Radical, enantioselective conjugate addition

Scheme 35 Fluxional template for radical enantioselective conjugate additions...

Grignard additions, 9, 66 radical addition of zincs, 2, 401 zinc-containing reagent additions, 2, 398 Nitroolefins, enantioselective conjugate additions, 10, 382 (Nitrophenylthio)osmocenes, preparation, 6, 634 (Nitrophenylthio)ruthenocenes, preparation, 6, 634 Nitropyridines, reductive aminocarbonylation, 11, 543 Nitroso aldol reaction... 

Sibi and He have described the formation of 8-lactone from an in situ formed 5-hydroxy ester in the synthesis of ricciocarpins A and B [65] (Scheme 25). Enantioselective conjugate addition of the tertiary radical derived from 133 onto... 

Radical chemistry has seen tremendous progress in the past two decades and can now be considered as an eminent sub discipline in synthetic organic chemistry [1-6]. Diastereoselective radical chemistry is well established and many examples of enantioselective radical reactions have appeared in the recent literature. For reviews on diastereoselective radical chemistry see [7-11] for reviews on enantioselective radical chemistry see [12-16] and for reviews on conjugate additions, see [17,18]. This review will detail different ways to introduce asymmetry during a radical reaction. These transformations can be broadly classified into atom transfer reactions, reductive alkylations, fragmentations, addition and trapping experiments, and electron transfer reactions. 

A recent application of enantioselective conjugate radical additions was seen in the synthesis of (+)-ricciocarpins A and B [95]. The key step in the synthesis was an asymmetric addition of a functionalized radical precursor 141 to afford intermediate 142 (Scheme 37). A chiral catalyst screening revealed that Mgt and bisoxazoline ligand 19 was optimal for achieving... 

Scheme 37 Application of enantioselective conjugate radical addition total synthesis of Ricciocarpin A and B...

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

Scheme 39 Acetate aldols by enantioselective conjugate radical 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... 

In one of the earliest reports on enantioselective radical reactions, chiral Lewis acid mediated conjugate addition followed by enantioselective H-atom transfer a to a carbonyl was reported by Sato and co-workers (Scheme 3) [22], The single point binding chiral aluminum complex presumably coordinates to the carbonyl oxygen of the lactone as shown in 10. The strong Lewis acidity of the aluminum complex activates the substrate 7 to nucleophilic conjugate addition, which is followed by an enantioselective H-atom transfer from BuaSnH in a chiral environment provided by BINOL ligand in 8. Only 28% ee was observed for product 9. 

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