Synthesis of Thiourea and Thioamide S-Oxides via SO Transfer from a Thiirane S-Oxide onto N-Heterocyclic Carbenes.

Thiourea S-oxides are labile compounds that suffer from a quick overoxidation when directly prepared from thioureas. Therefore, we have developed an alternative route on the basis of the SO transfer from a thiirane S-oxide onto sterically encumbered N-heterocyclic carbenes, including imidazole- and imidazoline-ylidenes, and a cyclic alkyl amino carbene. Reaction conditions and DFT computations suggest a concerted SO transfer mechanism. Thiourea S-oxides are nucleophiles adding to dimethyl acetylenedicarboxylate under fission of the S-O bond.

From Criegee to Breslow: How π-Donors Steer the Route of Olefin Ozonolysis.

While π-bonds typically undergo cycloaddition with ozone, resulting in the release of much-noticed carbonyl O-oxide Criegee intermediates, lone-pairs of electrons tend to selectively accept a single oxygen atom from O3, producing singlet dioxygen. We questioned whether the introduction of potent electron-donating groups, akin to N-heterocyclic olefins, could influence the reactivity of double bonds - shifting from cycloaddition to oxygen atom transfer or generating lesser-known, yet stabilized, donor-substituted Criegee intermediates. Consequently, we conducted a comparative computational study using density functional theory on a series of model olefins with increasing polarity due to (asymmetric) π-donor substitution. Reaction path computations indicate that highly polarized double bonds, instead of forming primary ozonides in their reaction with O3, exhibit a preference for accepting a single oxygen atom, resulting in a zwitterionic species formally identified as a carbene-carbonyl adduct. This previously unexplored reactivity potentially introduces aldehyde umpolung chemistry (Breslow intermediate) through olefin ozonolysis. Considering solvent effects implicitly reveals that increased solvent polarity further directs the trajectories toward a single oxygen atom transfer reactivity by stabilizing the zwitterionic character of the transition state. The competing modes of chemical reactivity can be explained by a bifurcation of the reaction valley in the post-transition state region.

Synthesis of Sterically Encumbered Thiourea S-Oxides through Direct Thiourea Oxidation.

Thiourea S-oxides can be viewed as formal analogs of the currently unknown diamino-substituted Criegee intermediates (urea O-oxides). However, the preparation of such S-oxides is rather challenging, and the direct oxidation of thioureas typically only leads to formation of desulfurized products. Employing the accurate revDSD-PBEP86-D4 double hybrid density functional, it was found that the peracid mediated oxidation of thiourea S-oxides exhibits a lower reaction barrier than the oxidation of the corresponding thiourea itself in contrast to most other ordinary thioketones. The undesired overoxidation reactivity, which is associated with strong π-donation from the thiourea's nitrogen atoms, can be partially suppressed by introduction of bulky substituents and the utilization of protic solvents. In this regard, we managed to prepare two sterically encumbered thiourea S-oxides in isolated yields of 35-40 %. The S-oxides are stable in the solid state and in alcoholic solutions at room temperature for extended periods of time, but swiftly decompose in aprotic solvents by disproportionation. A dimesityl-substituted thiourea S-oxide complexed with residual mCBA could be characterized by means of X-ray crystallography, confirming the importance of hydrogen bonding in the stabilization of the amino-substituted C=S+ -O- moiety.