Intermolecular Heck Coupling with Hindered Alkenes Directed by Potassium Carboxylates

Article abstract of DOI:10.1002/anie.201813233

Pd⁰-catalyzed Mizoroki–Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular reactions with simple, all-carbon tetrasubstituted alkenes are unprecedented. Herein we report that pendant carboxylic acids, combined with bulky monophospine ligands on palladium, can direct the arylation of tri- and tetrasubstituted olefins. Quaternary carbons are established at high Fsp³ attached-ring junctures and the carboxylate directing group can be removed after coupling. Carboxylate directivity prevents over-arylation of the new, less substituted alkene, which can be diversified in subsequent reactions.

Full text of DOI:10.1002/anie.201813233

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Accepted Article
Title: Intermolecular Heck Coupling with Hindered Alkenes Directed by
Potassium Carboxylates
Authors: Tucker Huffman, Yebin Wu, Alexis Emmerich, and Ryan
Ashok Shenvi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201813233
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10.1002/anie.201813233
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Intermolecular Heck Coupling
with Hindered Alkenes Directed
by Potassium Carboxylates
Tucker R. Huffman, Yebin Wu, Alexis Emmerich,
and Ryan A. Shenvi*
Abstract: Pd(0)-catalyzed Mizoroki-Heck reactions traditionally
exhibit poor reactivity with polysubstituted, unbiased alkenes.
Intermolecular reactions with simple, all-carbon tetrasubstituted
alkenes are unprecedented. Here we report that pendant carboxylic
acids, combined with bulky monophospine ligands on palladium, can
direct the arylation of tri- and tetrasubstituted olefins. Quaternary
carbons are established at high Fsp3 attached-ring junctures and the
carboxylate directing group can be removed after coupling.
Carboxylate directivity prevents over-arylation of the new, less
substituted alkene, which can be diversified in subsequent reactions.
Figure 1: Approaches to the Heck reaction on challenging substrates.
The Mizoroki-Heck reaction 1 has become a staple of cross
coupling and has transformed how molecules are synthesized. A
White and coworkers in 2008 established that oxidative Heck
conditions could engage unbiased terminal olefins using weakly
directing functional groups to yield terminally arylated products,12
and Sigman in 2014 extended the asymmetric redox-relay Heck
reaction to trisubstituted olefins with oxidative conditions.13, 14
With the exception of enelactams, redox-relay Heck reactions do
not tolerate cyclic substrates, which tend to yield mixtures of
regioisomers.15
Heck reactions with sterically hindered and unbiased
olefins remain non-trivial in many cases, evidenced by recent
syntheses of κ-opioid receptor agonists 20-nor-SalA16 and O6C-
20-nor-SalA. 17 A late-stage Heck arylation on a hindered,
unbiased olefin could not be achieved using traditional or
large volume of research in the decades since its discovery has
2
identified some limitations in its scope.
For example,
electronically unbiased, cyclic and sterically hindered olefins
remain challenging substrates with low inherent reactivity and
selectivity3 in traditional Heck arylations.4 Intermolecular Heck
reactions are unprecedented with all-carbon tetrasubstituted
5
olefins, with the exception of strained hydrocarbons like
bicyclopropylidene.6 Here we show that potassium carboxylates
serve as directing groups to enable single Heck reactions of tri-
and tetrasubstituted alkenes, including hindered cyclic motifs.
Products avoid polyarylation and include sp2-sp3 attached-ring
motifs and diversifiable unsaturated building blocks, otherwise
inaccessible by cross-coupling methods.
oxidative Heck conditions. However, incorporation of
a
carboxylic acid close to the alkene significantly accelerated
arylation relative to deactivation of the palladium catalyst or
decomposition of the aryl halide, 3-bromofuran (Figure 1c).16
Reactivity enhancement from the direction of carboxylic acids
had been observed in the C-H activation literature, but until now
has not been established in Heck arylation.18 We wondered if
Many different approaches have been applied to extend
the classical Heck reaction to more traditionally challenging
substrates (Figure 1a). Early work by Grigg7 and Overman8
demonstrated the utility of intramolecular Heck reactions to
overcome the reactivity barrier for highly substituted substrates,
with their groups and others forging various spiro- and polycyclic
systems from tri- and some tetrasubstiuted olefins. The reactivity
enhancement from intramolecular delivery of the PdII-Ar species
was leveraged in several directed Heck reactions.9 Notably, the
carboxylate-directivity could be applied to traditionally unreactive
19
Heck substrates.
Here we report that carboxylic acids
accelerate and direct the intermolecular Heck reaction of tri- and
tetrasubstituted olefins (Figure 1d) in substrate types (unbiased,
cyclic, hindered) that are unrepresented in the Heck literature,
directed or undirected. The reactivity enhancement of the
potassium carboxylate allows the formation of quaternary
centers from linear, cyclic, bicyclic, aliphatic, and hindered
styrenyl substrates. Carboxylate-directivity seems to inhabit a
‘goldilocks region’ among Mizoroki-Heck regimes: cationic-Pd
conditions favor chain-walking into a terminating group13,14 and
chelating directing groups prevent β-hydride elimination
altogether.19 In addition, previously-established directing groups
like amines and esters are ineffective in promoting the coupling.
Carboxylate-directivity promotes regioselective engagement of
hindered alkenes yet allows regio- and stereoselective β-hydride
elimination without iterative arylation of the new, less hindered
alkene.
10
11
groundbreaking work of Hallberg
and Carretero
used
tethered functional groups bearing basic nitrogens to alter
arylation regiochemistry and relay stereochemical information,
with the former able to form quaternary centers from a fully-
substituted, albeit polarized substrate. A seminal report from
[*]
Tucker R. Huffman, Yebin Wu, Alexis Emmerich, Prof. Ryan A.
Shenvi
Department of Chemistry, The Scripps Research Institute (TSRI)
10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
E-mail: rshenvi@scripps.edu
Supporting information for this article is given via a link at the end of
the document.
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Table 1. Reaction Optimization
propensity towards oxidative addition. No reaction was observed
in the absence of palladium.
The arylation exhibits high regio- and stereoselectivity,
delivering the E-alkene and the arene distal to the directing
group, which is consistent with a 6-membered chelate of the
carboxylate to the PdII-alkyl intermediate (see Scheme 2, below).
In contrast to redox-relay Heck reactions of trisubstituted olefins,
the unsaturation does not migrate into conjugation22 with the
carboxylic acid but remains adjacent to the newly formed
quaternary center. Additionally, the alkene isomer preferentially
formed is internal and trisubstituted rather than terminal and
disubstituted.23 The carboxylic acid was essential for reaction:
substrates containing weakly Lewis basic esters, alcohols, and
amides were completely unreacted under the optimized
conditions after 16 hours. Tertiary amine 7 reacted to low
conversion and gave a complex mixture of arylated materials.
The carboxylate-directed Heck was successfully applied to
a wide range of tri- and tetrasubstituted olefins in modest to
good yields after a second esterification step (Table 2). Unless
otherwise noted, stereoselectivity was excellent (>20:1 E/Z by
1H NMR) and regiocontrol was excellent in all cases except a
cyclopentane substrate (3t–w). Only olefins proximal to the
carboxylic acid underwent reaction; the distal olefin of 3d was
unreactive. In addition to simple linear aliphatic substrates, cyclic
and styrenyl tri- and tetrasubstituted olefins were competent
Heck partners. The intrinsic electronic bias of the styrene was
completely overridden in the cases of 3e, 3f, and 3m, giving
valuable diarylated quaternary centers. Rearrangement of the
styrene substitution did not change delivery of the arene
electrophile (see 3s). The use of carbo- and heterocyclic olefins
produced challenging all-carbon quaternary centers at Csp3-
Csp2 attached-ring motifs, including the bicycle 3n and
cyclododecane 3o. These motifs represent high fraction-sp3
(Fsp3) equivalents of biaryls and valuable scaffolds for medicinal
chemistry.24 For example, phenyl substituted cyclohexane 8, an
intermediate in the synthesis of S1P1 agonists, could be
prepared in a concise and higher-yielding 3 step route as
compared to the reported 6 step sequence. 25 Electron-rich
Entry
Variations from above
% yield[a]
1
2
none
Li2CO3 / Na2CO3 / Cs2CO3 vs K2CO3
Et3N vs K2CO3
80
0 / 37 / 53
3
0
0
4
BINAP vs TrixiePhos
dppe vs TrixiePhos
5
0
6
dppf vs TrixiePhos
17
0
7
XPhos vs TrixiePhos
PPh3 vs TrixiePhos
4-OMe-PhBr vs PhBr
4-OMe-PhBr vs PhBr, PPh3 vs TrixiePhos
PhI vs PhBr
8
67
85[b]
22[b]
18
0
9
10
11
12
no Pd
[a] 0.1 mmol scale, yield determined by quantitative LCMS. [b] Ar = 4-OMe-Ph,
1H NMR yield after 1 h.
We identified tetrasubstituted alkene 1a as a model
substrate to explore and optimize carboxylate directivity (for a
full table of optimization, see the Supporting Information). Type
of base significantly influenced yield: lithium, sodium and cesium
cations were inferior to potassium, and ammonium cation was
ineffective. A strong influence of cation has previously been
observed in carboxylate-directed C-H insertion chemistry, where
a proposed κ2 binding of alkali cation is suggested to induce a κ1
Pd-carboxylate binding mode.18 The effect here can alternatively
be explained by altered aggregation states of different alkali
cations,20 or perturbed Lewis basicity of the alkali carboxylates.
Choice of phosphine proved crucial for efficiency and breadth of
scope. Bisphosphines were ineffective, likely due to occupancy
of the Pd valence necessary for carboxylate coordination
bromoarenes performed best, in contrast to nickel-catalyzed
26
hydroarylations,
which also form quaternary carbons at
attached-ring bridgeheads, but usually prefer electron-deficient
haloarenes.27 Diastereoselectivity in the Heck reaction could be
effected by: substitution α to the directing carboxylic acid, (3w),
existing stereocenters on cyclic substrates (3k), or bridging-ring
topology (3n). While most reactions in Table 2 were performed
on small scale (0.1 mmol), scale-up proved uneventful and
allowed over 500 mg of 3u to be prepared in one batch from the
tetrasubstituted cyclopentene.28
Aryl scope is explored in Table 3 using tetrasubstituted
substrate 1a. Para- and meta- substitution is well tolerated, and
mono-, di-, and trisubstituted arenes could be installed with
similar ease. Electron rich and electron neutral arenes
outperform electron poor, with electron rich aryl bromides noted
to complete fastest. Even highly electron-rich trimethoxyphenyl
3ag was delivered in good yield. Aryl bromides with strongly
electron-withdrawing groups in the para position were found to
stall at low conversion from apparent catalyst deactivation (see
Scheme 2 and Supporting Information). Heterocycles were
acceptable coupling partners in this chemistry, exemplified by
benzodioxole 3ah and protected indole 3aj.
(entries 4-5). Rapidly dissociating,
larger bite-angle
bisphosphines delivered small amounts of product (entry 6). A
bulky mono-phosphine proved optimal for the reaction, either
favoring an L1Pd-Ar species with open binding sites for both
carboxylate and alkene, or dissociating from Pd to promote a
cationic pathway.
although it offered the highest yields in 20-nor-SalA.16 While
simple triphenylphosphine was capable of promoting the
reaction, it was outcompeted by the bulkier TrixiePhos,
especially with electron rich arenes (entry 9 vs. 10). Interestingly,
iodoarenes reacted to low conversion despite their greater
21
Interestingly, XPhos performed poorly,
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Table 2. Olefin Scope
[a] 0.1 mmol scale, isolated yield over 2 steps, reaction time 16 h. Esterification conditions unless otherwise noted: (COCl)2 (2 eq), DCM (0.1M); MeOH (excess).
[b] 1H NMR Yield of crude material. [c] 1 eqivalent of ArBr used. [d] Esterification: DIC, DMAP, MeOH, DCM. [e] Esterification: N,N’-diiPr-O-tBu isourea, DCM. [f]
Ratio of endocyclic to exocyclic olefin products.
The products of carboxylate-directed Heck reaction exhibit
high synthetic utility by virtue of the olefin and carboxylic acid
functional groups, both of which are versatile synthetic handles.
To demonstrate this versatility, we diversified 3u to form the
densely functionalized products of Scheme 1. The olefin was
capable of functionalization by Drago-Mukaiyama hydration,29
epoxidation, and dihydroxylation, and treatment of the
dihydroxylation product with oxalyl chloride in methanol
furnished 5-membered lactone 12. Formation of redox active
ester in place of the methyl ester allowed straightforward
decarboxylation or decarboxylative arylation. 30 As a result,
motifs that were previously inaccessible by Mizoroki-Heck
chemistry can now be unmasked and retrosynthetically
transformed to unsaturated carboxylates.
Several interesting mechanistic features are also worth
noting. Although less-substituted olefins were generated, over-
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Table 3. Aryl halide scope with a tetrasubstituted alkene.
Scheme 1. Product Diversification[a]
[a] Conditions: a) R = NHPI, Ph2Zn, Fe(acac)2, dppBz (34%); b) R = NHPI, Zn0,
PhSiH3, NiCl2•6H2O (39%; c) R = Me, Mn(acac)2, PhSiH3, PPh3, O2 (64%, 2:1
dr); d) R = Me, i. NMO, OsO4; ii. (COCl)2, MeOH (65%, 6:1 dr); e) R = Me, m-
CPBA (100%, 2:1 dr)
TrixiePhos to engage hindered olefins was unexpected given its
large size among monodentate phosphine ligands and may
suggest that dissociation occurs prior to alkene coordination.
Alternatively, the monoligated palladium L1Pd–Ar favored by
bulky phosphines34 may be necessary to allow coordination of
both the carboxylate and the alkene. Another surprising feature
was the poor performance of both aryl iodides and electron
deficient aryl bromides, which typically couple well in Heck
reactions but in our system led to catalyst deactivation. Analysis
of the crude reaction mixture in reactions of electron poor arenes
revealed formation of biaryls and LCMS peaks corresponding to
substrate dehydrogenation. Catalyst deactivation possibly
occurs downstream of reductive homocoupling to generate
biaryls and inactive PdII salts,35 a process that is bimolecular in
XPdII-Ar and would be disproportionality favored by rapid
oxidative addition compared to the productive reaction pathway
(Scheme 2c). This hypothesis also accounts for the superiority
of sterically bulky ligands, which may prevent PdII-Ar association
leading to deactivation — an observation made previously in
styrenyl Heck reactions.36
[a] 0.1 mmol scale, isolated yield over
2 steps, reaction time 16 h.
Esterification conditions unless otherwise noted: (COCl)2 (2 eq), DCM (0.1M);
MeOH (excess) [b] Esterification conditions: DIC, DMAP, MeOH, DCM [c] 12:1
ratio of isomers favoring the internal [d] Combined yield including deprotected
product.
arylation of products in Table 2 only occurred rarely and only in
small quantities. The adjacent quaternary carbons were not
solely responsible for enforcing single arylation: a homologated
analog of the products in Tables 2 and 3 underwent facile
carboxylate-directed Heck reaction (14→15, Scheme 2a) but the
less hindered β,γ-unsaturated product (15) did not undergo
arylation. Therefore, transition state geometry may play a role in
In conclusion, carboxylate-directivity advances the Heck
reaction to a new milestone: the intermolecular coupling of
tetrasubstituted alkenes. In addition to providing products of high
synthetic value, the success of this strategy underscores the
profound rate enhancement imparted by carboxylate directing
groups.18 The reactivity trend in counter-cation is noteworthy and
distinguishes the carboxylate from neutral protecting groups like
amines or esters, which are ineffective to promote the reaction.
The absence of chain walking and the regioselectivity of β-
hydride elimination may also point to a role of the carboxylate
downstream of arene insertion.37,38 The observations here invite
further mechanistic inquiry and the insights gained from this
work may be translatable to other modes of olefin cross-coupling.
effecting
monoarylation.
A
low-energy,
pseudo-chair
conformation might be involved, which fits the relative
regiochemistry of arylation and stereochemistry generated in 3w
(Scheme 2b). This assembly would be geometrically unfavorable
for β,γ-unsaturated products (15 and Tables 2 and 3) and distant
alkenes (3d). Additionally, β-hydride elimination generates an
olefin out of conjugation with the carboxylic acid, which suggests
that chain-walking processes cannot occur. The preference for
tetrasubstituted substrates to form the internal, trisubstituted
olefin over the terminal 1,1-disubstituted olefin (see Table 3, ca.
10:1 on average)23,31 is striking given that statistics should favor
β-hydride elimination to the terminal position. 32 , 33 That the
observed alkene isomer avoids the thermodynamic sink of
conjugation and the statistically favored product suggests that
the carboxylate directing group has a role enforcing β-hydride
elimination, kinetically or thermodynamically, in addition to
directing the regiochemistry of arene insertion. The superiority of
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[10] a) C.-M. Andersson, J. Larsson, A. Hallberg, J. Org. Chem. 1990, 55¸
5757; b) M. Larhed, C.-M. Andersson, A. Hallberg, Acta Chem. Scand.
1993, 47, 212; c) M. Larhed, C.-M. Andersson, A. Hallberg, Tetrahedron
1994, 50, 285. d) P. Nilsson, M. Larhed, A. Hallberg, J. Am. Chem. Soc.
2003, 125, 3430.
[11] N. D. Buezo, I. Alonso, J. C. Carretero, J. Am. Chem. Soc. 1998, 120,
7129.
[12] a) J. H. Delcamp, A. P. Brucks, M. C. White, J. Am. Chem. Soc. 2008,
130, 11270; b) J. H. Delcamp, P. E. Gormisky, M. C. White, J. Am.
Chem. Soc. 2013, 135, 8460.
[13] T.-S. Mei, H. H. Patel, M. S. Sigman, Nature 2014, 508, 340
[14] For other work on migratory Heck reactions, see: a) Y. Tamaru, Y.
Yamada, Z.-I. Yoshida, Tetrahedron, 1979, 35, 329. b) R. C. Larock, W.-
Y. Leung, S. Stolz-Dunn, Tetrahedron Lett., 1989, 30, 6629. c) R. C.
Larock, Y.-d. Lu, A. C. Bain, J. Org. Chem. 1991, 56, 4589. d) C. C.
Oliveira, A. Pfaltz, C. R. D. Correia, Angew. Chem. Int. Ed. 2015, 54,
14036.
[15] Q. Yuan, M. S. Sigman, J. Am. Chem. Soc. 2018, 140, 6527.
[16] J. J. Roach, Y. Sasano, C. L. Schmidt, S. Zaidi, V. Katritch, R. C.
Stevens, L. M. Bohn, R. A. Shenvi, ACS Cent. Sci., 2017, 3, 1329.
[17] S. Hirasawa, M. Cho, T. F. Brust, J. J. Roach, L. M. Bohn, R. A. Shenvi,
Bioorganic Med. Chem. Lett. 2018, 28, 2770.
[18] a) R. Giri, J.-Q. Yu, J. Am. Chem. Soc. 2008, 130, 14082. b) K. M.
Engle, T.-S. Mei, M. Wasa, J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788.
[19] For use of 8-aminoquinoline directing groups for palladium catalyzed
aryl-olefin cross-coupling, see: a) K. Yang, J. A. Gurak Jr., Z. Liu, K. M.
Engle, J. Am. Chem. Soc. 2016, 138, 14705; b) Z. Liu, T. Zeng, K. S.
Yang, K. M. Engle, J. Am. Chem. Soc. 2016, 138, 15122.
[20] R. F. Algera, Y. Ma, D. B. Collum, J. Am. Chem. Soc. 2017, 139, 7921.
[21] W. Cabri, I. Candiani, A. Bedeschi, J. Org. Chem. 1993, 58, 7421.
[22] C. Zhang, C. B. Santiago, L. Kou, M. S. Sigman, J. Am. Chem. Soc.
2015, 137, 7290.
[23] The terminal, γ,δ-unsaturated olefin is not observed by 1H NMR in the
crude reaction mixtures. However, a diarylated compound arising from
its intermediacy is occasionally present as
Supporting Information).
a ~10% impurity (see
[24] a) F. Lovering, J. Bikker, C. Humbolt, J. Med. Chem. 2009, 52, 6752; b)
D. G. Brown, J. Boström, J. Med. Chem. 2016, 59, 4443.
[25] J. Das, K. Soo Sung, International Patent WO2012040532. 2012.
[26] S. A. Green, S. Vásquez-Céspedes, R. A. Shenvi, J. Am. Chem. Soc.
2018, 140, 11317.
[27] For a recent exception using electron-rich iodoarenes, see: X. Wang, G.
Ma, Y. Peng, C. E. Pitsch, B. J. Moll, T. D. Ly, X.Wang, and H. Gong, J.
Am. Chem. Soc. 2018, 140, 14490.
Scheme 2. Mechanistic model for regio- and stereochemistry.
[28] In some cases, excess aryl halide led to diarylation of γ,δ-unsaturated
products, which could be lessened through fewer equivalents of arene.
[29] S. W. M. Crossley, C. Obradors, R. M. Martinez, R. A. Shenvi, Chem.
Rev. 2016, 116, 8912.
Acknowledgements
[30] a) F. Toriyama, J. Cornella, L. Wimmer, T.-G. Chen, D. D. Dixon, G.
Creech, P. S. Baran, J. Am. Chem. Soc. 2016, 138, 11132. b) T. Qin, L.
R. Malins, J. T. Edwards, R. R. Merchant, A. J. E. Novak, J. Z. Zhong, R.
B. Mills, M. Yan, C. Yuan, M. D. Eastgate, P. S. Baran, Angew. Chem.
Int. Ed. 2017, 56, 260.
[31] Small amounts of the alternative alkene regioisomer (1,1-disubstition)
could be observed when electron-deficient arenes were used (3ac and
3ae), but the trisubstituted alkene still predominated 12:1.
[32] Cf. Ref. 19. Professor Engle first noted the ‘goldilocks’ effect of
carboxylate-directivity on β-hydride elimination: the alkyl-palladium is not
too stable and not too labile.
Generous support was provided by the National Institutes of
Health (R35 GM122606), Nanjing University of Science &
Technology (scholarship to Y. W.) and Westfꢀlische Wilhelms-
Universitꢀt Mꢁnster (scholarship to A. E.). We thank Zefeng
Chen for early contributions to substrate scope and Jeremy J.
Roach to early discovery efforts. Professors Keary Engle and
Jin-Quan Yu are acknowledged for helpful input.
Keywords: Mizoroki-Heck • cross-coupling • carboxylic acid •
[33] B. M. Trost, M. Lautens, C. Chan, D. J. Jebaratnam, T. Mueller, J. Am.
Chem. Soc. 1991, 113, 636.
directing group effects
[34] a) J. F. Hartwig, Angew. Chem., Int. Ed. 1998, 37, 2046; b) R. Martin, S.
L. Buchwald, Acc. Chem. Res. 2008, 41, 1461.
[35] Attempts to rescue inactive Pd(II) using stoichiometric reductants proved
unsuccessful.
[1] T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581; b) R.
F. Heck; J. P. Nolley, J. Org. Chem. 1972, 37, 2320.
[36] G. P. F. van Strijdonck, M. D. K. Boele, P. C. J. Kamer, J. G. de Vries, P.
W. N. M. van Leewen, Eur. J. Inorg. Chem. 1999, 1073.
[37] For carboxylate assistance in haloarene oxidative addition, see: a) I. N.
Houpis, J.-P. Van Hoeck, U. Tilstam, Synlett 2007, 14, 2179; b) I. N.
Houpis, C. Huang, U. Nettekoven, J. G. Chen, R. Liu, M. Canters, Org.
Lett. 2008, 10, 5601.
[38] For carboxylate assistance in iridium-catalyzed asymmetric alkene
hydrogenation, see: S.-F. Zhu, Q.-L. Zhou, Acc. Chem. Res. 2017, 50,
988.
[2] For selected reviews and books, see: a) R. F. Heck, Acc. Chem. Res.
1979, 12, 146; b) W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28, 2; c)
I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009; d) K. C.
Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem. Int. Ed. 2005, 44,
4442; e) B. Karimi, H. Behzadnia, D. Elhamifar, P. F. Akhavan, F. K.
Esfahani, A. Zamani, Synthesis, 2010, 1399.
[3] H. A. Dieck, R. F. Heck, J. Am Chem. Soc. 1974, 96, 1133.
[4] a) Ref. 2a; b) R. Bates, Organic synthesis using transition metals. John
Wiley & Sons, 2012, pp. 153-190; c) C. Zheng, S. S. Stahl, Chem.
Commun. 2015, 51, 12771.
[5] G. Dyker, J. Körning, P. G. Jones, P. Bubenitschek, Angew. Chem. Int.
Ed. Engl. 1993, 32, 1733.
[6] S. Bräse, A. de Meijere, Angew. Chem. Int. Ed. 1995, 34, 2545.
[7] R. Grigg, V. Sridharan, P. Stevenson, T. Worakun, J. Chem. Soc.,
Chem. Commun. 1986, 1697.
[8] M. M. Abelman, T. Oh, L. E. Overman, J. Org. Chem., 1987, 52, 4130.
[9] M. Oestreich, Eur. J. Org. Chem. 2005, 783.
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