Conjugate addition intramolecular radicals

For a review on intramolecular radical conjugate addition reactions, see W. Zhang, Tetrahedron, 57 (2001), 7237. 

Unsaturated aldonolactones 18 and 20 are converted in good yields to the functionalized homochiral cyclopentanoids 19 and 21 respectively, by intramolecular radical conjugate additions (Scheme 2). Intramolecular radical conjugate addition has also been employed on the acyclic Wittig-derived 22 with concomitant lactonization to give the cyclopentanoid 23 in 64% yield (Scheme 3). The reaction was not diastereospecific, with Cl and C5 epimers of 23 also being formed. ... 

Scheme 10. Intramolecular free radical conjugate addition in Hart s synthesis of perhydroindane 58.

Free radical conjugate additions of carbon radicals onto alkenes which results in formation of carbon-carbon bonds have been important reactions in organic chemistry. This type of reaction was first explored in an intramolecular fashion, but quickly gained attention of heterocyclic chemists and a plethora of novel ring systems have been synthesized by this methodology <2001T7237>. 

Intramolecular free-radical conjugate additions 01T7237. 

The initial radical addition reactions can also be sequenced with a second, nucleophilic reaction. Thus radical conjugate addition and subsequent reduction leads to an enolate. Enolates thus generated can undergo a variety of reactions [8] including aldol reactions [9], Claisen condensations, intramolecular Michael reactions, and intermolecular Tischenko redox processes (Eqs. 7, 8). 

Intramolecular Free Radical Conjugate Additions," Zhang. W. Tetrahedron, 2001, 57, 7237. 

The success of intramolecular conjugate additions of carbon-centered radicals in multifunctional contexts is noteworthy. Compound 57 (see Scheme 10), prepared by an interesting sequence starting from meto-toluic acid (54) (see 54 > 55 > 56 > 57), can be converted to the highly functionalized perhydroindane 58 through an intramolecular conjugate addition of a hindered secondary radical.21-22 This radical cyclization actually furnishes a 6 1 mixture of perhydroindane diastereoisomers, epimeric at C-7, in favor of 58 (96 % total yield). It should be noted that a substantially less strained cis-fused bicyclo[4.3.0] substructure is formed in this cyclization. 

This reaction is extended to the intramolecular ring closure of the intermediate radical 224 with olefinic or trimethylsilylacetylenic side chains [121]. Cu(BF4)2 is also effective as an oxidant (Scheme 89) [122]. Conjugate addition of Grignard reagents to 2-eyclopenten-l-one followed by cyclopropanation of the resulting silyl enol ethers gives the substituted cyclopropyl silyl ethers, which are oxidized to 4-substituted-2-cyclohexen-l-ones according to the above-mentioned method [123]. (Scheme 88 and 89)... 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

A distinctly different reaction cascade leading to tetrahydrofurans is illustrated in Scheme 40 [74]. It was proposed that these reactions proceed by iodine-mediated deoxygenation of the peroxyl radical to an alkoxyl radical, which undergoes intramolecular C-H abstraction to form a y9-keto radical [74], Elimination of an a-hydrogen atom generates an enone, which is ultimately captured intramolecularly by conjugate hydroxyl addition to give a tetrahydrofuran (Scheme 40). 

Zard also used a xanthate-mediated radical cascade sequence to synthesize indolines from vinyl sulfanilides in three steps [54]. The initial peroxide-initiated intermolecular addition of the xanthate to the vinyl sulfanilide was followed by an intramolecular cyclization onto the ortho position of the aromatic ring. Further heating with DBU generated the dihydroindole through a base-induced isomerization of the olefinic bond followed by conjugate addition. 

---