Palladium-Catalyzed Ortho-Silylation of Aryl Iodides with Concomitant Arylsilylation of Oxanorbornadiene: Accessing Functionalized (Z)-β-Substituted Vinylsilanes and Their Analogues

Article abstract of DOI:10.1021/acs.orglett.8b02106

A palladium-catalyzed ortho-silylation of aryl iodides/arylsilylation of oxanorbornadiene/retro-Diels-Alder domino reaction was developed. Such a transformation provides access to various functionalized (Z)-β-substituted vinylsilanes with exclusive selectivity using hexamethyldisilane as a bis-silylation reagent and 2,3-dicarbomethoxy-7-oxanorbornadiene (ONBD) as an ortho-C-H activator and ethylene surrogate. A variety of (Z)-β-substituted vinylgermanes and (Z)-β-substituted vinylstannanes were also obtained under mild reaction conditions. This atom-economical, stereoselective, and scalable approach is compatible with a diverse range of readily available functionalized aryl iodides.

Full text of DOI:10.1021/acs.orglett.8b02106

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Palladium-Catalyzed Ortho-Silylation of Aryl Iodides with
Concomitant Arylsilylation of Oxanorbornadiene: Accessing
Functionalized (Z)‑β-Substituted Vinylsilanes and Their Analogues
Weiwei Lv, Si Wen, Jia Yu, and Guolin Cheng*
College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
S
* Supporting Information
ABSTRACT: A palladium-catalyzed ortho-silylation of aryl iodides/
arylsilylation of oxanorbornadiene/retro-Diels−Alder domino reaction
was developed. Such a transformation provides access to various
functionalized (Z)-β-substituted vinylsilanes with exclusive selectivity
using hexamethyldisilane as a bis-silylation reagent and 2,3-dicarbome-
thoxy-7-oxanorbornadiene (ONBD) as an ortho-C−H activator and
ethylene surrogate. A variety of (Z)-β-substituted vinylgermanes and
(Z)-β-substituted vinylstannanes were also obtained under mild reaction
conditions. This atom-economical, stereoselective, and scalable approach
is compatible with a diverse range of readily available functionalized aryl
iodides.
Scheme 1. Palladium/NBE-Based Ipso- and Ortho-Dual
Functionalizations of Aryl Iodides
inylsilanes are valuable synthetic intermediates in organic
synthesis.1 Thus, methods for the synthesis of vinylsilanes
V
in a practical, efficient, and divergent manner have been
attracting significant interest. Indeed, numerous transition-
metal-catalyzed reactions have been developed for the
preparation of (E)-β-substituted vinylsilanes.2 In contrast, only
a few reports on the selective synthesis of thermodynamically
less stable (Z)-β-isomers have appeared to date. Current
methods to access (Z)-β-substituted vinylsilanes include the
alkyne hydrosilylation3 and direct dehydrogenative silylation of
alkenes;4 both of the methods carry significant drawbacks,
including the requirement of sophisticated transition-metal
complexes as catalysts and the formation of the (E)-β-isomers as
byproducts. The generation of the (Z)-β-isomers using simple
transition-metal catalysts with exclusive selectivity is regarded as
a long-standing challenge.
On the other hand, transition-metal-catalyzed domino
reactions that form complex molecules from simple starting
materials in a single operation without the isolation of
intermediates are of great significance in organic syntheses.5
Noteworthy among them is the Pd/norbornene (NBE)-based
ortho-functionalization with ipso-termination of aryl iodides
leading to highly substituted arenes.6 The reaction was first
reported by Catellani’s group7 and further developed by several
groups, including those of Lautens,8 Dong,9 Gu,10 and
others.11−14 A variety of nucleophiles or olefins were used as
terminal reagents via C−H, C−C, C−B, C−N, C−O, and C−S
bond formations at the ipso-position in the past decades
(Scheme 1a). However, the chemical bonds constructed at the
ortho-position via this approach have been restricted to C−C
and C−N bonds. To the best of our knowledge, the
compatibility of the Catellani reaction with silylation,
germanylation, or stannylation has not yet been demonstrated
to date. Inspired by recent innovative research on Pd-catalyzed
C(sp2)−H and C(sp3)−H silylation reactions,15 we envisioned
that hexamethyldisilane may be qualified as a silylating reagent
to facilitate the installation of a TMS group at the ortho-position
of aryl iodides. The resulting intermediate (V) could undergo
reductive elimination to give disilanes bearing an NBE fragment.
Then (Z)-β-substituted vinylsilanes may be formed via a retro-
Diels−Alder reaction (Scheme 1b). Herein, we report our
observation that the bis-silylation reaction of aryl iodides,
Received: July 5, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02106
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
hexamethyldisilane, and ONBD afforded functionalized (Z)-β-
substituted vinylsilanes chemo-, regio-, and stereoselectively
with high efficiency.
Scheme 2. Scope of Aryl Iodides
Initially, we began the studies with 1-iodonaphthalene (1a),
hexamethyldisilane (2a), and ONBD (3a) to explore the
reaction conditions (see the Supporting Information for details).
After systematic screening of the reaction conditions, the
optimal conditions were achieved to be Pd(OAc)2 (10 mol %),
tri(2-furyl)phosphane (TFP, 20 mol %), and K2CO3 (2 equiv)
in DMF under N2 at 100 °C to yield the desired (Z)-β-
substituted vinylsilane product (4a) in 84% yield (Table 1, entry
a
Table 1. Screening of Norbornadiene Derivatives
b
entry
deviation from standard conditions
yield (%)
1
2
3
4
5
none
84
83
12
20
0
3b instead of 3a
3c instead of 3a
3d instead of 3a
3e instead of 3a
a
1-Bromonaphthalene was used as substrate.
a
Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), 3 (0.2 mmol),
Pd(OAc)2 (10 mol %), TFP (20 mol %), and K2CO3 (0.2 mmol) in
b
thalene was also subjected to the reaction conditions, giving 4a
in 40% yield. It should be noted that exclusive (Z)-isomers were
formed in all cases of the aforementioned bis-silylation reactions,
as indicated by the X-ray structure of 4t.
DMF (1 mL) under nitrogen atmosphere for 12 h. Determined by
1H NMR analysis of the crude products using CH2Br2 as an internal
standard. DMF = N,N-dimethylformamide.
1). A similar result was obtained using 3b as the mediator (entry
2). Only 12% yield was obtained when the sterically hindered 3c
was used (entry 3). Azanorbornadiene 3d could also be
employed uner the reaction conditions, giving 20% yield of 4a
(entry 4). However, interestingly, no desired product was
detected when norbornadiene (NBD, 3e) was used in lieu of 3a
(entry 5).
Encouraged by the successful Si−Si bond-cleavage reaction,
we proceed to explore this strategy for other similar types of
bonds. The Ge−Ge bond has been applied in palladium-
catalyzed C−H functionalization as an Si−Si bond.15b,g Thus,
we conceived that the (Z)-β-substituted vinylgermane products
might also be formed by using hexamethyldigermane (2b)
instead of hexamethyldisilane under similar reaction conditions,
and this indeed proved to be the case. For a series of aryl iodides,
the palladium-catalyzed domino reactions with 2b and 3a
afforded the corresponding (Z)-β-substituted vinylgermanes
(5a−f) in moderate to good yields (Scheme 3a).
Organostannanes are important compounds because of their
application in Stille coupling reaction.16 The syntheses of these
organostannanes usually require expensive functionalized
precursors.17 The direct construction of the C−Sn bond
through catalytic C−H bond activation reactions is highly
desirable. We are pleased to find that C−Sn bond could be
formed via our approach using hexabutyldistannane as Sn source
(6a−d). However, efforts on further improving this reaction
efficiency are still needed (Scheme 3b).18
To further demonstrate the utility of this chemistry, the
reaction was conducted on a 5 mmol scale. The reaction of 1a,
2a, and 3a was complete within 24 h, generating the desired
products (4a) in 78% yield (Scheme 4a). Importantly, we found
that disilane 7 could be successfully isolated in 70% yield at
lower temperature (Scheme 4b). It is worth mentioning that aryl
silanes are versatile synthetic intermediates and could be
selectively converted into various compounds with retention
With the optimal conditions in hand, the bis-silylation
reaction was extended to a variety of aryl iodides by using 2a
and 3a as coupling partners (Scheme 2). In general, the reaction
process can be extended to various ortho-, meta-, para-, as well as
disubstituted iodobenzenes, thus giving the corresponding (Z)-
β-substituted vinylsilanes (4a−t) in 36−86% yields. Various
valuable functional groups were tolerated, including halogen,
ester, Weinreb amide, acetamide, as well as hydroxyl. For meta-
substituted iodobenzenes (4j), the C−H silylation occurred
regioselectively at the sterically less hindered position.
Importantly, the acetamide directing group did not prevent
the 3a-mediated C−H activation, and the desired product (4o)
was obtained in 62% yield. Notably, benzyl alcohol substrate was
also compatible with the reaction conditions (4p). 2-
Iodothiophene was found to be an applicable substrate, albeit
giving lower yield (4q, 36%). It is noted that the reaction with
the more coordinative pyridyl iodide gave the corresponding
product (4r) in 64% yield. The phenylalanine substrate was
successfully converted into the corresponding (Z)-β-substituted
vinylsilane (4s) in 60% yield. Notably, estrone derivative was
modified by this protocol without obstacles (4t). 1-Bromonaph-
B
DOI: 10.1021/acs.orglett.8b02106
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Letter
conditions. The corresponding noncrossover products (4a) and
(5a) were obtained in 40% and 38% yields, respectively. The
crossover products were not observed, which indicated that both
of the two TMS groups of 4a are derived from one
hexamethyldisilane molecule (Scheme 5a). Moreover, a solution
Scheme 3. Scope of Aryl Iodides
Scheme 5. Control Experiments
a
K3PO4 was used instead of K2CO3.
Scheme 4. Derivatization Reactions
of 7 in DMF was heated at 100 °C for 12 h, and both 4a and 3,4-
dicarbomethoxy furan (10) were obtained in quantitative yields
(Scheme 5b). Iodide (8) could also be successfully converted
into (Z)-β-substituted vinylsilane (11) via a retro-Diels−Alder
reaction in quantitative yield. It is well-known that electron-
deficient dienophiles are prone to form Diels−Alder adducts
with electron-rich dienes. Thus, we proposed that the release of
an electron-rich dienophile (4a) and an electron-deficient
aromatic diene (10) may provide the driving force for the retro-
Diels−Alder process.
On the basis of these results and the literature reports, we
proposed that the reaction would proceed as shown in the
Scheme 6. This reaction is initiated by Ar−I oxidative addition
to Pd0 and subsequent ONBD-mediated vicinal C−H activation
Scheme 6. Plausible Catalytic Cycle
of the alkyl TMS group. For example, when the trimethylsilyl
entity was used as a transformable group, the C−I bond was
formed (Scheme 4c). We then sought to explore the possibility
of performing iterative bis-silylation, wherein the newly
synthesized aryl iodide (8) would serve as the starting material
for an additional bis-silylation. Gratifyingly, the trisilylated
product (9) was obtained in 45% yield (Scheme 4d).
To further understand the reaction mechanism, we conducted
a double-crossover experiment of 1a and 3a with hexamethyldi-
silane and hexamethyldigermane under the standard reaction
C
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(3) For selected recent examples, see: (a) Du, X.; Hou, W.; Zhang, Y.;
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to generate a palladacycle (III), which can react with
hexamethyldisilane leading to the palladacycle (IV).15b Then
palladacycle (IV) undergoes reductive elimination to give
intermediate (V), which could further undergo a second
reductive elimination to furnish the desired exo-product 7 and
regenerate the Pd0 catalyst. Finally, 7 could be converted into
(Z)-β-substituted vinylsilane 4 via a retro-Diels−Alder reaction.
In conclusion, we have described the first palladium-catalyzed
Catellani-type ortho-silylation of aryl rings with arylsilylation of
oxanorbornadiene to form (Z)-β-substituted vinylsilanes, thus
expanding the Catellani reaction beyond the construction of C−
C and C−N bonds. A variety of functional groups are
compatible with this method, which could be readily extended
to the rapid preparation of (Z)-β-substituted vinylgermanes and
(Z)-β-substituted vinylstannanes. We believed that the utility of
2,3-dicarbomethoxy-7-oxanorbornadiene as an ortho-C−H
activator and ethylene synthon in Catellani-type reactions
should have broad implications.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b02106.
General experimental procedures, characterization data,
and 1H and 13C NMR spectra of new compounds (PDF)
(12) For selected examples using a palladium/norbornene relay
process to achieve meta-C−H functionalizations, see: (a) Li, Q.;
Ferreira, E. M. Chem. - Eur. J. 2017, 23, 11519. (b) Cheng, G.; Wang, P.;
Yu, J.-Q. Angew. Chem., Int. Ed. 2017, 56, 8183. (c) Ling, P.-X.; Chen,
K.; Shi, B.-F. Chem. Commun. 2017, 53, 2166. (d) Han, J.; Zhang, L.;
Zhu, Y.; Zheng, Y.; Chen, X.; Huang, Z.-B.; Shi, D.-Q.; Zhao, Y. Chem.
Commun. 2016, 52, 6903. (e) Wang, X.-C.; Gong, W.; Fang, L.-Z.; Zhu,
R.-Y.; Li, S.; Engle, K. M.; Yu, J.-Q. Nature 2015, 519, 334. (f) Dong, Z.;
Wang, J.; Dong, G. J. Am. Chem. Soc. 2015, 137, 5887.
Accession Codes
CCDC 1849591 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 data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
(13) For indole C2 C−H functionalizations using norbornene as a
transient mediator, see: (a) Jiao, L.; Herdtweck, E.; Bach, T. J. J. Am.
Chem. Soc. 2012, 134, 14563. (b) Jiao, L.; Bach, T. J. Am. Chem. Soc.
2011, 133, 12990.
(14) For borono-Catellani reactions: (a) Chen, S.; Liu, Z.-S.; Yang, T.;
Hua, Y.; Zhou, Z.; Cheng, H.-G.; Zhou, Q. Angew. Chem., Int. Ed. 2018,
57, 7161. (b) Shi, G.; Shao, C.; Ma, X.; Gu, Y.; Zhang, Y. ACS Catal.
2018, 8, 3775.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: glcheng@hqu.edu.cn.
ORCID
Guolin Cheng: 0000-0003-1013-2456
Notes
(15) (a) Lu, A.; Ji, X.; Zhou, B.; Wu, Z.; Zhang, Y. Angew. Chem., Int.
Ed. 2018, 57, 3233. (b) Maji, A.; Guin, S.; Feng, S.; Dahiya, A.; Singh, V.
K.; Liu, P.; Maiti, D. Angew. Chem., Int. Ed. 2017, 56, 14903. (c) Deb,
A.; Singh, S.; Seth, K.; Pimparkar, S.; Bhaskararao, B.; Guin, S.; Sunoj,
R. B.; Maiti, D. ACS Catal. 2017, 7, 8171. (d) Pan, J.-L.; Chen, C.; Ma,
Z.-G.; Zhou, J.; Wang, L.-R.; Zhang, S.-Y. Org. Lett. 2017, 19, 5216.
(e) Liu, Y.-J.; Liu, Y.-H.; Zhang, Z.-Z.; Yan, S.-Y.; Chen, K.; Shi, B.-F.
Angew. Chem., Int. Ed. 2016, 55, 13859. (f) Chen, C.; Guan, M.; Zhang,
J.; Wen, Z.; Zhao, Y. Org. Lett. 2015, 17, 3646. (g) Kanyiva, K. S.;
Kuninobu, Y.; Kanai, M. Org. Lett. 2014, 16, 1968.
(16) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
(17) For selected recent examples, see: (a) Yue, H.; Zhu, C.; Rueping,
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2017, 56, 3187.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the NSF of China (21672075) and
the Program for New Century Excellent Talents in Fujian
Province University.
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DOI: 10.1021/acs.orglett.8b02106
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