1,4-Diradicals, formation

Thermal dimerization of ethylene to cyclobutane is forbidden by orbital symmetry (Sect 3.5 in Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). The activation barrier is high E =44 kcal mof ) [9]. Cyclobutane cannot be prepared on a preparative scale by the dimerization of ethylenes despite a favorable reaction enthalpy (AH = -19 kcal mol" ). Thermal reactions between alkenes usually proceed via diradical intermediates [10-12]. The process of the diradical formation is the most favored by the HOMO-LUMO interaction (Scheme 25b in chapter Elements of a Chemical Orbital Theory ). The intervention of the diradical intermediates impfies loss of stereochemical integrity. This is a characteric feature of the thermal reactions between alkenes in the delocalization band of the mechanistic spectrum. 

Since both a acceptors and n donors at the alkyne termini are known to facilitate the Bergman cyclization, Zaleski and coworkers established a model46 in which the coordination of a Lewis acid (metal ion) would change the electronic environment in favor of diradical formation (Scheme 11). 

Benzenediyl diradical formation from enediyne via electrocyclization. 

Stereochemical equilibration can arise from bond rotation in the 1,4-diradical and/or reversibility of diradical formation resulting in stereochemical equilibration of the starting alkene. 

Photolysis of the 1,2,3,5-oxathiadiazine (132) in the presence of ethanol leads to the quinazolone (133). The product is not formed in the absence of ethanol, and the proposed mechanism involves electrocyclic ring opening, addition of ethanol, photochemical diradical formation and closure on to the C-6 phenyl ring followed by aromatization as shown in Scheme 8 (79JOC4435). 

To avoid Norrish II photolysis of pyranosid-2-uloses derivatives containing aglycones derived from primary and secondary alcohols, t-butoxy derivatives 58 can be successfully photolyzed by a Norrish I reaction to yield, by C-l, C-2 cleavage and diradical formation, compounds 59 [30 %) and 60 [40 %) (Scheme 32) [62],... 

It is assumed that a CT complex precedes diradical formation 140,143,146). primarily because of the regioselectivity of addition to unsymmetrical olefins. If different complexes are indeed involved, the final product ratio is a complex function of many competing rates. For example, let us assume the least complicated scheme as shown below for cyclopentenone. 

There is no clear evidence which carbon of the double bond forms the first covalent bond in diradical formation. In fact, there is evidence from rearrangement products that each does 148>. 

Flash vacuum pyrolysis of the dibenzodioxocine 6 was reported to give the 2-(2 -hydroxybenzyl)benzaldehyde 178 (Equation 39), presumably via the intermediate diradical formation <1995JOC8410>. 

Fig. 11. Diradical formation upon UV-irradiation. The calculated dependencies have been fitted to the experimental points...

Allenyl phosphine oxides (75) have been prepared by the reaction of the enediyne alcohols (74) with chlorodiphenylphosphine. When heated at 37°C in the presence of 1,4-cyclohexadiene, (75) gave mixtures of aromatic compounds (76), (77) and (78) (Scheme 12). Evidence for the biradical (79) acting as an intermediate was obtained by heating (75) i n perdeuterotetrahydrofuran. O The enediyne alcohol (74, R = CH2CH20Ac) shows DNA-cleaving activity which is presumably related to diradical formation. ... 

The different modes of attack depending on the hetero substitution and the electronic nature of the dienophile have been explained in terms of the molecular orbital theory. Quadricy-clanes with a high lying HOMO react with dienophiles in a concerted manner with 1,5-attack, whereas the heteroatom in heterasystems provides a driving force for diradical formation and a stepwise reaction via 2,4-attack. The HOMO-LUMO gap between 3-oxaquadricyclane and TCNE, however, is small because of the extremely low lying LUMO of TCNE and thus diradical formation not withstanding the concerted pathway and 1,5-attack is favored. 

Semmelhack, M.F. Neu, T. Foubelo, F. Arene 1,4-Diradical formation from o-dialkynylarenes. Tetrahedron Lett. 1992, 33, 3277-3280. 

Semmelhack, M,F, Gallagher, J.J. Minami, T. Date, T, The enol-keto trigger in initiating arene diradical formation in calicheamicin/esperamicin analogs. J. Am. Chem. Soc. 1993, 115, 11618-11619. 

Because of the DNA-cleaving ability and antitumor properties of such naturally occurring diyl precursors as calicheamicin, there has been a great deal of study directed toward the mechanism of diyl formation [32]. The rate of diradical formation has been found to depend on many factors, including (1) the distance between the two alkyne subunits (2) concentration of the trapping agent (3) substituent effects and (4) the difference in strain energy between the enediyne and the cycliza-tion transition state. 

It is also possible that epoxide opening is initiated by electron push from the nitrogen atom rather than the phenol, and this will be discussed in a later section. In either case, epoxide opening is the trigger for cycloaromatization, diradical formation and DNA damage [118-120]. 

Figure 5.2.9 Cis-tmns isomerization of polyenes may occur not only by light, but also by thermal twisting and resulting diradical formation. The process is, however, very slow at room temperature.

The question of irreversible diradical formation can be answered by the following thermochemical argument. In Figure 7, irreversible diradical formation requires either ks >> 2 or fco >> sls sl necessary condition. While, except for ki, none of these rate constants have been measured for any olefin, we can examine the plausibility of the necessary condition for irreversible diradical formation through theoretical considerations. 

We would expect k > k> since the entropies of Reactions 2 and 7 should be comparable, and Reaction 7 is the more exothermic. Since Reaction 6 requires intersystem crossing during reaction while Reaction 3 does not, we would expect k > k. Therefore, disproof of > > 2 is a condition sufficient to disprove irreversible diradical formation since this condition would also rule against h >> h-... 

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