Cyclohexadienyl radical, reduction

Homolytic aromatic substitution often requires high temperatures, high concentrations of initiator, long reaction times and typically occurs in moderate yields.Such reactions are often conducted under reducing conditions with (TMSlsSiH, even though the reactions are not reductions and often finish with oxidative rearomatization. Reaction (68) shows an example where a solution containing silane (2 equiv) and AIBN (2 equiv) is slowly added (8h) in heated pyridine containing 2-bromopyridine (1 equiv) The synthesis of 2,3 -bipyridine 75 presumably occurs via the formation of cyclohexadienyl radicals 74 and its rearomatization by disproportionation with the alkyl radical from AIBN. ... 

Perhaps it should be mentioned also the orientation of the Birch reduction which is strongly dependent on the nature of the aromatic substituents. Donor-substituted benzenes furnish predominantly 1-substituted 1,4-cyclohexadienes while acceptor-substituted analogues give 3-substituted 1,4-cyclohexadienes. The regioselectivities can be explained by the destabilizing d-d pairing in the intermediates from d-substi-tuted cyclohexadienyl radical anions leading to the 3-substituted products, and the... 

A syn displacement of the bromine by benzylamine in the presence of triethylamine led, by a Sn2 reaction, to the a and p amino compounds which were separated into 326 (18%) and 327 (81%) respectively. The dichloroacetamide 328 derived from the latter, when subjected to the action of tri-n-butyltinhydride (2eq) and 2,2 -azobisisobutyronitrile underwent a 5-ero ring closure to furnish via the radical 329, the hydrooxindole 330 (51%) and significant amount of the rearrangement product 331 (30%). The latter is believed to be formed by fragmentation of the cyclohexadienyl radical 332 generated from the cyclohexyl radical 329. On diborane reduction, 330 provided the cis hydroindole 333, which on 0,N-debenzylation afforded ( )-c -fused bicyclic aminoalcohol 334, a compound that had been previously cyclised with formaldehyde to ( )-elwesine (320) by Stevens et al [85]. 

If the mechanism in Scheme 10.24 is correct and cyclohexadienyl radicals do indeed react with the initiator, their presence should retard other radical processes. To test this, the reduction of 1-bromo-octane was investigated in the presence of 24 (Fig. 10.7), which readily undergoes cyclisation so should form intermediate cyclohexadienyl radicals. The initial reaction rates were measured between 2 and 12 minutes. During this period, less than 10% of the BusSnH in the reaction was consumed and so, to a fair approximation, the... 

The mechanism of the Birch reduction (shown next) is similar to the sodium/liquid ammonia reduction of alkynes to fnmy-alkencs (Section 9-9C). A solution of sodium in liquid ammonia contains solvated electrons that can add to benzene, forming a radical anion. The strongly basic radical anion abstracts a proton from the alcohol in the solvent, giving a cyclohexadienyl radical. The radical quickly adds another solvated electron to form a cyclohexadienyl anion. Protonation of this anion gives the reduced product. 

Scheme 58. Proposed pathways for reduction of the cyclohexadienyl radical 67 (245).

The HAS reaction proceeds via a sigma (a) complex (1) with substitution being completed by the loss of the leaving group Y, which is usually hydrogen (Scheme 9.1, Y = H). Examples where the cyclohexadienyl radicals become trapped by fast reductants to form cyclohexadiene [2] and the detection of radical intermediates by ESR or CIDNP provide evidence that the cyclohexadienyl radicals are intermediates in this reaction [3]. In some systems, the addition of a radical onto the arene is the rate-determining step, because of the loss of aromaticity. For example, the rate constant for the addition of the ferf-butyl radical to benzene at 79°C is 3.8 x 10 M s [4], which is clearly at the lower end of a useful radical reaction. The arene needs to be used at high concentration, or as the solvent, in order to compensate for poor rates. On the other hand, as the rate of addition of the phenyl radical to benzene is 4.5 x 10 s" [5], it is more useful in these kind of reactions. 

FIGURE 13.68 The radical anion is protonated to give a resonance-stabilized cyclohexadienyl radical that goes on to produce the 1,4-cyclohexadiene through another reduction- rotonation sequence (Et = CH2CH3). 

Cyclization on to aromatic rings has been investigated by a number of workers. The use of reductive conditions (BusSnH-AIBN) facilitates an intramolecular homolytic substitution of imidazoles and benzimidazoles (Scheme 15). This chemistry allowed for a range of ring sizes to be produced. Another oxidative cyclization, this time mediated by the addition of the p-toluenesulfinate radical to an alkene, has been reported. Oxidative addition occurs in the presence of Cu (OAc)2 which oxidizes any intermediate cyclohexadienyl radicals back to the aromatic ring (Scheme 16)." ... 

Obviously the structures and yields of Birch reduction products are determined at the two protonation stages. The ring positions at which both protonations occur are determined kinetically the first protonation or 7t-complex collapse is rate determining and irreversible, and the second protonation normally is irreversible under the reaction conditions. In theory, the radical-anion could protonate at any one of the six carbon atoms of the ring and each of the possible cyclohexadienyl carbanions formed subsequently could protonate at any one of three positions. Undoubtedly the steric and electronic factors discussed above determine the kinetically favored positions of protonation, but at present it is difficult to evaluate the importance of each factor in specific cases. A brief summary of some empirical and theoretical data regarding the favored positions of protonation follows. 

Electron-deficient aryl diazonium salts such as the pentafluoro derivative can offer the attractive option to conduct radical arylations as chain reactions with an SrnI mechanism (Scheme 35) [151]. In these special cases, only catalytic amounts of an initiating reductant, such as sodium iodide, are required. In the propagation step, the diazonium salt 92 acts as oxidant for the cyclohexadienyl intermediate 93. Rearomatization of 93 to 94 as well as the generation of a new pentafluorophenyl radical are achieved through this step. 

The electron adduct of benzonitrile has also been found to be converted into a cyclohexadienyl-type radical (Chutny and Swallow, 1970). Aliphatic nitriles, on the other hand, protonate rapidly on the CN carbon following reduction [reaction (82)] (Neta and Fessenden, 1970b). 

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