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The Cu(i)-mediated click reaction of proteins with affinity tags enables their selective isolation from complex mixtures. However, irreversible protein modification limits the interpretation of results from subsequent biophysical and biochemical assays. We report a facile and modular chemical strategy to reversibly modify peptides and proteins with biotin and FLAG affinity tags at a clickable glutamine (CliQ) residue.

Protonation of an iron C–H activated complex containing pendant amines in the presence of N2 generated a cis-(H)FeII–N2 complex. Addition of acid protonates the pendant amines. Reduction of the protonated complex results in N2 loss and H2 formation, followed by N2 binding. The origin of H2 formation in this Fe system is compared to proposed mechanisms for H2 loss and N2 coordination in the E4 state of nitrogenase.

α,β-Unsaturated 2-imidazolyl ketones undergo [2 + 2] cycloaddition with a variety of Michael acceptors upon irradiation with visible light in the presence of Ru(bpy)(3)(2+). Cleavage of the imidazolyl auxiliary from the cycloadducts affords cyclobutane carboxamides, esters, thioesters, and acids that would not be accessible from direct cycloaddition of the corresponding unsaturated carbonyl compounds.

The use of this strategy enables the synthesis of a variety of cyclobutane carboxylic acid derivatives which are not accessible from direct cycloaddition of the corresponding unsaturated carbonyl compounds.

Domino reactions were designed to allow the byproduct of an upstream reaction to be internally recycled to catalyze a downstream reaction in a one-pot tandem sequence. Nitroarene reduction by In(0) generates an amine and In (III) byproducts. Addition of aldehyde followed by Danishefsky's diene or silyl ketene acetal provides access to dihydropyridin-4-ones or beta-amino esters, respectively, in yields that are comparable or superior to the reported stepwise reactions.