The selective installation of azide
groups into C(sp3)–H bonds is a priority research
topic in organic synthesis,
particularly in pharmaceutical discovery and late-stage diversification.
Herein, we demonstrate a generalized manganese-catalyzed oxidative
azidation methodology of C(sp3)–H bonds using nucleophilic
NaN3 as an azide source under electrophotocatalytic conditions.
This approach allows us to perform the reaction without the necessity
of adding an excess of the substrate and successfully avoiding the
use of stoichiometric chemical oxidants such as iodine(III) reagent
or NFSI. A series of tertiary and secondary benzylic C(sp3)–H, aliphatic C(sp3)–H, and drug-molecule-based
C(sp3)–H bonds in substrates are well tolerated
under our protocol. The simultaneous gram-scale synthesis and the
ease of transformation of azide to amine collectively advocate for
the potential application in the preparative synthesis. Good reactivity
of the tertiary benzylic C(sp3)–H bond and selectivity
of the tertiary aliphatic C(sp3)–H bond in substrates
to incorporate nitrogen-based functionality at the tertiary alkyl
group also provide opportunities to manipulate numerous potential
medicinal candidates. We anticipate our synthetic protocol, consisting
of metal catalysis, electrochemistry, and photochemistry, would provide
a new sustainable option to execute challenging organic synthetic
transformations.
Benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one derivatives are
prevalent in many synthetic intermediates,
pharmaceuticals, and organic materials. Herein, we develop a Mn-catalyzed
electrochemical radical cascade cyclization reaction that uses electricity
as the primary energy input to promote the reaction, leading to a
series of benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one derivatives under exogenous-oxidant-free conditions.
It is worth noting that this electrochemical method can not only realize
the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one derivatives but also provides a new strategy for
generating alkyl radicals from alkylboronic acids.
The
cross-coupling of C(sp3)–H and N–H
represents one of the most straightforward approaches to construct
saturated nitrogen-containing compounds. The additional oxidants or
halogenated reagents are generally required in such processes. Herein,
we developed an electrochemical oxidative intramolecular C(sp3)–H amination of amides by employing a carbon rod anode
and a platinum plate cathode in an undivided cell under constant-current
electrolysis conditions. Tetrabutylammonium acetate was not only employed
as an electrolyte, but also can form the intermolecular hydrogen bond
with amide and promote cleavage of the N–H bond. The additional
oxidants and N-halogenation step can be obviated
in this methodology. A variety of benzylic and nonactivated tertiary,
secondary, primary C(sp3)–H amination can be achieved
with good yields.
Considering that stoichiometric borane and oxidant are required in the classical alkene anti-Markovnikov hydration process, it remains appealing to achieve the transformation in a catalytic protocol. Herein, a visible-lightmediated anti-Markovnikov addition of water to alkenes by using an organic photoredox catalyst in conjunction with a redox-active hydrogen atom donor was developed, which avoided the need for a transition-metal catalyst, stoichiometric borane, as well as oxidant. Both terminal and internal olefins are readily accommodated in this transformation to obtain corresponding primary and secondary alcohols in good yields with single regioselectivity. This procedure can be scaled up to gram scale with a 230 turnover number based on photocatalyst.
Deuterated compounds are valuable in synthetic, pharmaceutical and analytical chemistry. The deuteration of halides is a widespread method for its good site-selectivity. However, the facile, efficient and economical deuterium incorporation still remains a big challenge. In this work, we introduced a practical deuteration of (hetero)arylhalides through electrochemical reduction method. This transformation proceeded smoothly under room temperature without metal catalysts, external-reductants, toxic or dangerous reagents. Remarkably, low-cost and chemical equivalent D 2 O was the sole deuterium source in this reaction. The professional electrosynthesis equipment was not essential, but common batteries and electrodes were enough.
The oxidative [4+2] annulation reaction represents an elegant and versatile synthetic protocol for the construction of six-membered heterocyclic compounds. Herein, a photoinduced oxidative [4+2] annulation of NH imines and alkenes was developed by utilizing a dual photoredox/cobaloxime catalytic system. Various multisubstituted 3,4-dihydroisoquinolines can be obtained in good yields. This method is not only obviated the need of stiochiometric amounts of oxidants but also exhibited excellent atom economy by generating H as the only byproduct. Remarkably, high regioselectivity and trans diastereoselectivity can be achieved in this transformation even if the Z/E mixture of alkenes were employed.
We formed C(sp3)–C(sp2) bonds under electrochemical conditions by using NHP esters and N-heteroarenes without any catalysts. Our approach could be a complement to the Kolbe reaction and a promising strategy for finding more new reactions.
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