Enantioselective reactions chiral complexing agent

An interesting intramolecular radical cyclization followed by enantioselective hydrogen atom transfer has recently been reported (Scheme 11) [40]. This reaction is carried out in the presence of a chiral complexing agent 38, which... 

While the chiral complexing agents (+)-12 and (-)-12 proved to be generally suitable for a wide range of enantioselective [2+2]-photocycloaddition reactions on the c-bond of 2(l//)-quinolones, their applicabil-... 

Radical reactions have been recognised only recently for the construction of enantiomerically pure compounds (Renaud and Sibi 2001 Zimmerman and Sibi 2006). In addition to substrate- or auxiliary-induced diastereoselective radical reactions, and in addition to the use of chiral Lewis acids, chiral hydrogen atom donors or chiral transition metal complexes, template molecules can be used to generate a chiral environment and induce chirality to the substrate. With the chiral complexing agent 12, enantioselective radical reactions were achieved with enantiomeric excesses up to 99% ee. 

The complexation of achiral metal enolates by chiral additives, e.g., solvents or complexing agents could, in principle, lead to reagent-induced stereoselectivity. In an early investigation, the Reformatsky reaction of ethyl bromoacetate was performed in the presence of the bidentate ligand (—)-sparteine20. The enantioselectivity of this reaction varies over a wide range and depends on the carbonyl Compound, as shown with bcnzaldehyde and acetophenone. 

A first example shows the enantioselective reductive radical cyclisation reaction of 3-(5 -iodopentylidene)-piperidin-2-one (24) (Scheme 9). After the primary cyclisation step the hydrogen abstraction leads to the formation of a stereogenic centre. The complexing agent (+)-12 was used as source of chirality (Aechtner et al. 2004 Dressel et al. 2006). 

Contrary to the asymmetric epoxidation of allylic alcohols, the presence of water in this reaction is crucial for the enantioselection. Nevertheless, the main drawback of this method was the use of a stoichiometric amount of titanium and the use of tert-butyl hydroperoxide (TBHP) as oxidant. Efforts have been devoted to the development of more sustainable processes focusing on catalytic reactions and on the nature of oxidising agent. In 1987, Kagan and coworkers reported a catalytic version using as low as 10 mol% of titanium chiral complex in the presence of activated molecular sieves (MS). It is noteworthy that they also improved the process by using less-explosive and less-reactive cumene hydroperoxide as oxidant. A few years later, the group of Uemura developed a complementary catalytic system based on the... 

This type of the poljnner may act as an effective complexing agent with cation by the polymer back-bone, and may exert a strong stereoregulation by the isotactic structure of the polymer and by the asymmetric environment produced by chiral amine functions. Preliminary results of the enantiomer selection in the reaction of potassium acetate and a-phenethyl bromide by the optically active isotactic polyepichlorohydrin functionalized by L-2-dimethylamino-3-methylbutylamine gave 5-7% of the stereoselection. Further efforts are needed to achieve high enantioselection. 

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