Vicinal diamines are privileged synthetic motifs in chemistry due to their prevalence and powerful applications in bioactive molecules, pharmaceuticals, and ligand design for transition metals. With organic diazides being regarded as modular precursors to vicinal diamines, enormous efforts have been devoted to developing efficient strategies to access organic diazide generated from olefins, themselves common feedstock chemicals. However, state-of-the-art methods for alkene diazidation rely on the usage of corrosive and expensive oxidants or complicated electrochemical setups, significantly limiting the substrate tolerance and practicality of these methods on large scale. Toward overcoming these limitations, here we show a photochemical diazidation of alkenes via iron-mediated ligand-to-metal charge transfer (LMCT) and radical ligand transfer (RLT). Leveraging the merger of these two reaction manifolds, we utilize a stable, earth abundant, and inexpensive iron salt to function as both radical initiator and terminator. Mild conditions, broad alkene scope and amenability to continuous-flow chemistry rendering the transformation photocatalytic were demonstrated. Preliminary mechanistic studies support the radical nature of the cooperative process in the photochemical diazidation, revealing this approach to be a powerful means of olefin difunctionalization.
Development of visible light-mediated
atom transfer radical addition
of haloalkanes onto unsaturated hydrocarbons has seen rapid growth
in recent years. However, due to its radical chain propagation mechanism,
diverse functionality other than the pre-existing (pseudo-)halide
on the alkyl halide source cannot be incorporated into target molecules
in a one-step, economic fashion. Inspired by the prominent reactivities
shown by cytochrome P450 hydroxylase and non-heme iron-dependent oxygenases,
we herein report the first modular, dual catalytic difunctionalization
of unactivated alkenes via manganese-catalyzed radical ligand transfer
(RLT). This RLT elementary step involves a coordinated nucleophile
rebounding to a carbon-centered radical to form a new C–X bond
in analogy to the radical rebound step in metalloenzymes. The protocol
leverages the synergetic cooperation of both a photocatalyst and earth-abundant
manganese complex to deliver two radical species in succession to
minimally functionalized alkenes, enabling modular diversification
of the radical intermediate by a high-valent manganese species capable
of delivering various external nucleophiles. A broad scope (97 examples,
including drugs/natural product motifs), mild conditions, and excellent
chemoselectivity were shown for a variety of substrates and fluoroalkyl
fragments. Mechanistic and kinetics studies provide insights into
the radical nature of the dual catalytic transformation and support
radical ligand transfer (RLT) as a new strategy to deliver diverse
functionality selectively to carbon-centered radicals.
Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel‐catalyzed monofluoromethylation of unactivated alkyl halides using a low‐cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross‐coupling of two alkyl halides. Results with 1‐bromo‐1‐fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3)‐C(sp3) cross‐coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first‐order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate‐determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides.
A novel and facile synthetic strategy for the construction of 1-benzazepines has been developed via copper-catalyzed oxidative C(sp)-H/C(sp)-H cross-coupling directly from two inert C-H bonds. This transformation represents an atom- and step-economical way to synthesize biologically important seven-membered benzo-heterocycles compared with the known methods.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.