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A photocatalytic methodology for the single step synthesis of γ-ketoacids from α-ketoacids has been developed. This method employs maleic anhydrides as traceless synthetic equivalents of acrylic acids, achieving a selective cross-coupling via a dual decarboxylative strategy, where molecular CO2 is released as the only waste byproduct. The method has also been expanded to incorporate a highly regioselective, 3-component coupling with various alcohols to access functionalized γ-ketoesters. 

The selective installation of fluorine-containing groups into biologically relevant molecules has been used as a common strategy for the development of pharmaceutically active molecules. However, the selective incorporation of gem-difluoromethylene groups next to sterically demanding secondary and tertiary alkyl groups remains a challenge. Herein, we report the first cobalt-catalyzed regioselective difluoroalkylation of carboxylic acid salts. The reaction allows for the facile construction of various difluoroalkylated products in good yields tolerating a wide range of functionalities on either reaction partner. The potential of the method is illustrated by the late-stage functionalization of molecules of biological relevance. Mechanistic studies support the in situ formation of a cobalt(I) species and the intermediacy of difluoroalkyl radicals, thus suggesting a Co(I)/Co(II)/Co(III) catalytic cycle. 

A method for directly calculating the temperature derivative of two-dimensional infrared (2D-IR) spectra from simulations at a single temperature is presented. The approach is demonstrated by application to the OD stretching spectrum of isotopically dilute aqueous (HOD in H 2 O) solutions of urea as a function of concentration. Urea is an important osmolyte because of its ability to denature proteins, which has motivated significant interest in its effect on the structure and dynamics of water. The present results show that the temperature dependence of both the linear IR and 2D-IR spectra, which report on the underlying energetic driving forces, is more sensitive to urea concentration than the spectra themselves. Additional physical insight is provided by calculation of the contributions to the temperature derivative from different interactions, e.g., water–water, water–urea, and urea–urea, present in the system. Finally, it is demonstrated how 2D-IR spectra at other temperatures can be obtained from only room temperature simulations.