Radicals Diels-Alder

Radical Diels-Alder reactions have been used mainly to synthesize polycyclic molecules. These reactions, like those that involve cations and anions as components, proceed quickly but generally do not give high yields. Thus, the tricyclic enone 14 is the result of an intramolecular Diels-Alder reaction of quenched vinyl radical intermediate 13 obtained by treating the iododienynone 12 with n-tributyltin hydride/2,2 -azobisisobutyronitrile (AIBN) [28] (Equation 1.11). 

The first studies on cation-radical Diels-Alder reactions were undertaken by Bauld in 1981 who showed [33a] the powerful catalytic effect of aminium cation radical salts on certain Diels-Alder cycloadditions. For example, the reaction of 1,3-cyclohexadiene with trans, iraw5-2,4-hexadiene in the presence of Ar3N is complete in 1 h and gives only the endo adduct (Equation 1.14) [33]. 

As a continuation of these studies, Bauld recently reported evidence of a stepwise mechanism in the cation-radical Diels-Alder reaction of phenyl vinyl sulfide with cyclopentadiene [34, 35] (Scheme 1.6). 

The cation radical Diels-Alder cycloadditions of cis- and franx-prop-1-enyl aryl ethers to cyclopenta-1,3-diene catalysed by tris(4-bromophenyl)aminium hexachloroantimonate are stepwise processes involving an intermediate distonic cation radical in which the carbocationic site is stabilized by the electron-donating functionality (Scheme 9). " ... 

Hence, cation-radical copolymerization leads to the formation of a polymer having a lower molecular weight and polydispersity index than the polymer got by cation-radical polymerization— homocyclobutanation. Nevertheless, copolymerization occnrs nnder very mild conditions and is regio-and stereospecihc (Bauld et al. 1998a). This reaction appears to occnr by a step-growth mechanism, rather than the more efficient cation-radical chain mechanism proposed for poly(cyclobutanation). As the authors concluded, the apparent suppression of the chain mechanism is viewed as an inherent problem with the copolymerization format of cation-radical Diels-Alder polymerization. ... 

The ion-radical Diels-Alder reactions represent a new development (see, e.g., reviews by Hintz et al. 1996, Berger and Tanko 1997). These reactions initiated with ion-radicals proceed faster by several orders of rate magnitude than the corresponding conventional reactions. This section presents the most important cyclizations developed through cation- and anion-radical schemes and the scheme that includes both cation- and anion-radicals. 

Naturally, the question arises as to whether the diene component really has to be in its i -cis form for the cation-radical Diels-Alder reaction. According to calculations by Hofmann and Schaefer 1999, the i-trani-butadiene is more stable than its s-cis, isomer by 12 kJ moE, and for the cation-radicals, the trans preference is even somewhat pronounced (16 kJ moE )-... 

Important general aspects of the cation-radical Diels-Alder reaction and other cation-radical sigmatropic reactions are summarized below ... 

However, it has been recently suggested that oxirane intermediates also play a part in this reaction, producing some of the minor products (Scheme 59)152. Dienes do not appear to be good substrates for this reaction, at least not with triplet oxygen, as the cation-radical Diels-Alder dimerization is much faster unless the alkene is sterically hindered153. 

Harirchian, B. and Bauld, N.L. (1989) Cation radical Diels-Alder cycloadditions in organic synthesis a formal total synthesis of (—)-(S-selrnene. Journal American Chemical Society, 111, 1826-1828. 

Cation Radical Diels-Alder Cycloadditions Historical... 

The aminium salt catalyzed cation radical Diels-Alder reaction... 

In 1981, this cation radical Diels-Alder cyclodimerization of 1,3-cyclohexadiene was shown to be more cleanly (only 1 % of the cyclobutane dimers is produced), conveniently (in a synthetic organic context), and efficiently (70 % yield) carried out by chemical ionization of the diene, using 3+ (Scheme 15) [39]. 

The reaction was carried out in dichloromethane solvent at 0°C for 5 min, using 5 mol % of the initiator. The endofexo ratio (4.5 1) was similar to that found in the thermal Diels-Alder cyclodimerization of this same diene. This encouraging result and the convenience of the procedure led to the extensive study of the cation radical Diels-Alder reaction and its utility in synthetic organic chemistry [40]. It is of further note that the same cyclodimerization was subsequently carried out by the PET... 

The uncatalyzed Diels-Alder reaction is well known to be highly stereospecific, preferentially occurring via syn addition to both the diene and dienophilic components. Stereochemical studies of the cation radical Diels-Alder reaction have confirmed an analogous stereospecificity in two distinctly different systems. The initial study was carried out using the cycloaddition of the three geometric isomers of 2,4-hexadiene as dienophilic components and 1,3-cyclohexadiene as the diene component [39]. Each of the three isomers of the acyclic diene was found to add stereo-specifically to cyclohexadiene. In a more recent study, the cis and trans isomers of 1,2-diaryloxyethenes were found to add stereospecifically to 1,3-cyclopentadiene (Scheme 17) and also to 2,3-dimethyl-l,3-butadiene [46]. 

In most cases the cation radical Diels-Alder reaction has proved to be highly re-giospecific with respect to the reaction of an unsymmetrical dienophile with an unsymmetrical diene. As examples, the cyclodimerizations of both 1-methyl-1,3-cyclohexadiene and 1-methoxy-1,3-cyclohexadiene are essentially regioexclusive (Scheme 18) [47-49]. 

Scheme 18. Regiospecificity of the cation radical Diels-Alder.

With respect to the matter of steric sensitivity, the reaction of 2,5-dimethyl-2,4-hexadiene with 1,3-cyclohexadiene is instructive [39]. Apparently, no Diels-Alder additions of this sterically hindered acyclic diene, either as the dienophilic or dienic component, have ever been reported. However, the cation radical Diels-Alder cycloaddition referred to above (Scheme 20) occurs smoothly, the readily ionizable acyclic diene serving as the dienophilic component. 

Although neutral Diels-Alder reactions of stilbene as a dienophile are unknown, the cation radical Diels-Alder reaction cited above occurs smoothly [51]. Trans stilbenes yields only trans adducts, while cw-stilbenes yield primarily, but not exclusively, cis adducts. The stereospecificity of the cycloaddition step in the latter reaction system was, however, not readily evaluated because of the occurrence of competing cis to trans isomerization of the starting material. It was established, however, that at low conversions, the reaction tends toward stereospecificity. Since cw-stilbene is much less readily ionizable than tran -stilbene, the Diels-Alder cycloadditions in the cw-stilbene system were studied using the p,p -6. vciQ hy derivative. 

It should also be born in mind that electron rich alkenes are also especially reactive neutral components of cation radical cycloaddition reactions, since they are also highly nucleophilic. Consequently, in appropriate instances, either role sense of the cation radical Diels-Alder reaction may be operative, i.e. either the diene or the electron rich alkene could be reacting as the cation radical. 

In view of the demonstrated stereospecificity of at least some cation radical Diels-Alder reactions, it is at least possible that these reactions, like the neutral Diels-Alder, are true pericyclic reactions, i.e., they may occur via a concerted cycloaddition. The results of a variety of calculations, however, make clear that the cydoadditions must at least be highly non-synchronous, so that the extent of the formation of the second bond, which completes the cyclic transition state, is no more than slight [55, 56]. If the cation radical Diels-Alder reaction is nevertheless interpreted as pericyclic and the concept of orbital correlation diagrams is applied to them, it emerges that the cycloaddition is symmetry allowed if the ionized (cation radical) component is the dienophile, but forbidden if it is the diene [39, 55], The former mode of reaction has been referred to as the [4-1-1] mode, and the latter as the [3 -t- 2] mode. Interestingly, the great majority of cation radical Diels-Alder reactions thus far observed seem to represent the formally allowed [4-1-1] mode. An interesting case in point is the reaction of l,l -dicyclohexenyl with 2,3-dimethylbutadiene (Scheme 24) [57]. 

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