Organic Letters
Letter
phenyl ring on the α-position 1n also showed good reactivity,
delivering the vinylated product 3n in 85% yield. Furthermore,
the allyl substituted acrylamide 1o also efficiently participated
in the reaction, giving the desired vinylated product 3o in 44%
yield without affecting the allyl moiety. Notably, the β-
substituted acrylamide 1p also efficiently reacted with 2a under
the optimized reaction conditions, providing the vinylated
product 3p in 42% yield.
Interestingly, switching the reaction condition to [RuCl2(p-
cymene)]2 (5 mol %), AgSbF6 (20 mol %), and DCE, an
alternative C−H olefination product 4a was observed in 76%
yield (Scheme 6). Encouraged by this result, a systematic
acrylamides bearing isobutyl 2b, butyl 2c, and ethyl 2d reacted
well with 2 and furnished corresponding alkenylated products
4b, 4c, and 4d in 74%, 79%, and 64% yields, respectively. The
reaction of synthetically valuable morpholinyl-derived acryl-
amide 1i with 2 afforded the butadiene product 4i in 62%
yield. The olefination reaction was also examined with
differently α-substituted acrylamides. The N-benzyl-2-benzyl
acrylamide 1k exhibited good reactivity toward vinyl acetate
(2), affording the alkenylated product 4k in 87% yield. The α-
alkyl such as ethyl and n-propylacrylamides 1l and 1m also
reacted with 2 giving the corresponding alkenylated products
4l and 4m in 73% and 71% yields, respectively. However, in
the case of α-substituted acrylamides such as 1k, 1l, and 1m, a
minor amount of the 2−3% vinylated product was also
observed. It is noteworthy that the homocoupling of
acrylamides was not observed under the present catalytic
reaction.9b,c
a b
,
Scheme 6. Ru(II)-Catalyzed Vinylation of 1 with 2
When N-benzylmethacrylamide (1a) was treated with
CD3OD in the presence of a ruthenium catalyst, a significant
amount of deuterium incorporation (28%) was observed on
the vinylic carbon of the acrylamide d-1a isolated in 78% yield,
exhibiting a possible reversible C−H activation step (Scheme
7). However, in the reaction of N-benzylmethacrylamide (1a)
Scheme 7. Deuterium-Labeling Studies
with CD3OD in the presence of a cobalt catalyst, no deuterium
incorporation was observed. It is may be due to the rapid
deuterium exchange with the alcoholic solvent TFE.
a
All reactions were carried out under the following reaction
conditions: 1a−m (50 mg), 2a (3.0 equiv), [Ru(p-cymene)Cl2]2 (5
mol %), AgSbF6 (20 mol %), and Cu(OAc)2·H2O (1.0 equiv) in DCE
Based on the previous reports, we propose a plausible
catalytic cycle for these transformations which was illustrated
in Scheme 8.6,8 Initially, the reaction proceeds with the
abstraction of halide from the metal complex A in the presence
of AgSbF6 and Cu(OAc)2·H2O and leads to the formation of
the catalytically active metal complex B. The coordination of
acrylamide 1 with the metal complex A and the catalytically
active metal complex B provides a metallacycle C via an
acetate-assisted concerted metalation-deprotonation mecha-
nism. Then, the coordination of vinyl acetate (2) with metal
complex C and subsequent regioselective migratory insertion
into the metal−carbon bond generate the intermediate D. It
may undergo β-hydride elimination generating a cobalt-
hydride intermediate E. Reinsertion of the Co−H bond in
intermediate E produces another intermediate F. The
metallacycle F further undergoes β-acetate elimination
affording the vinylated product 3. The olefinated product 4
could be generated through β-hydride elimination followed by
reductive elimination of intermediate D. The resulting metal
intermediate G was oxidized in the presence of copper(II)
acetate to regenerate the catalytically active metal complex B
for the next catalytic cycle. Based on the observed selectivity,
we believe that in the case of ruthenium, the β-hydride
b
c
(3 mL) at 120 °C for 24 h under air. Isolated yields. One mmol
scale.
optimization of oxidants, solvents, additives, and temperature
was performed (for detailed optimization studies, see the SI).
After screening a range of experimental parameters, we were
pleased to identify the optimized reaction conditions for the
C−H olefination reaction. The reaction of 1a with 2 in the
presence of [RuCl2(p-cymene)]2 (5 mol %), AgSbF6 (20 mol
%), and Cu(OAc)2·H2O (1.0 equiv) in DCE at 120 °C for 24
h under air led to the formation of the olefinated product 4a in
81% yield with excellent stereoselectivity (Z/E > 99:1). The
reaction of N-benzylmethacrylamide (1a) with vinyl acetate
(2) was also examined on a 1 mmol scale, and the product 4a
was isolated in 78% yield.
Next, we turned to examine the substrate scope of the
ruthenium-catalyzed C−H alkenylation reaction of substituted
acrylamides 1 with vinyl acetate (2) (Scheme 6). Similar to
that of the C−H vinylation reaction, in this case too, the scope
of olefination reaction extends to secondary to tertiary amides
as well as differently substituted acrylamides. Secondary
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Org. Lett. 2021, 23, 5679−5683