Project Summary
The overarching objective of the proposed research is to develop and explore the mode of operation of a
novel family of first-row transition-metal reagents for the amination of unfunctionalized hydrocarbons. The
proposed reagents deliver nitrogen groups (nitrenes, amidos, nitrenoids) to aliphatic hydrocarbons (C–H
bonds) and olefins (C=C bonds) for the construction of C–N bonds. Sites of amination are present in a plethora
of natural and synthetic products, including pharmaceuticals, agrochemicals, catalytic agents and solid-state
materials, in order to confer backbone characteristics and specific functionalities necessary for activity. The
principal objective will be accomplished via three specific aims, accomplished in a parallel and mutually
informed fashion. First, a novel library of stereo-electronically diverse ligand scaffolds will be synthesized and
used as a robust framework to anchor metal sites, producing divalent iron, manganese, cobalt, and
monovalent copper reagents, functioning as catalysts for amination reactions. Secondly, the metal reagents
will be explored as catalysts for the transfer of nitrogen groups (nitrenes, amidos, nitrenoids) from suitable
precursors to versatile carbonaceous substrate acceptors (alkanes, alkenes), leading to the formation of
important functional units (amines, diamines, unprotected aziridines). Stoichiometric reactions involving the
metal reagents and the nitrogen-group sources (in the absence of substrates) will be conducted to identify
critical metal-centered intermediates responsible for delivering the nitrogen group to the substrate. Thirdly, the
most promising reagents will be mechanistically investigated, to report on the mode of transfer and subsequent
insertion/addition of the nitrogen group unit to the substrate, and further guide catalyst development for efficient
and selective aminations. The proposed work relies on the availability of a library of house-made novel metal
reagents, featuring members with a proven record in C–N bond construction, but requiring expansion to
achieve appropriate levels of selectivity in the synthesis of a wider range of amination products. Moreover, the
proposed research explores reactivity patterns that may share common characteristics in catalysis and
enzymology, to indirectly address mechanistic questions arising from emerging classes of enzymes involved in
amination reactions. The eventual outcome of the proposed activities is to introduce novel reagents in the
arsenal of the synthetic chemist, deriving from the abundant first-row transition elements, and aspiring to
surpass or complement current C–N bond construction methodologies in terms of scope, selectivity, and
mechanistic insight.