RESUMO
Herein we report the three-component copper-catalyzed carboiminolactonization of α,ß-unsaturated carbonyl derivatives. In the presence of a Cu(I) catalyst, α-haloesters, electron-deficient alkenes, and primary amines couple to generate γ-iminolactones in a single step. The scope of the reaction is explored with respect to the three coupling partners. Nineteen examples are presented with yields of these hydrolytically labile heterocycles of up to 69%. Mechanistic investigations support the formation of an oxocarbenium by way of an atom transfer radical addition (ATRA) intermediate.
RESUMO
The synthesis of α-haloboronic esters via atom transfer radical addition (ATRA) is constrained due to its limited range of compatible substrates or the need to manipulate the olefin coupling partners. Herein, we present a novel approach for their synthesis via Cu-catalyzed ATRA to vinyl boronic esters. The catalyst is proposed to mediate a traditionally inefficient halogen atom transfer of the α-boryl radical intermediate, thus significantly expanding the range of participating substrates relative to established methods. The forty-eight examples illustrate that a wide range of radical precursors, including primary, secondary, and tertiary alkyl halides, readily add across both unsubstituted and α-substituted vinyl pinacol boronic esters. Further, a one-pot, two-step protocol is presented for direct access to an array of α-functionalized products. Finally, the synthetic utility of this methodology is demonstrated in the synthesis of an ixazomib analogue.
