Radicals cycloadditions

In another example of a radical process at the pyrrole C-2 position, it has been reported that reductive radical cycloaddition of l-(2-iodoethyl)pyrrole and activated olefins, or l-(oj-iodo-alkyl)pyrroles 34 lead to cycloalkano[a]pyrroles 35 via electroreduction of the iodides using a nickel(II) complex as an electron transfer catalyst <96CPB2020>. Thus, it appears the radical chemistry of pyrroles portends to be a fertile area of research in the immediate or near future. 

If the attacking radical contains an adequately placed radical acceptor functionality, the possibility of a radical cycloaddition is provided, offering a procedure to construct cyclic products from acyclic precursors. For this type of ring-forming process, in which two molecular fragments are united with the formation of two new bonds, the term annulation has been adopted (Scheme 3.3). 

Along with homopolymerization, copolymerization has also been studied within the framework of initiation by tris(4-bromophenyl)ammoniumyl hexachloroantimonate (Bauld et al. 1998a). Generally, cation-radical cycloaddition occurs more efficiently when the reactive cation-radical is the ionized dienophile (Bauld 1989, 1992). In the cited work on copolymerization, the bis(diene) was chosen to be resistant against ionization by the initiator used. As to the dienophile functionality, propenyl rather than vinyl moieties were selected because terminal methyl groups sharply enhance the ionizability of the alkene functions. The polymerization shown in Scheme 7.18 was performed in dichloromethane at 0°C. 

Without ion-radical initiation, the yield of the resulted product reaches 50% for 24 h. Practically the same yield can be achieved for the same time in the presence of tris(4-bromophenyl)ammoniumyl hexachloroantimonate and for only 6 h on sonication (Nebois et al. 1996). Sonication accelerates the rate-determining formation of the diene cation-radical. Of course, hydroxynaphthoquinone is strong enough as an electron-acceptor with respect to 2-butenal Af,Af-dimethylhydrazone. Therefore, the question remains whether sonication is more or less the general method for the initiation of ion-radical cycloaddition. A possible role of sonication in optimization of ion-radical reactions was considered in Section 5.2.5. 

The properties of a compound with isolated double bonds, such as 1,4-pentadiene, generally are similar to those of simple alkenes because the double bonds are essentially isolated from one another by the intervening CH2 group. However, with a conjugated alkadiene, such as 1,3-pentadiene, or a cumulated alkadiene, such as 2,3-pentadiene, the properties are sufficiently different from those of simple alkenes (and from each other) to warrant separate discussion. Some aspects of the effects of conjugation already have been mentioned, such as the influence on spectroscopic properties (see Section 9-9B). The emphasis here will be on the effects of conjugation on chemical properties. The reactions of greatest interest are addition reactions, and this chapter will include various types of addition reactions electrophilic, radical, cycloaddition, and polymerization. 

Bauld, N. (1989) Cation radical cycloadditions and related sigmatropic reactions. Tetrahedron, 45, 5307—5363. 

Cyclopentane ring annulation by a 3 + 2 radical cycloaddition reaction of 3-alkenyl type radicals 68 and 69 to electron-deficient olefins like 70-71, represents a useful methodology for the construction of polysubstituted cyclic molecules 72, 73 etc.2-4,46-48 Cekovic and coworkers have exercised... 

Scheme 56 Synthesis of snlfur-containing heteroq cles through [4+1] radical cycloadditions...

Bauld and coworkers have examined the cation radical cycloadditions of 1,3-dienes with electron-rich alkenes and found that, under photosensitized electron-transfer conditions, [2 -i- 2] cycloaddition is in many cases favored over Diels-Alder addition. Thus, as illustrated in equation (30), 1, T-dicyclopentenyl (186) reacts with p-chloroethyl vinyl ether under electron transfer conditions to afford the cyclobutane adduct (187), which was cleaved to the cyclobutanol (188) in 70% yield upon treatment with n-butyl-iithium. Oxyanion-accelerated VCB rearrangement then provided (189) as a mixture of diastereomers in... 

Scheme 13. Oxetane formation by cation-radical cycloaddition to dioxygen.

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. 

Scheme 23. Cation radical cycloadditions of ketenes and allenes.

An intriguing competition arises in the context of cation radical cycloadditions (as in the context of Diels-Alder cycloadditions) which involve at least one conjugated diene component. Since both cyclobutanation and Diels-Alder addition are extremely facile reactions on the cation radical potential energy surface, it would not be surprising to find a mixture of cyclobutane (CB) and Diels-Alder (DA) addition to the diene component in such cases. Even in the cyclodimerization of 1,3-cyclohexadiene, syn and anti cyclobutadimers are observed as 1 % of the total dimeric product. Incidentally, the DA dimers have been shown not to arise indirectly via the CB dimers in this case [58]. The cross addition of tw 5-anethole to 1,3-cyclohexadiene also proceeds directly and essentially exclusively to the Diels-Alder adducts [endo > exo). Similarly, additions to 1,3-cyclopentadiene yield essentially only Diels-Alder adducts. However, additions to acyclic dienes, which typically exist predominantly in the s-trans conformation which is inherently unsuitable for Diels Alder cycloaddition, can yield either exclusively CB adducts, a mixture of CB and DA adducts or essentially exclusively DA adducts (Scheme 26) [59]. 

The cation radical cycloaddition reactions of conjugated dienes which can adopt either the s-cis or s-trans conformation with a dienophile can proceed to yield either CB or DA adducts or an admixture of both, as noted above. In the case where the dienophile is an electron rich alkene, the tendency toward CB adduct formation appears to be even more pronounced than in the case of a dienophile of the diene or... 

Mechanistic Diagnosis of Cation Radical Cycloadditions Qualitative diagnosis... 

Scheme 36. Mechanistic diagnosis of cation radical cycloadditions.

A more quantitative criterion for the operation of a cation radical cycloaddition mechanism has been carried out for a Diels-Alder reaction system consisting of various substituted derivatives of /ran -stilbene (as the ionizable dienophile) and 2,3-dimethyl-1,3-butadiene (Scheme 37) [71]. 

Scheme 40. The kinetic impetus for cation radical cycloadditions. R = reactant, P = product, R = reactant cation radical, P+ = product cation radical, IP = ionization potential, Ea = activation energy.

General Theoretical Considerations in Cation Radical Cycloadditions... 

From this perspective, it emerges that the kinetic driving force for the cation radical cycloaddition relative to the corresponding neutral one can be expressed as the difference in the ionizabilities of the reactant and the transition state. As a specific example, we may consider a highly non-synchronous TS for cation radical Diels-Alder cycloaddition—which is supported by theoretical calculations (vide infra). This transition state is essentially a distonic cation radical, the radical site of which is easily ionized because the odd electron is in a non-bonding MO. In contrast, the... 

Natural Product Synthesis and Synthetic Methodology using Cation Radical Cycloaddition Reactions... 

It was demonstrated that the use of phenyl vinyl sulfoxide or sulfone in a thermal Diels-Alder reaction was highly unsatisfactory as an alternate route. The synthesis of the neolignins galbulin, isogalbulin [82], magnoshinin, and magnosalin [83] have all been accomplished by means of a cation radical cycloaddition (Scheme 42). 

Scheme 42. Cation radical cycloadditions in the synthesis of magnosalin and magnoshinin.

Cation Radical Cycloadditions Forming Five-membered Rings... 

---