Organic Letters
Letter
alkenes (4g−4k). Trimethyl vinyl silane and N,N-dimethyl
acrylamide were well tolerated (4l and 4m). However, styrene
afforded both mono- and bisolefinated products, whereas
diethyl vinylphosphonate and phenylvinylsulfone yielded only
mono-olefinated products under the present reaction con-
ditions.
Scheme 6. Synthetic Utilities
We have investigated the efficiency of the carboxylate
directing group of sterically crowded mono-olefination
products in the sequential bisolefination process (Scheme 4).
The optimal reaction conditions were also studied, and it was
found that using 10 mol % of Pd(OAc)2, 2 equiv of Ag(OAc),
and 1 equiv of Cu(OAc)2·H2O at 80 °C in dioxane for 24 h
Information for details). From mono-olefinated styrene, both
symmetrical and unsymmetrical bisolefinated products were
afforded in good to excellent yields (4n, 5a−5e). Similarly,
with acrylates, desired products were obtained in excellent
yields (5f and 5g).
Mono-olefinated ester was well compatible with styrene
(5g), diethyl vinyl phosphonate (5h), phenyl vinyl sulfone
(5i), N,N-dimethyl acrylamide (5j), acrylonitrile (5k), and
isobutyl acrylate (5l) resulting in excellent yields. Mono-
olefinated silane was also compatible with methyl acrylate and
delivered the product 5m in excellent yield.
Mechanistic studies were performed to gain insights into the
proaromatic C(alkenyl)−H olefination (Scheme 5). The
reversibility experiment was conducted in the presence of
D4-AcOH, and a higher level of deuterium incorporation was
found at both proximal positions (1a-d2), suggesting that the
C(alkenyl)−H activation is a reversible process (Scheme 5a).
Kinetic isotope effect experiments revealed that C(alkenyl)−H
activation of the proaromatic acid is the rate-determining step
(Scheme 5b, c). Moreover, 6 was subjected to standard
conditions; an ester did not confer to carboxylate palladacycle
and failed to deliver the product. This highlights the crucial
involvement of carboxylic acid in the palladacycle for
proaromatic C(alkenyl)−H activation (Scheme 5d). Relative
rate experiments were conducted for carboxylic acids and
alkenes (Scheme 5e). In the reaction event of different steric
hindrance substituents at the 4-position of acids, the β-H
elimination was analogous and the competition of C(alkenyl)−
H bond activation and decarboxylative aromatization was
solely influenced by electronic and steric properties. The
results implied that C(alkenyl)−H activation highly favored
tert-butyl substituents. Similarly, the C(alkenyl)−H bond
activation was identical in several electronically varied styrenes,
but β-H elimination was influenced by electronic properties.
Results demonstrated that electronic bias on the styrene ring
could not influence β-H elimination.
a
b
Scale-up and practical gram-scale. Postsynthetic transformations. [4
c
+ 2] cyclization. Decarboxylative aromatization.
Scheme 7. Proposed Mechanism
The proaromatic C(alkenyl)−H olefination is practically
applicable and amenable to scale up and use for gram-scale
synthesis without any modification of reaction conditions
(Scheme 6a). We also demonstrated the postsynthetic
applications of olefinated cyclic carboxylic acids. Mono-
olefinated acids reacted well with o-silyl aryl triflates through
O-arylation of the acid followed by [4 + 2] cycloaddition,
which directly provides multiple rings of cyclic aryl ester
products 7−11 in good yields. The trimethylsilyl group was
detached, and the product 8 was obtained with a 69% yield.
Moreover, in the presence of 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone, bisolefinated acids underwent decarboxylative
aromatization quantitatively and readily converted into
alkylated divinylbenzene derivatives 12−23, which also
led to good yields (3s and 3t). It is worth mentioning that
halide-containing styrenes such as chloro and bromo also
performed well under the reaction conditions (3u−3w).
C(alkenyl)−H bisolefination was also achieved with slight
modification of optimum reaction conditions (see Table S2 in
omatic acids was investigated with a range of proaromatic acids
and functionalized alkenes (Scheme 3). Different proaromatic
acids with methyl acrylate produced bisolefinated products in
good yields (4a−4c). Again, methylene proaromatic acid was
ineffective (4d).
Isopropyl and tert-butyl acrylates generated products in good
yields (4e and 4f). α-Methyl, α-hexyl, and α-methylene ester-
bearing acids proceeded well with various functionalized
D
Org. Lett. XXXX, XXX, XXX−XXX