Nonclassical intermediate

Furthermore, 48 solvolyzed 350 times faster than its endo isomer 51. Similar high exo/endo rate ratios have been found in many other [2.2.1] systems. These two results—(1) that solvolysis of an optically active exo isomer gave only racemic exo isomers and (2) the high exo/endo rate ratio—were interpreted by Winstein and Trifan as indicating that the 1,6 bond assists in the departure of the leaving group and that a nonclassical intermediate (52) is involved. They reasoned that solvolysis of the endo isomer 51 is not assisted by the 1,6 bond because it is not in a favorable position for backside attack, and that consequently solvolysis of 51 takes... 

Cyclobutyl substrates also solvolyze abnormally rapidly and give similar products. Furthermore, when the reactions are carried out with labeled substrates, considerable, though not complete, scrambling is observed. For these reasons, it has been suggested that a common intermediate (some kind of nonclassical intermediate, e.g., 25, p. 408) is present in these cases. This common intermediate could then be obtained by three routes ... 

The concept of bridged ions provides an alternative explanation of stereospecificity. The equilibrating pair of carbocations, (2) (2), is replaced by a o-delocalized ( nonclassical ) intermediate (10). A two-electron, three-center bond is characteristic of (10). Other compounds have structures which indicate delocalized o bonds. Well known examples are diborane and the dimer of trimethylaluminum. Because of... 

Since the 1950 s, an enormous amount of work has been carried out on other nucleophilic substitutions of norbornane derivatives and related compounds. This was particularly due to the alternative mechanistic explanation proposed by H. C. Brown in 1962 (see also Brown, 1966, 1976, 1977). He postulated that instead of the nonclassical intermediate 7.97, the expected classical carbocation 7.100 is formed in a rapid equilibrium with the ion 7.101. In his opinion, 7.97 is not an intermediate, but corresponds to the transition state in the equilibrium 7.100 7.101 (Scheme 7-33). Arguments for and against Winstein s and Brown s proposals by other researchers can be found first of all in Bartlett s anthology (1965) and in the literature until the present day (see some 30 references in the period 1977-1988 in March s book, 1992, p. 321) ... 

As should be the case with the establishment of any new principle, the concept of cr-bridged nonclassical intermediates was subjected to a searching analysis. An alternative explanation, based on classical carbocations, was put forth by H. C. Brown of Purdue University. Brown pointed out that the evidence in support of the nonclassical formulation for norbornyl cation consisted of ... 

Nonclassical ions, a term first used by John Roberts (an outstanding Caltech chemist and pioneer in the field), were defined by Paul Bartlett of Harvard as containing too few electrons to allow a pair for each bond i.e., they must contain delocalized (T-electrons. This is where the question stood in the early 1960s. The structure of the intermediate 2-norbornyl ion could only be suggested indirectly from rate (kinetic) data and observation of stereochemistry no direct observation or structural study was possible at the time. 

Both acetolyses were considered to proceed by way of a rate-determining formation of a carbocation. The rate of ionization of the ewdo-brosylate was considered normal, because its reactivity was comparable to that of cyclohexyl brosylate. Elaborating on a suggestion made earlier concerning rearrangement of camphene Itydrochloride, Winstein proposed that ionization of the ero-brosylate was assisted by the C(l)—C(6) bonding electrons and led directly to the formation of a nonclassical ion as an intermediate. 

The description of the nonclassical norbomyl cation developed by Wnstein implies that the nonclassical ion is stabilized, relative to a secondary ion, by C—C a bond delocalization. H. C. Brown of Purdue University put forward an alternative interpreta-tioiL He argued that all the available data were consistent with describing the intermediate as a rapidly equilibrating classical ion. The 1,2-shift that interconverts the two ions was presumed to be rapid relative to capture of the nucleophile. Such a rapid rearrangement would account for the isolation of racemic product, and Brown proposed that die rapid migration would lead to preferential approach of the nucleophile fiom the exo direction. 

Fig. 5.11. Contrasting potential energy diagrams for stable and unstable bridged norbomyl cation. (A) Bridged ion is a transition state for rearrangement between classical structures. (B) Bridged ion is an intermediate in rearrangement of one classical structure to the other. (C) Bridged nonclassical ion is the only stable structure.

As an explanation of the preferred formation of pyrrolidines as compared to lower and higher membered heterocyclic rings, the necessity of a nearly linear arrangement of the involved centers in the hydrogen transfer step and a minimum of nonclassical strain in a cyclic 6-membered chair-like intermediate was postulated although the experimental evidence is not conclusive. 

As discussed by Zollinger, 1995 (Sec. 7.5) this hypothesis of a detour around intermediates of very low stability is also useful for the differentiation of classical and nonclassical ion intermediates in nucleophilic substitutions of 2-norbornyl and related compounds. 

In discussing nonclassical carbocations we must be careful to make the distinction between neighboring-group participation and the existence of nonclassical carbocations. ° If a nonclassical carbocation exists in any reaction, then an ion with electron delocalization, as shown in the above examples, is a discrete reaction intermediate. If a carbon-carbon double or single bond participates in the departure of the leaving group to form a carbocation, it may be that a nonclassical carbocation is involved, but there is no necessary relation. In any particular case, either or both of these possibilities can be taking place. 

An alternative explanation for the enhanced rates made its appearance. It was proposed that cr-participation in certain nonclassical ions provided a more satisfactory interpretation. This stimulated a detailed study of the norbornyl system, considered to provide the best available case for such nonclassical carbonium ion intermediates. The results failed to confirm the presence of significant -participation and supported the conclusion that the phenomena must be largely, if not entirely, steric in origin. 

The secondary, a-methylcyclobutylmethyl cation shows an unsymmetrically delocalized nonclassical type of intermediate at B3LYP/6-311+G level.19 The... 

Recently, some attempts were nndertaken to uncover the intimate mechanism of cation-radical deprotonation. Thns, the reaction of the 9-methyl-lO-phenylanthracene cation-radical with 2,6-Intidine (a base) was stndied (Ln et al. 2001). The reaction proceeds through two steps that involve the intermediary formation of a cation-radical/base complex before unimolecular proton transfer and separation of prodncts. Based on the value of the kinetic isotope effect observed, it was concluded that extensive proton tnnneling is involved in the proton-transfer reaction. The assumed structure of the intermediate complex involves n bonding between the unshared electron pair on nitrogen of the Intidine base with the electron-deficient n system of the cation-radical. Nonclassical cation-radicals wonld also be interesting reactants for snch a reaction. The cation-radical of the nonclassical natnre are known see Ikeda et al. (2005) and references cited therein. 

Protonated alkanes are important highly reactive intermediates in the acid-catalyzed transformations of hydrocarbons. However, the simplest protonated alkane, the methonium ion, which exemplifies the entire family of nonclassical... 

In 1967 Cava and Pollack obtained derivatives of the fourth, so-called nonclassical , thienothiophene— thieno[3,4-c]thiophene (4), a condensed heterocycle with formdly tetracovalent sulfur (42)j. The reaction of 3,4-bischloromethyl-2,5-dimethylthiophene (141) with sodium sulfide afforded 4,6-dimethyl-lif,3ff-thieno[3,4-c]thiophene (142) periodate oxidation of 142 gave die corresponding sulfoxide (143) in 91% yield. Attempts to convert the sulfoxide (143) into the thieno-[3,4-c]thiophene by the method used for S3mthesizing benzo[c]-thiophene led only to polymer. However, 24% of adduct 144 and 10% of 145 were obtained by refluxing sulfoxide (143) with N-phenylmaleimide in acetic anhydride, indicating that the thieno[3,4-c]-thiophene was formed as an intermediate. 

Carbocations are a class of reactive intermediates that have been studied for 100 years, since the colored solution formed when triphenylmethanol was dissolved in sulfuric acid was characterized as containing the triphenylmethyl cation. In the early literature, cations such as Ph3C and the tert-butyl cation were referred to as carbonium ions. Following suggestions of Olah, such cations where the positive carbon has a coordination number of 3 are now termed carbenium ions with carbonium ions reserved for cases such as nonclassical ions where the coordination number is 5 or greater. Carbocation is the generic name for an ion with a positive charge on carbon. 

In the early days of stable ion chemistry, the experimental measurements of parameters such as NMR chemical shifts and IR frequencies were mainly descriptive, with the structures of the carbocations being inferred from such measurements. While in cases such as the tert-butyl cation there could be no doubt of the namre of the intermediate, in many cases, such as the 2-butyl cation and the nonclassical ions, ambiguity existed. A major advance in reliably resolving such uncertainties... 

The study of carbocations has now passed its centenary since the observation and assignment of the triphenylmethyl cation. Their existence as reactive intermediates in a number of important organic and biological reactions is well established. In some respects, the field is quite mature. Exhaustive studies of solvolysis and electrophilic addition and substitution reactions have been performed, and the role of carbocations, where they are intermediates, is delineated. The stable ion observations have provided important information about their structure, and the rapid rates of their intramolecular rearrangements. Modem computational methods, often in combination with stable ion experiments, provide details of the stmcture of the cations with reasonable precision. The controversial issue of nonclassical ions has more or less been resolved. A significant amount of reactivity data also now exists, in particular reactivity data for carbocations obtained using time-resolved methods under conditions where the cation is normally found as a reactive intermediate. Having said this, there is still an enormous amount of activity in the field. 

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