Electrochemical Dehydrogenative Coupling of Alcohols with Hydrogen Phosphoryl Compounds: A Green Protocol for P?O Bond Formation

Article abstract of DOI:10.1002/adsc.201801723

This study reports the environment-friendly electrochemical transformation of structurally diverse phosphorus compounds and alcohol into phosphonates in the presence of ammonium iodide as electrolyte and redox catalyst in acetonitrile at ambient temperature. This method for P?O bond formation exhibits remarkable features, such as transition metal- and oxidant-free conditions. A reliable mechanism is proposed after control and cyclic voltammetry experiments. (Figure presented.).

Full text of DOI:10.1002/adsc.201801723

Title: Electrochemical dehydrogenative coupling of alcohols with
hydrogen phosphoryl compounds: A green protocol for P–O bond
formation
Authors: Qian-Yu Li, Toreshettahally R. Swaroop, Cheng Hou, Zi-
Qiang Wang, Ying-ming Pan, and Hai-Tao Tang
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801723
Link to VoR: http://dx.doi.org/10.1002/adsc.201801723

10.1002/adsc.201801723
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201
Electrochemical Dehydrogenative Coupling of Alcohols with
Hydrogen Phosphoryl Compounds: A Green Protocol for P–O
Bond Formation
Qian-Yu Li a, Toreshettahally R. Swaroop a, Cheng Hou a,*, Zi-Qiang Wang a, Ying-
Ming Pan a, Hai-Tao Tang a,*
a
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and
Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, People’s Republic of China
E-mail: cheng.hou@qq.com; httang@gxnu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
oxidant-free conditions. A reliable mechanism is proposed
after control and cyclic voltammetry experiments.
Abstract: This study reports the environment-friendly
electrochemical transformation of structurally diverse
phosphorus compounds and alcohol into phosphonates
in the presence of ammonium iodide as electrolyte and
redox catalyst in acetonitrile at ambient temperature.
This method for P-O bond formation exhibits
remarkable features, such as transition metal- and
Keywords: Electroorganic chemistry; CDC reaction; P-O
bond formation; NH4I catalysis; Cyclic voltammetry
Introduction
Electroorganic chemistry is an ideal alternative
method for synthesizing new compounds through
oxidative R1–H/R2–H dehydrogenation cross-
coupling and has attracted considerable interest in
organic chemistry (Scheme 1, Eq. 2).[3,5]
Electroorganic synthesis utilizes electrons as
“reagents” to complete the redox process. In the
previous decade, electrochemical anodic oxidation
has emerged as a promising method to achieve R1–
H/R2–H dehydrogenation cross-coupling.[6] For
example, Lei’s group recently outlined the
application of electrochemical oxidative R1–H/R2–H
dehydrogenation cross-coupling in C−O, C−C, N–N,
C−N, and C–S bond formations.[3] Xu’s group
In modern organic synthesis, production of chemical
products in a green and sustainable manner is
important.[1] Oxidative R1–H/R2–H dehydrogenation
cross-coupling has been developed as a valuable
method for constructing chemical bonds, because it
uses readily available starting materials without
substrate prefunctionalization, and it is one of the
highest atom-economical methods in organic
synthesis, with only one molecule of hydrogen gas
produced
as
byproduct.[2]
of oxidative
However,
the
thermodynamics
R1–H/R2–H
dehydrogenation cross-coupling with the elimination
of one molecule of hydrogen gas is usually
unfavorable.[3] Thus, traditional oxidative R1–H/R2–
H dehydrogenation cross-coupling reactions usually
require stoichiometric amounts of oxidants or
precious metals as catalysts. The use of oxidants in
reactions constantly leads to decreased atom
economy and obtains oxidation side reactions
(Scheme 1, Eq. 1).[4] Thus, the development of a
metal-free and oxidizing-agent-free oxidative R1–
H/R2–H dehydrogenation cross-coupling represents a
major advancement toward achieving low cost and
remarkable environmental sustainability in the
preparation of new compounds.
realized
the
C−H/N−H
electroorganic
dehydrogenation cross-coupling reactions to
construct various heterocyclic structures.[7]
Scheme 1. Comparison of traditional coupling and
electrocatalytic coupling
1
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10.1002/adsc.201801723
Advanced Synthesis & Catalysis
To optimize the reaction conditions, we initially
selected 1a with 2a using 15 mol% NH4I as catalyst
and electrolyte containing the solvent of methanol
with RVC as anode and platinum as cathode in an
undivided cell at a constant current of 15 mA. We
isolated the target product 3aa with a yield of 70%
(Table 1, Entry 1). Replacement of methanol by
other solvents, such as DMSO, DCE, and toluene
caused no substantial improvement in the yield. No
product was detected with DMSO. Acetonitrile was
an excellent solvent for this reaction. The product
was obtained with good yield of 85% (Table 1,
Entries 2-5). No product was obtained in RVC,
which is an anode and cathode at the same time
(Table 1, Entry 6). 3aa was isolated in 32% yield in
the experiment in which platinum was an anode and
cathode (Table 1, Entry 7). 3aa was obtained in 49%
and 62% yields, respectively, when NH4I was
substituted with NaI and KI (Table 1, Entries 8 and
9). The desired product was isolated in 81% yield
when tetrabutyl NH4I was used as electrolyte (Table
1, Entry 10). NH4Cl and NH4Br did not improve the
yield of 3aa (Table 1, Entries 11 and 12). The
product yield was unremarkably increased by
increasing the amount of electrolyte to 20 mol%
(Table 1, Entry 13). 3aa was not detected in the
absence of electricity (Table 1, Entry 14).
Organophosphorus compounds are an important
class of compounds in organic chemistry, medicinal
chemistry, and materials science.[8] Development of
new synthetic methods for this class of compounds
has attracted an increasing amount of interest
because of their various applications. The classical
methods for the formation of phosphorus–oxygen
bond in phosphinate esters include the
Atherton−Todd reaction.[9] Another approach is
dehydrogenative/oxidative coupling of diaryl
phosphites with alcohols, which can be achieved by
using various stoichiometric amounts of oxidants or
precious metals as catalysts.[10] It's worth mentioning
that Chen and Han reported a dehydrogenative
coupling between H-phosphine oxides and alcohols
with hydrogen release, in which cheap iron was used
as a catalyst. In this study, we report an effective
method for the synthesis of phosphinate esters
through electrochemical construction of P–O bond
with metal- and oxidant-free conditions based on our
previous work in electrochemical oxidative R1–
H/R2–H dehydrogenation cross-coupling[6c,6d]. After
the submission of this manuscript, Han et al. reported
a
similar reaction also using electrochemical
dehydrogenation coupling.[11]
Table 1. Optimization of reaction conditionsa
Scheme 2. Phosphorylation of different alcoholsa, b
Entry
1
Electrode
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/RVC
Pt/Pt
Electrolyte
NH4I
Solvent
MeOH
DMSO
DCE
Yieldb
70%
0%
2
NH4I
3
NH4I
Trace
20%
85%
0%
4
NH4I
toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
5
NH4I
NH4I
6
7
NH4I
32%
49%
62%
81%
10%
57%
82%
0
8
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
NaI
9
KI
10
11
12
13c
14d
n-Bu4NI
NH4Cl
NH4Br
NH4I
NH4I
a) Reaction conditions: Reticulated vitreous carbon (RVC)
anode (100 PPI, 1 cm × 1 cm × 1.2 cm), Pt plate cathode
(1 cm × 1 cm), undivided cell, constant current = 15 mA,
1a (0.3 mmol, 1 equiv.), 2a (0.9 mmol, 3 equiv.), NH4I
(15 mol%), solvent (5 mL), under air atmosphere at room
temperature for 3.5 h. b) Isolated yield. c) NH4I (20 mol%).
d) Without electricity.
a)Reaction conditions: RVC anode (100 PPI, 1 cm × 1 cm
× 1.2 cm), Pt plate cathode (1 cm × 1 cm), undivided cell,
constant current = 15 mA, 1a (0.3 mmol), alcohols (0.9
mmol), NH4I (15 mol%), and CH3CN (5 mL), under air
atmosphere at room temperature for 3.5 h. b)Isolated yield.
2
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10.1002/adsc.201801723
Advanced Synthesis & Catalysis
We investigated the phosphorylation of various
yield. The generality of the reaction was
demonstrated through the phosphorylation of diethyl
phosphonate, methyl phenylphosphinate, and 6H-
dibenzo[c,e][1,2]oxa-phosphinine 6-oxide, which
yielded products in 79%, 48%, and 75% yields,
respectively.
alcohols under the optimized reaction conditions.
Ethanol, isopropyl alcohol, and n-propanol were
successfully phosphorylated by diphenylphosphinate
1a to afford products 3ab (83% yield), 3ac (82%
yield), and 3ad (80% yield), respectively (Scheme 2).
3-Phenylpropan-1-ol also underwent smooth reaction
to provide product 3ae in 80% yield. Similarly,
propargyl alcohol reacted with 1a to provide the
required product 3af in 75% yield. Cyclohexanol and
substituted cyclohexanol successfully yielded
products 3ag (79% yield) and 3ah (69% yield),
respectively. Sterically hindered tricyclic and
bicyclic alcohols furnished the desired products 3ai
(71% yield) and 3aj (66% yield), respectively.
Ethylene glycol was monophophorylated by 1a to
form the required product 3ak in 65% yield. The
reaction failed to form the corresponding product 3al
when compound 1a and phenol were used as the
reaction substrates.
Scheme 4. Control experiments
Scheme 3. Different phosphorus compounds reacting with
methanola, b
We performed the following reactions to clarify
the reaction mechanism (Scheme 4). Only a trace
amount of 3aa (23% yield) was observed when
radical scavenger 2,2,6,6-tetramethylpiperidine N-
oxyl was added to the reaction. Meanwhile, 2aa was
detected by high-resolution electrospray ionization
mass spectrometry. Addition of other radical
trapping reagents inhibited this reaction (Scheme 4,
Eq. 1). The reaction of 1a with 2a was conducted by
using I2 as the oxidant. A small amount of the desired
product was observed (Scheme 4, Eq. 2). The
reaction between diphenylphosphinyl chloride 6 and
alcohol 2a was conducted under room temperature
without electricity because of the instability of
diphenylphosphinyl iodide. As expected, the desired
product 3aa was obtained with 45% yield (Scheme 4,
Eq. 3). These experiments indicated that the reaction
involved a partial radical pathway, and diphenyl
phosphinyl iodide was a key intermediate for this
reaction.
a)Reaction conditions: RVC anode (100 PPI, 1 cm × 1 cm
× 1.2 cm), Pt plate cathode (1 cm × 1 cm), undivided cell,
constant current = 15 mA, 1a (0.3 mmol), alcohols (0.9
mmol), NH4I (15 mol%), and CH3CN (5 mL), under air
atmosphere at room temperature for 3.5 h. b)Isolated yield.
We conducted various reactions to extend the
substrate scope of phosphinates. Di-p-tolylphosphine
oxide and bis(3,5-dimethylphenyl)phosphine oxide
were esterified by methanol under the optimized
reaction conditions to obtain products 3ba (83%
yield) and 3ca (81% yield), respectively (Scheme 3).
Similarly,
bis(4-methoxy/fluorophenyl)phosphine
oxide furnished products 3da and 3ea in 81% and
74% yield, respectively. Similarly, di(naphthalen-2-
yl)phosphine oxide produced product 3fa in 79%
yield. The reaction with dibutylphosphine oxide was
successful in forming the required product in 70%
Figure 1. Cyclic voltammograms of reactants and their
mixtures in 0.1 M LiClO4/CH3CN using a glassy carbon-
disk working electrode (diameter, 3 mm). Pt disk and
3
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10.1002/adsc.201801723
Advanced Synthesis & Catalysis
Ag/AgCl as counter and reference electrode, respectively,
at 100 mV/s scan rate: (a) background, (b) 1a (10 mmol/L),
(c) 2a (10 mmol/L), (d) 1a (10 mmol/L) + NH4I (2
mmol/L), (e) NH4I (2 mmol/L), and (f) 1a (10 mmol/L) +
2a (10 mmol/L) + NH4I (2 mmol/L).
undergoes a reduction reaction to liberate alcohol
anion and hydrogen, which completes the
electrochemical cycle.
In conclusion, we developed a new metal- and
oxidant-free electrochemical method for coupling of
alcohols with phosphinates in high yields. The
presented method exhibits a series of advantages,
including excellent functional-group tolerance, high
atom economy, and environment-friendly conditions.
A reliable mechanism is proposed after control
experiments and CV experiments.
We also conducted cyclic voltammograms (CV)
experiments and cyclic voltagrams to determine the
redox behavior of the reactants and their mixtures
(Figure 1). As depicted in Figure 1, substrates 1a and
2a presented no evident oxidation peak in the range
of 0.0−1.0 V versus Ag/AgCl (curves b and c)
without NH4I. The CV of NH4I manifested two
oxidation peaks at 0.45 V and 0.68 V (curve e),
which correspond to the oxidation of I− to I3− and I3−
to I2, respectively.[12] A similar curve was displayed
when 1a and NH4I were combined (curve d). Thus,
1a cannot be oxidized to its corresponding radical.
The CV of the mixture of 1a, 2a, and NH4I
demonstrated a remarkable increase in the catalytic
current (curve f), which reflects the chemical
interaction between the three compounds.
Experimental Section
Diaryl(alkyl) phosphine oxides (0.3 mmol, 1.0 equiv) and
NH4I (15 mol%) were placed in 10 mL three-necked
round-bottomed flask. The flask was equipped with a
RVC (100 PPI, 1 cm x 1 cm x 1.2 cm) anode and a
platinum plate (1 cm x 1 cm) cathode. MeOH (5.0 mL)
were added. Electrolysis was conducted at RT under a
constant current of 15 mA until substrate consumption is
completed (monitored by TLC, approximate 3.5 h). The
reaction mixture was concentrated and the residue was
chromatographed through silica gel eluting with ethyl
acetate/petroleum ether to give the products.
Acknowledgements
We thank the National Natural Science Foundation of China
(21861006), Guangxi Natural Science Foundation of China
(2016GXNSFEA380001 and 2016GXNSFGA380005) and State
Key Laboratory for Chemistry and Molecular Engineering of
Medicinal Resources (CMEMR2017-A02 and CMEMR2017-
A07) for financial support.
Scheme 5. Proposed mechanism
A possible mechanism is proposed based on the
above results and DFT calculations (See supporting
information for details), as shown in Scheme 5. At
the anode surface, oxidation of iodide provides
iodine radical or molecular iodine. The iodine radical
can induce diphenylphosphine oxide to yield
phosphorus radical 4 with the aid of alcohol, which is
confirmed through CV experiments. Subsequently,
radical coupling reaction occurs between 4 and
iodine radical to afford intermediate 5 (Path A).
Meanwhile, iodine cation can directly react with
substrate 1 to produce intermediate 5 (Path B). The
DFT calculated reaction free energy is exothermic
for the two mechanisms, thereby indicating that the
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Advanced Synthesis & Catalysis
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5
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10.1002/adsc.201801723
Advanced Synthesis & Catalysis
COMMUNICATION
Electrochemical dehydrogenative coupling of
alcohols with hydrogen phosphoryl compounds:
A green protocol for P-O bond formation
Adv. Synth. Catal. Year, Volume, Page – Page
Qian-Yu Lia, Toreshettahally R. Swaroopa, Cheng
Houa,*, Zi-Qiang Wanga, Ying-Ming Pana, Hai-Tao
Tanga,*
6
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