Conspectus
Nitrogen-centered radicals (NCRs) are a versatile
class of highly
reactive species that have a longer history than the classical carbon-based
radicals in synthetic chemistry. Depending on the N-hybridization
and substitution patterns, NCRs can serve as electrophiles or nucleophiles
to undergo various radical transformations. Despite their power, progress
in nitrogen-radical chemistry is still slow compared with the popularity
of carbon radicals, and their considerable synthetic potential has
been largely underexplored, which is, as concluded by Zard, mainly
hampered by “a dearth of convenient access to these species
and a lack of awareness pertaining to their reactivity”.
Over the past decade, visible-light photoredox catalysis has been
established as a powerful toolbox that synthetic chemists can use
to generate a diverse range of radical intermediates from native organic
functional groups via a single electron transfer process or energy
transfer under mild reaction conditions. This catalytic strategy typically
obviates the need for external stoichiometric activation reagents
or toxic initiators and often enables traditionally inaccessible ionic
chemical reactions. On the basis of our long-standing interest in
nitrogen chemistry and catalysis, we have emphasized the use of visible-light
photoredox catalysis as a tactic to discover and develop novel methods
for generating NCRs in a controlled fashion and synthetic applications.
In this Account, we describe our recent advances in the development
of visible-light-driven photoredox-catalyzed generation of NCRs and
their synthetic applications.
Inspired by the natural biological
proton-coupled electron transfer
(PCET) process, we first developed a strategy of visible-light-driven
photoredox-catalyzed oxidative deprotonation electron transfer to
activate the N–H bonds of hydrazones, benzamides, and sulfonamides
to give the corresponding NCRs under mild reaction conditions. With
these reactive species, we then achieved a range of 5-exo and 6-endo
radical cyclizations as well as cascade reactions in a highly regioselective
manner, providing access to a variety of potentially useful nitrogen
heterocycles. To further expand the repertoire of possible reactions
of NCRs, we also revealed that iminyl radicals, derived from O-acyl cycloalkanone oxime esters, can undergo facile ring-opening
C–C bond cleavage to give cyanoalkyl radicals. These newly
formed radical species can further undergo a variety of C–C
bond-forming reactions to allow the synthesis of diverse distally
functionalized alkyl nitriles. Stimulated by these studies, we further
developed a wide variety of visible-light-driven copper-catalyzed
radical cross-coupling reactions of cyanoalkyl radicals. Because of
their inherent highly reactive and transient properties, the strategy
of heteroatom-centered radical catalysis is still largely underexplored
in organic synthesis. Building on our understanding of the fundamental
chemistry of NCRs, we also developed for the first time the concept
of NCR covalent c...
Compared with the popularity of various C-centred radicals, the N-centred radicals remain largely unexplored in catalytic radical cascade reactions because of a lack of convenient methods for their generation. Known methods for their generation typically require the use of N-functionalized precursors or various toxic, potentially explosive or unstable radical initiators. Recently, visible-light photocatalysis has emerged as an attractive tool for the catalytic formation of N-centred radicals, but the pre-incorporation of a photolabile groups at the nitrogen atom largely limited the reaction scope. Here, we present a visible-light photocatalytic oxidative deprotonation electron transfer/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediation strategy for catalytic N-radical cascade reaction of unsaturated hydrazones. This mild protocol provides a broadly applicable synthesis of 1,6-dihydropyradazines with complete regioselectivity and good yields. The 1,6-dihydropyradazines can be easily transformed into diazinium salts that showed promising in vitro antifungal activities against fungal pathogens. DFT calculations are conducted to explain the mechanism.
A visible‐light‐driven, copper‐catalyzed three‐component radical cross‐coupling of oxime esters, styrenes, and boronic acids has been developed. Key steps of this protocol involve catalytic generation of an iminyl radical from a redox‐active oxime ester and subsequent C−C bond cleavage to generate a cyanoalkyl radical. Upon its addition to styrene, the newly formed benzylic radical undergoes coupling with a boronic‐acid‐derived ArCuII complex to achieve 1,1‐diarylmethane‐containing alkylnitriles.
A photoinduced, copper-catalyzed three-component radical cross-coupling of cycloketone oxime esters, alkenes, and terminal alkynes is described for the first time. Key to the success of this process was the integration of photoinduced iminyl radicalmediated C−C bond cleavage with the conceptual simplicity of copper-catalyzed radical cross-coupling. This protocol provides access to cyanoalkyl-containing propargylic compounds in good yields.
An efficient visible light photocatalytic and external oxidant-free N-radical 5-exo cyclization/addition/aromatization cascade of β,γ-unsaturated hydrazones is described, which provides a practical route to various biologically interesting dihydropyrazole-fused benzosultams in satisfactory yields.
The stable 3D integral electrode structure and the heteroatom-doping effect of Sn0.9Co0.1S2/CC nanosheets lead to outstanding electrochemical properties for sodium ion batteries.
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