Platinum(II) photo-catalysis for highly selective difluoroalkylation reactions

Article abstract of DOI:10.1039/c7cc03823b

The platinum(ii) photo-catalyzed difluoroalkylation of cinnamic acids and alkynes for selective construction of E-,Z-difluoroalkyl alkenes and difluoroalkyl alkenyl iodides, respectively, were achieved under mild conditions. The high efficiency, good substrate scope and high selectivity altogether highlight the prospect of Pt(ii) photocatalysts in visible-light-driven organic transformation reactions.

Full text of DOI:10.1039/c7cc03823b

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Platinum(II) photo-catalysis for highly selective
difluoroalkylation reactions†
Cite this:DOI: 10.1039/c7cc03823b
ab
cd
ac
ab
a
Jian-Ji Zhong, acdChen Yang, Xiao-Yong Chang, Chao Zou,
Chi-Ming Che*
Wei Lu
and
Received 17th May 2017,
Accepted 19th June 2017
DOI: 10.1039/c7cc03823b
rsc.li/chemcomm
The platinum(II) photo-catalyzed difluoroalkylation of cinnamic acids for both outer sphere and inner sphere interactions with substrates.
and alkynes for selective construction of E-,Z-difluoroalkyl alkenes However, few studies of photo-induced organic transformation
9
and difluoroalkyl alkenyl iodides, respectively, were achieved under reactions by Pt(II) complexes have been reported. Recently, Liu
1
0
mild conditions. The high efficiency, good substrate scope and high and co-workers reported a strategy for difluoroalkylation of
selectivity altogether highlight the prospect of Pt(II) photocatalysts in cinnamic acids by harnessing the photo-redox properties of a
visible-light-driven organic transformation reactions.
Ru(II) complex and the reductive capability of a Cu(I) catalyst.
Herein we report the high photocatalytic reactivity of Pt(II) complexes
The incorporation of a difluoromethyl (CF
molecules to improve their physicochemical properties is combines photo-redox and substrate binding capabilities. Further-
particularly intriguing. Recently, visible light photo-catalysis has more, we have extended the substrate scope of photocatalytic
emerged as a powerful tool for difluoromethylation reactions owing difluoroalkylation reactions from cinnamic acids to ethyl difluoro-
2
) group into organic for the difluoroalkylation reactions. The present Pt(II) photo-catalysis
1
2
3
to the inherently green and mild reaction conditions. In this regard, bromoacetate and alkynes. In addition, the selectivity of E-,Z-
photocatalysts play a critical role in activating substrates to generate difluoroalkyl alkenes and difluoroalkyl alkenyl iodides can be easily
reactive intermediates for desired transformations. Therefore, achieved by simply altering the reaction conditions.
extending the diversity of photocatalysts is of significant interest.
A series of new cyclometalated Pt(II) complexes containing diphos-
4
5
Transition metal complexes, organic dyes and heterogeneous phine (P^P) ligand were synthesized (Scheme 1). Details of
6
semiconductors are commonly used photocatalysts; much attention their synthesis and characterization are given in the ESI†
II
has been focused on transition metal photocatalysts owing to their (Schemes S1–S3). Complex 1 was prepared by reacting Pt [R(C^N^N)]Cl
excellent photophysics and modification flexibility.
Octahedral Ru(II) and Ir(III) chromophores are common photo- binaphthyl (R-BINAP)) in a CH
0 0
(R = 4-MeOC H ) with ((R)-(+)-2,2 -bis(diphenylphosphino)-1,1 -
6 4
3 3
CN/CH OH mixture (Scheme 1).
catalysts for organic transformations primarily via outer sphere Single-crystal X-ray analysis of 1 revealed that the Pt(II) ion is
7
interactions with substrates. Meggers and co-workers reported a coordinated to a bidentate cyclometalating C^N ligand and a P^P
type of Ir(III) complexes containing labile coordinated ligand for
photochemical reactions via inner sphere interactions. Compared to
8
the octahedral Ru(II) and Ir(III) chromophores, Pt(II) complexes with
vacant axial coordination sites could provide greater opportunities
a
Department of Chemistry, South University of Science and Technology of China,
Shenzhen, Guangdong 518055, P. R. China. E-mail: cmche@hku.hk
b
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan,
Hubei 430072, P. R. China
c
State Key Laboratory of Synthetic Chemistry, Department of Chemistry,
The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China
d
HKU Shenzhen Institute of Research and Innovation, Shenzhen,
Guangdong 518057, P. R. China
†
Electronic supplementary information (ESI) available: Experimental procedures,
characterization of products, Tables S1–S3, Schemes S1–S4, and Fig. S1–S5. CCDC
544039. For ESI and crystallographic data in CIF or other electronic format see
1
Scheme 1 Chemical structures of Pt(II) complexes and crystal structure
of 1.
DOI: 10.1039/c7cc03823b
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Fig. 1 (a) Electronic absorption, emission and excitation spectra of 1
Scheme 2 Other efficient Pt(II) photocatalysts for difluoroalkylation reactions.
(
(
concentration ca. 1.0 ꢁ 10ꢀ5 M) in degassed CH
b) Excited state potential of 1.
3
CN at room temperature.
benzyl group or no pending pyridyl motif in the bidentate C^N
ligand scaffold, moderate reactivity was observed (Table 1,
entries 6–8). However, similar good reactivity was observed when
chelate in a distorted square planar geometry (Scheme 1) with a
pending pyridyl motif. In CH CN solution, 1 exhibits intense
3
1
1
0
the diphosphine ligand was changed to 2,2 -bis(diphenylphos-
absorption at l 300–450 nm, attributable to a mixture of metal-
to-ligand and ligand-to-ligand charge transfer transitions (Fig. 1a),
and a broad emission with l 543 nm (lifetime: 93 ns, quantum
yield: 0.2%) at room temperature. Nanosecond time-resolved
emission (ns-TRE) and absorption (ns-TA) spectra of 1 were
recorded (see the ESI,† Fig. S1). The ns-TA spectra are characterized
by a positive signal assigned to an excited state absorption of 1 at
l 350–700 nm. The excited state potentials of 1 (Fig. 1b) can
0
phino)-1,1 -biphenyl (5) or 1,2-bis(diphenylphosphino)benzene (6)
II
(
Scheme 2). The other Pt(II) complex Pt [R(C^N^N)(CCC
6
H
4
-4-Me)]
1
2
(R = 4-MeOC
H
6 4
, 7) was also found to be good photocatalyst for
]PF and Ir(ppy) were
this reaction. Furthermore, Ir[(dtbpy)(ppy)
2
6
3
also observed to exhibit photo-activity for this reaction with
moderate product yields (30%, 45%), while Ru(bpy) Cl2 gave
3
trace amount of c1 (Table 1, entries 9–11). We conceive that the
+
+
excited state reduction potential of Ru(bpy) Cl is not sufficient
3
2
be estimated from the equations: E(1 /1*) = E(1 /1) ꢀ E0–0(1);
ꢀ
ꢀ
+
ꢀ
to reduce b1 to generate reactive intermediate, and inner-sphere
substrate binding may facilitate the Pt(II) photo-catalysis. Notably,
for substrate a1, the reaction proceeded smoothly on a gram scale
with a 72% product yield (Table 2, c1).
E(*1/1 ) = E(1/1 ) + E (1) (E(1 /1) and E(1/1 ) were taken as the
0–0
+/0
respective Epa (0.61 V) and Epc (ꢀ1.69 V vs. Cp Fe ) values from
2
the cyclic voltammogram shown in Fig. S2 (ESI†); E
was
0–0
estimated to be B495 nm (2.51 eV)).
As shown in Table 2, a wide range of cinnamic acids were
readily converted to their corresponding E-difluoroacetyl alkenes in
good to excellent yields. Both electron-withdrawing and -donating
substituents on the aromatic ring of the cinnamic acids were
well tolerated (Table 2, c1–c24). Notably, upon substitution of the
a,b-vinyl carboxylic acids at the b-position, no obvious decrease in
the reaction efficiency was observed (Table 2, c25, c26). However,
when the a-position was occupied by a methyl group (Table 2, c27),
the product yield decreased sharply to 30% attributed to steric
hindrance. Unfortunately, alkyl-substituted a,b-vinyl carboxylic acid
The photocatalytic activity of 1 was examined by using the
coupling of cinnamic acid a1 and ethyl difluoroiodoacetate b1 as a
model reaction. As shown in Table 1, optimization of the reaction
conditions revealed that 0.5 mol% of 1 with excess sodium
bicarbonate under nitrogen atmosphere resulted in highly
chemo- and regio-selective generation of E-difluoroalkyl alkene
in 90% yield. Control experiments revealed that each component
of the reaction conditions was essential to the reaction efficiency.
The effect of coordinated ligands on the photocatalytic activity
was examined. For complexes 2, 3, and 4 having no methoxyl
a
Table 2 Scope of cinnamic acids
a
Table 1 Optimization of reaction conditions
Yield of
c1 (%)
a
b
Entry Conditions
1
2
3
4
5
6
7
8
9
1
1
1% 1, CH
1% 1, 1.1 equiv. NaHCO
0.5% 1, 1.1 equiv. NaHCO
0.5% 1, 1.1 equiv. NaHCO
1.1 equiv. NaHCO
0.5% 2, 1.1 equiv. NaHCO
0.5% 3, 1.1 equiv. NaHCO
0.5% 4, 1.1 equiv. NaHCO
2% Ru(bpy)
2% Ir[(dtbpy)(ppy)
2% Ir(ppy) , 1.1 equiv. NaHCO
3
CN, N
2
—
92
90
—
—
25
65
42
3
, CH
3
CN, N
2
3
, CH
, CH
3
CN, N
2
3
3
CN, air
3
, CH
3
CN, N
2
3
3
3
, CH
, CH
, CH
3
3
3
CN, N
CN, N
CN, N
2
2
2
Cl
3 2
, 1.1 equiv. NaHCO
3
, CH
3
CN, N Trace
3 2
, CH CN, N 30
2
0
1
2
]PF
6
, 1.1 equiv. NaHCO
, CH Cl , N
3
3
3
2
2
2
45
a
0
3
.2 mmol a, 0.22 mmol b, 0.5 mol% 1 and 1.1 equiv. NaHCO were
a
b
0
.2 mmol a1, 0.22 mmol b1, 5 mL solvent, blue LED irradiation. dissolved and degassed for 15 min, blue LED irradiation for 12 h.
Isolated yield.
b
c
Isolated yield. Starting materials recovered.
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a
Table 3 Scope of cinnamic acids in ethyl difluorobromoacetate reaction
a
0
3
.2 mmol a, 0.6 mmol b2, 2 mol% 1 and 1.1 equiv. NaHCO were
dissolved and degassed for 15 min, blue LED irradiation for 12 h.
b
Isolated yield.
(Table 2, c28) was ineffective in this catalytic system. Further
experiments showed that this reaction could be extended to ethyl
difluorobromoacetate with moderate product yields (Table 3).
ꢀ
5
Fig. 2 ns-TA spectra of 1 (5 ꢁ 10 M) in CH
3
CN in the presence of
ꢀ
In subsequent mechanistic investigation, we found that a 20 equiv. of substrate b1 and a1 + b1 (1 mM for each component) after
3
55 nm laser excitation recorded at 0 s.
radical inhibitor (2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO))
completely inhibited the reaction and afforded the TEMPO-
trapped difluoroacetyl product in 85% yield, revealing that a
difluoroacetyl radical was involved in the reaction (Scheme 3).
When 1 was mixed with substrate b1, a species with a molecular
weight of [1 + HI] was detected by high-resolution mass spectro-
metry (HRMS) (Fig. S3, ESI†). This result, along with the emission
quenching of 1 by b1 (Fig. S4, ESI†), suggests that inner sphere
interaction occurred between b1 and 1. Furthermore, the oxidation
(
Fig. S4h, ESI†). This short-lived component is attributed to the
reaction between a1 with R , and the long-lived component is
assigned to a radical species of the product (s-1 in Scheme 4).
Based on these results, a plausible reaction pathway is proposed
Scheme 4). Upon excitation of 1 by visible light, a single electron-
transfer reduction of R I by excited Pt(II) complex *1 generates one-
electron-oxidized species 1 and radical R , and the latter reacts
ꢀ
ꢂ
F
(
F
+
ꢂ
F
+
potential of the excited state of 1 (E(1 /1*)) was estimated to be
ꢀ
with the deprotonated a,b-vinyl carboxylic acids a to generate
radical s-1. Subsequent oxidation of s-1 by 1 generated carboxyl
+
/0
ꢀ
1.90 V vs. Cp Fe . The Epc of substrate b1 was measured to be
+
2
+
/0
ꢀ
1.66 V vs. Cp Fe by cyclic voltammetry, as shown in Fig. S5
2
radical intermediate s-2, which gave the desired E-difluoroacetyl
alkene c through a decarboxylation process. The role of the
carboxylic acid group on the alkenes was revealed using styrene
having no COOH group as the substrate (Scheme S4, ESI†). In
this case, only a 25% product yield was obtained, suggesting that
both the deprotonated carboxylic acid and substrate play a vital
role in the recovery of photocatalyst 1.
As depicted in Scheme 4, the difluoroacetyl radical could be
efficiently generated by the Pt(II) photocatalyst. We speculate
that this radical intermediate may be able to perform more
reactions. Indeed, when terminal aryl alkyne was added to
(
ESI†). Therefore, the free energy change (DG) was estimated to be
ꢀ
0.24 eV using the equation: DG = Eox ꢀ Ered ꢀ E00. Therefore, the
photoinduced electron transfer from 1 to b1 is thermodynamically
feasible.
The ns-TA spectra of 1, recorded immediately after the laser
flash and in the absence of a1, presence of a1 and presence of
ꢀ
deprotonated a1 (noted as a1 ), are similar (Fig. S4a, ESI†),
with a positive absorption band at 350–500 nm region. Remark-
ably, the ns-TA spectrum of 1 in the presence of b1 (Fig. 2)
exhibited a distinctive spectral profile with a negative bleaching
signal at 363 nm and a broad positive band at wavelength
beyond 410 nm. Kinetic analysis of the decay at 363 nm
revealed a species that was stable beyond 300 ms with a decay
CH CN solution containing 0.5 mol% 1 and 1.1 equivalent of b1,
3
the difluoroacetyl alkenyl iodide product was formed in good to
excellent yields with good selectivity irrespective of the substituent(s)
on the aryl group (Table 4). In addition, E-difluoroacetyl alkenyl
iodides were the major products. When the ortho-position of the
terminal aryl alkyne was substituted, the products were formed with
good selectivity (Table 4, c41–c45). A plausible reaction pathway is
time constant of around 130 ms (Fig. S4, ESI†). This long-lived
ꢂ
species, which is assigned to the difluoroacetyl radical ( R ),
F
ꢀ
could be further quenched by a1 , leading to new species with a
different time-resolved absorption spectral profile and a peak
maximum at 400 nm. Kinetic studies of this peak yielded one
short-lived growth component and one long-lived decay com-
ponent with time constants of 4.2 ms and 158 ms, respectively
Scheme 3 The radical inhibitor TEMPO inhibited the reaction.
Scheme 4 Proposed reaction pathway.
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a
Table 4 Alkyne scope in atom transfer radical addition reactions
In summary, the Pt(II) photo-catalyzed controlled and selec-
tive difluoroalkylation reactions of cinnamic acids and alkynes
affording E-,Z-difluoroalkyl alkenes and difluoroalkyl alkenyl
iodides, respectively, have been reported. The high efficiency,
good substrate scope and high selectivity highlight the promise
of Pt(II) photo-catalysis in visible-light-driven organic transfor-
mation reactions.
This work was supported by the National Natural Science
Foundation of China (21272197), National Key Basic Research
Program of China (973 Program 2013CB834802), and Science
and Technology Innovation Commission of Shenzhen Municipality
(JCYJ20160229123546997).
a
0
.2 mmol alkynes, 0.22 mmol b1, 0.5 mol% 1 were dissolved and
b
degassed for 15 min, blue LED irradiation for 6 h. Isolated yield.
Notes and references
a
Table 5 Alkyne scope in Z-difluoroalkyl alkene generation reactions
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Isolated yield.
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5
6
7
Scheme 5 Proposed reaction pathway.
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shown in Scheme S5 (ESI†). Photoreduction of b1 by 1 generated
+
ꢂ
one-electron oxidized species 1 and difluoroacetyl radical ( R
F
). The
ꢂ
R
F
radical reacts with the terminal alkyne to afford difluoroacetyl
alkenyl radical s-3, the latter abstracts an iodine atom from b1 to
generate the final product.
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