Metal-free oxidative phosphinylation of aryl alkynes to β-ketophosphine oxides via visible-light photoredox catalysis

Article abstract of DOI:10.1039/c5cy01541c

A method for photocatalytic oxidative coupling of diaryl phosphine oxide and arylacetylene under mild conditions was developed. Rhodamine B, an inexpensive and commercially available organic dye, was used as the photocatalyst. This protocol realizes a reg

Full text of DOI:10.1039/c5cy01541c

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Metal-free Oxidative Phosphinylation of Aryl Alkynes to β-
Ketophosphine Oxides via Visible-Light Photoredox Catalysis
†
Received 00th January 20xx,
Accepted 00th January 20xx
Mei-jie Bu, Guo-ping Lu and Chun Cai*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
method for photocatalytic oxidative coupling of diaryl phosphinylation reagent. Recently, a silver/copper catalysis
phosphine oxides and arylacetylenes under mild conditions was system was demonstrated to be effective for the direct oxidative
developed. Rhodamine B, an inexpensive and commercially phosphinylation of alkynes with oxygen in the air.10b Almost at
available organic dye, was used as the photocatalyst. This protocol the same time, He11c and Song11d reported the copper/ironꢀ
realizes a regioselective 1,2-difunctionalization of arylacetylenes catalyzed reactions for the formation of βꢀketophosphine
and provides
a
metal-free access toward
a
series of β- oxides, respectively (Scheme 1c). Although existing methods
are undoubtedly useful, the development of more
ketophosphine oxides.
a
environmentally benign method to produce βꢀketophosphine
oxides is still highly desirable in modern organic chemistry.
The past several years have witnessed a rapid, prominent
development of visibleꢀlight photoredox catalysis,13 which is
highly desirable from the viewpoint of energy saving and
environmental friendliness. And efforts have been made by
several groups for the construction of C–P bonds facilitated by
visibleꢀlight photocatalysis.14 In fact, reductive quenching of
the excited state of photocatalyst with SPO could generate the
phosphorus radical. In 2013, Kobayashi introduced this elegant
method for the first time, and applied the method to the
hydrophosphinylation of unactivated alkenes.15 Later, a similar
strategy was used by Lu and Xiao for the arylation of SPOs by
combining nickel catalysis and visibleꢀlightꢀinduced
photoredox catalysis.16 We hypothesized that the Pꢀcentered
radicals generated in this manner might also engage in
oxidative couplings with aryl alkynes to realize a regioselective
difunctionalization of arylacetylenes for the generation of βꢀ
ketophosphine oxides (Scheme 1).
The construction of carbon–phosphorus bonds is synthetically
important, because organophosphorus compounds are an
important class of chemicals that have broad utilities as
reagents for organic synthesis,1 ligands for transition metal
catalysts,2 pharmaceuticals,3 and functional materials.4 In
particular, βꢀketophosphine oxides, which can be applied in the
HornerꢀWadsworthꢀEmmons reactions,5 are typical structures
of
organophosphorus
compounds.
Traditionally,
βꢀ
ketophosphine oxides are prepared by Arbuzov reaction, which
involves the reactions between αꢀhaloketones with
trialkylphosphites,6 and the reaction often requires high
temperature (Scheme 1a). Acylation of alkylphosphine oxides
provides another reliable approach to βꢀketophosphine oxides,7
however, stoichiometric amounts of the hazardous
organometallic reagents are needed in this protocol (Scheme
1b). Other approaches, hydration of alkynylphosphine oxides8
and oxidation of βꢀhydroxyalkylphosphines,9 suffer limitations
like inaccessible materials and tedious procedures.
Difunctionalization of alkynes is currently an attractive
strategy. It allows the introduction of two functional groups in a
single stroke. Oxidative phosphinylation of alkynes can
efficiently afford βꢀketophosphine oxides in one step from
simple starting materials, and this method could be put into
practice using transition metal catalysis. Oxidation of secondary
phosphine oxide (SPO) by silver,10 copper,11 or manganese12
could afford Pꢀcentered radical, which is a highly reactive
To this end, we began our investigations with the oxidative
coupling between diphenylphosphine oxide 1a and
phenylacetylene 2a. When the experiment was catalyzed by
Ru(bpy)3Cl2·6H2O, one of the most commonly employed
visibleꢀlight photocatalysts, and irradiated with a white LED
lamp in isopropanol under O2 at room temperature, the desired
O
P(OR)3
+
X
(c)
(a)
Heat
R2
O
P
R1
R1
transition metal
catalysis
O
P
O
R1
R1
H
R2
R2
(b)
LDA
this work
O
R1
O
O2
+
photoredox catalysis
P
MeO
R2
R1
Scheme 1 General routes to βꢀketophosphine oxides.
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Table 1 Optimization studiesa
alkynes, the results of which are summarized in Table 2.
Various aryl alkynes carrying electronꢀdonating and
ꢀ
withdrawing substituents at the para position could
successfully react with diphenylphosphine oxide to give the
targeted products. Arylacetylenes bearing halogen substituents
(
2f-h, 2n) on the aromatic ring all gave the corresponding
products with an intact carbonꢀhalogen bond, which can be
used for further transformation in transitionꢀmetal catalyzed
reactions. Ortho and metaꢀsubstituents at the aryl moiety were
also tolerated (3n-p). Moderate yield was gained with the
naphthyl derivative (2l), and 4ꢀethynylꢀ1,1'ꢀbiphenyl (2m) also
worked well. It is worth noting that only one ethynyl group
reacted with 1a in 1,3ꢀdiethynylbenzene
(2k). However,
products were not detected with 3ꢀethynylaniline and
ethynylcyclohexane. The reactions of SPO 1a with internal
alkynes, 1ꢀphenylꢀ1ꢀpropyne and 1ꢀphenylꢀ1ꢀbutyne, both
resulted in a complex mixture, and the products could not be
separated.
Two other electronꢀrich SPOs were also surveyed to
Table 2 Scope of the photocatalytic oxidative phosphinylationa
Entry
1
Catalyst
Solvent
iꢀPrOH
iꢀPrOH
iꢀPrOH
iꢀPrOH
iꢀPrOH
iꢀPrOH
CH3OH
EtOH
Yield (%)b
52
Ru(bpy)3Cl2·6H2O (2 mol%)
Rhodamine B (2 mol%)
Eosin Y (2 mol%)
2
79
3
68
4
5
Eosin B (2 mol%)
45
30
Rose Bengal (2 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
Rhodamine B (0.5 mol%)
None
6
91
7
67
8
83
9
CH3CN
THF
DCM
85
10
11
12
13
14c
15
83
59
DMF
77
DMSO
iꢀPrOH
iꢀPrOH
67
75
trace
a
Reaction conditions: 1a (0.4 mmol), 2a (1.2 mmol), photocatalyst, solvent (0.4
mL), irradiation with a white LED lamp under an oxygen atmosphere at r.t. for 12
h. b Isolated yields of product 3a. c The reaction was conducted in the air.
product 3a was obtained in 52% yield after a reaction time of
12 hours (Table 1, entry 1). As an alternative to transition metal
complexes in photoredox catalysts, organic dyes are less
expensive and less toxic.13g, 17 So we evaluated some organic
dyes, and the results indicated that the best photocatalyst for
this reaction was rhodamine B (Table 1, entry 2), which was
also employed in Kobayashi’s report as photocatalyst for the
generation of Pꢀcentered radicals.15 Then, the catalyst loading
was cut to 0.5 mol%, which resulted in an improved yield of
91% (Table 1, entry 6).18 Finally, different solvents were
screened, and isopropanol remained to be the best for the
oxidative phosphinylation. When the experiment was directly
exposed to air, the yield declined to 75% (Table 1, entry 14).
When no phtotocatalyst was added, the reaction became
sluggish and trace product was observed after the reaction time
(Table 1, entry 15).
a
Reaction conditions: 1 (0.4 mmol), 2 (1.2 mmol), rhodamine B (0.5 mol%),
With the optimized conditions in hand,‡ this approach was
then applied to the reaction of SPO 1a and a variety of aryl
solvent (0.4 mL), irradiation with a white LED lamp under an oxygen atmosphere
at r.t. for 12 h. Isolated yields.
2 | J. Name., 2012, 00, 1-3
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to generate hydroperoxide VI 20
afford peroxy radical
,
or react with dioxygen to
V
. Peroxy radical V would convert into
hydroperoxide VI by Hꢀabstraction from the solvent. The
reaction of VI with IV could result in the homolysis of the
oxygenꢀoxygen bond. Upon the homolysis, hydroperoxide VI
reacts with phosphinous acid
II, along with the enol VII. Finally, product
I
to generate another molecule of
is afforded via
3
a
quick tautomerization. It’s crucial that singlet oxygen should
not be produced by excitedꢀstate photocatalyst via energy
transfer, because it tends to react with most alkynes. Thus,
rhodamine B should be suitable and efficient for this reaction.21
In conclusion, we have developed an oxidative
phosphinylation of aryl alkynes under aerobic conditions
facilitated by visible light. With a low catalyst loading of
rhodamine B, these reactions proceed smoothly under mild
conditions via a radical process and provide a wide range of βꢀ
ketophosphine oxides in good yields. This protocol is metalꢀ
free and operationally simple, using an inexpensive organic dye
as the photocatalyst and visible light as a green source of
energy.
Scheme 2 Experiments for the mechanistic study.
Acknowledgements
We acknowledge financial support from Jiangsu Natural
Science Foundation (BK 20131346).
Notes and references
Scheme 3 Possible mechanism.
‡ The photocatalytic reactions were irradiated with a 23W
investigate the scope of the reaction. To our delight, the household white LED lamp which was directly got from the
reactions with phenylacetylene 2a afforded the corresponding supermarket. A 10 mL reaction vessel was equipped with
products (3q
Some control experiments were conducted to gain insight mmol) and a magnetic stirring bar.
into the mechanism. When the photocatalytic reaction was followed by aryl alkyne
(1.2 mmol, 3 equiv.). The mixture
,
3r) with the yields of 77% and 80%.
rhodamine B (1 mg, 0.002 mmol, 0.5 mol%), SPO
1 (0.4
i
ꢀPrOH (0.4 mL) was added,
2
performed in the presence of 1.5 equivalents of the radical was irradiated with the white LED lamp and stirred under O2
scavenger 2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinꢀ1ꢀoxyl (TEMPO), it (balloon) at room temperature for 12 h. After the reaction, the
was completely restrained (Scheme 2a), thus indicating a reaction was quenched by 10 mL ethyl acetate. The resulting
possible radical process. And when this experiment was carried mixture was passed through a plug of silica gel, concentrated
out in a nitrogen atmosphere, trace product was obtained under reduced pressure. Purification of the crude product was
1
(Scheme 2b), suggesting this protocol requires the presence of achieved by column chromatography or preparative TLC. H,
oxygen. The reaction conducted under anhydrous conditions 13C, 31P and 19F NMR spectra were recorded on an AVANCE
gave βꢀketophosphine oxide 3a in 85% yield (Scheme 2c).19 III 500 Bruker spectrometer operating at 500 MHz, 125 MHz,
These two results indicated that oxygen in the product came 202 MHz and 470 MHz, respectively.
from O2.
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exists in equilibrium with its trivalent tautomer phosphinous
acid
a single electron transfer (SET) with electronꢀrich phosphinous
acid to produce the corresponding radicalꢀcation intermediate
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2
3
I
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A visible-light-induced oxidative phosphinylation of arylacetylenes catalyzed by an inexpensive
organic dye was demonstrated to be effective under mild conditions.