Oxaziridine-mediated enantioselective aminohydroxylation of styrenes catalyzed by copper(II) bis(oxazoline) complexes

Abstract

We report an oxaziridine-mediated enantioselective aminohydroxylation of olefins catalyzed by a chiral copper(II) bis(oxazoline) complex. A variety of styrenic olefins undergo efficient aminohydroxylation with excellent regioselectivity and synthetically useful levels of enantioselectivty (up to 84% ee). The reaction can be conducted on multi-gram scale with as little as 2 mol% of the copper(II) catalyst. Hydrolysis of the resulting 1,3-oxazolines under acidic conditions produces N-sulfonyl amino alcohols that can be purified by recrystallization to afford very high levels of enantioselectivity.

Advances in the Chemistry of Oxaziridines

“…Oxyamination of a variety of styrenes proceeded in good yield and modest to good enantioselectivity in the presence of commercially available copper(II) hexafluoroacetylacetonate [Cu(F 6 acac) 2 )] and ( R , R )-Ph-Box 210 (eq 42). 144 The amino alcohol products that result from this protocol are highly crystalline, and very highly enantioenriched amino alcohols can easily be prepared by recrystallization. Thus, while the stereocontrol available from this method are lower than those generally observed in the Sharpless aminohydroxylation reaction, 145 the regioselectivity is much higher for styrenes.…”

Recent Developments in Methodology for the Direct Oxyamination of Olefins

“…[53] These developments make this intermolecular, highly regio-and enantioselective oxaziridine mediated oxyamina- tion of olefins a useful complementary transformation to the Sharpless AA reaction. The main limitation of this methodology is the lack of stereospecificity; as illustrated by the formation of the same major reaction product whether cisor trans-stilbene is subjected to the reaction conditions.…”

Evolution of copper(II) as a new alkene amination promoter and catalyst

“…Due to the considerable interest of the products, the alkene aminooxygenation (aminohydroxylation, aminoetherifcation, aminoacetoxylation) has been actively developed by a number of research groups [54,55]. …”