to the endo direction for apocamphor. Berson argued that a similar change should be expected for a rapidly equilibrating pair of classical cations, so that the failure to observe endo attack in the 7,7-dimethylnorbornyl cation requires a bridged species to account for the stereo­ chemistry. This is a reasonable argument and provides the last major hurdle for the alternative interpretation which is being forced upon us by the continued failure to obtain evidence for nonclassical resonance in the norbornyl transition state. However, we should recognize that this argument rests upon largely unexplored foundations. We really know very little about the relative steric requirements for the reaction of cations with solvent and the reactions of ketones with complex hydrides. It was previously pointed out by Winstein that "the stereochemical results corresponding to formation and opening of \'Li:-*o?

may, in some cases,

be simulated by a dynamic pair of isomeric cations" [J. Am. Chem. Soc, 74, 1133 ( 1 9 5 2 ) ] . We know almost nothing about the degree of steric control that such rapid equilibra­ tion might introduce into the solvation of the cation and the stereochemistry of its reaction with solvent or other nucleophiles.

Finally, the extent of our ignorance of the precise steric requirements of the 7,7-dimethyl substituents is indicated by the recent report that deuterium exchange in norcamphor, isofenchone, and camphor gives, essentially ex­ clusively, monodeuteration in the exo position [A. F. Thomas and B. Willham, Tetrahedron Letters, 18, 1309 ( 1965) ; D. E. Sunko, et al, Ibid., 49, 4465 ( 1965) ].

The reasoning previously applied to the apobornyl cation would lead to the prediction that 7,7-dimethyl substituents should direct deuteration preferentially to the endo position. It should be noted that the preferred deuteration in the exo position of nor camphor, isofenchone, and camphor is precisely the type of stereospecificity that has been considered to require a bridged cation in the solvolysis reaction. Should we now begin to consider bridged struc­ tures for the enolate intermediates to rationalize the ob­ served stereospecificity? Conclusions At the St. Louis symposium referred to earlier, one speaker who was questioned as to why he proposed a par­ ticular nonclassical structure, replied, "Because it is fashion­ able." Another speaker advanced as his reason for pro­ posing a particular structure, "Because it looks so nice." Although these replies may have been in part facetious, they are illustrative of the tenor of the times. I have found it difficult to recognize my own position from that attributed to me in some recent publications [G. D. Sargent, Quart. Rev. (London), 20, 301 (1966)]. For example, in a recent book review of "Nonclassical Ions," it was stated [R. J. P. Williams, Nature, 455 ( 1 9 6 6 ) ] : " . . . I also found a short review in Chemistry in Britain (199, 1966) which denies the whole concept. I do not advise my fellow students to use this book un­ less they want a non-classical outlook on neo-classical ions." As the author of the short review referred to by Williams, I wish to make it clear that in my review I did not deny the whole concept. (It would be unscientific to take a dogmatic position that any particular phenomenon is incapable of existence in this fascinating, versatile world of ours.) My position then and now is merely that my students and I have been unable to find any experimental evidence whatever for σ-bridging in the solvolysis of norbornyl derivatives. In view of the misunderstanding of my position indi­ cated by these and other publications, it may be desirable to summarize my actual position. • Structures proposed for carbonium ions should rest on the same type of sound experimental foundations now used to make structural assignments for uncharged organic molecules. The fact that we are dealing with fugitive

intermediates should not convey license [R. B. Woodward, in "Perspectives in Organic Chemistry," pp. 177-178, In­ terscience Publishers, New York, 1956] to propose highly fanciful structures without adequate experimental support. (I hope that my questioning has contributed to the evi­ dent decrease in the number of such highly exotic struc­ tures currently appearing in the literature. ) • No experimental evidence is presently available to support the long-accepted proposal for σ-participation in symmetrical norbornyl derivatives. The behavior of such derivatives in solvolysis conforms to the general pattern of reactivity observed in norbornyl derivatives not involv­ ing carbonium ions. Consequently, there does not appear to be any sound reason to continue to interpret solvolysis results on a theoretical basis that is totally different from that used to account for the observed strong preference for the exo position in other reactions. • In contrast to σ-participation, ττ-participation by neigh­ boring aryl groups is clearly established. However, the magnitude of the effect varies over a wide range. Conse­ quently, we should expect a gradual transition between static classical, equilibrating classical, equilibrating ττbridged, and static bridged cations. • Steric influences of the structure should be capable of altering the stereochemistry of substitution of a classical cation from predominant inversion to predominant reten­ tion. Consequently, stereochemistry alone should not be used as the sole justification for postulating a bridged ion. Numerous individual studies of many phenomena have been published recently, purporting to throw light on the problem of the structure of the norbornyl cation. Many of these involve exceedingly long chains of reasoning, some of them mutually contradictory. Unfortunately, space does not permit their analysis and discussion here. In my opinion the heart of the problem is the factor responsible for the difference in energy of the exo and endo transition states, as indicated by the Goering-Schewene diagram. Therefore, my own studies and this discussion have been focused on this point. I should like to close by quoting from my Sheffield lecture [Chemistry in Britain, 199 (1966)]. "It is evident from the literature that this enquiry into the structure of the norbornyl cation and other cations for which nonclassical structures have been proposed has aroused con­ siderable emotion and controversy. This is indeed un­ fortunate. Any concept in science should be subject to examination and re-examination. We can have no 'sacred cows/ I hope this summary of my evidence and views will convince the chemical public interested in the struc­ ture of carbonium ions that there remains a problem to be solved. I am confident that if this is explored with the reason and ingenuity of which the human mind is capable the problem will soon be resolved. Whichever way the decision goes, organic chemistry will be enriched by a new understanding of the factors influencing the behavior of carbonium ions." FEB. 13, 1967 C&EN 97

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