De novo design of novel processes for organic synthesis purely from calculations is a highly desirable but challenging target. A less ambitious yet productive approach has been the joint work with experimental chemists in the optimization and tuning of already existing reactions. In this communication we will describe our recent work with DFT and DFT/MM methods on the mechanisms of three different processes. We have studied the iodine(III)-mediated oxidative amination of alkenes and explained the experimentally observed dependence of product distribution on the nature of the substrate. Calculations on the reaction between PhI(N(SO2Me)2)2 and three representative substrates (styrene, α-methylstyrene and E-methylstylbene) show hat the process starts always with electrophilic attack by a cationic PhI(N(SO2Me)2)+ unit on the double bond, and the mechanisms diverge afterwards. The mechanism of a novel method for for the stereoselective synthesis of tri- and tetrasub- stituted allylic amines based on Pd-catalyzed conversion of cyclic vinyl carbonates has been characterized. The key for the selective formation of (Z)-configured allylic amine products happens to be the formation of a six-memebered palladacycle intermediate. A combination of DFT calculations and kinetic models has been applied to fully elucidate the seemingly complex reactivity of α-cyano arylacetates toward metal-free photoinitiated aromatic perfluoroalkylation. The resulting mechanistic framework rationalizes the observed quantum yield as well as the differences in reactivity and/or selectivity of seemingly similar substrates. All these computational findings on the reaction mechanisms have led to further optimization and extension of the synthetic procedures.

From experiment to calculation and back: A round trip ride on the DFT and DFT/MM train

253rd National Meeting (2017)

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