Photochemical Synthesis of Lactones, Cyclopropanes and ATRA Products: Revealing the Role of Sodium Ascorbate.

Light-mediated processes have received significant attention, since they have re-surfaced unconventional reactivity platforms, complementary to conventional polar chemistry. γ-Lactones and cyclopropanes are prevalent moieties, found in numerous natural products and pharmaceuticals. Among various methods for their synthesis, light-mediated protocols are coming to the spotlight, although these are contingent upon the use of photoorgano- or metal-based catalysts. Herein, we introduce a novel photochemical activation of iodo-reagents via the use of cheap sodium ascorbate or ascorbic acid to enable their homolytic scission and addition onto double bonds. The developed protocol was applied successfully to the formal [3+2] cycloaddition for the synthesis of γ-lactones, traditional atom transfer radical addition (ATRA) reactions and the one-pot two-step conversion of alkenes to cyclopropanes. In all cases, the desired products were obtained in good to high yields, while the reaction mechanism was thoroughly investigated. Depending on the nature of the iodo-reagent, a halogen or a hydrogen-bonded complex is formed, which initiates the process.

Computational and Spectroscopic Studies on the Formation of Halogen-Bonded Complexes Between Tertiary Amines and CBr4 and Application in the Light-Mediated Amino Acid Coupling.

In recent years, halogen-bonded complexes (XBCs), in solution, have played a pivotal role in inducing photochemical organic reactions. In this work, we explore the ability of various tertiary amines to act as XB acceptors in the presence of the XB donor CBr4 by computational and spectroscopic studies. DFT studies clearly showcase the formation of XBCs between the studied tertiary amines and CBr4. Simultaneously, computational and experimental UV-Vis studies display intense red shifts that are consistent with charge transfer observed from tertiary amines to CBr4. A detailed NMR study revealed a clear chemical shift of the carbon carrying the bromine atoms upon mixing the XB acceptor with the donor, suggesting that this spectroscopic technique is indeed an experimental tool to identify the generation of XBCs. An application of the ability of such XBCs to activate a carboxylic acid under UVA irradiation or sunlight is presented for amino acid coupling. Among the various tertiary amines studied, the pair DABCO-CBr4 was found to work well for the photochemical amide bond formation. Direct infusion-HRMS studies allowed us to propose a general mechanism for the photochemical amino acid coupling in the presence of a tertiary amine and CBr4, initiated by the photoactivation of an XBC.