Dehydrative Allylation of Alkenyl sp2C-H Bonds

Article abstract of DOI:10.1021/acs.orglett.1c01309

We designed a cooperative catalytic system by combining commercially available Ca(NTf2)PF6 and Pd(PPh3)4 to address the dehydrative allylation of alkenyl sp2 C-H bonds in an environmentally benign manner. A novel C-OH bond cleavage method was found to be crucial for this practical protocol. A variety of alkenes and allylic alcohols equipped with wide-spectrum functional groups can be successfully incorporated into the desired cross-coupling, affording 1,4-dienes with moderate to excellent yields and high stereo- and regioselectivity.

Full text of DOI:10.1021/acs.orglett.1c01309

pubs.acs.org/OrgLett
Letter
Dehydrative Allylation of Alkenyl sp2 C−H Bonds
Xinying Cai, Huicong Xing, Ju Qiu, Bowen Li, and Peizhong Xie*
Cite This: Org. Lett. 2021, 23, 4368−4373
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: We designed a cooperative catalytic system by
combining commercially available Ca(NTf2)PF6 and Pd(PPh3)4 to
address the dehydrative allylation of alkenyl sp2 C−H bonds in an
environmentally benign manner. A novel C−OH bond cleavage
method was found to be crucial for this practical protocol. A variety
of alkenes and allylic alcohols equipped with wide-spectrum
functional groups can be successfully incorporated into the desired cross-coupling, affording 1,4-dienes with moderate to excellent
yields and high stereo- and regioselectivity.
lkenyl sp2 C−H bond functionalization with concomitant
coupling of allylic alcohols with disubstituted alkenes to afford
1,5-dienes.16 Reek and Bruin realized pioneering allylstyrene
Acarbon−carbon bond formation is in great demand in the
organic synthesis and pharmaceutical industry.1 Particularly
important achievements are palladium-catalyzed arylation/
alkenylation of alkenes via Heck-reaction2 or sp2 C−H bond
activation,3 which has been extensively applied to synthetic
communities.2,3 In sharp contrast, the allylation of alkenes by
delivering 1,4-dienes lags behind, although this structural motif
has seen amplified interest from medicine as a result of its
prevalence in biologically and pharmaceutically active mole-
cules, such as ripostatin, piericidin, jerangolid, etc.4 The
present complications ascribed to olefins are unreactive
nucleophile equivalents in the presence of allylic palladium
intermediates but facilitate competitive di-/polymerization.5 In
the rarely successful case, alkenes have to be selected as the
solvent.6 Therefore, highly active allylic compounds and
alkenylmetals7 rather than alkenes have been considered the
only suitable precursors for accessing 1,4-dienes. Although few
carefully tailored Rh8/Ni9/Ir10 catalytic systems, with the
assistance of stoichiometric additives,9 have been developed
concerning styrene8,10 or alkylalkenes,9 the incorporation of
functionalized alkenes, such as acrylates, into 1,4-dienes
remains elusive. To circumvent formidable challenges, other
impressive strategies, such as hydroalkenylation of 1,3-dienes11
and hydroallylation of alkynes1c,12 have been documented for
the construction of 1,4-dienes from alkenes or alkynes.
coupling to obtain (1,5-di)aryl-substituted 1,4-dienes17 in
moderate yield and selectivity. These investigations revealed
that C−OH bond activation and selectivity (chemo-/stereo-
selectivity) alternation are significant challenges.15−17 With our
continuing interest in green chemistry,18 we envisioned that
the nature of the cocatalyst used to activate the C−OH bond is
the key factor. The version which enables C−OH bond
cleavage with the generation of allylic metals and hydroxide
ions (rather than water) is crucial (Scheme 1, top, step 1).
Theoretically, the alkene insertion (Scheme 1, top, step 2) and
Scheme 1. 1,4-Diene Skeletons and Dehydrative Allylation
of Alkenyl sp2 C−H Bond Strategy
Taking sustainability and waste minimization into account,
the direct dehydrative cross-coupling13 of generally available
alcohols with olefins is highly sought after and represents a
much greener, atom- and step-economical approach for alkenyl
sp2 C−H bond functionalization. However, it is challenging to
break the inherently strong C−O14 and alkenyl sp2 C−H
bond.3 In 2011, the elegant catalyst [(C6H6)(PCy3)(CO)-
RuH]BF4 was developed by Yi and co-workers for the coupling
of simple alkenes with various alcohols.15 However, 1,4-dienes
are typically inaccessible in this catalytic circumstance. With
the {Ir(cod)Cl}2 catalyst, Carreira realized the impressive
Received: April 16, 2021
Published: May 14, 2021
https://doi.org/10.1021/acs.orglett.1c01309
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4368−4373
4368

Organic Letters
pubs.acs.org/OrgLett
Letter
β-hydride elimination process (Scheme 1, top, step 3) will be
favored by “quenching” the metal hydride with hydroxide ions.
Meanwhile, the transition-metal-migration process (Scheme 1,
top, step 4) can also be suppressed, thus enabling the delivery
of 1,4-dienes as a major product (Scheme 1, top). Herein, we
developed a Ca(NTf2)PF6/Pd(PPh3)4 cooperative catalytic
system to efficiently address the obstacles for dehydrative
allylation of alkenyl sp2 C−H bonds (Scheme 1, bottom).
At the outset of our work, we began by evaluating the
challenging dehydrative allyl−alkene coupling reaction of
allylic alcohol 1a (methyl 2-(hydroxy(phenyl)methyl)acrylate)
with butyl acrylate 2a under a palladium catalytic system.
Notably, acrylates are the largest volume feedstock (over 2
million tons annual production)11b but have scarcely been
incorporated into 1,4-dienes due to their homodimerization
and thermodynamically favored isomerization process from
1,4-dienes to 1,3-dienes.19 The utility of this reaction will be
vastly enhanced if functionalized alkene acrylates can be used
as suitable coupling partners. We have demonstrated that
abundant alkaline-earth metals can affect the activation of C−
OH bond.20 Extensive investigations of reaction parameters
indicated that the nature of alkaline-earth metals and their
combination with palladium was crucial for this protocol
(Supporting Information (SI) Table 1, entries 1−8). In this
respect, the strong oxophilicity and Lewis acidity of Ca(NTf2)-
PF6 were identified as the best partners for palladium (SI Table
1, entries 3, 9−11). In all of the tested cases, Pd(PPh3)4
showed the best performance (SI Table 1, entries 3, 12−16),
while PdII was ineffective for this transformation (SI Table 1,
entries 13−16). For the solvent, DME (1,2-dimethoxyethane)
gave a much more positive result than others, such as THF,
1,4-dioxane, CH3CN, and DMF (SI Table 1, entries 17−23).
Notably, neither palladium nor alkaline-earth metals them-
selves can promote ideal dehydrative cross-coupling (SI Table
1, entries 24−27). By combining Pd(PPh3)4 (3 mol %) with
Ca(NTf2)PF6 (10 mol %) and DME (1,2-dimethoxyethane),
the desired 1,4-diene 3a was isolated in 92% yield (SI Table 1,
entry 3). The reaction was sensitive to the temperature;
decreasing the temperature resulting in a diminished yield (SI
Table 1, entries 28 and 29). Upon decreasing the catalyst
loading to Pd(PPh3)4 (1 mol %)/Ca(NTf2)PF6 (5 mol %), 3a
can also be obtained in 65% yield (SI Table 1, entries 30−32),
which further proves the high efficiency of the catalyst system
for this process.
Subsequently, the general reaction involving a variety of
allylic alcohols was explored under the optimized conditions.
As depicted in Scheme 2, pri-, sec-, and tert-allylic alcohols can
be successfully incorporated into cross-coupling with butyl
acrylate 2a, affording the corresponding 1,4-dienes with linear
selectivity. In the attempt to access multifunctionalized 1,4-
dienes, Morita−Baylis−Hillman (MBH) alcohols were first
selected to investigate the generality of this protocol. As
expected, the electronic properties and position of the
substituents on the phenyl ring have limited effects on the
yield (3a−3h). To some extent, the stereoselectivity was
sensitive to the electronic properties, and a phenyl ring bearing
an electron-withdrawing group resulted in the desired product
with lower E/Z selectivity (3e, 3f). Multisubstituted aromatic
allylic alcohols were also suitable substances for this reaction
(3f, 3h). It should be noted that the functional groups CN (3i)
and CHO (3j) on the phenyl ring were well tolerated, albeit
giving the corresponding 1,4-dienes in a slightly lower yield.
Sterically demanding (3k) and fused aromatic allylic alcohols
Scheme 2. Dehydrative Cross-Coupling between Allylic
Alcohols and Butyl Acrylate
a
a
Reaction conditions: 1 (0.4 mmol), 2 (1.2 mmol), and catalyst
Pd(PPh3)4 (3−5 mol %), Ca(NTf2)2 (10 mol %), KPF6 (10 mol %)
in 4.0 mL of solvent (DME) in argon atmosphere at 100 °C for 12 h.
Isolated total yield. The ratio of (2E,5E)/(2E,5Z) isomer was
determined by crude 1H NMR. For 3a−3q, Pd(PPh3)4 (3 mol %); for
3r−3ac, Pd(PPh3)4 (5 mol %).
(3l) can also be successfully incorporated into this trans-
formation. Ferrocenyl-substituted allylic alcohols were amend-
able to this protocol and afforded the corresponding 3m in
moderate yield. In addition to the MBH alcohols equipped
with ester groups, the CN-substituted version was also
tolerated for this reaction (3n). In addition, alkyl-substituted
MBH alcohols can also serve as powerful substrates for this
reaction (3o). 1-Butyl 6-methyl (E)-5-methylenehex-2-ene-
dioate (3p) was also isolated in moderate yield when the MBH
alcohols generated from ethyl acrylate and formaldehyde were
employed. The double-dehydrative allyl−alkene coupling
reaction was performed well by using ethyl 3-(4-(2-
(ethoxycarbonyl)-1-hydroxyallyl)phenyl)-2-hydroxybut-3-
enoate (3q). Moreover, the configuration of 1,4-diene 3q was
determined by X-ray analysis (for details, see the SI). In
addition to the MBH alcohols, other α-substituted sec- and tert-
4369
https://doi.org/10.1021/acs.orglett.1c01309
Org. Lett. 2021, 23, 4368−4373

Organic Letters
pubs.acs.org/OrgLett
Letter
allylic alcohols were screened (3r−3ac). As expected, a variety
of α-aromatic substituted allylic alcohols were found to be
suitable coupling partners regardless of the electron-with-
drawing or -donating group on the phenyl ring (3s−3w).
Remarkably, either acyclic (3x, 3y) or cyclic (3z) alkyl-
substituted allylic alcohols were well tolerated, affording the
corresponding 1,4-dienes in moderate to high yields. Even the
tert-allylic alcohol 2-phenylbut-3-en-2-ol, which favored the
competitive self-dehydration process with the generation of
conjugated 1,3-dienes, can be successfully incorporated into
the desired cross-coupling with butyl acrylate, efficiently
producing 3aa. With the attempt to access 3-substituted 1,4-
diene skeletons, (E)-4-phenylbut-3-en-2-ol was then selected
as the starting material. To our delight, the corresponding 3ab
was also successfully generated in moderate yield. Remarkably,
the β-blocked allylic alcohol 2-methyl-1-phenylprop-2-en-1-ol
was identified as a powerful precursor, affording 3ac in 67%
yield.
3) when reacted with butyl acrylate. These results reveal that
the same π-allylpalladium intermediates can be generated from
these two kinds of isomeric allylic alcohols (3r−3t). In
addition, sterically demanding cinnamyl alcohol derivatives can
be successfully incorporated into this transformation, albeit
affording 3ad in a slightly lower yield. (E)-Oct-2-en-1-ol was
also proven to be an amenable substrate for this protocol
(3ae). As presented in Scheme 3, a variety of alkenes readily
participate as coupling partners in this reaction with cinnamyl
alcohol. In addition to the standard butyl acrylate 2a, volatile
ethyl acrylate (3af) and multifluoro-substituted butyl acrylate
(3ag) also provided the respective corresponding products
effectively. Even the highly active ketone carbonyl groups
could be introduced into the corresponding 1,4-dienes when
oct-1-en-3-one was selected as the initial substance (3ah). To
our satisfaction, other electron-deficient alkenes, such as
phenyl ethenesulfonate (3ai) and diethyl vinylphosphonate
(3aj), were proven to be viable coupling partners for this
reaction. In addition to terminal olefins, diethyl maleate (3ak)
and (E)-3-(dimethylamino)acrylonitrile (3al) can also react
with cinnamyl alcohol well, affording the corresponding 1,4-
dienes in moderate to high yields. The L-(−)-methenyl group
can be incorporated into multifunctionalized 1,4-dienes (3am).
This newly developed catalytic protocol is not only suitable for
electron-deficient alkenes but is also applicable to styrene
derivatives (3an−3ap), regardless of the electron-withdrawing
or electron-donating groups on the phenyl ring. α-Alkyl- (3aq)
or aryl-substituted (3ar) styrenes smoothly completed the
desired cross-coupling process. Pleasingly, benzofuran (3as)
and 1H-indene (3at) were identified as practical substances
involved in this dehydrative cross-coupling. Unfortunately,
only a trace amount of the desired product was detected when
simple olefins such as dec-1-ene (3au) were used as the
coupling partner. Remarkably, the reaction also can perform
well on gram scale affording 3r in 1.43 g (73% yield), which
has been proven as a powerful synthetic intermediate for
multifunctionalized pyrrolidines.21
pri-Allylic alcohols were then explored under identical
conditions. As shown in Schemes 2 and 3, only the linear
selective products (3r−3t) were obtained with either 1-aryl-2-
en-1-ol (Scheme 2) or cinnamyl alcohol derivatives (Scheme
Scheme 3. Dehydrative Cross-Coupling between Primary
a
Allylic Alcohols and Various Alkenes
Next, we examined the allyl−alkene coupling concerning
several biologically active skeletons. The acrylates, bearing the
motifs of α-D-galactopyranose or cholesterol, can be consumed
smoothly, affording the corresponding 3av and 3aw in high
yields. Even an estraliol moiety with an active hydroxyl group
was also well tolerated (3ax). These results further highlight
the utility of this method in pharmaceutical-related studies.
Recently, 4,4′-((1E,4E)-penta-1,4-diene-1,5-diyl)bis(2-me-
thoxyphenol) (3ay) was recently found to be highly potent
against cancer and human promyelocytic leukemia (HL-60
cells with an IC50 of 65 μM).22 With our developed method,
the desired 3ay can be conveniently obtained in moderate
yield, which is much better than the reported method (less
than 10% yield22).
Having demonstrated the versatility of the resultant
products, we attempted to gain insight into the key step of
C−OH bond activation. We preliminarily studied the binding
of allylic alcohols and Ca(NTf2)PF6 by using the method of
continuous variation (Job’s method), which revealed that a 1/1
stoichiometry for the Ca(NTf2)PF6/C−OH complex was
formed, regardless of cinnamyl alcohol or MBH versions
(Scheme 4a). Moreover, diffusion-ordered spectroscopy
(DOSY) can also account for the formation of the
aforementioned complex (Scheme 4b). For cinnamyl alcohol
(Da = 11.6 * 10−10 m2 s−1), the translational diffusion
coefficient significantly decreased to Da = 8.9 * 10−10 m2 s−1
a
Reaction conditions: 1 (0.4 mmol), 2 (1.2 mmol), and Pd(PPh3)4 (5
mol %), Ca(NTf2)2 (10 mol %), KPF6 (10 mol %) in 4.0 mL of
solvent (DME) in argon atmosphere at 100 °C for 12 h. Isolated total
yield. Only one isomer was detected. Two isomers were detected
b
(5E/5Z = 10/1).
4370
https://doi.org/10.1021/acs.orglett.1c01309
Org. Lett. 2021, 23, 4368−4373

Organic Letters
pubs.acs.org/OrgLett
Letter
Based upon this investigation, a reaction mechanism was
proposed and is shown in Scheme 5. Initially, the interaction
Scheme 4. Investigations Concerning Calcium-Promoted
C−OH Bond Cleavage
Scheme 5. Proposed Allyl−Alkene Coupling Mechanism
between calcium and hydroxyl groups realized C−OH bond
activation (A), which was followed by the oxidative addition of
palladium (A−B−C) to afford intermediate C. In this key step,
the elimination of OH was from the face of palladium (B)
through a neighborhood-participation-like process. This can be
attributed to the coordination effect of electron-rich oxygen
atoms (NTf2) to palladium as well as the interaction between
OH and palladium. The following oxidative addition of
palladium to the C−OH bond was facilitated by Ca(NTf2)PF6
owing to the Ca−OH bond formation. Subsequently, the
combination of intermediate C with alkenes through the
interaction between palladium and double bonds delivered
intermediate D. Then the Heck-like double-bond insertion
process (D−E) and subsequent β-elimination process (E-3)
afforded the desired 1,4-dienes with regeneration of the
palladium catalyst and calcium salt.
In conclusion, we have developed an efficient Ca(NTf2)PF6/
Pd(PPh3)4 catalytic system to address the allylation of alkenyl
sp2 C−H bonds with the largest volume of feedstock allylic
alcohols and alkenes. This investigation revealed that Ca-
(NTf2)PF6 used to activate the C−OH bond is crucial for this
protocol. With all commercially available and economical
catalysts, dehydrative allyl−alkene coupling proceeded
smoothly with water as the only byproduct. This reaction
tolerated a broad range of alkenes and allylic alcohols,
providing a conceptually new and practical protocol to give
1,4-dienes in moderate to excellent yields.
when stoichiometric amounts of Ca(NTf2)PF6 were intro-
duced. Remarkably, Da = 9.4 * 10−10 m2 s−1 was observed
when Ca(NTf2)PF6 was replaced by Ca(NTf2)2. This result, to
some extent, indicated the stronger coordinating effect of C-
OH to Ca(NTf2)PF6 than Ca(NTf2)2, which is in line with the
catalytic activity for C−OH bond activation (Scheme 4c). In
the presence of Ca(NTf2)PF6, a sharper decrease in the
translational diffusion coefficient was detected (from 11.5 ×
10−10 m2 s−1 to 7.9 × 10−10 m2 s−1) for MBH alcohol, probably
because it contains other ester binding sites.
Control experiments were then conducted. No reaction
occurred when Ca(NTf2)PF6 was replaced by traditional
Bronsted acids (HNTf2, TsOH, PhCO2H, CPA), which
further proved that calcium salts with suitable Lewis acidity
are crucial for this transformation (SI, Scheme 1a). Upon
treatment of butyl acrylate 2a with isotopically labeled
experiments, no H/D exchange was detected in the absence
of allylic alcohols. Moreover, an intermolecular KIE for this
allyl−alkene cross coupling was determined to be kH/kD = 0.7,
which indicated that alkenyl sp2 C−H bond cleavage was not
involved in the rate-determining step for this cross-coupling
protocol (SI, Scheme 1b). This result combined with the
results (3an−3au) can be used to safely lead to the conclusion
that this reaction was initiated with the generation of allylic
palladium intermediates followed by Heck-like alkene insertion
and β-hydride elimination processes.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01309.
Experimental procedures, screening reaction conditions,
analytical data for all new compounds (3a−3ay), and
NMR spectra for the products (PDF)
Accession Codes
CCDC 2034599 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
4371
https://doi.org/10.1021/acs.orglett.1c01309
Org. Lett. 2021, 23, 4368−4373

Organic Letters
pubs.acs.org/OrgLett
Letter
(5) DiRenzo, G. M.; White, P. S.; Brookhart, M. Mechanistic Studies
of Catalytic Olefin Dimerization Reactions Using Electrophilic η3-
Allyl-Palladium(II) Complexes. J. Am. Chem. Soc. 1996, 118, 6225−
6234.
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(6) Tsukada, N.; Sato, T.; Inoue, Y. Palladium-Catalyzed Allylic
Alkenylation of Allylic Alcohols with n-Butyl Acrylate. Chem.
Commun. 2003, 2404−2405.
AUTHOR INFORMATION
Corresponding Author
■
(7) For some selected examples, see: (a) Hamilton, J. Y.; Sarlah, D.;
Carreira, E. M. Iridium-Catalyzed Enantioselective Allylic Vinylation.
J. Am. Chem. Soc. 2013, 135, 994−997. (b) Vosburg, D. A.;
Vanderwal, C. D.; Sorenson, E. J. A Synthesis of (+)-FR182877,
Featuring Tandem Transannular Diels-Alder Reactions Inspired by a
Postulated Biogenesis. J. Am. Chem. Soc. 2002, 124, 4552−4553.
(8) Tsukada, N.; Sato, T.; Inoue, Y. Rhodium-Catalyzed Allylation
of Styrenes with Allyl Tosylate. Chem. Commun. 2001, 237−238.
(9) Matsubara, R.; Jamison, T. F. Nickel-Catalyzed Allylic
Substitution of Simple Alkenes. J. Am. Chem. Soc. 2010, 132, 6880−
6881.
Peizhong Xie − School of Chemistry and Molecular
Engineering, Nanjing Tech University, Nanjing 211816, P.R.
China; orcid.org/0000-0002-6777-0443;
Email: peizhongxie@njtech.edu.cn
Authors
Xinying Cai − School of Chemistry and Molecular Engineering,
Nanjing Tech University, Nanjing 211816, P.R. China
Huicong Xing − School of Chemistry and Molecular
Engineering, Nanjing Tech University, Nanjing 211816, P.R.
China
Ju Qiu − School of Chemistry and Molecular Engineering,
Nanjing Tech University, Nanjing 211816, P.R. China
Bowen Li − School of Chemistry and Molecular Engineering,
Nanjing Tech University, Nanjing 211816, P.R. China
(10) Ye, K.-Y.; Liu, W.-B.; Dai, L.-X.; Helmchen, G.; You, S.-L.
Iridium-Catalyzed Allylic Vinylation and Asymmetric Allylic Amina-
tion Reactions with o-Aminostyrenes. J. Am. Chem. Soc. 2011, 133,
19006−19014.
(11) For some selected recent examples, see: (a) Chen, Y.; Dang, L.;
Ho, C.-Y. NHC-Ni Catalyzed Enantioselective Synthesis of 1,4-
Dienes by Cross-Hydroalkenylation of Cyclic 1,3-dienes and
Heterosubstituted Terminal Olefins. Nat. Commun. 2020, 11, 2269.
(b) Jing, S. M.; Balasanthiran, V.; Pagar, V.; Gallucci, J. C.;
RajanBabu, T. V. Catalytic Enantioselective Hetero-dimerization of
Acrylates and 1,3-Dienes. J. Am. Chem. Soc. 2017, 139, 18034−18043.
(12) For some selected examples, see: (a) Troshin, K.; Hartwig, J. F.
Snap Deconvolution: an Informatics Approach to High-Throughput
Discovery of Catalytic Reactions. Science 2017, 357, 175−181. (c) Ji,
D.-W.; Hu, Y.-C.; Zheng, H.; Zhao, C.-Y.; Chen, Q.-A.; Dong, Vy M.
A Regioselectivity Switch in Pd-Catalyzed Hydroallylation of Alkynes.
Chem. Sci. 2019, 10, 6311−6315.
(13) (a) Kumar, R.; Van der Eycken, E. V. Recent Approaches for C-
C Bond Formation via Direct Dehydrative Coupling Strategies. Chem.
Soc. Rev. 2013, 42, 1121−1146. (b) Sundararaju, B.; Achard, M.;
Bruneau, C. Transition Metal Catalyzed Nucleophilic Allylic
Substitution: Activation of Allylic Alcohols via π-Allylic Species.
Chem. Soc. Rev. 2012, 41, 4467−4483. (c) Butt, N. A.; Zhang, W.
Transition Metal-Catalyzed Allylic Substitution Reactions with
Unactivated Allylic Substrates. Chem. Soc. Rev. 2015, 44, 7929−7967.
(14) (a) Mao, J.; Zhang, J.; Jiang, H.; Bellomo, A.; Zhang, M.; Gao,
Z.; Dreher, S. D.; Walsh, P. J. Palladium-Catalyzed Asymmetric Allylic
Alkylations with Toluene Derivatives as Pronucleophiles. Angew.
Chem., Int. Ed. 2016, 55, 2526−2530. (b) Meng, J.; Fan, L.-F.; Han,
Z.-Y.; Gong, L.-Z. α-Quaternary Chiral Aldehydes from Styrenes,
Allylic Alcohols, and Syngas via Multi-catalyst Relay Catalysis. Chem.
2018, 4, 1047−1058.
(15) Lee, D.-H.; Kwon, K.-H.; Yi, C. S. Selective Catalytic C-H
Alkylation of Alkenes with Alcohols. Science 2011, 333, 1613−1616.
(16) Hamilton, J. Y.; Sarlah, D.; Carreira, E. M. Iridium-Catalyzed
Enantioselective Allyl-Alkene Coupling. J. Am. Chem. Soc. 2014, 136,
3006−3009.
(17) Gumrukcu, Y.; de Bruin, B.; Reek, J. N. H. Dehydrative Cross-
Coupling Reactions of Allylic Alcohols with Olefins. Chem. - Eur. J.
2014, 20, 10905−10909.
(18) Xie, P.; Wang, J.; Liu, Y.; Fan, J.; Wo, X.; Fu, W.; Sun, Z.; Loh,
T.-P. Water-Promoted C-S Bond Formation Reactions. Nat. Commun.
2018, 9, 1321.
(19) Mitsudo, T.; Zhang, S.-W.; Kondo, T.; Watanabe, Y.
Ruthenium Complex-Catalyzed Selective Syntheses of 3,5-Dienoic
Acid Derivatives by Coupling of 1,3-Dienes or Allylic Carbonates with
Acrylic Compounds. Tetrahedron Lett. 1992, 33, 341−344.
(20) (a) Xie, P.; Li, S.; Liu, Y.; Cai, X.; Wang, J.; Yang, X.; Loh, T.-P.
Alkaline-Earth Metal Catalyzed Dehydrative Allylic Alkylation. Org.
Lett. 2020, 22, 31−35. (b) Xie, P.; Sun, Z.; Li, S.; Zhang, L.; Cai, X.;
Fu, W.; Yang, X.; Liu, Y.; Wo, X.; Loh, T.-P. Dehydrative Cross-
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01309
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (21702108), the Natural
Science Foundation of Jiangsu Province, China
(BK20160977), and the Six Talent Peaks Project in Jiangsu
Province (YY-033).
REFERENCES
■
(1) (a) Song, F.; Wang, F.; Guo, L.; Feng, X.; Zhang, Y.; Chu, L.
Visible-Light-Enabled Stereodivergent Synthesis of E-and Z-Config-
ured 1,4-Dienes by Photoredox/Nickel Dual Catalysis. Angew. Chem.,
Int. Ed. 2020, 59, 177−181. (b) Zimmerman, J. B.; Anastas, P. T.;
Erythropel, H. C.; Leitner, W. Designing for a Green Chemistry
Future. Science 2020, 367, 397−400. (c) Li, W.; Yu, S.; Li, J.; Zhao, Y.
Nickel-Catalyzed Allylmethylation of Alkynes with Allylic Alcohols
and AlMe3: Facile Access to Skipped Dienes and Trienes. Angew.
Chem., Int. Ed. 2020, 59, 14404−14408.
(2) For some selected reports, see: (a) Gao, S.; Shi, L.; Chang, L.;
Wang, B.; Fu, J. Recent Developments in Heck-Type Reaction of
Unactivated Alkenes and Alkyl Electrophiles. Synthesis 2021, 53, 861.
(b) Oestreich, M., Ed. The Mizoroki−Heck Reaction; John Wiley and
Sons, 2009.
(3) For a selected recent review, see: (a) Maraswami, M.; Loh, T.-P.
Transition-Metal-Catalyzed Alkenyl sp2 C-H Activation: A Short
Account. Synthesis 2019, 51, 1049−1062. For a selected example, see:
(b) Jiang, B.; Zhao, M.; Li, S. S.; Xu, Y. H.; Loh, T.-P. Macrolide
Synthesis through Intramolecular Oxidative Cross-Coupling of
Alkenes. Angew. Chem., Int. Ed. 2018, 57, 555−559.
(4) (a) Tang, W. F.; Liu, S.; Degen, D.; Ebright, R. H.; Prusov, E. V.
Synthesis and Evaluation of Novel Analogues of Ripostatins. Chem. -
Eur. J. 2014, 20, 12310−12319. (b) Trost, B. M.; Gholami, H.
Propene as an Atom-Economical Linchpin for Concise Total
Synthesis of Polyenes: Piericidin A. J. Am. Chem. Soc. 2018, 140,
11623−11626. (c) Hoecker, J.; Gademann, K. Enantioselective Total
Syntheses and Absolute Configuration of JBIR-02 and Mer-A2026B.
Org. Lett. 2013, 15, 670−673. (d) Hanessian, S.; Focken, T.; Oza, R.
Total Synthesis of Jerangolid A. Org. Lett. 2010, 12, 3172−3175.
4372
https://doi.org/10.1021/acs.orglett.1c01309
Org. Lett. 2021, 23, 4368−4373

Organic Letters
pubs.acs.org/OrgLett
Letter
Coupling of Allylic Alcohols with Alkynes. Org. Lett. 2020, 22, 1599−
1604.
(21) Musacchio, A. J.; Nguyen, L. Q.; Beard, G. H.; Knowles, R. R.
Catalytic Olefin Hydroamination with Aminium Radical Cations: A
Photoredox Method for Direct C−N Bond Formation. J. Am. Chem.
Soc. 2014, 136, 12217−12220.
(22) Matuskawa, T.; Kishi, A.; Doi, S.; Nojima, M.; Matsui, T.;
Yamada, Y.; Yamada, I. Preparation of Coniferyl Alcohol Polymer-
ization Product or Its Pharmaceutically Acceptable Salts, and Their
Use For Anticancer Agents, Foods or Pharmaceuticals. Patent
JP.2012031092, 2012.
4373
https://doi.org/10.1021/acs.orglett.1c01309
Org. Lett. 2021, 23, 4368−4373