Comprehensive Mechanistic Scenario for the Cu-Mediated Asymmetric Propargylic Sulfonylation Forging Tertiary Carbon Stereocenters.

Metal-catalyzed propargylic transformations represent a powerful tool in organic synthesis to achieve new carbon-carbon and carbon-heteroatom bonds. However, detailed knowledge about the mechanistic intricacies related to the asymmetric formation of propargylic products featuring challenging heteroatom-substituted tertiary stereocenters is scarce and therefore provides an inspiring challenge. Here, we present a meticulous mechanistic analysis of a propargylic sulfonylation reaction promoted by a chiral Cu catalyst through a combination of experimental techniques and computational studies. Surprisingly, the enantio-discriminating step is not the coupling between the nucleophile and the propargylic precursor but rather the following proto-demetalation step, a scenario further validated by computing enantio-induction levels under other previously reported experimental conditions. A full mechanistic scenario for this propargylic substitution reaction is provided, including a catalyst pre-activation stage, a productive catalytic cycle, and an unanticipated non-linear effect at the Cu(I) oxidation level.

Introducing the Catalytic Amination of Silanes via Nitrene Insertion.

The direct functionalization of Si-H bonds by the nitrene insertion methodology is described. A copper(I) complex bearing a trispyrazolylborate ligand catalyzes the transfer of a nitrene group from PhI═NTs to the Si-H bond of silanes, disilanes, and siloxanes, leading to the exclusive formation of Si-NH moieties in the first example of this transformation. The process tolerates other functionalities in the substrate such as several C-H bonds and alkyne and alkene moieties directly bonded to the silicon center. Density functional theory (DFT) calculations provide a mechanistic interpretation consisting of a Si-H homolytic cleavage and subsequent rebound to the Si-centered radical.

Photodissociation of acryloyl chloride at 193 nm: interpretation of the product energy distributions, and new elimination pathways.

The ground electronic state potential energy surface of acryloyl chloride, CH2CHC(O)Cl, has been mapped using an automated transition state search procedure. A total of 174 minima, 527 TSs, and 20 different dissociation channels have been found. Among others, three novel HCl elimination pathways, namely, a five-center mechanism and two three-body dissociations (leading to CO + HCl + HCCH) have been discovered. While the bimodal character of the experimental HCl rotational distributions was previously attributed to the presence of two competing channels, our dynamics simulations show that a single channel, the four-center HCl elimination of CH2ClCHCO following a 1,3-Cl-shift of CH2CHC(O)Cl, displays a bimodal distribution in nearly prefect agreement with the experiment. Overall, our simulation results suggest that, as far as molecular elimination is concerned, this channel dominates in the 193 nm photodissociation of the molecule. The simulations also show evidence of non-IRC dynamics for this channel.

The Challenge of Reproducing with Calculations Raw Experimental Kinetic Data for an Organic Reaction.

DFT calculations and microkinetic simulations are applied to the reproduction of previously reported experimental results on the evolution of product concentration versus time in the condensation reaction of n-butylamine and benzaldehyde. The mechanism is complicated by the role played by water impurities as proton shuttles. Several functionals and other approaches are tested, yet good agreement is only achieved upon the usage of an adjustment consisting of a directed biasing of the computed DFT free energies.