Reactive Intermediate Chemistry
.pdf234 ORGANIC RADICAL IONS
The selection of distonic radical ions covered here is far from complete. Many additional distonic species have been characterized in frozen glasses, in solution, and in the gas phase. Alas, a more detailed coverage would go beyond the scope of this chapter.
5. RADICAL CATION REACTIONS: RELATIONSHIPS WITH OTHER INTERMEDIATES
Organic radical ions undergo a wide range of uniand bimolecular reactions. While unimolecular reactions are limited to reorganization and bond cleavage reactions, bimolecular reactions cover a wide range of reaction types (Scheme 6.3). Because radical ions have an unpaired electron and a charge, they can undergo reactions typical of free radicals as well as ions. Radical ions react with: (a) alkenes and arenes (electron or hole transfer, cycloadditions, s- or p-complex formation);
(b)ionic, protic, or polar reagents (protonation, nucleoor electrophilic capture);
(c)free radicals (spin labeling); (d) radical ions of opposite charge (back electron transfer, proton, atom or group transfer, or coupling); and (e) radical ions of like charge (dimerization, disproportionation). These transformations convert radical
REACTIONS OF ORGANIC RADICAL IONS
I.Unimolecular Reactions Electron, hydride, or alkyl Shift
Bond reorganization
Bond cleavage
II.Intra-Pair Reactions Back electron transfer
Proton, atom, or group transfer
Coupling
III.Bimolecular Reactions
a.With neutral molecules Electron transfer
Addition (to olefins), cycloaddition s- or p- Complex formation
b.With protic, ionic, or polar reagents Protonation/deprotonation Nucleo-/electrophilic capture
c.With Radicals
Spin labeling
Coupling
Oxygenation (3O2)
d.Between Radical Ions of like Charge Dimerization
Disproportionation
Scheme 6.3
RADICAL CATION REACTIONS: RELATIONSHIPS WITH OTHER INTERMEDIATES |
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ions into several classes of intermediates or products, which may retain the unpaired spin(s), the charge(s), spin and charge, or neither.
The competition between the various reactions depends on many factors, including the distance between the ions. Radical ion pairs generated by PET can be con-
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Scheme 6.4
Scheme 6.4, S denotes solvent molecules). Although they may diffuse apart generating ‘‘free’’ radical ions (FRI), reactions within the geminate pair can be quite fast. Unimolecular radical ion reactions compete with pair reactions, as do bimolecular reactions. The competition is aided by a spin multiplicity requirement governing electron return and coupling: in many cases, only singlet pairs can recombine or couple; pairs generated from triplet precursors must first undergo intersystem crossing and, therefore, have longer lifetimes. The rates of unimolecular reactions are determined by their (intrinsic) barriers; their efficiency depends on the rate of intersystem crossing and the efficiency of ion pair and bimolecular reactions; the latter can be ‘‘turned on or off’’ by the reagent concentration.
By various transformations, radical ions are related to several classes of intermediates or products (Scheme 6.5). The simplest relationship is that to their
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Scheme 6.5
236 ORGANIC RADICAL IONS
parents; radical ions are readily interconverted with their neutral precursors by ET/ BET (back electron transfer). Similarly, BET converts distonic radical cations to biradicals or zwitterions. Some nondistonic radical cations generate (triplet) biradicals upon BET. Bond cleavage reactions, such as dissociation or fragmentation, can proceed in two directions: the charged (odd electron, OE) radical ion may generate a smaller radical ion by losing a neutral (even electron, EE) molecule, or cleave forming an OE free radical and an EE positive or negative ion. These reactions are well documented in the gas phase, but also in the condensed phase. For example, radical anions lose negative ions (Cl , CN ), whereas radical cations lose positive ions (Hþ, Rþ). Bond cleavage reactions of cyclic radical ions generate bifunctional distonic species, in which spin and charge are localized (or delocalized) in separate segments of the molecule.
An intriguing relationship exists between carbene cations and anions, on the one hand, and the corresponding radical ions, on the other (Scheme 6.5). Although the reactivity of carbene ions is not explored in detail, one could envisage insertion and addition reactions similar to those of carbenes.
5.1. Unimolecular Radical Ion Reactions
Radical ions undergo various unimolecular reorganization reactions, of which we mention electron, hydride, or methyl shift, and several rearrangements. For example, radical ions of systems containing two donor or acceptor sites may undergo intramolecular ET, as observed for a series of radical anions of type A–Sp–biphenyl (45 ) containing two acceptors linked by a 5a-androstan unit as spacer (Sp). The electron-transfer rates observed for the mono-anions of these systems, generated by radiolysis in cryogenic matrices, showed a striking deviation from the classical Brønsted relationship.209,210
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A
45 • –
Stereorigid radical cations may undergo stereospecific sigmatropic shifts; for example, the puckered ions, antiand syn- 5-methyl-19þ, undergo stereospecific
hydride or methyl migration, respectively, forming the 1-methylcyclopentene ion (46þ) and the 3-methyl isomer (47þ).171
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RADICAL CATION REACTIONS: RELATIONSHIPS WITH OTHER INTERMEDIATES |
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Similarly, the radical cation (48þ) of sabinene generated the b-phellandrene radical cation (49þ).211 This rearrangement occurs with high retention of optical purity, but only in the absence of nucleophiles (see below).
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The 9,10-dicyanoanthracene sensitized irradiation of cis-stilbene results in nearly quantitative isomerization (>98%) to the trans isomer with quantum yields greater than unity.212 Therefore, the isomerization was formulated as a free radical cation chain mechanism with two key features: (1) rearrangement of the cis-stilbene radical cation; and (2) electron transfer from the unreacted cis-olefin to the rearranged (trans-) radical cation.
Radiolysis of the diacetylene hexa-1,5-diyne (50) generates the hexa-1,2,4,5- tetraene radical cation (51þ) via a Cope rearrangement in the Freon matrix.213
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Intramolecular bond formations include (net) [2 þ 2] cycloadditions; for example, diolefin 52, containing two double bonds in close proximity, forms the cage structure 53. This intramolecular bond formation is a notable reversal of the more general cycloreversion of cyclobutane type olefin dimers (e.g., 15þ to
16þ). The cycloaddition occurs only in polar solvents and has a quantum yield greater than unity.214 In analogy to several cycloreversions215,216 these results
were interpreted in terms of a free radical cation chain mechanism.
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The monocyclic 1,2,5,6-tetraphenylcycloocta-1,5-diene (54) undergoes a ‘‘cross’’-cycloaddition,217 forming a tricyclic product (56), most likely by 1,5-cycli- zation of 54þ forming the bicyclic bifunctional radical cation 55þ as an intermediate.
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238 ORGANIC RADICAL IONS
Radiolysis of deca-2,8-diyne (57) results in an interesting cycloaddition, forming a cyclobutadiene radical cation (58þ) at 77 K without requiring annealing at higher temperatures.218
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An ET induced rearrangement of tetra-tert-butyltetrahedrane generates the corresponding tetra-tert-butylcyclobutadiene radical cation (60þ) via 59þ.219
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In addition to rearrangements, many radical ions undergo cleavage reactions. We have already encountered such a reaction: Electron attachment to halocarbon matrix molecules results in fragmentation to a halide ion and a free radical.
R X þ e ! R X ! R þ X
R ¼ haloalkyl
In the case of halocarbon matrices, the SOMO is of the s* type and the cleavage is facilitated by the antibonding nature of the SOMO. In other ions, s or s* orbitals of scissile bonds interact with a p or p* orbital, causing them to be weakened. Accordingly, radical anions of benzyl halides may generate benzylic radicals with loss of a halide ion. Conversely, benzylsilane radical cations may form benzylic radicals with loss of a silyl cation (Fig. 6.15).
Concerning C C bond cleavage reactions, the strained radical cation of quadricyclane (15þ) readily undergoes opening of the cyclobutane ring, forming the norbornadiene radical cation (16þ).146 The ring opening of 1,2-diaryloxycyclobutane (13) forming the 1,4-bifunctional intermediate (14þ) was invoked to explain the electron transfer sensitized cis to trans-isomerization (see above).155
Figure 6.15. Schematic orbital diagrams explaining the weakening of a C Si s bond due to overlap with an adjacent p orbital (a) and the weakening of a C X (halogen) bond due to overlap of the s* orbital with an adjacent p* orbital (b).
RADICAL CATION REACTIONS: RELATIONSHIPS WITH OTHER INTERMEDIATES |
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Many distonic radical ions are involved in unimolecular dissociation reactions. For example, the McLafferty rearrangement of carbonyl compounds proceeds by
C C bond cleavage of distonic ions.220 Alternatively, bond-cleavage reactions of cyclic molecular ions may generate distonic ions (see above).200–202 For example,
C C bond cleavage of cyclic ketone molecular ions (e.g., 61þ) generates 62þ.221
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In analogy to the cleavage of quadricyclane radical ion, radical ions containing cyclobutane units frequently undergo cleavage of two C C bonds. This finding is of interest in connection with the ‘‘photoreactivation’’ of DNA, damaged due to photochemical cyclobutane formation between adjacent thymine units. The DNA is restored by a photoreactivating enzyme, via ET to or from the pyrimidine dimer (63), that is, by cleavage of either the radical anion or cation.
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The mechanism of dimer cleavage has been probed in model systems,222–225
including bifunctional ones in which a sensitizer (e.g., indole) is linked to the pyrimidine dimer.226,227 Work on a linked dimer (64), suggested that a dimer
radical cation is a discrete (short-lived) minimum.225
5.2. Intra-Pair Reactions
Intra-pair reactions include BET, proton, atom, or group transfer within the pair, or coupling (bond formation) of the geminate radical ions. Intra-pair reactions can be quite fast, particularly for singlet pairs and for CRIPs generated by PET from charge-transfer complexes (Scheme 6.4). In a majority of cases, only pairs of singlet spin multiplicity undergo BET; this process is an energy-wasting step that seriously limits the yield (and synthetic utility) of bimolecular radical ion reactions.
In some systems, triplet BET can occur, as deduced from time-resolved optical spectroscopy, magnetic field effects, CIDNP, or optoacoustic calorimetry.228–234 Triplet BET is governed by energetic factors, which determine rates, and by the relative topologies of the potential surfaces of parent molecule, radical ions, and of accessible triplet or biradical states. Divergent topologies for different states may cause rearrangements.
240 ORGANIC RADICAL IONS
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The potential surfaces of the different states of a reagent may be related in three ways (Scheme 6.6): (a) the three surfaces have minima at closely related geometries; (b) the radical ion geometry is related to that of the parent, but the triplet state or biradical has a different geometry; (c) in systems giving rise to bifunctional– distonic radical ions (see above) triplet states or biradicals may have structures related to the radical ions.235
Typical aromatic donors and acceptors undergo only minor geometry changes upon oxidation or reduction or upon population of the triplet state; for these compounds, the reaction sequence ET followed by BET has no effect on the structure. If the triplet state or biradical belongs to a different structure type than radical ion and ground-state precursor, as is the case for cisor trans-1,2-diphenylcyclopropane
(65)236,237 or norbornadiene (16)238,239 BET may occur with cleavage236,237 or formation238,239 of one or more C C bonds. In such cases, the sequence ET–BET may
result in rearrangements.235 For distonic radical ions (e.g., 24þ) triplet BET will
populate structurally related biradicals (e.g., 24 ), which may decay to rearranged products.240,241
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RADICAL CATION REACTIONS: RELATIONSHIPS WITH OTHER INTERMEDIATES |
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The energetic requirements for triplet BET go beyond the trivial prerequisite that a triplet state of energy ET, or a biradical of energy EBR, exist below the ion-pair energy, G0SSRP; intersystem crossing can be slow if the singlet–triplet gap is large. In fact, triplet recombination can become competitive upon either raising or lowering the ion-pair energy (using sensitizers with higher or lower excited state reduction potentials). For example, ET from 65 to triplet-chloranil generates an ion pair whose energy lies too low to access any triplet state;236 using cyanoaromatics instead raises the pair energy and allows triplet recombination.236 On the other hand, electron transfer from sabinene (48) to 1,4-dicyanobenzene generates an ion pair well above an available triplet state; however, triplet recombination is achieved by lowering the pair energy (using triphenylpyrylium ion as the electron acceptor).242
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(Z ) -3 66••
(E ) -3 66 ••
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Scheme 6.7
242 ORGANIC RADICAL IONS
We illustrate triplet BET resulting in isomerization with two examples: the reaction of transand cis-65 with either chloranil or 1,4-dicyanonaphthalene; and the reaction of 1,1-diaryl-2-methylenecyclopropane (23) with various sensitizers. The radical cations of transand cis-65þ each are related uniquely to the geometry of their precursor, transand cis-65. With chloranil as sensitizer, a relatively low-lying ion pair is formed; accordingly, BET occurs exclusively in singlet pairs, exclusively regenerating the reagent ground state. With 1,4-dicyanonaphthalene as sensitizer– acceptor, the identical radical cations transand cis-65þ, are formed; however, the pair energy is significantly higher. Therefore, BET in triplet pairs becomes feasible, populating a triplet species, (E)- or (Z)-366 , with a broken C C bond. Upon intersystem crossing, the two rotamers regenerate both cisand trans-365. A schematic energy diagram is given in Scheme 6.7.
The second example of triplet BET in radical ion pairs involves the (ring-
opened, distonic) trimethylenemethane radical cation (24þ) generated in the PET reaction of 23.181,182 The corresponding triplet biradical (24 ) is sufficiently
low in energy,240 so that it is accessible by triplet BET.
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Radical ion pairs also react by proton, atom, or group transfer. We illustrate proton transfer in reactions of aromatic hydrocarbons with tertiary amines. These reactions cause reduction or reductive coupling. In the reduction of naphthalene,
the initial ET is followed by Hþ transfer from cation to anion, forming 67 paired with an aminoalkyl radical; the pair combines to generate 68.243,244
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Similarly, the stilbene isomers (69) react with tertiary amines by ET followed by proton transfer and coupling, forming 70.245 During the irradiation of cis-stilbene in the presence of ethyldiisopropylamine, the trans-stilbene radical anion, trans-69 , was observed by Raman spectroscopy.246 The ET mechanism is also supported by a pronounced dependence of the quantum yields on solvent polarity.
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RADICAL CATION REACTIONS: RELATIONSHIPS WITH OTHER INTERMEDIATES |
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The radical pair generated by proton transfer from tertiary amine radical cations
to a,b-unsaturated ketone radical anions (e.g., 71) couple in the b position, forming
72.247
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Alkene radical cations may transfer protons to cyanoaromatic radical anions, followed by coupling of the resulting radicals. For example, 1,4-dicyanobenzene and other cyano-aromatic acceptors form substitution products (e.g., 73) with 2,3-dimethylbutene via coupling and loss of HCN.248
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The third intra-pair reaction to be discussed involves bond formation between radical anion and cation without intervening Hþ transfer; both singlet and triplet radical ion pairs can couple. For example, the bifunctional radical cation 24þ generates two chloranil adducts, most likely via zwitterions (e.g., 74þ and 75þ), initiated by forming a C O bond. The CIDNP results indicate that 74 and 75 are formed from a singlet radical ion pair.182 Adduct 75 is a minor product, as the major spin density of 24þ is located in the allyl function which, therefore, is expected to be the principal site of coupling.
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Chloranil forms two types of cycloadducts with 3,3-dimethylindene. In the early stages, oxetane (76) is formed via adduct 76 , by addition of the carbonyl oxygen