Enantioselective radical reactions

In instances where a chiral Lewis acid complex is used in order to impart stereocontrol, several issues are at hand  

By incorporating all of the issues outlined above, researchers have met the challenge of performing highly enantioselective free-radical reactions with great success. Sibi and Porter have recently summarized this progress in a comprehensive review 

Radical reductions typically involve a hydrogen atom transfer from a suitable donor (organotin or silicon hydride) to an acceptor, commonly a radical intermediate generated a to a earbonyl. In eases where enantiomerieally pure products are desired, a chiral Lewis acid is employed in order to coordinate to the Lewis basic carbonyl oxygen(s) and provide faeial bias for the ensuing hydrogen atom transfer. 

This concept has proven suecessful for the enantioselective reduction sequence shown in Eq. (1) [3], 

A prochiral radical intermediate is generated from a-methoxymethyl-a-iododihy-drocoumarin (la) which is coordinated via the carbonyl oxygen to the chiral Lewis acid/ligand combination of MgL and 2. Enantiomeric excesses of up to 62% and yields of 88% have been obtained in this enantioselective reduction using tributyltin 

---

Mg11 complexes are also effective for controlling asymmetric radical reactions.33,34 Moreover, enantioselective radical reactions using chiral Mg11 complexes have been studied, and high enantioselectivities have been realized in the presence of stoichiometric or catalytic amounts of chiral auxiliaries such as bis-oxazolines (Scheme 8).35-39 In most cases, substrates having bidentate chelating moieties are required. 

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. 

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. 

An enantioselective reduction of an a-iodolactone under radical conditions has been reported [95CC481]. Treatment of 207 with tin hydride, magnesium(II) iodide and in the presence of a chiral amine gave the 8-lactone 208 in good yield and moderate enantioselectivity. This is one of the first examples of chiral Lewis acid mediated enantioselective radical reactions. 

---