Regioselective Ni-Catalyzed Carboxylation of Allylic and Propargylic Alcohols with Carbon Dioxide

Article abstract of DOI:10.1021/acs.orglett.7b01208

An efficient Ni-catalyzed reductive carboxylation of allylic alcohols with CO₂ has been successfully developed, providing linear β,γ-unsaturated carboxylic acids as the sole regioisomer with generally high E/Z stereoselectivity. In addition, the carboxylic acids can be generated from propargylic alcohols via hydrogenation to give allylic alcohol intermediates, followed by carboxylation. A preliminary mechanistic investigation suggests that the hydrogenation step is made possible by a Ni hydride intermediate produced by a hydrogen atom transfer from water.

Full text of DOI:10.1021/acs.orglett.7b01208

Letter
pubs.acs.org/OrgLett
Regioselective Ni-Catalyzed Carboxylation of Allylic and Propargylic
Alcohols with Carbon Dioxide
Yue-Gang Chen,†,‡ Bin Shuai,†,‡ Cong Ma,† Xiu-Jie Zhang,† Ping Fang,†
and Tian-Sheng Mei*,†,‡
†State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Road, Shanghai 200032, P. R. China
‡University of Chinese Academy of Sciences, Beijing 100049, P. R. China
S
* Supporting Information
ABSTRACT: An efficient Ni-catalyzed reductive carboxylation of
allylic alcohols with CO2 has been successfully developed, providing
linear β,γ-unsaturated carboxylic acids as the sole regioisomer with
generally high E/Z stereoselectivity. In addition, the carboxylic acids
can be generated from propargylic alcohols via hydrogenation to give
allylic alcohol intermediates, followed by carboxylation. A preliminary
mechanistic investigation suggests that the hydrogenation step is
made possible by a Ni hydride intermediate produced by a hydrogen
atom transfer from water.
Scheme 1. Strategies for the Carboxylation of Allylic and
Propargylic Alcohols
wing to its abundance, nontoxicity, and low cost, carbon
dioxide (CO2) is an ideal, renewable C1 building block
O
for organic synthesis.1 Thus, the conversion of carbon dioxide
into carboxylic acids, one of the most ubiquitous motifs in a
myriad of organic compounds, via C−C bond-forming
reactions, has received considerable attention in synthetic
organic chemistry.2 In particular, transition-metal-catalyzed
carboxylation of allyl electrophiles has emerged as a promising
tool to construct β,γ-unsaturated carboxylic acids.3−5 For
example, Martin and co-workers elegantly developed Ni-
catalyzed, reductive carboxylation of allyl esters with CO2.6
However, carboxylation with allylic alcohols without preactiva-
tion is highly desirable and remains a significant challenge due
to the poor leaving ability of the hydroxy group.7,8
Very recently, Sato and co-workers demonstrated the Pd-
catalyzed carboxylation of allylic alcohols via formal activation
of C−OH bonds using ZnEt2 to give α-branched carboxylic
acids (Scheme 1a).9 The utility of this method is limited by the
use of pyrophoric ZnEt2 as the reducing reagent.10 We
therefore became interested in developing carboxylations of
allylic alcohols using a less precious catalyst and a cheaper
nonpyrophoric reducing agent. Herein, we report Ni-catalyzed
carboxylations of allylic alcohols with CO2 using easy-to-handle
Mn powder as a reducing agent,11 delivering linear β,γ-
unsaturated carboxylic acids as sole regioisomer with generally
high E/Z stereoselectivity (Scheme 1b). Mechanistically, we
hypothesized that, following the oxidative addition of Ni(0) to
the allylic alcohol A to give B,8e−g ligand exchange of hydroxide
with acetate gives Ni(II) complex C. Then, reduction by the
manganese results in Ni(I) intermediate D, which after
carboxylation with CO2 delivers the product (Scheme 1c).
Alternatively, it is also possible that allylic alcohols could react
with CO2 to form carbonic acids, which take place oxidative
addition into Ni(0) complex.12 Preliminary mechanistic
evidence suggests that, in the case of propargylic alcohols A′,
reduction to the allylic alcohol A by a Ni hydride intermediate
produced by a hydrogen atom transfer from water, occurs first.
Carboxylation of model substrate 5-phenylpent-1-en-3-ol
(1a) was carried out in the presence of [Ni(acac)2],
neocuproine (L1), Mn powder, and n-Bu4NOAc in DMF at
room temperature under 1 atm of CO2 (Table 1). Under these
conditions, (E)-6-phenylhex-3-enoic acid (2a) was obtained as
the sole regioisomer in 86% isolated yield with excellent
Received: April 21, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01208
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a,b
Table 1. Reaction Optimization
Scheme 2. Substrate Scope of Allylic Alcohols
a
Reaction conditions: 1a (0.25 mmol), Ni(acac)2 (10 mol %),
neocuproine (20 mol %), Mn (0.5 mmol), n-Bu4NOAc (0.75 mmol),
b
CO2 (1 atm) in DMF (2 mL) at rt for 15 h. Yields determined by 1H
NMR using 1,4-dimethoxybenzene as internal standard. Yield of
c
isolated product.
a
Reaction conditions: 1 (0.5 mmol), Ni(acac)2 (10 mol %),
neocuproine (20 mol %), Mn (1 mmol), n-Bu4NOAc (1.5 mmol),
stereoselectivity (E/Z > 20:1) (entry 1). Other nickel catalysts
such as NiCl2, NiBr2, or Ni(cod)2 also provided 2a in high
yields (entries 2−4). When L2 and L6 were used in lieu of
neocuproine, however, no conversion of 1a was observed
(entries 5 and 9). Interestingly, subtle changes in the electronic
or steric environment of the 1,10-phenanthroline backbone
resulted in lower product yields (entries 6 and 7). Using
bipyridine (bpy) as a ligand provided 2a in a low yield (entry
8). The use of the structurally related solvent dimethylaceta-
mide (DMA) resulted in a lower yield (entry 10). Inferior
results were found using other reducing agents such as Zn
powder (entry 11). Other additives such as LiOAc and KOAc
gave a moderate yield, which revealed that acetate ion was
crucial (entries 12 and 13). The acetate anion could activate an
allylic alcohol and generate a highly reactive π-allyl acetate
nickel intermediate through an exchange of hydroxide with the
acetate ligand (Scheme 1c). A control experiment revealed that
nickel catalyst, ligand, n-Bu4NOAc, and Mn reducing agent are
all crucial to the reaction (entries 14 and 15).
With optimal conditions in hand, we next examined the
scope of the Ni-catalyzed carboxylation by evaluating a series of
allylic alcohol substrates (Scheme 2). As shown, allylic alcohols
(1b−q) were carboxylated to give linear regioisomers
exclusively. Yields and E-stereoselectivity were generally high.
A variety of functional groups, including hydroxyl (1c),
benzyloxy (1d), silyl ether (1e), arene and heteroarene (1f−
m), cyano (1n), and acetoxy (1o), were well tolerated in the
reaction system. It is worth emphasizing that an aryl sulfide
(1m) did not arrest catalysis. The gram-scale synthesis of E-
carboxylic acid from readily available allylic alcohol 1k
demonstrates the efficiency of this protocol. In addition, both
cis-allylic and trans-allylic alcohols predominantly provided E-
configured carboxylic acids (1p and 1q), which suggests that
b
CO2 (1 atm) in DMF (4 mL) at rt for 15 h. E/Z ratio shown in
c
d
parentheses. 1.30 g, 8 mmol, 80% yield. 1:1 E/Z.
the reaction occurred via π-allylnickel intermediates (Scheme
1c).5 To our satisfaction, the mixture of 1p and 1q provides
(E)-hept-3-enoic acid in 91% yield, with great stereoselectivity
(E/Z = 14:1; 1r). Lastly, allylic alcohols wherein the alkene is
conjugated with an arene (1s, 1t) or is trisubstituted (1u)
afforded low yield, suggesting that steric hindrance has a
negative influence on the reaction.
Recently, the cobalt-catalyzed carboxylation of propargylic
acetates was elegantly developed by Tsuji and co-workers.13
However, to the best of our knowledge, the direct carboxylation
of propargylic alcohols has not yet been described in the
literature.14 Surprisingly, carboxylation of propargylic alcohols
occurs smoothly under similar conditions via sequential
hydrogenation and carboxylation (Scheme 3). Linear and
branched propargylic alcohols were both carboxylated to afford
linear carboxylic acids as the major regioisomer with good E/Z
stereoselectivity (3a−c). Substrates bearing hydroxyl (3d),
acetoxyl (3e), silyl ether (3f), trifluoromethyl (3g), furyl (3h),
and ester (3i) groups also afforded the corresponding products
in moderate-to-good yields.
We selected 3a as a model substrate for probing the
mechanism of this reaction. Without CO2, cis-allylic alcohol (5)
was obtained in 86% yield. This indicates that allylic alcohol is
likely the intermediate for the carboxylation of propargyl
alcohols (Scheme 4a). To identify the source of H atoms,15 we
studied the D atom incorporation by adding D2O to the
reaction and using homemade ammonium salt (7) instead of n-
Bu4NOAc. Subjection of 6 to our optimized conditions with 2
B
DOI: 10.1021/acs.orglett.7b01208
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 3. Substrate Scope of Propargylic Alcohols
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.7b01208.
Detailed experimental procedures, compound character-
ization data, and NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: mei7900@sioc.ac.cn.
ORCID
Yue-Gang Chen: 0000-0001-6012-1849
Bin Shuai: 0000-0002-2323-5158
Cong Ma: 0000-0001-7568-1347
Xiu-Jie Zhang: 0000-0003-1600-595X
Ping Fang: 0000-0002-3421-2613
Tian-Sheng Mei: 0000-0002-4985-1071
Notes
a
Reaction conditions: 3 (0.5 mmol), Ni(acac)2 (10 mol %),
neocuproine (20 mol %), Mn (2 mmol), n-Bu4NOAc (2.5 mmol),
CO2 (1 atm) in DMF (4 mL) at rt for 15 h.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the Strategic Priority
Research Program of the Chinese Academy of Sciences (Grant
No. XDB20000000), “1000-Youth Talents Plan”, NSF of China
(Grant Nos. 21421091 and 21572245), and S&TCSM of
Shanghai (Grant No. 15PJ1410200).
Scheme 4. Mechanistic Experiments
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