Radical conjugate addition

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

Scheme 38 Enantioselective lactone formation via haloalcohol radical conjugate addition...

Scheme 43 /S-Substituted a-amino acids via enantioselective radical conjugate additions... 

TABLE 9.29. ENANTIOSELECTIVE FREE RADICAL CONJUGATE ADDITIONS TO a,p-UNSATURATED N-ACYL OXAZOLIDINONES... 

TABLE 9.26 ENANTIOSELECTIVE ALIX)L REACTION MEDIATED BY BU-BOX, 566 TABLE 9.27 Cu(II)-BU-BOX-MEDIATED MUKAIYAMA ALDOL REACTIONS, 566 TABLE 9.28 PHE-BOX-MEDIATED FREE RADICAL CONJUGATE ADDITION, 567... 

Photohydroalkylations are in most cases carbon-centered radical conjugate additions onto electron-deficient olefins [7]. Scheme 3.3 summarizes in detail the pathways for the photogeneration of radicals from R-H(Y) 1. In path a, a photocatalyst P (when excited) cleaves homolytically a suitable C—H bond, and the resultant radical adds to the olefin 2 to form the adduct radical 3. a,(3-Unsaturated nitriles, ketones, and esters... 

The photoaddition of alkanes onto electron-poor alkynes (e.g., propiolate or acetilendicarboxylate esters) can be accomplished by a radical conjugate addition reaction [7]. Radicals have been generated either via hydrogen abstraction from cycloalkanes or via electron transfer from 2-alkyl-2-phenyl-l,3-dioxolanes. In the first case, the irradiation was pursued on an alkane solution of an aromatic ketone (used as the photomediator) and the alkyne. Under these conditions, methyl propiolate was alkylated upon irradiation in the presence of 4-trifluoromethylacetophenone to form acrylate 48 in 97% yield (E/Z= 1.3 1 Scheme 3.31) [78]. 

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>. 

In the presence of stoichiometric or catalytic chiral ligand 2.60, a stereoselective radical conjugate addition is observed. 

Enantioselective radical conjugate addition of an alkyl group to 587 was promoted by alkyltin hydride in the presence of chiral bis-isoxazoline derivatives <2002JA984>. 

Mayon, P, Euvrard, M.-N, Moufid, N, Chapleur, Y, Diastereoselective anionic and radical conjugate addition on a chiral enone a route to multichiral arrays, J. Chem. Soc., Chem. Commun., 399-401, 1994. 

Renaud, P., Ollivier, C., Weber, V. One-Pot Rhodium(l)-Catalyzed Hydroboration of Alkenes Radical Conjugate Addition. J. Org. Chem. 2003, 68, 5769-5772. 

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). 

Giese has investigated this effect in detail and applied it for highly stereoselective synthesis of C-disaccharides [18, 19]. For instance, the radical conjugate addition... 

A somewhat different approach towards enantioselective reductions a to a carbonyl involved a radical conjugate addition to a-methylene-y-butyrolactone followed by stereoselective hydrogen atom transfer as shown in Eq. (2) [5]. 

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

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

Radical conjugate additions with participation and formation of heterocycles including stereoselective reactions, cascade reactions, and application of conjugate additions in total synthesis of natural products 05T10377. 

Advances In Radical Conjugate Additions Srikanth, G.S.C. Castle, S.L. Tetrahedron 2005, 61, 10377. 

Scheme 5.15 Organoboranes-mediated domino radical conjugated addition/aldol cyclization.

Fraser-Reid has reported the synthesis of 96, corresponding to a conqx>nent of the insea antifeedant azadirachtin, from galtK tose-daived starting material. Radical conjugate addition gave the lactone intermediate 94, and subsequent glycoside cleavage to form a dimethyl acetal, enolate hydroxylation and oxidation led to 95, elaborated in six steps to 96 (Scheme 24). 

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