1.4- Diradical intermediates

Cychc diacyl peroxides decompose thermally and photolyticaHy to yield products derived from diradical intermediates (188,198,205) (eq. 31). 

For conjugated carbonyl compounds, such as a,) -enones, the orbital diagram would be similar, except for the recognition that the HOMO of the ground state is ij/2 of the enone system, rather than the oxygen lone-pair orbital. The excited states can sometimes be usefully represented as dipolar or diradical intermediates ... 

The competition between these two reactions is determined by the effect of substituents on the conformation and reactivity of the diradical intermediate. 

Ketones such as 2,2,5,5-tetraphenylcyclopentanone and 2,2,6,6-tetraphenylcyclohex-anone decarbonylate rapidly because of the stabilization afforded by the phenyl groups. The products result from recombination, disproportionation, or fragmentation of the diradical intermediate. ... 

Intramolecular hydrogen-atom abstraction is also an important process for acyclic a,/ -unsaturated ketones. The intermediate diradical then cyclizes to give the enol of a cyclobutyl ketone. Among the by-products of such photolyses are cyclobutanols resulting from alternative modes of cyclization of the diradical intermediate ... 

In cyclic ketones, the diradical intermediates can recombine, leading to isomerized ketones ... 

The reaction is ordinarily stereoselective, favoring the more stable adduct for either alkene isomer, and a long-lived triplet diradical intermediate is implicated. ... 

The transformation can be formulated in terms of bonding between C-2 and C-4 involving a cyclopropyl diradical intermediate ... 

Limited reports on the mechanism of the Greabe-Ullmann reaction have appeared. A diradical intermediate is presumably involved in the thermolysis of the triazole 4. ... 

Pyrolyses of Nl- or N3-substituted derivatives of compounds 4 and 5 have continued to find use as routes to azacarbazoles, although the yields are often indifferent and there are no recent examples. The photochemical reactions are dealt with in Section IV.G. Pyrolysis media are paraffin (P) or PPA, and examples of products are compounds 247 (P, cytostatic) (83MI2), 248 (P) (84MI1), and 249 (from a 1-substituted derivative) (86MI2). Indications of diradical intermediates are provided by the thermolysis of compound 250 (P) (83MI2) where one product is a dimer. 

Myers has discovered a related reaction of the natural product neocarzinostatine 8 (simplified structure). As in the case of the Bergman cyclization a diradical intermediate is generated by a chemical activation step taking place at the reaction site, where it then can cleave DNA. Because of this feature, together with its discriminating affinity towards different DNA strands, neocarzinostatine is regarded as a potential antitumor agent. 

For most Diels-Alder reactions a concerted mechanism as described above, is generally accepted. In some cases, the kinetic data may suggest the intermediacy of a diradical intermediate 18 ... 

Diradical species 4 is more stable than diradical 5, and the oxetane 6 is thus formed preferentially oxetane 7 is obtained as minor product only. Evidence for diradical intermediates came from trapping experiments, as well as spectroscopic investigations. ... 

In addition to cyclopentenes, other types of compounds may be formed upon heating of vinylcyclopropanes. For example pentadienes 6a/b may be formed by a competitive route from a diradical intermediate. 

Hydrogen shifts are often observed in thermal isomerizations of vinylaziridines. Heating of compounds 221 at 180 °C produced mixture of 3-pyrrolines 222 and hydrazones 223 (Scheme 2.54) [87]. The formation of 223 can be explained in terms either of a concerted hydrogen shift as depicted in 224 or of diradical intermediates 225, both of which would be followed by thermal isomerization of the (Z)-carbon-carbon double bonds to provide the ( ) isomers 223. 

Dimer and trimer byproducts have been isolated from MMA polymerizations and these are suggestive of 1,4-diradical intermediates.323 28 Lingnau and Mcycrhoff523 found that rates of spontaneous polymerization of MMA were substantially higher in the presence of transfer agents (RH). They were able to isolate the compound (98) that might come from trapping of the biradical intermediate (Scheme 3.65). 

The frontier orbital interaction can be free from the symmetry restriction. A pair of the reaction sites is close to each other while the other pair of the sites is far from each other (Scheme 25b). This is the geometry of the transition state leading to diradical intermediates. 

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. 

A perepoxide intermediate [77] or a peroxy diradical intermediate [78-81] have been proposed. 

Head-to-head [2+2]photocycloaddition of 1,2-diarylethanediones and 2-aminopropene nitriles (CH2 C(CN)NR2) occurs to yield oxetanes 10 in moderate to good yields. The formation of only one diastereoisomer in each of the cases investigated is rationalized in terms of the most easily accessible and stabilized 1,4-diradical intermediate <95RTC498>. 2,3,4-Trisubstituted oxetanes 11 are obtained in high yield by intramolecular nucleophilic attack of the anion from certain 2-(l-alkoxyethyl)-3-substituted oxiranes <96JOC4466>. 

The anticancer activity of complex natural products having a cyclodecenediyne system [for a review see <96MI93>] has prompted the synthesis of 54 (X = CH2 and OCH2) <96CC749> and 55 (R = a-OH and p-OH) <95AG(E)2393> on the basis that such compounds are expected to develop anticancer activity as the P-lactam ring opens. This is because cycloaromatization can only occur in the monocyclic enediyne and the diradical intermediate in the cyclization is thought to be the cytotoxic species. 

Carbocation-carbanion zwitterionic intermediates were proposed for the thermal cleavage of several cyclic compounds. In most of these reactions the ionically dissociating bond belongs to one of four strained ring systems, i.e. cyclopropane (13), cyclobutane (14), cyclobutene (15) or norbornadiene (16). The mechanism is distinguished from the formation of a diradical intermediate through homolysis in terms of solvent and substituent effects... 

The higher strain energy in thiirene dioxides (19) compared to thiirane dioxides (17) is obvious. Yet, the elimination of sulfur dioxide from the latter is significantly faster than one would expect for a thermally allowed concerted process. Consequently, either aromatic-type conjugative stabilization effects are operative in thiirene dioxides or the relative ease of SOj elimination reflects the relative thermodynamic stability of the (diradical ) intermediates involved in the nonconcerted stepwise elimination process. 

The photoadditions proceed through 1,4-diradical intermediates. Trapping experiments with hydrogen atom donors indicate that the initial bond formation can take place at either the a- or (3-carbon of the enone. The excited enone has its highest nucleophilic character at the (3-carbon. The initial bond formation occurs at the (3-carbon for electron-poor alkenes but at the a-carbon for electron-rich alkenes.191 Selectivity is low for alkenes without strong donor or acceptor substituents.192 The final product ratio also reflects the rate and efficiency of ring closure relative to fragmentation of the biradical.193... 

The reaction is stereospecific for at least some aliphatic ketones but not for aromatic carbonyls.197 This result suggests that the reactive excited state is a singlet for aliphatics and a triplets for aromatics. With aromatic ketones, the regioselectivity of addition can usually be predicted on the basis of formation of the more stable of the two possible diradical intermediates obtained by bond formation between oxygen and the alkene.198... 

The stereochemistry of the nonconcerted reaction has been a topic of considerable study. Frequently, there is partial stereorandomization, indicating a short-lived diradical intermediate. The details vary from case to case, and both preferential inversion and retention of relative stereochemistry have been observed. 

These results can be interpreted in terms of competition between recombination of the diradical intermediate and conformational equilibration, which would destroy the stereochemical relationships present in the azo compound. The main synthetic application of azo compound decomposition is in the synthesis of cyclopropanes and other strained-ring systems. Some of the required azo compounds can be made by 1,3-dipolar cycloadditions of diazo compounds (see Section 6.2). 

An interesting mechanistic issue was raised by Firestone on the aqueous Diels-Alder reaction between 2-methylfuran and maleic acid in water, which is found to be 99.9% stereospecific.80 By adding heavy atom (defined as any below the first complete row of the periodic table) salts to the aqueous media, it was found that addition of heavy but not light atom salts reduced the degree of stereospecificity significantly in the retrodiene reaction. The results suggest that a large portion of the Diels-Alder reaction occurs via diradical intermediates (Scheme 12.2). 

High stereospecificity is observed when the rotation of the diradical intermediate is slow in comparison with cyclization to cycloadduct or reversion to reactants. With the presence of external heavy atoms, it could facilitate the intersystem crossing (ISC) of the first-formed singlet diradical to the longer-lived triplet counterpart. The triplet diradical will have a chance to undergo rotation before it reverts back to singlet and cyclizes or cleaves to reactants. This then accounts for the reduced stereospecificity. The alternative possibility of a zwitterionic intermediate is considered unlikely because there is no interception of zwitterions by water. 

Another example of ring closure involving a 1,5-H shift appears to be that provided by Jung,119 who reported that the heteroatom-substituted silenes 144 rearranged to give 1,3-disilacyclobutanes 145 via a diradical intermediate (Eq. 51). When R = Cl the yield was 30%, and with R = MeO the yield of the disilacyclobutane was 44%. 

Barltrop and Coyle<12) have presented strong evidence for the participation of a discrete diradical intermediate in type I cleavage. In this study a... 

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