Copper-Catalyzed Imidovinylation of Alkynes via 1,3-Vinyl Migration

Article abstract of DOI:10.1021/acs.orglett.7b01599

The first copper-catalyzed imidovinylation of alkynes has been developed, which grants facile access to various (E)-2-imido-2,4-dienals with high stereoselectivity under mild conditions. This transformation also represents the first 1,3-carbon migration o

Full text of DOI:10.1021/acs.orglett.7b01599

Letter
pubs.acs.org/OrgLett
Copper-Catalyzed Imidovinylation of Alkynes via 1,3-Vinyl Migration
†
Jiaqiong Sun, Guangfan Zheng, Qiao Zhang, Yimin Wang, Shengbiao Yang, Qian Zhang, Yan Li,*
,†
and Qian Zhang*
Key Laboratory of Functional Organic Molecule Design & Synthesis of Jilin Province, Department of Chemistry, Northeast Normal
University, Changchun 130024, China
*
S Supporting Information
ABSTRACT: The first copper-catalyzed imidovinylation of alkynes has been developed, which grants facile access to various
E)-2-imido-2,4-dienals with high stereoselectivity under mild conditions. This transformation also represents the first 1,3-carbon
migration of propargylic alcohols and their derivatives.
(
1
ransition-metal-catalyzed functionalization of alkynes has
become an important strategy for the synthesis of
substituted alkenes, a versatile structural motifs prevalent in
Scheme 1. Copper-Catalyzed Imidovinylation of Alkynes
T
2
a−c
2b,d
pharmacologically active compounds,
natural products,
2e
and functional materials. Among the numerous alkynes
functionalization strategies, vinylation processes enable a
straightforward and powerful approach to functionalized
conjugated dienes. Accordingly, various vinylative bisfunction-
Initially, 1-(4-ethylphenyl)-5-methylhex-4-en-1-yn-3-ol (1a)
was chosen as the model substrate. Propargylic alcohols and
their derivatives are among the most useful synthetic building
3a−c
3d−f
alization, such as boravinylation,
aminovinylation,
and
3
g
arylovinylation of alkynes with vinyl boranes, vinyl
zirconiums, vinyl halides, vinyl triflates, and activated alkenes,
have been achieved. However, direct alkynes vinylation with
simple olefins still remains unexplored.
12
blocks due to their ready availability. When 1a and N-
fluorobenzenesulfonimide (NFSI, 2a, 1.2 equiv) were treated
with CuCl (10 mol %) and 1.5 equiv of pyridine in CHCl at 40
3
Recently, we described alkynes functionalization reactions
°
C under nitrogen atmosphere for 16 h, the desired
imidovinylation product (E)-2-imido-2,4-dienal 3a was ob-
involving addition of nitrogen radical, during which 1,4-aryl
4
migration occurred. Inspired by these observation, we set out
tained in 51% yield (Scheme 2). Use of methanol, toluene,
to explore vinylative functionalization of alkynes via more
5
challenging 1,3-vinyl migration from vinyl alkynol derivatives.
Scheme 2. Copper-Catalyzed Aminovinylation of 1a and 2a
6
In contrast to the facile phenyl migration, the vinyl migration
7
−11
has been shown to be more difficult to achieve.
Most of the
existing vinyl migrations are 1,2-migration that proceed through
cationic intermediate (pinaco rearrangement, Wagner-Meer-
7
wein rearrangement), anionic intermediate (witting rearrange-
8
9
ment), radical intermediate, or carbene intermediate (free
10
carbene or metal carbene). To date, the 1,3-vinyl migration
remains rare. The only report involves a 1,3-vinyl migration of
acetonitrile, or tetrahydrofuran as solvents resulted in no 3a
formation. Among various copper catalysts, such as CuCl2,
1
,1,4-triphenyl-1,4-pentadiene under photolytic conditions
(
irradiated by 450-W Hanovia medium-pressure mercury
CuOAc, CuCN, CuBr, CuCl, CuTc, and Cu(OTf) , CuCl gave
2
1
1
lamp). To realize efficient 1,3-vinyl migration, the chemo-
selectivity issue arising from selective functinalizetion of CC
or CC bonds needs to be addressed. Herein, we report a
novel Cu-catalyzed imidovinylation of proparylic alcohols via
alkynes imidation/1,3-vinyl migration sequence, which allows
for facile, high stereoselective synthesis of (E)-2-imido-2,4-
dienals (Scheme 1).
the best result. Elevation of the temperature to 50 °C led to an
improved yield of 67%, but an even higher temperature could
not further improve the yield. The yield of 3a dramatically
decreased to 26% when the amount of pyridine was decreased
Received: May 30, 2017
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01599
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Letter
to 10 mol %. Other additives such as 3-bromoprydine, 4-
cyanoprydine, 4-methylprydine, and triethylamine were not
efficient. Upon increasing the amount of 2a to 2.0 equiv, the
yield of 3a decreased to 45%. When 0.2 g of 4 Å molecular
sieves was added to the reaction, 3a was obtained in 75% yield
-withdrawing groups, such as alkyl, alkoxyl, halide, carbonyl,
nitro, cynao, and trifluoromethyl, were tolerant, which led to
desired (E)-2-imido-2,4-dienals 3a−3w in moderate to high
yields. It is worthy to note that the halide (3i−3k, 3t, 3v−3w),
carbonyl group (3l, 3m, and 3p), nitro group (3n), and cyano
group (3o) are very valuable handles for further manipulation.
Furthermore, substrates with naphthyl and thienyl rings are
viable with the corresponding 3x and 3y being retrieved in 62%
and 62% yields, respectively. Notably, these imidovinylation
reactions showed an interesting stereoselectivity, and no
formation of any other stereoisomers was detected. (E)-2,2-
Dimethyldec-6-en-3-yn-5-ol (1z) was also tested. Unfortu-
nately, the alkyl substituted alkyne was oxidized to ketone
without the formation of the desired imidovinylation product.
Next, we explored the scope of the vinyl moieties (Scheme
(
for details of the reaction optimization, see Table S1 of the
Supporting Information). It should be noted that although
13
14
transition-metal catalyzed 1,2-/1,3-oxygen or 1,2-carbon
migration of propargylic alcohol and their derivatives have been
fully developed, the related 1,3-carbon migration has never
been reported. The formation of 3a from 1a represents the first
1,3-carbon migration reaction of propargylic alcohol and their
derivatives.
With the optimized conditions in hand, we began to
investigate the scope and the limitation of this imidovinylation
reaction. First, variation of alkynyl substitutions in propargylic
alcohol 1 was performed, with the data being summarized in
Scheme 3. Substituted aryls bearing both electron-donating and
4
). The (E)-monosubstituted propargylic alcohols with alkyl
a
Scheme 4. Scope of Vinyl Moieties
a
Scheme 3. Varieties of Different Alkynyl Groups
a
Reaction conditions: 4 (0.2 mmol), 2a (1.2 equiv), CuCl (10 mol %),
pyridine (1.5 equiv), 0.2 g of 4 Å molecular sieves, CHCl (2 mL), 50
3
°
C, N , 16 h. The yield was determined after isolation of products by
column chromatography.
2
(
4a−4e) or aryl groups (4f and 4g) were suitable for the
imidovinylation reaction and provided (E)-2-imido-2,4-dienals
a−5g in moderate to good yields. Interestingly, (Z)-
5
propargylic alcohol 4b′ afforded a product identical to that
from 4b. Ketal moiety (4h) was also nicely tolerated in this
transformation to produce the desired product 5h in 43% yield,
which showcased the mild nature of the conditions. The gem-
diphenyl substituted propargylic alcohol 4i also worked well
and afforded the corresponding (E)-2-imido-2,4-dienals 5i in an
accepted yield. Remarkably, substrates (4f, 4g, and 4i) with a
styrene unit underwent the imidovinylation reaction exclusively,
15
a
and no aminative functionalization of styrene was observed.
Reaction conditions: 1 (0.2 mmol), 2a (1.2 equiv), CuCl (10 mol %),
Product 5j−5l bearing alkylidenecyclobuane, alkylidenecyclo-
pentane, and alkylidenecycloheptane were also furnished in
good yields. Moreover, a bulky adamantan-2-ylidene sub-
pyridine (1.5 equiv), 0.2 g of 4 Å molecular sieves, CHCl (2 mL), 50
3
°C, N , 16 h. The yield was determined after isolation of products by
2
column chromatography.
B
DOI: 10.1021/acs.orglett.7b01599
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Organic Letters
Letter
stituted propargylic alcohol 4m worked efficiently, producing
deliver alkyl radical D with a cyclobutenyl motif. Scission of
intermediate D resulted in a 1,3-vinyl migration to generate
(2Z, 4E)-radical E, which further transformed into a more
stable (2E, 4E)-radical G through resonance structure F.
Finally, homolysis of Cu−O bond of radical G afforded 3b with
concomitant regeneration of the Cu(I) species was regenerated
for the next catalytic cycle.
5m in 77% yield. Nevertheless, the propargylic alcohol 4n with
a terminal alkene motif did not work. Additionally, the
configurations of (E)-2-imido-2,4-dienals 5a and 5m were
16
further confirmed by X-ray analysis. Finally, some NFSI
derivatives were tested (Scheme 5). Symmetric N−F reagents 2
Scheme 5. Reaction of NFSI Derivatives
To conclude, the first imidovinylation of alkynes has been
developed with copper as catalyst to access to various (E)-2-
imido-2,4-dienals. This reaction also presents the first 1,3-
carbon migration of propargylic alcohols and their derivatives
via novel vinyl migration. These transformations proceed under
mild conditions and show good functional group compatibility.
The strategy for alkynes imidovinylation via 1,3-vinyl migration
might provide an new way toward vinylative functionalization
of unsaturated system. Further studies on the vinyl migration
strategy are under way in our laboratory.
bearing either electron-withdrawing group (F) or electron-
donating groups (Me, t-Bu) on benzene rings furnished
corresponding (E)-2-imido-2,4-dienals 6a−6c in 41−76%
yields under this mild conditions. The unsymmetrical ones
with different groups on the two benzene rings also worked
well and delivered desired products 6d−6f in good to excellent
yields.
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.7b01599.
To clarify the reaction mechanism, a radical inhibition
experiment was performed. Adding 1.5 equiv of 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO) to the reaction of 1c
and NFSI (2a) under the standard reaction conditions
completely suppressed the expected imidovinylation reaction,
and only an oxidized product alkynyl alkenyl ketone was
formed (for details, see the Supporting Information). This
result suggested that the transformation might involve radical
intermediates. On the basis of the experimental results and our
Experimental procedures, spectral data for new com-
pounds (PDF)
Crystallographic data for 5a (CIF)
Crystallographic data for 5m (CIF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: liy078@nenu.edu.cn.
*E-mail: zhangq651@nenu.edu.cn.
4
,15,17
previous works,
we proposed a plausible mechanism for
this novel reaction (Scheme 6). Initially, nitrogen-centered
ORCID
Yan Li: 0000-0003-2083-6991
Author Contributions
Scheme 6. Plausible Mechanism
†These authors are different persons.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge the financial support for this work from the
National NSF of China (21372041), Changbai Mountain
Scholarship Program, and the Fundamental Research Funds for
the Central Universities (2412016KJ006).
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DOI: 10.1021/acs.orglett.7b01599
Org. Lett. XXXX, XXX, XXX−XXX