Electrochemically dehydrogenative C-H/P-H cross-coupling: Effective synthesis of phosphonated quinoxalin-2(1: H)-ones and xanthenes

Article abstract of DOI:10.1039/c9gc01474h

An efficient electrochemical approach for the C(sp²)-H phosphonation of quinoxalin-2(1H)-ones and C(sp³)-H phosphonation of xanthenes has been developed. The chemistry was performed in an undivided cell under constant current conditions and features a wide range of substrates, up to 99% yield and it is free of transition-metal catalysts- A nd external oxidants, thereby providing a straightforward approach for dehydrogenative C-H/P-H cross-coupling. In addition, control experiments disclose that some of the reactions may involve a radical pathway.

Full text of DOI:10.1039/c9gc01474h

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DOI: 10.1039/C9GC01474H
Electrochemically Dehydrogenative C-H/P-H Cross-Coupling: Effective Synthesis
of Phosphonated Quinoxalin-2(1H)-ones and Xanthenes
Ke-Jing Li,1,2 Yang-Ye Jiang,2 Kun Xu, 2 Cheng-Chu Zeng*1,2 and Bao-Guo Sun1
1
Beijing advanced innovation center for food nutrition and human health, School of
Food and Chemical Engineering, Beijing Technology and Business University, Beijing
100048, China
2 Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science
& Bioengineering, Beijing University of Technology, Beijing 100124, China.
Corresponding author: zengcc@bjut.edu.cn
Abstract:
An efficient electrochemical approach for the C(sp2)-H phosphonation of
quinoxalin-2(1H)-ones and C(sp3)-H phosphonation of xanthene has been developed.
The chemistry was performed in an undivided cell under constant current conditions
and features wide range of substrates, up to 99% yield as well as transition-metal
catalyst- and external oxidant-free, thereby providing a straightforward approach for
the dehydrogenative C-H/P-H cross-coupling. In addition, control experiments disclose
that some of the reactions may involve a radical pathway.
Key words: Electrochemically dehydrogenative cross-coupling, oxidative
phosphonation, quinoxalin-2(1H)-ones, xanthene
Graphical Abstract:
O
H P R
R
O
electrolysis
in the air
metal-based redox catalyst-free
undivided cell
+
H
P R
R
+
H2
SP2-C, SP3-C
constant current electrolysis
23 examples, up to 99% yield

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DOI: 10.1039/C9GC01474H
Introduction
The efficient construction of diverse C-P bonds is of great important since
organophosphorus compounds exists widely in agrichemicals, organic ligands, material
[1]
and bioactive compounds. The reactions of trialkyl phosphite with an electrophilic
alkyl halide at elevated temperature are the most traditional pathway to construct a
[2]
[3]
C(sp3)-P bond,
whereas, transition metal based catalysts (such as palladium,
[4]
[5]
copper, manganese, and silver [6]) have been widely employed to form various
C(sp2)-P bonds. Recently, owing to the intrinsic sustainability and green chemistry
character, visible light-induced photoredox catalysis has also been extensively applied
[7]
in the formation of various C-P bonds. On the other hand, quinoxalin-2(1H)-one,
especially 3-substituted quinoxalin-2(1H)-ones are broadly existed in natural products
and bioactive compounds [8] due to their antibacterial, [8a] antiviral [8b-c] and anticancer
properties. [8d-e] As a result, the synthesis of 3-phosphonated quinoxalin-2(1H)-ones has
attracted much attention. In this context, Cui and coworkers reported the phosphonation
of quinoxalin-2(1H)-ones under transition-metal-free conditions using 3.0 equiv of
K2S2O8 as oxidant at elevated temperature (Scheme 1a).[9] Alternatively, Kim et al
developed a visible light photoredox-catalyzed phosphorylation of quinoxalin-2(1H)-
[10]
ones with diphenylphosphine oxide (Scheme 1a).
Nevertheless, these protocols
suffer from the use of excess amounts of oxidizing reagents, as well as the limited
substrate scopes.
Organic electrosynthesis, which utilizes traceless electrons as the clean reactants,
has been recognized as a green synthetic tool since electrons produce no waste in
contrast with chemical redox reagents. [11] The past decade has witnessed an increasing
interest in organic electrosynthesis that expanded the toolbox of organic chemists for
[15]
green synthesis.[12] A variety of electroorganic reactions for C-C,[13] C-N,[14] C-O
[16]
and C-S
bonds formation have been developed under environmentally-friendly
conditions. Despite these advances, electrochemically dehydrogenative C-H/P-H cross
coupling is less studied. Budnikova and coworkers first reported the elegant
electrochemical phosphorylation of arenes and coumarins catalyzed by transition metal
[17a]
complex, such as bimetallic catalyst system MnCl2bpy/Ni(BF4)2bpy
or bpyCoCl2

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[17b]
DOI: 10.1039/C9GC01474H
Later on, silver-based catalysts were employed for the
(Scheme 1b).
electrochemical phosphorylation of azole derivatives [17c] and caffeine [17d] (Scheme 1b).
These transition metal catalyzed electrochemical phosphorylations were performed in
three-electrode divided cell under controlled potential conditions, which is not suitable
for scale-up, especially for industrial preparation. Moreover, the electrolysis efficiency
is not excellent due to the strong coordination of phosphorus reagents with the metal
catalyst.[18] In addition, as far as we know, the electrochemical C(sp3)-P formation has
not been reported.
a) Cross-coupling of C(sp2)-H/P-H via chemical oxidant or photocatalyzed
R2
N
R2
N
O
O
H
O
P
K2S2O8, CH3CN, 100 oC
or Ensio B, CH3CN, rt.
R1
H P R3
R3
R1
+
O
N
N
R3
R3
b) Electrochemically cross-coupling of C(sp2)-H/P-H mediated by metal catalysts
O
Ar
or
H
Ar P R
O
H P R
R
Catalysts: Pd, Ag, Co, Ni, etc
R
O
+
or
divided cell, three electrode system
controlled potential
HetAr
H
P R
HetAr
R
c) This work: electrochemically cross-coupling of C(sp2)-H/P-H
R2
N
R2
O
P
O
N
O
H
direct electrolysis
R1
R1
H P R3
R3
+
O
N
N
R3
R3
metal-based redox catalyst-free
undivided cell
constant current electrolysis
up to 99% yield
Scheme 1. Cross-coupling of C(sp2)-H/P-H
In continuation to our interests in electrochemical C-H functionalization,[19] we
herein reported an efficient intermolecular electrochemical cross-coupling of
quinoxalin-2(1H)-one with H-phosphonates and H-phosphine oxides to obtain 3-
phosphonated quinoxalin-2(1H)-ones (Scheme 1c). The protocol could also extend to