The Staudinger ligation of azides and phosphines has found widespread use in the field of chemical biology, but the mechanism of the transformation has not been characterized in detail. In this work, we undertook a mechanistic study of the Staudinger ligation with a focus on factors that affect reaction kinetics and on the identification of intermediates. The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. Hammett analyses demonstrated that electron-donating substituents on the phosphine accelerate the overall reaction. The electronic and steric properties of the ester had no significant impact on the overall rate but did affect product ratios. Finally, the structure of an intermediate that accumulates under anhydrous conditions was identified. These findings establish a platform for optimizing the Staudinger ligation for expanded use in biological applications.

A family of cationic, neutral, and anionic bis(imino)pyridine iron alkyl complexes has been prepared, and their electronic and molecular structures have been established by a combination of X-ray diffraction, Mössbauer spectroscopy, magnetochemistry, and open-shell density functional theory. For the cationic complexes, [((iPr)PDI)Fe-R][BPh(4)] ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)N═CMe)(2)C(5)H(3)N; R = CH(2)SiMe(3), CH(2)CMe(3), or CH(3)), which are known single-component ethylene polymerization catalysts, the data establish high spin ferrous compounds (S(Fe) = 2) with neutral, redox-innocent bis(imino)pyridine chelates. One-electron reduction to the corresponding neutral alkyls, ((iPr)PDI)Fe(CH(2)SiMe(3)) or ((iPr)PDI)Fe(CH(2)CMe(3)), is chelate-based, resulting in a bis(imino)pyridine radical anion (S(PDI) = 1/2) antiferromagnetically coupled to a high spin ferrous ion (S(Fe) = 2). The neutral neopentyl derivative was reduced by an additional electron and furnished the corresponding anion, [Li(Et(2)O)(3)][((iPr)PDI)Fe(CH(2)CMe(3))N(2)], with concomitant coordination of dinitrogen. The experimental and computational data establish that this S = 0 compound is best described as a low spin ferrous compound (S(Fe) = 0) with a closed-shell singlet bis(imino)pyridine dianion (S(PDI) = 0), demonstrating that the reduction is ligand-based. The change in field strength of the bis(imino)pyridine coupled with the placement of the alkyl ligand into the apical position of the molecule induced a spin state change at the iron center from high to low spin. The relevance of the compounds and their electronic structures to olefin polymerization catalysis is also presented.