Bronsted acid catalyzed PhSe transfer versus radical aryl transfer: Linear codimerization of styrenes and internal olefins

Article abstract of DOI:10.1021/ol503731s

Bronsted acid p-TsOH·H₂O-catalyzed hydrovinylation of styrenes with internal olefins α-oxo ketene dithioacetals was efficiently achieved in the presence of N-phenylselenophthalimide (N-PSP), regioselectively affording Markovnikov phenylselenati

Full text of DOI:10.1021/ol503731s

Letter
pubs.acs.org/OrgLett
Brønsted Acid Catalyzed PhSe Transfer versus Radical Aryl Transfer:
Linear Codimerization of Styrenes and Internal Olefins
Ping Wu,† Liandi Wang,† Kaikai Wu,† and Zhengkun Yu*,†,‡
†Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, P. R. China
S
* Supporting Information
ABSTRACT: Brønsted acid p-TsOH·H2O-catalyzed hydrovinylation of
styrenes with internal olefins α-oxo ketene dithioacetals was efficiently
achieved in the presence of N-phenylselenophthalimide (N-PSP), regio-
selectively affording Markovnikov phenylselenative hydrovinylation
products through PhSe transfer of the phenylseleno ketene dithioacetal
intermediates. Radical reduction of the resultant PhSe-alkyl-substituted ketene dithioacetals with AIBN/n-Bu3SnH gave the
corresponding anti-Markovnikov hydrovinylation products formally from the linear codimerization of styrenes and the internal
olefins.
ighly selective carbon−carbon bond formation has been
anti-Markovnikov-type linear alkylarenes or facilitate dominant
Hone of the most important tasks in organic chemistry. formation of the linear products by means of directing groups or
using specific heteroarene substrates.10 Unfortunately, Brønsted
Metal-catalyzed hydrovinylation, that is, the addition of a vinyl
acids have not yet been reported to catalyze a hydrovinylation
reaction of two olefins to date.
group and a hydrogen (donor) across an olefin (acceptor), has
been paid considerable attention for C−C bond construc-
tion since its first report in 1965.1 Transition-metal-catalyzed
hydrovinylation,2,3 in particular, codimerization of styrene and
other vinylarenes with ethylene gas, has been extensively
investigated because the resultant 3-aryl-1-butenes are important
intermediates for the synthesis of 2-arylpropionic acids that are
widely used as anti-inflammatory drugs.4 However, side reactions
are always encountered in transition-metal-catalyzed hydro-
vinylation, including dimerization of either styrene5 or ethylene,6
isomerization of the 3-aryl-1-butene to the more stable 3-aryl-2-
butenes, and olefin oligomerization.2 Lewis acids were seldom
reported as the sole catalysts for hydrovinylation of vinylarenes.7
Although hydrovinylation has been known for about half a
century and shown promising potential in organic synthesis, it is
still an underused reaction due to the above-mentioned side
reactions occurring in the overall catalytic cycle. In order to
overcome the reaction limitations, continuous efforts have been
directed toward tuning the transition-metal catalyst systems
to reach good selectivity for the target products. In general,
transition-metal or Lewis acid catalyzed hydrovinylation
reactions usually afford branched alkyl-substituted olefin
products from the head-to-tail (Markovnikov type) codimeriza-
tion of two olefins, while head-to-head (anti-Markovnikov type)
linear codimerization between olefins has only been rarely
reported.8 Both Markovnikov and anti-Markovnikov functional-
izations of olefins are of extraordinary importance for the
selective synthesis of many organic compounds.9 Brønsted and
Lewis acids have been well-known to promote hydro(hetero)-
arylation of olefins to furnish Markovnikov-type branched
alkylarenes, and transition-metal catalysts may alter the
regioselectivity of a hydro(hetero)arylation process to form
Internal olefin α-oxo ketene dithioacetals are versatile building
blocks in organic synthesis,11 and we recently found that they
could be used as alkenylating reagents under Brønsted acid or
transition-metal catalysis.12 Thus, we reasonably envisioned
Brønsted acid catalyzed hydrovinylation of styrene and
α-oxo ketene dithioacetals. However, tentative treatment of
styrene with an α-oxo ketene dithioacetal in the presence of
p-TsOH·H2O (p-toluenesulfonic acid monohydrate) at ambient
temperature did not result in any detectable product. To our
delight, N-phenylselenophthalimide (N-PSP) was found to
facilitate such a reaction as we previously reported.13 Herein,
we report p-TsOH·H2O-catalyzed phenylselenative hydro-
vinylation between styrene and other vinylarenes with α-oxo
ketene dithioacetals as well as the radical reductive aryl transfer of
the resultant Markovnikov-type codimerization products (Scheme 1).
Initially, the reaction of α-oxo ketene dithioacetal 1a, N-PSP
(2), and styrene (3a) in a 1:1.1:3 molar ratio was conducted in
the presence of 5 mol % of p-TsOH·H2O in 1,2-dichloroethane
(DCE) at ambient temperature (eq 1). Over a period of
5 h, most of the starting 1a was consumed to form a mixture
of phenylseleno-substituted olefin 4a and the branched
Received: December 26, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/ol503731s
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Letter
Scheme 1. PhSe-Assisted Hydroheteroarylation and
Hydrovinylation
Scheme 2. Brønsted Acid-Catalyzed Codimerization of α-Oxo
Ketene Dithioacetals (1) with Styrene (3a)
a,b
phenylselenative hydrovinylation product 5a, from which 4a and
5a were difficult to separate by silica gel column chromatography.
As the reaction proceeded, 4a was gradually converted to 5a, and
at the end of 17 h 4a disappeared to form 5a as the only product
in 79% isolated yield. It is noteworthy that 1a did not react with
styrene (3a) in the absence of N-PSP, and 4a could be prepared
in 96% yield from the reaction of 1a with 2 (see the Supporting
Information). N-PSP played a key role in initating and directing
such a Markovnikov-type hydrovinylation reaction.13 In order to
ease separation of the target product 5a, a one-pot, two-step
procedure was developed under the following conditions: (1)
The first step, phenylselenation of 1a with 2 (1:1.1 molar ratio),
was conducted with 10 mol % of p-TsOH·H2O as the catalyst
in DCE at ambient temperature for 5 h, completely converting
1a to intermediate species 4a. (2) At the end of the first step,
3 equiv of styrene was added and the reaction was continued for
2 h until 4a was completely consumed by TLC monitoring.
Under the optimal conditions, 5a was obtained in 88% isolated
yield. Lewis acid TiCl4-mediated or radical-driven PhSe trans-
fer has been reported to functionalize organic compounds,14
but our case unambiguously featured a Brønsted acid catalysis
pathway.
a
Conditions: 1 (0.5 mmol), 2 (0.55 mmol), 3a (1.5 mmol), p-TsOH·
b
H2O (10 mg, 0.05 mmol), DCE (5 mL), 25 °C. Isolated yields based
on 1. Using 20 mol % p-TsOH·H2O.
c
The substrate scope was then extended to other vinylarenes by
using the same one-pot, two-step procedure as shown in Scheme 2
(Scheme 3). The reactions of internal olefins 1 with 2, followed
Next, the protocol generality was explored under the
optimized conditions by varying the second-step reaction time
(Scheme 2). A variety of α-oxo ketene dithioacetals (1) were
treated with N-PSP (2) to form phenylselenation compounds 4
in situ, which were directly used to react with styrene (3a) for the
phenylselenative codimerization of the two olefins via Brønsted
acid catalyzed PhSe transfer. α-Acetyl-, aroyl-, and cinnamoyl-
functionalized ketene dithioacetals reacted to give the target
products 5 in 44−96% yields. The substituted aroyl-function-
alized substrates usually exhibited a reactivity higher than their
unsubstituted analogue 1b, and the 2-substituents in 1c, 1f, and
1i showed an obvious steric effect on the yields of 5c, 5f, and 5i
(44−61%). In the cases of using para-substituted substrates such
as 1e, 1h, and 1k, the corresponding products 5e (86%), 5h
(95%), and 5k (96%) were efficiently produced. Methyl, chloro,
bromo, fluoro, trifluoromethyl, and methoxy were tolerated in
substrates 1. 2-Furoyl- and thienoylketene dithioacetals under-
went the reactions efficiently to give 5m (95%) and 5n (96%),
respectively. Although α-cinnamoyl ketene dithioacetals have
two reactive C−H sites α-adjacent to the carbonyl moiety, the
first step, phenylselenation, regioselectively occurred at the C−H
site of the dithioketene moiety, which is attributed to the push−
pull effect of the two thioalkyls and the α-oxo moiety on the
internal C−H bond activation.11b The dithioethyl substrates
1v−x also efficiently underwent the reactions to afford 5v−x
(88−89%), while cyclic substrate 1y exhibited a rather low
reactivity to form 5y (69%).
Scheme 3. Brønsted Acid Catalyzed Codimerization of 1 with
Vinylarenes (3)
a,b
a
Conditions: 1 (0.5 mmol), 2 (0.55 mmol), 3 (1.5 mmol), p-TsOH·
b
H2O (10 mg, 0.05 mmol), DCE (5 mL), 25 °C. Isolated yields based
on 1.
B
DOI: 10.1021/ol503731s
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Letter
by treating with terminal vinylarenes 3, proceeded smoothly
to afford the target products 6 in 70−95% yields. Substituents
such as methyl, fluoro, chloro, bromo, phenyl, and tert-butyl
were tolerated on the aryl moieties of the vinylarene substrates.
2-Vinylnaphthalene also reacted to form 6r (83%) and 6s (85%),
respectively. It is noted that vinylarenes bearing a strong
electron-withdrawing group (EWG = NO2, AcO, or CN) on
the aryl moiety could not undergo the second-step reactions in
the overall one-pot, two-step reaction sequence. Internal olefins
trans-β-methylstyrene and cyclohexene, terminal olefins α-
methylstyrene, phenyl vinyl sulfone, and allylbenzene did not
participate in the second-step reactions either. 2-Vinylpyridine
did not react due to its easy protonation by the acid catalyst.
Compounds 5 and 6 are the Markovnikov-type phenylselen-
ative hydrovinylation products of styrene and other vinylarenes 3
with internal olefins 1 under Brønsted acid catalysis. Incorpo-
ration of a phenylseleno functionality into the products led to
absolute control of the regioselectivity for the Markovnikov
hydrovinylation of the two olefins, which is differentiated from
those transition metal catalyzed-hydrovinylation reactions
accompanied by the above-mentioned side reactions. The
formation pathway of 5 and 6 is depicted in Scheme 4. The
Scheme 5. Radical Dephenylselenative Aryl Transfer of 5 and
6 To Form Linear Hydrovinylation Products 8
a,b
a
Conditions: 5 or 6 (0.3 mmol), 7 (1.8 mmol, added in three
portions), AIBN (6 mol %), toluene/dioxane (3 mL, v/v = 1:1), argon,
100 °C for 8a−k, 110 °C for 8l−x, 45 min. Isolated yields.
Scheme 4. Proposed Mechanism for Brønsted Acid Catalyzed
Branched Phenylselenative Hydrovinylation
b
Scheme 6. Radical Reductive Aryl Transfer of 5 and 6
such as chloro and fluoro on the aryl moiety of the starting
vinylarenes lessened the product yields to some extent. In the
cases of using the substrates bearing a bulkyl aryl group such
as 4-PhC6H4 or 2-naphthyl, i.e., 6h and 6r, the reactions
produced the target products 8j (55%) and 8k (58%) as well as
monodesulfurative products 9a (34%) and 9b (24%) (eq 2),
Brønsted acid initiates the in situ generation of cation PhSe+ (A)
from N-PSP (2), which attacks the electron-rich vinylic carbon of
α-oxo ketene dithioacetal 1, forming episelenonium ion B.13,15
Proton release from species B affords the phenylselenative
intermediate 4 (path a). Upon addition of styrene or a vinylarene
3 to the reaction system at the end of step one reaction, the
equilibrated species B interacts with 3 to generate cation C via
regioselective insertion of the vinylic CC bond of 3 into the
C−Se bond of B. Regeneration of the catalyst gives the target
product 5 or 6 (path b).
In order to obtain the dephenylselenative products, radical
reduction was tentatively applied to compound 5a by means of
AIBN (2,2′-azobis(isobutyronitrile))/n-Bu3SnH. Surprisingly,
the desired Markovnikov-type dephenylselenative product of
type 8′ was not obtained, whereas the linear alkylated olefin 8a,
formally formed from the anti-Markovnikov linear codimeriza-
tion of styrene and α-oxo ketene dithioacetal 1a was un-
ambiguously formed (Scheme 5). The AIBN/n-Bu3SnH system
has been known to promote radical aryl migration from silicon to
carbon.16 In our case, unusual radical aryl transfer from carbon to
carbon was thus achieved, demonstrating a rare example of
regioselectivity inconversion in carbon−carbon bond formation
(Scheme 6). Under heating 5 and 6 underwent the radical
reductive dephenylselenation/aryl transfer to form the anti-
Markovnikov-type linear alkylated olefin products 8a−i in 65−
92% yields (Scheme 5). The electron-withdrawing substituents
respectively. Treatment of α-aroyl-bearing substrates 5 and 6
under the same conditions also gave linear alkylated olefins, that
is, 8l−x, in good to excellent yields (69−90%), and the chloro
and fluoro substituents exhibited a negative impact on the prod-
uct yields (Scheme 5). However, with bromoaroyl-functionalized
substrates 5i−k double reduction (reductive dephenylselena-
tion−aryl transfer/hydrodebromination) occurred to form linear
α-benzoyl-α-(2-phenylethyl) ketene dithioacetal 8l as the prod-
uct (31−87%), and the 2-Br substituent exhibited an obvious
steric effect (eq 3). Double reduction also happened to cinnamoyl-
bearing compounds 5p−t and 6v (eq 4). It is interesting that the
fully functionalized CC bond of the dithioketene moiety
C
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Letter
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withstood the reaction conditions, while the less substituted
CC bond of the cinnamoyl was reduced to an alkyl. Com-
pounds 10a−f were thus obtained in 60−68% isolated yields. It
should be noted that in all the reduction reactions the
tributyltin moiety was transformed to n-Bu3SnSePh,17 and
the molecular structures of 5k and 8u were structurally
confirmed by X-ray crystallographic determinations (see the
Supporting Information).
In conclusion, PhSe-assisted, Brønsted acid p-TsOH·H2O-
catalyzed hydrovinylation of styrene and vinylarenes with α-oxo
ketene dithioacetals efficiently afforded the branched phenyl-
selenative codimerization products. Radical reductive aryl
transfer occurred to transform the resultant Markovnikov-type
olefins to the corresponding linear codimerization prod-
ucts formally from the anti-Markovnikov hydrovinylation of
the two olefins. The present protocol provides a novel route to
regioselectivity-tunable hydrovinylation of olefins.
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ASSOCIATED CONTENT
* Supporting Information
Complete experimental procedures and characterization data for
the prepared compounds, X-ray crystallographic data for 5k and
8u. This material is available free of charge via the Internet at
http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: zkyu@dicp.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Basic Research
Program of China (2015CB856600) and the National Natural
Science Foundation of China (21472185).
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