Transition-Metal-Free Reductive Deoxygenative Olefination with CO2

Article abstract of DOI:10.1021/acs.orglett.8b01155

A new transition-metal-free reductive deoxygenative olefination of phosphorus ylides with CO₂, an abundant and sustainable C1 chemical feedstock, is described. This catalytic CO₂ fixation afforded β-unsubstituted acrylates and vinyl ketones in good yields with broad scope and good functional group tolerance under mild reaction conditions. Cost-effective and easily handled polymethylhydrosiloxane was used as a reductant. Bis(silyl)acetal was proved to be the key intermediate in this reductive functionalization of CO₂.

Full text of DOI:10.1021/acs.orglett.8b01155

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Transition-Metal-Free Reductive Deoxygenative Olefination with CO2
Dao-Yong Zhu, Wen-Duo Li, Ce Yang, Jie Chen, and Ji-Bao Xia*
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical
Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: A new transition-metal-free reductive deoxygenative
olefination of phosphorus ylides with CO2, an abundant and
sustainable C1 chemical feedstock, is described. This catalytic CO2
fixation afforded β-unsubstituted acrylates and vinyl ketones in good
yields with broad scope and good functional group tolerance under
mild reaction conditions. Cost-effective and easily handled
polymethylhydrosiloxane was used as a reductant. Bis(silyl)acetal was proved to be the key intermediate in this reductive
functionalization of CO2.
he development of new carbon−carbon (C−C) bond-
formylation,3 and hydroxymethylation4 reactions with CO2
affording the corresponding carboxylic acids (derivatives),
aldehydes, and alcohols. However, the high cost of transition
metals and the risk of heavy metal residues may hamper the
application of these methods in pharmaceutical industry.
Accordingly, transition-metal-free carboxylations with CO2
have been developed via photocatalysis5 or under basic
conditions.6 Alternatively, deoxygenative C−C bond-forming
reactions are less studied. It was not until recently that
transition-metal-catalyzed deoxygenative methylation of arenes
was achieved with high pressures of CO2 (20 atm) and H2 (40
atm) at high temperatures.7
T
forming reactions based on sustainable chemical feedstock
constitutes a fundamental task in synthetic organic chemistry.
As an abundant, nontoxic, cost-effective, and renewable one-
carbon source, carbon dioxide (CO2) has been widely utilized
as a C1-synthon in both academic and industrial laboratories.1
In this respect, transformations of CO2 into valuable C2 and
high chemicals have gained considerable attention in recent
years. These transformations can be possibly divided into two
types of reactions, oxygen-retaining C−C bond-forming
reactions and deoxygenative C−C bond-forming reactions
(Scheme 1a). In the first case, the past decade has witnessed a
great advance in transition-metal-catalyzed carboxylation,2
Alkenes are one of the fundamental chemicals and reaction
intermediates in synthetic chemistry and chemical industry. In
this regard, development of new synthetic routes toward
alkenes is highly desirable. Among the numerous reported
methods, the Wittig reaction of phosphorus ylides and carbonyl
compounds is the most well-known due to its easy operation,
good functional group tolerance, and ready availability of the
starting materials.8 In 1966, Matthews et al. first reported that
nucleophilic addition of phosphorus ylides to CO2 afforded
phosphonium−CO2 inner salts easily (Scheme 1b).9 This kind
of salt could be transformed into other products, such as
ketene, carboxylic acids, etc.10 Notably, Zhou, Lu, and co-
workers recently used it as a stable catalyst for efficient CO2
transformation.11 In 1996, Gong and co-workers disclosed a
Wittig-type reaction of strongly nucleophilic phosphorus ylide
Me3PCH2 to Aresta’s Ni−CO2 complex (PCy3)2Ni(CO2),12
producing a nickel ketene complex (Scheme 1c).13 Recently,
we reported a reductive tandem C−C and C−N bond-forming
reaction with CO2, in which CO2 was reduced as a bridging
methylene group.14 A bis(silyl)acetal from CO2 was proposed
as the intermediate, which has reactivity similar to that of
formaldehyde. Continuing our interest in the development of
new C−C bond-forming reactions with CO2, we hypothesized
Scheme 1. C−C Bond-Forming Reactions with CO2
Received: April 12, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01155
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
that alkenes could be generated by reaction of phosphorus
ylides and CO2 under suitable reductive conditions with
bis(silyl)acetal as the intermediate. Herein, we reported a
transition-metal-free reductive deoxygenative olefination with
CO2 using cost-effective and easily handled polymethylhy-
drosiloxane (PMHS) as a reductant (Scheme 1d).
We started our research by choosing commercially available
phosphorus ylide 1 as a model substrate to test our hypothesis.
We were glad to find that the desired alkene product 2 was
obtained in 65% yield using TBD as a catalyst and phenylsilane
(PhSiH3) as a reductant in CH3CN with CO2 (1 atm) for the
first attempt (Table 1, entry 1). Further investigation of the
Considering that inorganic bases can be disolved slightly in
highly polar DMF, a variety of inorganic bases were tested in
DMF with PMHS (Table S4). Most inorganic bases afforded 2
in good yields, such as Cs2CO3, Na2CO3, and KOEt (entries
11−13). The best result was obtained when NaOtBu, a strong
base in DMF, was used (entry 14). Lower yield was observed
when the temperature was reduced from 100 to 80 °C (entry
15). No reaction occurred at room temperature (entry 16). An
83% isolated yield was obtained when the reaction was
conducted with 0.5 mmol of 1 (entry 17). Surprisingly, the
reaction still occurred in DMF without catalyst, albeit in low
yield (entry 18). This result may be attributed to the weak
basicity of DMF because no reaction occurred in CH3CN
without catalyst (entry 19). No reaction occurred without CO2,
indicating that the carbon source is not from DMF (entry 20).
With the optimized reaction conditions in hand, we began to
examine the scope of the reductive deoxygenative olefination
reaction. As illustrated in Table 2, the α carbonyl phosphorus
ylide 5 was synthesized in situ from commercially available acyl
chloride 3 and alkyl phosphonium bromide salt 4 under simple
conditions and used directly in the reductive deoxygenative
olefination without further purification. A series of terminal
alkenes 6 were obtained in good to excellent yields. Simple
ethyltriphenylphosphonium bromide 4a was first selected as a
model substrate for the investigation of various acyl chlorides. A
good yield of 6a was obtained with benzyl carbonochloridate 3a
(entry 1). Benzoyl chloride (3b) was then tested and afforded
6b in good yield (entry 2). The electron-donating group (Me,
MeO, CF3O) and electron-withdrawing group (CF3) on the
para-position of benzoyl chlorides were all well tolerated and
produced the corresponding alkenes 6 in good yields (entries
3−6). Meanwhile, benzoyl chlorides bearing halogen sub-
stituents (F, Cl, Br, I) reacted smoothly, affording vinyl ketones
6 in good yields (entries 7−10). The moderate yield of 6l
obtained with 2,4,6-trimethylbenzoyl chloride may be attrib-
uted to the steric hindrance of the o-dimethyl group (entry 12).
In addition, reactions using 2-naphthoyl chloride (3m) and
heteroaryl acyl chloride (3n and 3o) as starting materials
provided 6 in good yield (entries 13−15). Next, long-chain
alkyl triphenylphosphonium bromides were tested, and the
corresponding 6p, 6q, and 6r were obtained in good yields
(entries 16−18). When (cyclopropylmethyl)triphenylphos-
phonium bromide was used in this reaction, a low yield of 6s
was obtained, but no ring-opening product was detected,
indicating that no α carbonyl radical was formed in the reaction
(entry 19). At last, isophthaloyl dichloride was employed as
substrate, and the corresponding 6t was obtained in good yield
(entry 20). Unfortunately, no reaction occurred when simple
alkyl triphenylphosphorus ylide without an α carbonyl group
was used, maybe because of its lower stability in our reaction
system.
Table 1. Development of the Reductive Deoxygenative
Olefination with CO2
a
entry
catalyst
reductant (x equiv)
solvent
yield (%)
1
TBD
PhSiH3 (2)
PhSiH3 (2)
PhSiH3 (2)
PhSiH3 (2)
PhSiH3 (2)
PhSiH3 (2)
Ph2SiH2 (3)
Ph3SiH (6)
(EtO)3SiH (6)
PMHS (6)
PMHS (6)
PMHS (6)
PMHS (6)
PMHS (6)
PMHS (6)
PMHS (6)
PMHS (6)
PMHS (6)
PhSiH3 (2)
PMHS (6)
CH3CN
CH3CN
CH3CN
CH3CN
DMF
65
44
43
68
70
18
77
0
2
DBU
3
DABCO
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
Cs2CO3
Na2CO3
NaOEt
NaOtBu
NaOtBu
NaOtBu
NaOtBu
4
5
6
THF
7
DMF
8
DMF
9
DMF
8
10
11
12
13
14
DMF
59
73
51
43
89
43
0
DMF
DMF
DMF
DMF
b
15
DMF
c
16
DMF
d
17
DMF
90 (83)
42
0
e
18
DMF
e
19
CH3CN
DMF
f
20
NaOtBu
0
a
All of the reactions were carried out on a 0.2 mmol scale in 2 mL of
solvent at 100 °C in a sealed 25 mL screw Schlenk tube; the yield was
b
determined by GC with n-dodecane as internal standard. At 80 °C.
c
d
e
At 25 °C. With 0.5 mmol of 1; isolated yield in parentheses. No
f
catalyst. Without CO2.
catalysts showed that DMAP, a common and inexpensive
organic base, gave a slightly higher yield (entry 4 and Table S1).
Switching the solvent from CH3CN to DMF afforded 2 with a
slightly higher yield (entry 5). However, other common
solvents, such as THF, dioxane, DCM, and toluene, produced
2 in low yields (entry 6 and Table S2). Then a series of
reductants were tested. Diphenylsilane (Ph2SiH2) gave a better
result (entry 7). Other reductants gave no reaction or afforded
2 in very low yields, such as triphenylsilane and triethoxysilane
(entries 8 and 9). To our delight, a promising yield was also
obtained when polymethylhydrosiloxane (PMHS),15 an abun-
dant chemical waste with nontoxicity, low cost, and high
moisture stability from silicone chemistry, was used (entry 10).
To test the scalability of the present reaction, a gram-scale
reaction was carried out with 5 mmol of benzoyl chloride 3b as
substrate, and the desired product 6b was obtained in 90%
isolated yield (Scheme 2).
To gain some preliminary insight into the reaction
mechanism, we carried out some experiments as shown in
Scheme 3. Bis(triethylsilyl)acetal 7 was synthesized according
the reported procedure.16 The reaction of phosphorus ylide 1
with 7 afforded 2 in 88% yield under the standard conditions
without silane and CO2 (eq 1). As expected, olefin 2 was also
obtained in 86% yield under the standard conditions with
triethylsilane as reductant (eq 2). This indicates that bis(silyl)-
B
DOI: 10.1021/acs.orglett.8b01155
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Organic Letters
Letter
a
Table 2. Scope of the Transition-Metal-Free Reductive Deoxygenative Olefination with CO2
a
b
The reaction was conducted on 0.5 mmol scale of 3; isolated yields are provided. With 0.25 mmol of 3t and 1.05 mmol of 4a.
Scheme 2. Gram-Scale Reaction
Scheme 4. Plausible Reaction Pathway for the Reductive
Deoxygenative Olefination
Scheme 3. Mechanistic Experiments
two-step reduction has also been suggested by Wang and
Zhang in the reduction of CO2 with hydrosilane.17 Then
nucleophilic addition of phosphorus ylide to bis(silyl)acetal I
affords phosphonium intermediate II. Subsequent elimination
produces alkene product and generates triphenylphosphine
oxide18 and silyl ether.
In summary, we have developed the first transition-metal-free
reductive deoxygenative olefination reaction for the synthesis of
terminal alkenes with CO2. A series of β-unsubstituted acrylates
acetal may be the intermediate in the reductive deoxygenative
olefination reaction with CO2.
On the basis of our experiments, a plausible reaction pathway
is proposed in Scheme 4. First, reduction of CO2 with silane
produces bis(silyl)acetal I efficiently through a formoxysilane
intermediate in the presence of catalytic amount of base. This
C
DOI: 10.1021/acs.orglett.8b01155
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b01155.
Experimental procedures and characterization data
(PDF)
AUTHOR INFORMATION
with CO2, see: (b) Frogneux, X.; Blondiaux, E.; Thuer
ACS Catal. 2015, 5, 3983.
́
y, P.; Cantat, T.
■
Corresponding Author
*E-mail: jibaoxia@licp.cas.cn.
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Ji-Bao Xia: 0000-0002-2262-5488
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We acknowledge financial support from the NNSFC
(21772208, 21602230, 21702212, 21633013), the NSFC of
Jiangsu Province (BK20161260, BK20170404), and the
Hundred-Talented Program of the Chinese Academy of
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DOI: 10.1021/acs.orglett.8b01155
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