Direct Oxidation of Aryl Malononitriles Enabling a Copper-Catalyzed Intermolecular Alkene Carbochlorination

Abstract

A copper-catalyzed carbochlorination of alkenes with aryl malononitriles and chloride is disclosed. This net oxidative transformation proceeds with activated and unactivated alkenes with moderate to excellent yields. Mechanism experiments suggest addition of the malononitrile radical to form a secondary carbon radical which is intercepted by a chloride source. The resultant products can be transformed into biologically important γ-lactones in one further step.

Three‐Component Reactions of Alkenes with C−C Bond Formation: Recent Developments

“…The Kozlowski group [14a] used aryl malononitriles 13.1 and LiCl to achieve carbochlorination 13.2 of alkenes. In the presence of K 2 S 2 O 8 , aryl malononitriles were oxidized to form dimer species 13.3 , which then became carbon‐centered radicals 13.4 .…”

Catalytic Photoredox Carbobromination of Unactivated Alkenes with α-Bromocarbonyls via the Mechanistically Distinct Radical-Addition Radical-Pairing Pathway

“…In particular, addition of an α-carbonyl fragment and a halogen would generate γ-halogenated carbonyl compounds, enabling further functional group incorporation at the γ-position distal to carbonyls that is otherwise difficult to attain without a multistep endeavor. To date, a number of methods have been developed for carbohalogenation of unactivated alkenes under both the metal and photoredox-catalyzed reaction conditions. , However, these methods are largely limited to either intramolecular processes or the use of activated reagents, such as Br 2 FCH, [Ph 3 PCF 2 H] + [Br] − , BrCH­(CO 2 R) 2 , Br 2 C­(CO 2 R) 2 , ICF 2 CO 2 R, F 2 BrCR, and F 2 CBrCO 2 R, as the source of carbon and halogen. Notable exceptions are the Ph 3 P-mediated photoredox alkene carbochlorination under ultraviolet-A (UV-A) and bromination under a blue-light-emitting diode (LED) reported by Dilman and co-workers as well as iodosulfonylation under blue LED disclosed by Filippini, Dell’Amico, and co-workers …”