Free radical-mediated acylation approach using acylphosphonate derivatives

Abstract

We have investigated an intriguing possibility of β-elimination of a phosphonate group from an alkoxyl radical. When a-alkoxyl phosphonate was reacted with V-40 as initiator in chlorobenzene for 3 h, aldehyde was isolated in high yield, indicating the facile β-elimination of organophosphorous group from the alkoxyl radical for the first time. On the basis of our findings, we have studied the feasibility of the use of an acylphosphonate as a carbonyl group radical acceptor. Radical cyclization of acylphosphonate in the presence of hexamethylditin at 300 nm for 2 h in benzene gave cyclopentanone in good yield without the formation of the direct reduction product. The reaction can be carried out in the presence of a catalytic amount of hexamethylditin (0.2 equiv) under the similar conditions because initially generated phosphonate radical reacts with an alkyl iodide to generate an alkyl radical. To achieve acylphosphorylation of intramolecular olefinic moiety, photochemical irradiation of ω-alkenoylphosphine oxide is studied along with the acylphosphorylation under thermal condition using benzoylperoxide and diethylphosphite. The cyclizations of phosphonoformates do not occur under thermal and photochemical conditions, apparently due to unfavorable E-conformation in carboxylic esters. However, an alkyl phosphonothiolformate group can act as an alkylthiocarbonyl group equivalent radical acceptor, providing a ready access to a thiolactone synthesis. As an extension of intramolecular approach, intermolecular acylation was studied. However, due to slow rate in intermolecular radical addition to acylphosphonates, the satisfactory yields were not obtained. We designed various cyanophosphonate derivatives for intermolecular radical cyanation. Intermolecular cyanation was successfully achieved under photochemical condition using diethylcyanophosphonate as a radical acceptor.