Ni-catalyzed cross-electrophile coupling of α-hydroxy carbonyl compound-derived oxalates with vinyl triflates

Article abstract of DOI:10.1016/j.tetlet.2021.153129

A nickel-catalyzed reductive vinylation of α-hydroxy carbonyl compound-derived C–O electrophiles to access β,γ-unsaturated carbonyl compounds is reported here. By this method, a library of vinyl triflates can serve as vinylating reagents, while various alkyl oxalates undergo C–O bond fragmentation to provide α-carbonyl radicals. This work expands the scope of cross-electrophile coupling reactions that employ two low toxic C–O electrophiles as coupling partners.

Full text of DOI:10.1016/j.tetlet.2021.153129

Tetrahedron Letters xxx (xxxx) xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ni-catalyzed cross-electrophile coupling of
a-hydroxy carbonyl
compound-derived oxalates with vinyl triflates
⇑
⇑
Xianghua Tao, Ken Yao , Weichao Xue
School of Materials Science and Engineering, Center for Supramolecular Chemistry and Catalysis, Department of Chemistry, Shanghai University, Shanghai 200444, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A nickel-catalyzed reductive vinylation of
a-hydroxy carbonyl compound-derived C–O electrophiles to
Received 10 March 2021
Revised 5 April 2021
Accepted 22 April 2021
Available online xxxx
access b,
can serve as vinylating reagents, while various alkyl oxalates undergo C–O bond fragmentation to provide
-carbonyl radicals. This work expands the scope of cross-electrophile coupling reactions that employ
two low toxic C–O electrophiles as coupling partners.
c-unsaturated carbonyl compounds is reported here. By this method, a library of vinyl triflates
a
Ó 2021 Elsevier Ltd. All rights reserved.
Keywords:
Nickel catalysis
Cross-electrophile coupling
Alkyl oxalate
Vinyl triflate
Radical
Introduction
the research group of Gong showcased that oxalates derived from
tertiary alcohols and hydroxy esters engaged in the nickel-cat-
a
The b,c-unsaturated carbonyl compounds containing two proxi-
alyzed reductive coupling reactions with aryl electrophilies
mal chromophores are often-used reagents and continue to be used
in synthetic chemistry [1]. Accordingly, their preparation has been
intensively explored, and remarkable progress has been attained
over the past few decades. The methods include the direct nucle-
ophilic substitution of acyl electrophiles using allylic organometallic
[11,12]. Inspired by these, we thus set out to explore the formation
of appealing b,
two easily accessible C–O electrophiles. Herein, we report a mild
nickel-catalyzed cross-electrophile coupling of -hydroxy ester
c-unsaturated carbonyl compounds, starting from
a
and ketone-derived oxalates with vinyl triflates via C–O/C–O bond
cleavage (Scheme 1c). This protocol features good coupling effi-
ciency and broad substrate scope, and is therefore a useful comple-
mentary to the existing methods to afford b,c-unsaturated
carbonyl compounds.
reagents [2], and the
vinyl nucleophiles by organocatalysis [3,4]. Alternatively, transition
metal-catalyzed -vinylation of enolates with vinyl electrophiles
has also emerged as an important strategy (Scheme 1a) [5,6]. More-
over, metal-catalyzed cross-coupling of -halocarbonyl elec-
trophiles with vinyl nucleophiles or halides provides another
effective approach to access b, -unsaturated carbonyl compounds
a-vinylation of nascent enolates employing
a
a
Result and discussion
c
(Scheme 1b) [7]. In this regard, nickel has displayed a unique ability
to promote such coupling reactions through radical pathways, in
particular for the enantioconvergent transformations [8].
On the other hand, the utilization of C–O electrophiles instead
of C–X (X = halide) electrophiles within the cross-coupling arena
has recently attached considerable attention [9]. This is largely
due to the hypotoxicity, ready accessibility and low cost of hydro-
xyl-containing compounds. For instance, Shu and co-workers
reported that primary benzyl oxalates were able to couple with
alkyl bromides under reductive conditions [10]. Independently,
We began by investigating the cross-coupling of
ester-derived oxalate 1a with cyclic vinyl triflate 2a to access b,
-unsaturated ester 3aa (Table 1). After substantial optimization,
a hydroxy
c
high yield was obtained by using NiCl2(dppe) as catalyst, dtbpy
as ligand and Zn as reductant in the presence of MgCl2 and tetra-
butylammonium iodide (TBAI) in dimethylformamide (DMF) (en-
try 1). Control experiments disclosed that nickel salt, ligand,
reductant and MgCl2 are necessary and TBAI as additive is crucial
to secure the high yield (entries 2–5) [13]. Changing different
nickel catalysts did not give better results (entries 6–9). It was
also found that other bidentate ligands L2–L4 resulted in lower
coupling efficiency (entries 10–12), and tridentate ligand L5 led
to the formation of coupled product in trace amount (entry 13).
⇑
Corresponding authors.
E-mail addresses: yao850618jp@yahoo.co.jp (K. Yao), wx244@cam.ac.uk
(W. Xue).
https://doi.org/10.1016/j.tetlet.2021.153129
0040-4039/Ó 2021 Elsevier Ltd. All rights reserved.
Please cite this article as: X. Tao, K. Yao and W. Xue, Ni-catalyzed cross-electrophile coupling of
triflates, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2021.153129
a-hydroxy carbonyl compound-derived oxalates with vinyl

X. Tao, K. Yao and W. Xue
Tetrahedron Letters xxx (xxxx) xxx
Scheme 1. Metal-catalyzed formation of b,c-unsaturated carbonyl compounds.
TM = transition metal. Tf = trifluoromethanesulfonate.
Of note, the practicality of this method was demonstrated in a
large scale reaction, wherein the desired product 3aa was formed
in 72% yield (entry 14).
Scheme 2. Scope of vinyl triflates for the coupling with 1a and 1b. aDetermined by
1H NMR analysis using 2,5-dimethylfuran as internal standard. 2-Nap = 2-naphthyl
group.
With the optimized conditions in hand, we then evaluated the
scope of vinyl triflates, which can be readily prepared from ubiqui-
tous ketone precursors (Scheme 2).[14,15] In addition to the model
substrate 2a, both nonsubstituted cyclic and heterocyclic vinyl tri-
flates were capable of coupling with 1a, providing corresponding
products 3ab–3af in moderate to good yields. Cyclohexenyl tri-
flates decorated with a variety of substituents were also effective
vinylation reagents, as exemplified by the formation of 3ag–3ai
and 3ak–3am in high yields. In contrast, phthalimide substituted
vinyl triflate converted into 3aj in rather moderate yield, and the
deoxygenative reduction of both electrophiles was observed as
side reactions. Likewise, such side reactions were deleterious to
the formation of esters 3an and 3ao, when conjugated vinyl tri-
flates 2n and 2o were utilized. Acyclic vinyl triflates were also
Table 1
tested to couple with 1b under the standard condition. b,c-Unsat-
Optimization of reaction conditions.
urated ester 3bp was formed in 50% yield, whereas more sterically
hindered 2q was less effective, providing 3bq in 20% yield.
Subsequently, we examined the generality of alkyl oxalates as
coupling partners in this protocol (Scheme 3). Notably, 2-hydrox-
ypropanoic acid-derived oxalates containing a wide range of O-aryl
and alkyl ester moieties, which vary in electronic effect, were all
amenable to the standard setup, thus furnishing 3ba–3ha in moder-
ate to high yields. Alkyl groups such as ethyl, butyl and functional-
ized alkyl chains at the
a-position of ester were investigated as
well. Coupled products 3ia–3la were produced in lower yields, likely
due to the higher steric hindrance compared to that of a methyl
group. Similarly, more hindered tertiary alkyl oxalates only afforded
3na in 10% 1H NMR yield. The method was also applicable to alkyl
oxalates derived from
and 3oh were delivered in moderate yields, respectively.
a hydroxy lactone and ketone, wherein 3ma
Entry
Variation of the standard condition
Yield (%)a,b
1
2
3
4
None
w/o NiCl2(dppe)
w/o Zn
w/o MgCl2
87(82)c
ND
ND
trace
70
Next, we turned to explore the enantioconvergent version of the
model reaction by changing the combination of reaction parame-
ters. It was eventually disclosed that 3aa was isolated in 50% yield
and 15% ee by using Ni(cod)2/L6 in THF at 0 °C (Eq. (1)).
5
w/o TBAI
6
7
8
9
10
11
12
13
14
Ni(cod)2 instead of NiCl2(dppe)
Ni(acac)2 instead of NiCl2(dppe)
NiCl2 instead of NiCl2(dppe)
NiCl2(dppf) instead of NiCl2(dppe)
L2 instead of L1
L3instead of L1
L4 instead of L1
L5 instead of L1
4.0 mmol of 1a
50
46
26
24
72
72
71
trace
72
ND = not detected; cod = 1,5-cyclooctadiene; acac = acetylacetone.
a
The reaction was performed on a 0.15 mmol scale.
b
Determined by 1H NMR analysis using 2,5-dimethylfuran as internal standard.
Isolated yield after column chromatography.
ð1Þ
c
2

X. Tao, K. Yao and W. Xue
Tetrahedron Letters xxx (xxxx) xxx
excess; hence, further studies will focus on improving the
enantiocontrol.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgment
This research was supported by National Natural Science Foun-
dation of China (No. 21871173 to Professor Hegui Gong).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2021.153129.
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3