Reactive Intermediate Chemistry

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Figure 6.16. Spartan representation of SOMO (b) and LUMO (a) for norcaradiene radical cation (see color insert). [Adapted from Ref. 152.]

the regioselectivity of nucleophilic capture is governed by the SOMO, or by the nature and topology of the LUMO.

Orbital control was evaluated in several theoretical treatments. Curve crossing methodologies suggest that nucleophilic capture of radical cations requires ‘‘double excitation;’’295 the excitation energy can be small and the resulting barrier low.296 Accordingly, nucleophiles attack the dibenzofuran radical cation at the site of the highest LUMO coefficient, which is also the site of highest spin density in the dibenzofuran triplet state.297 Similarly, the stereochemical course of nucleophilic

displacement of a s bond (with inversion of configuration) was ascribed to involvement of the s* orbital of the weakened bond (the LUMO).298,299

The product-determining role of the LUMO can also explain the regioselective capture of other radical cations, including the nucleophilic attack on 1-aryl-2- alkylcyclopropanes (112þ). The SOMO and LUMO of disubstituted cyclopropane radical cations (e.g., 1,2-dimethylcyclopropane; Fig 6.17) suggest that the observed regioselectivity reflects electronic factors: capture at the unsubstituted cyclopropane

carbon is unlikely, since neither SOMO nor LUMO have orbital coefficients at C3.164

Internal alcohol functions also may capture a radical cationic function in suitable substrates. The radical cation 125þ of a bicyclo[4.1.0]heptane system bearing a (3-hydroxybutyl) substituent and a p-tolylthio moiety in the 1- and 6-positions,

256 ORGANIC RADICAL IONS

In contrast, homo-chrysanthemol (129) reacts exclusively by capture at the quaternary cyclopropane carbon, generating the five-membered cyclic ether (130 ).301 Apparently, the five-membered transition state leading to 130 is significantly favored over the seven-membered one required for capture at the terminal carbon of the double bond of 129þ.

In addition to nucleophilic capture by alcohols, nonprotic nucleophiles also react with these intermediates. For example, the distonic dimer radical cation 96þ can be trapped by acetonitrile; a hydride shift, followed by electron return, gave rise to the pyridine derivative 131.272 Similar acetonitrile adducts are formed in the electrontransfer photochemistry of terpenes such as a- and b-pinene302 or sabinene.303

5.3.3. Reactions of Radical Anions With Radicals. The coupling of arene or alkene radical anions with radicals is an important reaction, and one that has significant synthetic potential. For example, radicals formed by nucleophilic capture of radical cations couple with the acceptor radical anion, resulting in (net) aromatic substitution. Thus, the 1-methoxy-3-phenylpropyl radical (113 ; R ¼ H) couples

with dicyanobenzene radical anion; loss of cyanide ion then generates the substitution product 132.291,304

• –

Coupling of alkyl radicals resulting from nucleophilic capture of alkenes with sensitizer radical anions in acetonitrile–methanol (3:1) was studied in detail.305,306

The photochemical nucleophile olefin combination, aromatic substitution (photoNOCAS) reaction, formulated below for 2,3-dimethylbutene–methanol–p-dicyano- benzene, has some synthetic utility. The final step, loss of cyanide ion, is not shown.

OMe

Similarly, radical 128 couples with dicyanobenzene radical anion generating the substitution product 133 after loss of cyanide ion.

Radicals of type 113 also couple with (protonated) N-methylphthalimide anion.307 The formation of ethers 132 and 134 and many related products shows that bimolecular nucleophilic capture is faster than coupling of the geminate radical ion pair.

In addition to nucleophilic capture of alkene or cyclopropane radical cations (see above) radicals may be generated by cleavage of C X bonds, particularly C Si bonds. Such cleavage is often assisted by a nucleophile. Because the radical is generated near the radical anion, to which it couples, the resulting C C bond formation may be considered a reaction of a ‘‘modified’’ radical (ion) pair.

For example, allylic silanes react with photoexcited iminium salts by ET resulting in photoallylation.308 Key steps in such reactions are the cleavage of the C Si

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bond in a silyl-substituted radical cation, and the coupling of the resulting allyl radical to the aminoalkyl radical (e.g., 135 ) generating products such as 136.

ET induced allylation of dicyanoalkenes (e.g., 137) is regioselective; the allyl radical couples to the carbon b to the cyano groups (! 138).309 The efficiency of these reactions can be improved by using a cosensitizer, such as phenanthrene.310

In addition to regiospecificity, appropriate substrates also show stereoselectivity. For example, the photoallylation of the rigid styrene (139) with phenanthrene as cosensitizer in acetonitrile, produced a 3 : 1 ratio of transto cis-allylated products.311

The role of the nucleophile was confirmed for a benzyldimethylsilane (141) bearing a nucleophile (OH, OMe) on an oligomethylene tether (n ¼ 3–5). The radical cations of these silanes have very short lifetimes even in nonpolar solvents, and the resulting benzyl radicals couple with the radical anion.312

In analogy to the a-deprotonation of tertiary amine radical cations (see above), amines bearing an a-trimethylsilyl group may undergo heterolytic cleavage of the C Si bond upon ET, particularly in the presence of nucleophiles. The resulting

aminoalkyl radical may couple, for example, to the enone radical anion (71 ) generating 142.247

Interesting variations of these reactions are observed when the a-silylamine donor funtion is tethered to an enone. For example, the intramolecular ET reaction of 143 results in two divergent cyclizations. Methanol assists the cleavage of the C Si bond; the resulting biradical anion 146 couples; protonation and tautomerization then leads to 147. In acetonitrile, on the other hand, transfer of an a proton to the enone radical anion function forms biradical 144 ; coupling and tautomerization then generates 145.247

5.3.4. Reactions with Radical Ions of Like Charge. In the final section, we briefly mention reactions between radical ions of like charge. One of the longstanding problems of radical ion chemistry involves the actual structure of ketyls. Following extensive conductivity and magnetic susceptibility studies in the 1930s detailed ESR and optical studies have demonstrated the existence and interconversion of at least four distinct species: a free ketyl anion; a monomer ion pair; a

260 ORGANIC RADICAL IONS

paramagnetic dimer ion pair; and a diamagnetic dimer dianion. The latter is the logical precursor for the pinacols generated in these reactions. The system is further complicated by different degrees of solvation of the individual ions as well as the pairs. The equilibria between these species show pronounced solvent effects. For example, the characteristic colors of benzophenone or fluorenone ketyls are reduced in nonpolar solvents, a change ascribed to formation of the pinacolate dianions. However, the change is reversible once the nonpolar solvent is removed.313 Details of these complex interactions exceed the scope of this chapter.

The acyloin condensation is closely related to the radical anion coupling forming pinacolate anions: two ester radical anions couple to form a dianion, which readily loses two alkoxide ions. The resulting diketone then is reduced by sodium, first to a semidione radical anion, then to the dianion.314 Finally, aqueous work-up produces the acyloin. Acyloins are convenient precursors for the generation of semidione radical anions.315

Pairs of radical ions of like charge also react by electron transfer (i.e., they disproportionate). One classic example involves reduction of tetraphenylethylene and subsequent ET between two tetraphenylethylene anions.316 A more recent interesting example is that of cyclooctatetrene radical anion 148 . Alkali metals readily reduce the nonplanar cyclooctatetraene, generating a persistent planar radical anion

(aH ¼ 0:32 mT, 8H);317 148 disproportionates generating the aromatic 10-p- dianion 1482 and the parent molecule.318

In this section, too, we need to emphasize that space limitations preclude a more thorough treatment of these interesting species and their chemistry.

6. CONCLUSION AND OUTLOOK

The rich variety of radical ion reactions and the diversity of structure types portrayed in this chapter may lead the reader to the conclusion that this field has exhausted its growth potential, especially when one considers that the selection of topics and the depth of coverage offered here had to be limited. Nevertheless, radical ion chemistry remains in a phase of rapid development and can be expected to retain a high level of attention for the foreseeable future.

Dividing possible approaches to radical ion research (and chemical research in general) into three principal branches, structure, energetics, and kinetics, it is clear that the state of the art in these areas has not advanced to the same degree. Kinetics is perhaps the most matured due to the significant recent advances in time resolved spectroscopy. Concerning energetics, redox potentials, ionization potentials, and electron affinities provide the energetics of electron removal or attachment; in addition, some pair energies, and biradical and triplet energies are available from optoacoustic calorimetry and laser spectroscopy. As for structural features, hyperfine couplings and their signs, available from ESR or CIDNP studies, reveal a pattern of electron spin densities; no other properties can be measured, aside from the occasional crystallographic characterization of stable radical ion salts. Bond lengths and angles and a host of radical ion properties are, however, accessible by ab initio MO calculations.

After a period where the radical cation field owed significant advances to experimental studies, the development of density functional methodologies and ever increasing computing power has given theory a significant boost in recent years. Molecular orbital calculations have become an invaluable tool to evaluate possible structure types, and the interplay between experiment and theory has become a major force in radical ion chemistry. Particularly, the application of matrix isolation IR studies has received a significant boost from sophisticated state-of-the-art calculations. Ab initio techniques also should play a significant role in elucidating details of the interplay between electron transfer and structural reorganization. The

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extension of time resolved spectroscopy into as yet inaccessible spectral regions surely will yield major new contributions.

Continuing research in radical ion chemistry will yield many advances; the continuing development of new techniques and their application to previously studied systems may add some new facets to the reaction mechanisms. Of course, progress will also include the rediscovery of facts, structures, and mechanisms, derived or formulated over the past five decades, which can now be veiled in new terminology. In short, research in radical ion chemistry will flourish for some years to come.

SUGGESTED READING

H.D. Roth, ‘‘A History of Electron Transfer and Related Reactions,’’ Topics Curr. Chem. 1990, 156, 1–19.

H.D. Roth, ‘‘Chemically induced dynamic nuclear polarization,’’ in Encyclopedia of Nuclear Magnetic Resonance, Vol. 2, D. M. Grant, R. K. Harris, Eds., 1996, John Wiley & Sons, Inc., New York, pp. 1337–1350.

N. L. Bauld, ‘‘Cation Radicals,’’ in Radicals, Ion Radicals, and Triplets, Wiley-VCH, New York, 1997, pp. 141–180.

N. L. Bauld, ‘‘Anion Radicals,’’ in Radicals, Ion Radicals, and Triplets, Wiley-VCH, New York, 1997, pp. 113–140.

Throughout this chapter, the author has cited Accounts of Chemical Research articles by leading researchers in the radical ion field, including those of Asmus,276 Bauld and coworkers,281 Courtneige and Davis,277 Gerson,167 Hoffmann,158 Knight,34 Ledwith,41 Mangione and Arnold,306 Mattes and Farid,278 McLauchlan and Stevens,62 Miyashi et al.,255 Nelsen,107 Ottolenghi,230 Roth,146 Shida et al.,85 and Yoon and Mariano.247 These articles are recommended to readers who may want a more detailed description of selected radical ion topics.

R.L. Smith, P. K. Chou, and H. I. Kentta¨maa, ‘‘Structure and reactivity of selected distonic radical cations’’, in Structure, Energetics and Dynamics of Organic Ions, T. Baer, C. Y. Ng, and I. Pawis, Eds., John Wiley & Sons, Inc., New York, 1996, p. 197.

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