Silver-Catalyzed anti-Markovnikov Hydroboration of C-C Multiple Bonds

Article abstract of DOI:10.1021/acs.orglett.9b01217

A simple silver salt (AgOAc)-catalyzed anti-Markovnikov-selective hydroboration of alkenes, 1,3-dienes, and alkynes with pinacolborane (HBpin) has been described. This strategy provides an efficient and practical method to access various alkyl-, allyl-, a

Full text of DOI:10.1021/acs.orglett.9b01217

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Silver-Catalyzed anti-Markovnikov Hydroboration of C−C Multiple
Bonds
Yan Wang,†,‡ Rui Guan,†,‡ Paramasivam Sivaguru,‡ Xuefeng Cong,‡ and Xihe Bi*,‡
†School of Chemistry and Life Science, Changchun University of Technology, Changchun 130012, China
‡Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry, Northeast Normal
University, Changchun 130024, China
S
* Supporting Information
ABSTRACT: A simple silver salt (AgOAc)-catalyzed anti-Markov-
nikov-selective hydroboration of alkenes, 1,3-dienes, and alkynes
with pinacolborane (HBpin) has been described. This strategy
provides an efficient and practical method to access various alkyl-,
allyl-, and (E)-alkenylboronate esters in good to excellent yields with
regio- and stereoselectivity under ligand- and base-free conditions.
atalytic hydrofunctionalizations of multiple bonds
C(alkenes, alkynes, carbonyls, nitriles, imines, etc.) provide
a versatile and atom-economical tool for the construction of
carbon−carbon and carbon−heteroatom bonds.1 Within the
field, hydroboration, the formal addition of a B−H bond across
a carbon−carbon multiple bond, has attracted increasing
interest.2 The resulting boronic acid derivatives are highly
valuable synthons in a variety of chemical transformations and
have found applications in the pharmaceutical, petroleum, and
fragrance industries.3 As a result, the development of efficient
methods for their synthesis is of great importance. In recent
decades, several noncatalyzed,4 transition-metal catalyzed,5,6
and transition-metal-free7 approaches have been documented.
Figure 1. Silver-catalyzed hydroborations of C−C multiple bonds.
Among them, transition-metal-catalyzed reactions have gained
significant momentum because these catalysts can control the
regio- and chemoselectivity of the hydroboration.5,6 However,
catalyzed regio- and stereoselective hydroboration of olefins,
in addition to metal precatalysts, additional bases, ligands, or
other additives are also often essential for achieving suitable
results.
alkynes, and dienes with HBpin, as a practical and general
method for the synthesis of a variety of organoboronic acids
without the use of a ligand, base, or any other additive (Figure
1b). While we were preparing this manuscript, Rit and co-
workers reported an elegant AgSbF6-catalyzed hydroboration
of terminal alkynes with HBpin, but this catalytic system failed
to catalyze the hydroboration of alkenes.11 Compared with this
work, our AgOAc-catalyzed protocol shows excellent reactivity
and selectivity toward the hydroboration of both CC and
CC bonds and afforded the desired organoboronic acids in
excellent yields (up to 95%).
Despite the significant progress made in copper-catalyzed
hydroboration reactions, investigations of the catalytic power
of other coinage metals, silver in this hydroboration reaction,
remain in their infancy.8 So far, only one silver-catalyzed
protocol, that reported by Yoshida and co-workers, has
achieved the hydroboration of CC/CC bonds with
bis(pinacolato)diboron (B2Pin2) using a Ag(I)-NHC complex
and t-BuOK combined catalytic system (Figure 1a).8b
Nevertheless, this method has some limitations, such as
requiring specially designed ligands and showing a poor
substrate scope (limited to aliphatic terminal alkynes), poor
atom economy (produces stoichiometric boron-bearing by-
products), and poor regioselectivity. Therefore, the develop-
ment of an atom-efficient method that can control the
regioselectivity using just a metal salt is of great interest.
With the rapid increase in reports on silver-catalyzed organic
reactions in the literature9 and our continued interest in silver
catalysis,10 we herein disclose a simple silver salt, AgOAc-
Initially, when we performed the hydroboration of styrene
(1a) with HBpin (2) in the presence of AgOAc (10 mol %) in
toluene at 120 °C, the desired anti-Markovnikov selective
hydroboration product (3a) was obtained in 83% yield (Table
1, entry 1). In the absence of AgOAc, only 8% of 3a was
formed (entry 16). None of the Markovnikov product was
1
observed by H NMR analysis of the crude mixture. This
Received: April 6, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01217
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
Scheme 1. Silver-Catalyzed Hydroboration of Various
a
Alkenes
b
entry
[Ag]
AgOAc
AgOTf
Ag2CO3
AgF
PhCO2Ag
CF3CO2Ag
C3F7CO2Ag
silver lactate
silver salicylate
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
--
solvent
T (°C)
yield of 3a
c
1
2
3
4
5
6
7
8
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
120
120
120
120
120
120
120
120
120
120
120
110
90
85% (83%)
n.d.
6%
5%
75%
74%
80%
trace
trace
39%
40%
56%
10%
5%
9
10
11
12
13
14
15
16
80
rt
120
n.d.
8%
a
Reaction conditions: 1a (0.5 mmol), 2 (0.75 mmol), [Ag] (10 mol
b
%), and solvent (1 mL) were stirred for 12 h under Ar. Determined
by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an
c
internal standard. Isolated yield.
promising result prompted us to evaluate the effectiveness of
other silver salts, such as AgOTf, Ag2CO3, and AgF, and none
of them were as effective as AgOAc (entries 2−4), which
indicated the crucial role of the carboxylate anion in this
reaction. Among the other silver carboxylate salts screened,
silver benzoate (PhCO2Ag), silver trifluoroacetate
(CF3CO2Ag), and silver perfluorobutyrate (C3F7CO2Ag)
produced 3a in 75%, 74%, and 80% yields, respectively
(entries 12−14), while silver lactate and silver salicylate gave
traces of product. The hydroboration of styrene to afford 3a
also proceeded in dichloroethane and 1,4-dioxane, albeit in
much poorer yields (entries 10 and 11). When the reaction
temperature was decreased to 110 °C, 90 °C, and 80 °C, the
efficiency of the reaction dramatically decreased, affording 3a
in 56%, 10%, and 5% yields, respectively (entries 12−14),
while at room temperature no detectable product 3a was
observed (entry 15). We thus selected AgOAc (10 mol %) in
toluene at 120 °C as the best catalytic system for subsequent
evaluation of the substrate scope.
a
Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), AgOAc (10 mol
%), and toluene (1 mL) were stirred at 120 °C for 12 h under Ar;
b
c
isolated yields. 18 h. 24 h.
respectively) in good yields and excellent regioselectivities.
Unfortunately, α- and β-substituted styrene derivatives, such as
α-methylstyrene (1p), α-phenylstyrene (1q), and (E)-β-
methylstyrene (1r), did not undergo any detectable con-
version.
Encouraged by these results, we next assessed the hydro-
boration of 1,3-dienes (Scheme 2), which could give rise to
two different addition products (the 1,2- or 1,4-derivatives).12
Under our optimal conditions, the hydroboration of a range of
1-aryl-substituted 1,3-dienes with HBpin selectively delivered
1,2-addition products 5a−g in good yields and with excellent
regioselectivities, regardless of the presence of an electron-
donating or halogen group at any position on the aryl ring,
With the optimized conditions (Table 1, entry 1) in hand,
we then explored the substrate scope and limitations of this
anti-Markovnikov hydroboration starting with a variety of
terminal alkenes (Scheme 1). A range of styrenes with either
electron-rich or electron-poor substituents smoothly reacted
with HBpin, providing desired anti-Markovnikov addition
products 3b−f in excellent yields and regioselectivities. The
reaction was not sensitive to ortho substituents, as a 2,5-
dimethyl substitution pattern was well tolerated, affording
corresponding product 3g in 83% yield. 2-Vinylnaphthalene
also gave desired anti-Markovnikov product 3h in 88% yield
with the same level of regioselectivity. The optimal reaction
conditions were not only limited to the hydroboration of
aromatic alkenes; aliphatic alkenes 1i−o were also successfully
converted into boranes. For instance, alkenes containing an
ether group, a bromide, or a trimethylsilyl substituent were
converted into the expected products (3j, 3l, and 3o,
a
Scheme 2. Silver-Catalyzed Hydroboration of 1,3-Dienes
a
Reaction conditions: 4 (0.25 mmol), 2 (0.375 mmol), AgOAc (20
mol %), and toluene (1 mL) were stirred at 120 °C for 24 h under Ar;
isolated yields.
B
DOI: 10.1021/acs.orglett.9b01217
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
with the recovery of a small amount of the 1,3-dienes. Furyl-
substituted 1,3-diene 4g also smoothly underwent the
hydroboration, giving 1,2-adduct 5g in 61% yield.
Finally, the applicability of this AgOAc-catalyzed hydro-
boration protocol was further tested with terminal alkynes. As
shown in Scheme 3, a range of aryl acetylenes bearing both
Scheme 3. Silver-Catalyzed Hydroboration of Various
a
Alkynes
Figure 2. Kinetics of the AgOAc-catalyzed hydroboration of styrene
1a with HBpin.
Scheme 4. Radical Trapping Experiment
hydroboration is proposed in Scheme 5. First, in the presence
of AgOAc, there is a homolytic cleavage of the H−B bond of 2,
Scheme 5. Proposed Catalytic Cycle
a
Reaction conditions: 6 (0.5 mmol), 2 (0.75 mmol), AgOAc (10 mol
%), and toluene (1 mL) were stirred at 120 °C for 18 h under Ar;
isolated yields.
electron-donating and electron-withdrawing groups exclusively
afforded (E)-alkenyl-boronate esters 7a−j in good to excellent
yields in a regio- and stereoselective manner. Aliphatic terminal
alkynes, such as benzyl acetylene (6k), 1-hexyne (6m), 1-
octyne (6n), and 6-chloro-1-hexyne (6o), were also productive
substrates for this hydroboration, delivering the anti-
Markovnikov addition products (7k, 7m−o) in high yields.
The hydroboration of enyne 6l delivered boronyl-conjugated
diene 7l as a single isomer in 63% yield.
Reaction kinetics is a potent tool for the elucidation of the
possible reaction mechanism of a catalytic reaction.13 The
AgOAc-catalyzed hydroboration of 1a with HBpin in toluene
at 120 °C was selected as a model reaction for kinetic study.
The progress of the reaction was systematically monitored by
1H NMR spectroscopy, and acquiring kinetic profile results is
depicted in Figure 2. It was observed that the reaction showed
a significant induction period (ca. 11 h), after which it
completed in 1 h with 83% yield. The induction period
observed in the kinetic study of this hydroboration can be
accounted for by the typical profile of the radical reaction.13
To further endorse the association of the radical mechanism,
we carried out a control reaction of styrene 1a, with HBpin in
the presence of a radical scavenger, butylated hydroxytoluene
(BHT, 1.0 equiv), in which the reaction was completely
inhibited (eq 2), thus confirming the involvement of the
radical process (Scheme 4).
a hydrogen radical along with the formation of AcOBpin,14
wherein Ag(I) possibly reduced to Ag(0). The formed
hydrogen radical tends to react with another molecule of 2
to form H2 gas and a Bpin radical. Then, the Bpin radical
perhaps reacts with 1/4/6 to generate the radical intermediate
A, which then reacts with dihydrogen and yields the
hydroborated product 3/5/7 with the elimination of a
hydrogen radical. In the meantime, the formed radical
intermediate A may donate an electron to AcOBpin to
produce a cationic intermediate B and Bpin radical, which may
combine with a hydrogen radical. An electron transfer from
formed Ag(0) to intermediate B would regenerate the AgOAc
and complete the catalytic cycle.
In summary, we have developed a simple silver salt, AgOAc-
catalyzed regio- and stereoselective hydroboration of unsatu-
rated hydrocarbons, including alkenes, 1,3-dienes, and alkynes.
This ligand- and base-free protocol provides an efficient and
convenient route to access a series of alkyl-, allyl-, and (E)-
alkenylboronate esters in good to excellent yields with broad
substrate scope and good functional group compatibility.
Preliminary kinetic and mechanistic studies suggested the
association of a radical mechanism. Our study provides a
According to our kinetic and experimental results, as well as
a previous report,11 a possible catalytic cycle for this
C
DOI: 10.1021/acs.orglett.9b01217
Org. Lett. XXXX, XXX, XXX−XXX

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Angew. Chem., Int. Ed. 2013, 52, 3676. (f) Zhang, L.; Zuo, Z.; Leng,
X.; Huang, Z. Angew. Chem., Int. Ed. 2014, 53, 2696. (g) Zhang, L.;
Zuo, Z.; Wan, X.; Huang, Z. J. Am. Chem. Soc. 2014, 136, 15501.
(h) Tseng, K.-N. T.; Kampf, J. W.; Szymczak, N. K. ACS Catal. 2015,
5, 411. (i) Chen, J.; Xi, T.; Lu, Z. Org. Lett. 2014, 16, 6452. (j) Chen,
J.; Xi, T.; Ren, X.; Cheng, B.; Guo, J.; Lu, Z. Org. Chem. Front. 2014,
1, 1306. (k) Zheng, J.; Sortais, J.-B.; Darcel, C. ChemCatChem 2014,
6, 763. (l) Zhang, G.; Zeng, H.; Wu, J.; Yin, Z.; Zheng, S.; Fettinger, J.
C. Angew. Chem., Int. Ed. 2016, 55, 14369. (m) Wang, Z.; He, X.;
Zhang, R.; Zhang, G.; Xu, G.; Zhang, Q.; Xiong, T.; Zhang, Q. Org.
Lett. 2017, 19, 3067. (n) Tamang, S. R.; Bedi, D.; Shafiei-Haghighi,
S.; Smith, C. R.; Crawford, C.; Findlater, M. Org. Lett. 2018, 20, 6695.
(7) (a) Ho, H. E.; Asao, N.; Yamamoto, Y.; Jin, T. Org. Lett. 2014,
16, 4670. (b) Bismuto, A.; Thomas, S. P.; Cowley, M. Angew. Chem.,
Int. Ed. 2016, 55, 15356. (c) Lawson, J. R.; Wilkins, L. C.; Melen, R.
L. Chem. - Eur. J. 2017, 23, 10997. (d) Wu, Y.; Shan, C.; Ying, J.; Su,
J.; Zhu, J.; Liu, L. L.; Zhao, Y. Green Chem. 2017, 19, 4169. (e) Xu, R.;
Lu, G.-P.; Cai, C. New J. Chem. 2018, 42, 16456.
(8) (a) Ramirez, J.; Corberan, R.; Sanau, M.; Peris, E.; Fernandez, E.
Chem. Commun. 2005, 3056. (b) Yoshida, H.; Kageyuki, I.; Takaki, K.
Org. Lett. 2014, 16, 3512.
(9) Silver Catalysis in Organic Synthesis; Li, C.-J., Bi, X., Eds.: Wiley-
VCH Verlag GmbH & Co. KGaA, 2019.
(10) (a) Liu, B.; Ning, Y.; Virelli, M.; Zanoni, G.; Anderson, E. A.;
Bi, X. J. Am. Chem. Soc. 2019, 141, 1593. (b) Liu, Z.; Zhang, X.;
Virelli, M.; Zanoni, G.; Anderson, E. A.; Bi, X. iScience 2018, 8, 54.
(c) Liu, Z.; Sivaguru, P.; Zanoni, G.; Anderson, E. A.; Bi, X. Angew.
Chem., Int. Ed. 2018, 57, 8927. (d) Ning, Y.; Ji, Q.; Liao, P.;
Anderson, E. A.; Bi, X. Angew. Chem., Int. Ed. 2017, 56, 13805.
(e) Liu, Z.; Liu, J.; Zhang, L.; Liao, P.; Song, J.; Bi, X. Angew. Chem.,
Int. Ed. 2014, 53, 5305. (f) Liu, J.; Fang, Z.; Zhang, Q.; Liu, Q.; Bi, X.
Angew. Chem., Int. Ed. 2013, 52, 6953.
(11) Mamidala, R.; Pandey, V. K.; Rit, A. Chem. Commun. 2019, 55,
989.
(12) (a) Cao, Y.; Zhang, Y.; Zhang, L.; Zhang, D.; Leng, X.; Huang,
Z. Org. Chem. Front. 2014, 1, 1101. (b) Zaidlewicz, M.; Meller, J.
Tetrahedron Lett. 1997, 38, 7279. (c) Matsumoto, Y.; Hayashi, T.
Tetrahedron Lett. 1991, 32, 3387.
(13) (a) Connors, K. A. Chemical Kinetics: The Study of Reaction
Rates in Solution; Wiley-VCH: New York, 1990. (b) Blackmond, D. G.
Angew. Chem., Int. Ed. 2005, 44, 4302. (c) Mathew, J. S.; Klussmann,
M.; Iwamura, H.; Valera, F.; Futran, A.; Emanuelsson, E. A. C.;
Blackmond, D. G. J. Org. Chem. 2006, 71, 4711.
(14) Wang, W.; Luo, M.; Zhu, D.; Yao, W.; Xu, L.; Ma, M. Org.
Biomol. Chem. 2019, 17, 3604.
platform for exploring the use of simple silver salts as catalysts
in other hydroboration reactions.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01217.
Experimental procedures and copies of spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: bixh507@nenu.edu.cn.
ORCID
Xihe Bi: 0000-0002-6694-6742
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the funding support of NSFC
(21871043), Department of Science and Technology of Jilin
Province (20180101185JC, 20190701012GH), and the
Fundamental Research Funds for the Central Universities
(2412019ZD001).
REFERENCES
■
(1) (a) Obligacion, J. V.; Chirik, P. J. Nat. Rev. Chem. 2018, 2, 15.
(b) Zeng, X. M. Chem. Rev. 2013, 113, 6864. (c) Wen, H.; Liu, G.;
Huang, Z. Coord. Chem. Rev. 2019, 386, 138. (d) Hydrofunctionaliza-
tion, Topics in Organometallic Chemistry; Ananikov, V. P., Tanaka, M.,
Eds.; Springer: Berlin, Heidelberg, 2013; Vol. 43.
(2) (a) Brown, H. C.; Rao, B. C. S. J. Am. Chem. Soc. 1956, 78, 5694.
(b) Zaidlewicz, M. Hydroboration; John Wiley & Sons, Inc.: 2000.
(c) Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988, 21, 287.
(d) Thomas, S. P.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2009, 48,
1896. (e) Bull, J. A. Angew. Chem., Int. Ed. 2012, 51, 8930. (f) Suzuki,
A. Angew. Chem., Int. Ed. 2011, 50, 6722.
(3) (a) Matteson, D. S. Stereodirected Synthesis with Organoboranes;
Springer: Berlin, Heidelberg, 1995. (b) Brown, H. C. Organic Synthesis
via Organoboranes; Wiley Interscience: New York, 1975. (c) Hall, D.
G. Boronic Acids: Preparation and Applications in Organic Synthesis and
Medicine; Wiley-VCH: Weinheim, 2005. (d) Lennox, A. J. J.; Lloyd-
Jones, G. C. Chem. Soc. Rev. 2014, 43, 412. (e) Neeve, E. C.; Geier, S.
J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Chem. Rev. 2016,
116, 9091.
(4) (a) Brown, H. C.; Subba Rao, B. C. J. Am. Chem. Soc. 1956, 78,
2582. (b) Carroll, A.-M.; O’Sullivan, T. P.; Guiry, P. J. Adv. Synth.
Catal. 2005, 347, 609. (c) Evans, D. A.; Ratz, A. M.; Huff, B. E.;
Sheppard, G. S. J. Am. Chem. Soc. 1995, 117, 3448.
(5) (a) Carreras, L.; Serrano-Torne, M.; van Leeuwen, P. W. N. M.;
Vidal-Ferran, A. Chem. Sci. 2018, 9, 3644. (b) Gunanathan, C.;
Holscher, M.; Pan, F.; Leitner, W. J. Am. Chem. Soc. 2012, 134, 14349.
(c) Ojha, D. P.; Prabhu, K. R. Org. Lett. 2016, 18, 432. (d) Leyva, A.;
Zhang, X.; Corma, A. Chem. Commun. 2009, 4947. (e) Gorgas, N.;
Alves, L. G.; Stoger, B.; Martins, A. M.; Veiros, L. F.; Kirchner, K. J.
Am. Chem. Soc. 2017, 139, 8130. (f) Obligacion, J. V.; Neely, J. M.;
Yazdani, A. N.; Pappas, I.; Chirik, P. J. J. Am. Chem. Soc. 2015, 137,
5855. (g) Chakrabarty, S.; Takacs, J. M. J. Am. Chem. Soc. 2017, 139,
6066.
(6) (a) Obligacion, J. V.; Chirik, P. J. Org. Lett. 2013, 15, 2680.
(b) Obligacion, J. V.; Chirik, P. J. J. Am. Chem. Soc. 2013, 135, 19107.
(c) Scheuermann, M. L.; Johnson, E. J.; Chirik, P. J. Org. Lett. 2015,
17, 2716. (d) Palmer, W. N.; Diao, T.; Pappas, I.; Chirik, P. J. ACS
Catal. 2015, 5, 622. (e) Zhang, L.; Peng, D.; Leng, X.; Huang, Z.
D
DOI: 10.1021/acs.orglett.9b01217
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