Formation of Fluorinated Amido Esters through Unexpected C3-C4 Bond Fission in 4-Trifluoromethyl-3-oxo-β-lactams.

4-Trifluoromethyl-3-oxo-β-lactams were unexpectedly transformed into 2-[(2,2-difluorovinyl)amino]-2-oxoacetates as major products, accompanied by minor amounts of 2-oxo-2-[(2,2,2-trifluoroethyl)amino]acetates, upon treatment with alkyl halides and triethylamine in DMSO. This peculiar C3-C4 bond fission reactivity was investigated in-depth, from both an experimental and a computational point of view, in order to shed light on the underlying reaction mechanism.

Reactivity of 3-Oxo-β-lactams with Respect to Primary Amines-An Experimental and Computational Approach.

The reactivity of 3-oxo-β-lactams with respect to primary amines was investigated in depth. Depending on the specific azetidin-2-one C4 substituent, this reaction was shown to selectively produce 3-imino-β-lactams (through dehydration), α-aminoamides (through CO elimination), or ethanediamides (through an unprecedented C3-C4 ring opening). In addition to the experimental results, the mechanisms and factors governing these peculiar transformations were also examined and elucidated by means of DFT calculations.

Tandem Addition of Phosphite Nucleophiles Across Unsaturated Nitrogen-Containing Systems: Mechanistic Insights on Regioselectivity.

The addition of phosphite nucleophiles across linear unsaturated imines is a powerful and atom-economical methodology for the synthesis of aminophosphonates. These products are of interest from both a biological and a synthetic point of view: they act as amino acid transition state analogs and Horner-Wadsworth-Emmons reagents, respectively. In this work the reaction between dialkyl trimethylsilyl phosphites and α,β,γ,δ-diunsaturated imines was evaluated as a continuation of our previous efforts in the field.

Influence of Solvation and Dynamics on the Mechanism and Kinetics of Nucleophilic Aromatic Substitution Reactions in Liquid Ammonia.

The role of the solvent and the influence of dynamics on the kinetics and mechanism of the SNAr reaction of several halonitrobenzenes in liquid ammonia, using both static calculations and dynamic ab initio molecular dynamics simulations, are investigated. A combination of metadynamics and committor analysis methods reveals how this reaction can change from a concerted, one-step mechanism in gas phase to a stepwise pathway, involving a metastable Meisenheimer complex, in liquid ammonia. This clearly establishes, among others, the important role of the solvent and highlights the fact that accurately treating solvation is of crucial importance to correctly unravel the reaction mechanism.

Nucleophile-dependent regio- and stereoselective ring opening of 1-azoniabicyclo[3.1.0]hexane tosylate.

1-[(1R)-(1-Phenylethyl)]-1-azoniabicyclo[3.1.0]hexane tosylate was generated as a stable bicyclic aziridinium salt from the corresponding 2-(3-hydroxypropyl)aziridine upon reaction with p-toluenesulfonyl anhydride.