Enantioselective Synthesis of anti-Propionate Aldols via Radical Addition

enantioselective radical addition - anti-propionates - α,β-unsaturated imides

Significance

Currently, there are relatively few methods for the synthesis of anti-propionate aldols with extremely high diastereo- and enantio­selectivity. Furthermore, standard aldol reactions are performed under basic conditions; limiting the functional group compatibility of the reagents. This method employs radical addition under neutral and fairly mild reaction conditions, providing products with extremely high diastereoselectivity (generally >95:5 anti/syn) and good enantioselectivity (generally >70% ee). This high degree of selectivity was obtained with various Mg²⁺-based Lewis acids, alkyl halides, and vinylic substituents, presenting an interesting new route towards aldol-like products.

Comment

It is believed that the ligand controls the enantioselectivity of the initial β-addition of the alkyl radical; and subsequent orientation of the β-stereocenter controlling the diastereoselectivity of hydrogen atom transfer. H-atom transfer is thought to occur quickly, as a rotameric equilibrium would not provide the observed diastereo­selectivities (for examples see: M. P. Sibi, J. Chen J. Am. Chem. Soc. 2001, 123, 9472, where slower transfer from allyltributyltin gave moderate dia­stereoselectivity). In addition, it was found that the N-H imide was essential for good yield and selectivity, as oxazolidinone imides afforded <10% yield.