Direct Synthesis of Alkenylboronates from Alkenes and Pinacol Diboron via Copper Catalysis

Article abstract of DOI:10.1021/acs.orglett.8b03599

We report an efficient approach for the direct synthesis of alkenylboronates using copper catalysis. The Cu/TEMPO catalyst system (where TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) exhibits both excellent reactivity and selectivity for the synthesis of alkenylboronates, starting from inexpensive and abundant alkenes and pinacol diboron. This approach allows for the direct functionalization of both aromatic and aliphatic terminal alkenes. Mechanistic experiments suggest that the alkenylboronates arise from oxyboration intermediates.

Full text of DOI:10.1021/acs.orglett.8b03599

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Direct Synthesis of Alkenylboronates from Alkenes and Pinacol
Diboron via Copper Catalysis
Wenkui Lu and Zengming Shen*
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao
Tong University, 800 Dongchuan Road, Shanghai, 200240, China
S
* Supporting Information
ABSTRACT: We report an efficient approach for the direct
synthesis of alkenylboronates using copper catalysis. The Cu/
TEMPO catalyst system (where TEMPO = (2,2,6,6-
tetramethylpiperidin-1-yl)oxyl) exhibits both excellent reac-
tivity and selectivity for the synthesis of alkenylboronates,
starting from inexpensive and abundant alkenes and pinacol
diboron. This approach allows for the direct functionalization
of both aromatic and aliphatic terminal alkenes. Mechanistic
experiments suggest that the alkenylboronates arise from oxyboration intermediates.
lkenylboronates are versatile building blocks that are
widely employed in academia and the pharmaceutical
genative borylation of alkenes by β−H elimination have
emerged (Scheme 1, path b).9a,b,10a−d,11a,12,14−16 Notably,
because of the inexpensive and environmentally benign aspects
of copper catalysis, investigations of Cu-catalyzed borylation of
alkynes and alkenes have been a trending topic in the past
decade.6a,c,17 However, to our knowledge, there are no
examples of Cu-catalyzed methods that operate through
radical-based pathways to furnish alkenylboronates starting
from alkene precursors. As such, we envisioned a Cu-catalyzed
radical pathway to access alkenylboronates using readily
acccessible alkenes as substrates instead of alkynes (Scheme
2), thus giving rise to a novel system with broad substrate
A
industry.1 These fundamentally and practically important
species can be readily transformed to a series of functional
groups such as C−C, C−O, C−N, C−F, C−Br, and C−I
bonds by transition-metal-catalyzed cross-coupling reactions.2,3
Given the significance of alkenylboronates, effective ap-
proaches for preparing alkenylboronates are highly desirable.
Traditionally, alkenylboronates are synthesized through
transition-metal-catalyzed (i.e., Pd, Cu, Rh, and Ru) hydro-
boration of alkynes (Scheme 1, path a)4−6 and from multistep
Scheme 1. Common Approaches to Alkenylboronates
Scheme 2. A Radical-Based Strategy for Synthesizing
Alkenylboronates
scope and good reactivity (Scheme 2). Herein, we detail a new
approach for the direct synthesis of alkenylboronates from
alkenes and pinacol diboron via copper catalysis by using
TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) as a mild
oxidant. Note that our new approach is compatible with
both aliphatic and aromatic alkenes.
To test our hypothesis, we examined the borylation of 2-
vinylnaphthalene (1a) using the Cu/TEMPO system. The
choice of TEMPO as the mild oxidant is based on our previous
boron-Wittig reaction of aldehydes.7 The starting materials
required for these approaches are more expensive and less
readily available than their alkene counterparts. Consequently,
the direct borylation of alkenes is attractive for both
economical and practical reasons.8−16
While there are significant advantages to the direct
borylation of alkenes, a major challenge that has long been
recognized is the undesired hydroboration of alkenes that leads
to alkylboronate side-products (Scheme 1, path c).6c,8 In
recent years, examples of transition-metal-catalyzed dehydro-
Received: November 10, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03599
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
studies.18 Initially, to our delight, alkenylboronate 3a and
hydroboration side-product 4a were obtained in a combined
24% yield in a ratio of 61:39 (3a/4a, in DMF, Table S1 in the
Supporting Information, entry 1).19 In the absence of TEMPO,
alkenylboronate 3a is not formed, suggesting that TEMPO
plays a significant role in the current direct borylation process.
Surprisingly, a significant solvent effect was observed during
the evaluation of solvents (Table S1, entries 1−10).19 DCE
was found to be the most effective solvent, providing 3a in high
chemoselectivity (3a:4a = 92:8) (Table S1, entry 10).19
Further optimization of the reaction parameters resulted in the
use of a combination of CuSCN and CyJohnPhos, which
produced alkenylboronate 3a in 85% yield with exclusive
chemoselectivity, regioselectivity, and stereoselectivity (3a:4a
= 100:0) (Table S1, entry 14).19 Moreover, only the E-
stereoisomer of 3a was formed. We reasoned that the observed
stereoselectivity is thermodynamically controlled. The optimal
condition for the current borylation of alkenes is the use of 10
mol % CuSCN/22 mol % CyJohnPhos, LiOtBu (1 equiv),
TEMPO (2 equiv), and B2(pin)2 (2 equiv) in DCE solvent at
80 °C (Table S1, entry 14).19
Table 1. Dehydrogenative Borylation of Various Terminal
Aryl Alkenes
a
With this protocol established, we explored the generality
and limitations of our Cu-catalyzed borylation of aromatic
terminal alkenes with B2(pin)2 (Table 1). To our delight, a
wide range of aromatic and heteroaromatic terminal alkenes
smoothly transformed to provide alkenylboronates in high
chemoselectivities and stereoselectivities. Electron-rich aro-
matic alkenes with alkyl (1d, 1e), ether (1f, 1g), amide (1h),
and acyloxy (1i) substitutions underwent efficient and selective
borylation with B2(pin)2 to afford the desired aromatic
alkenylboronates in up to 89% yield, 100:0 ratio of 3/4, and
as single E-stereoisomers (3a−3i). Notably, varying the size of
the substituents from methyl (1d) to tert-butyl (1e) displayed
good compatibility. In addition, inductively electron-with-
drawing groups on aromatic rings were also well-tolerated, with
the desired products formed in good selectivities and high
yields. For example, styrenes substituted with F, Cl, and Br
atoms at various positions of the phenyl ring performed well to
furnish exclusively 3ja−3jg in up to 84% yield (Table 1, entry
10). Substrate 1l with the trifluoromethyl substitution also
worked well (Table 1, entry 12). However, strongly electron-
withdrawing groups such as 4-keto-(1m), 4-cyano-(1n), and 4-
nitro-(1o) groups on the phenyl ring drastically influenced
both the chemoselectivity and reactivity. In these reactions,
competitive hydroborylation was a major side-reaction (Table
1, entries 13−15). To our surprise, the scope of this method
smoothly extended to heteroaromatic alkenes with excellent
chemoselectivity and high yields. For example, 2-vinyl-
thiophene (1p), 2-vinylpyridine (1q), 5-vinylpyrimidine (1r),
5-vinyl-N-Ts-indole (1s), 5-vinylbenzofuran (1t), and 3-vinyl-
9H-carbazole (1u) underwent efficient borylation in up to 76%
yield, 100:0 ratio of 3/4, and as single E-stereoisomers (Table
1, entries 16−21). However, while 4-vinylquinoline (1v) and
5-vinylisoquinoline (1w) exhibited high reactivity, lower levels
of chemoselectivities were observed (97%−100% combined
yields of 3 and 4; Table 1, entries 22 and 23). Finally, to
demonstrate utility in organic synthesis, a more complex alkene
containing the estrone (1x) motif was examined. The reaction
proceeded smoothly to afford the corresponding product 3x in
76% yield with complete chemoselectivity (100:0 ratio of 3/4),
thus providing a promising approach for late-stage modifica-
tion of bioactive compounds.
a
Conditions: 1a (0.3 mmol, 1 equiv), B2(pin)2 (2 equiv), LiOtBu (1
equiv), TEMPO (2 equiv), CuSCN (10 mol %), CyJohnPhos (22
mol %), 80 °C, DCE (2 mL). The corresponding reaction time is
shown in the Supporting Information. bIsolated yield. cThe ratio of 3/
4 was determined by 1H NMR spectroscopy analysis. dTotal yield of 3
and 4 after chromatographic purification.
Inspired by the above results, we turned our attention to
more challenging unactivated aliphatic alkenes. We chose 5a as
the model substrate to test the borylation of aliphatic alkenes
(Table S2 in the Supporting Information).19 We found that the
choice of ligand has a significant effect on the formation of
aliphatic alkenylboronates. By surveying a series of ligands, we
found XantPhos to be particularly promising and completely
inhibited the competitive hydroborylation (Table S2, entry
1).19 By further examining other parameters of the reaction
conditions, efficient and selective borylation smoothly
occurred to provide 6a in 93% yield and 87:13 E/Z ratio in
the presence of CuSCN (10 mol %), Xantphos (20 mol %),
tBuOLi (2.5 equiv), and TEMPO (2.1 equiv) in CH3CN at
100 °C (Table S2, entry 4).19 We also found that the reaction
temperature strongly influenced the generation of alkenylbor-
onates (Table S2, entries 1−5).19 Various aliphatic alkenes
containing a long alkyl chain (6b) or cyclohexyl (6c), silylether
(6d), ether (6e), and ester (6f) groups (Scheme 3) performed
B
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Scheme 3. Scope of Aliphatic Alkenes
Scheme 4. Plausible Reaction Mechanism
well under the optimal conditions to furnish the borylated
products in up to 95% yield with excellent regioselectivity and
stereoselectivity. In all cases, the E-stereoisomer is exclusively
1
formed (determined by H NMR analysis).
generate LnCu(I)Bpin A and pinBOtBu. Next, alkene 1 inserts
into the Cu-Bpin bond to form β-boryl alkyl copper(I) B,
which can undergo two competing pathways. We considered
that the electronic properties of the R groups can significantly
influence both the reactivity and chemoselectivity in this
step.22 In addition, the optimized combination of CuSCN,
ligand, and solvent plays a key role in suppressing the
hydroborylation process. Intermediate B then reacts with
TEMPO to form the C−Cu(II) complex C, which can
undergo homolytic cleavage to provide alkyl radical E and
LnCu(I)OTMP D. Complex D is treated with LiOtBu to
regenerate the active LnCu(I)OtBu. Alkyl radical E is trapped
by a second equivalent of TEMPO to afford oxyboration
intermediate F, which is thermally transformed to alkenylbor-
onate. TEMPOH is observed by GC analysis, which provides
support for this proposed mechanism.19 Over the course of the
reaction, the starting material is never completely consumed,
even under prolonged reaction time. A plausible explanation
for this is that intermediate F provides terminal alkenes in low
yields upon heating (see eq 3).
To gain insight into the reaction mechanism, a series of
mechanistic studies was performed. First, we synthesized a
deuterium-labeled 2-vinylnaphthalene 1a-D20 to test whether
the alkenylboronate product is formed through a β-H
elimination pathway (eq 1). In this case, deuterium is not
In summary, the results described herein show that the Cu−
TEMPO catalyst system exhibits both excellent reactivity and
selectivity for the direct synthesis of alkenylboronates using
inexpensive and abundant alkenes as starting materials. Not
only are aromatic terminal alkenes accommodated, but
aliphatic terminal alkenes are also compatible in forming the
corresponding products in high yields with excellent chemo-
selectivity, regioselectivity, and stereoselectivity. The compet-
itive hydroborylation of alkenes is efficiently suppressed in our
newly reported system. Detailed mechanistic studies revealed
that the reaction undergoes a radical pathway and TEMPO
plays a significant role in this transformation. Mechanistic
support suggests that the formation of alkenylboronate comes
from oxyboration intermediate F. We were able to rule out a β-
H elimination pathway. Furthermore, the diverse trans-
formations of alkenylboronates in the literature23 suggest that
these reactions could find widespread applications in both
academia and industry.
incorporated into the β-position of alkenylboronate 3a-D
(nearly 100% H at the β-position, 93% D at the α-position of
alkenylboronate). Thus, a Cu-catalyzed β-H elimination
pathway is effectively ruled out. Second, we obtained a
reaction profile for the Cu-catalyzed borylation of 1a under the
standard conditions. We found that substrate 1a was quickly
consumed and a new intermediate was formed, followed by
gradual generation of product 3a (Figure S1).19 The new
signal suggests that this intermediate is a key component of
this reaction. We trapped it and determined its structure to be
oxyborylated 3a-int by 1H NMR, 13C NMR spectra, and
HRMS. Two additional control experiments were performed:
(1) intermediate 3a-int was subjected to the standard reactions
conditions, which gave rise to the borylated product 3a in 85%
yield (eq 2); (2) direct heating of 3a-int in DCE at 80 °C also
led to the formation of 3a in 83% yield, along with 10% yield of
terminal alkene 1a (eq 3). These unexpected results suggest
that alkenylboronate product 3a can be derived from
intermediate 3a-int by direct heating without any external
reagents.
ASSOCIATED CONTENT
* Supporting Information
■
S
On the basis of our mechanistic studies and previous
report,21 a tentative reaction mechanism for this Cu-catalyzed
alkene borylation is proposed. As shown in Scheme 4, CuSCN
first reacts with LiOtBu to produce the active LnCu(I)OtBu
complex, followed by transmetalation with pinacol diboron to
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03599.
Experimental details and spectroscopic data (PDF)
C
DOI: 10.1021/acs.orglett.8b03599
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Letter
(c) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Tetrahedron 2015, 71,
2183−2197.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: shenzengming@sjtu.edu.cn.
ORCID
(7) (a) Coombs, J. R.; Zhang, L.; Morken, J. P. Org. Lett. 2015, 17,
1708−1711. (b) Tanaka, S.; Saito, Y.; Yamamoto, T.; Hattori, T. Org.
Lett. 2018, 20, 1828−1831.
(8) Geier, S. J.; Westcott, S. A. Rev. Inorg. Chem. 2015, 35, 69−74.
(9) For Pd-catalyzed borylation of alkenes, see: (a) Takaya, J.; Kirai,
N.; Iwasawa, N. J. Am. Chem. Soc. 2011, 133, 12980−12983. (b) Reid,
W. B.; Spillane, J. J.; Krause, S. B.; Watson, D. A. J. Am. Chem. Soc.
2016, 138, 5539−5542. (c) Kirai, N.; Iguchi, S.; Ito, T.; Takaya, J.;
Iwasawa, N. Bull. Chem. Soc. Jpn. 2013, 86, 784−799. (d) Davan, T.;
Corcoran, E. W., Jr; Sneddon, L. G. Organometallics 1983, 2, 1693−
1694. (e) Takagi, J.; Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Am.
Chem. Soc. 2002, 124, 8001−8006.
Zengming Shen: 0000-0001-5706-349X
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Dedicated to Professor Xiyan Lu on the occasion of his 90th
birthday. This work was supported by the National Natural
Sciences Foundation of China (No. 21672144) and Shanghai
Key Laboratory for Molecular Engineering of Chiral Drugs
(No. 17DZ2260400). We are grateful to the Instrumental
Analysis Center of SJTU for compound analyses.
(10) For Rh-catalyzed borylation of alkenes, see: (a) Brown, J. M.;
Lloyd-Jones, G. C. J. Am. Chem. Soc. 1994, 116, 866−878.
(b) Kondoh, A.; Jamison, T. F. Chem. Commun. 2010, 46, 907−
909. (c) Brown, A. N.; Zakharov, L. N.; Mikulas, T.; Dixon, D. A.;
Liu, S.-Y. Org. Lett. 2014, 16, 3340−3343. (d) Morimoto, M.; Miura,
T.; Murakami, M. Angew. Chem., Int. Ed. 2015, 54, 12659−12663.
(e) Burgess, K.; Van der Donk, W. A.; Westcott, S. A.; Marder, T. B.;
Baker, R. T.; Calabrese, J. C. J. Am. Chem. Soc. 1992, 114, 9350−
9359. (f) Vogels, C. M.; Hayes, P. G.; Shaver, M. P.; Westcott, S. A.
Chem. Commun. 2000, 36, 51−52. (g) Coapes, R. B.; Souza, F. E. S.;
Thomas, R. L.; Hall, J. J.; Marder, T. B. Chem. Commun. 2003, 39,
614−615. (h) Mkhalid, I. A. I.; Coapes, R. B.; Edes, S. N.; Coventry,
D. N.; Souza, F. E. S.; Thomas, R. L.; Hall, J. J.; Bi, S.-W.; Lin, Z.;
Marder, T. B. Dalton Trans 2008, 8, 1055−1064.
REFERENCES
■
(1) (a) Roupe, K.; Remsberg, C.; Yanez, J.; Davies, N. Curr. Clin.
Pharmacol. 2006, 1, 81−101. (b) Cottart, C.-H.; Nivet-Antoine, V.;
Beaudeux, J.-L. Mol. Nutr. Food Res. 2014, 58, 7−21. (c) Meier, H.
Angew. Chem., Int. Ed. Engl. 1992, 31, 1399−1420. (d) Lo, S.-C. P.;
Burn, L. Chem. Rev. 2007, 107, 1097−1116. (e) Likhtenshtein, G. I.
Stilbenes: Applications in Chemistry, Life Sciences and Materials Science;
Wiley: New York, 2010.
(2) For selected examples, see: (a) Yoo, K. S.; Yoon, C. H.; Jung, K.
W. J. Am. Chem. Soc. 2006, 128, 16384−16393. (b) Delcamp, J. H.;
Brucks, A. P.; White, M. C. J. Am. Chem. Soc. 2008, 130, 11270−
11271. (c) Shang, R.; Ilies, L.; Asako, S.; Nakamura, E. J. Am. Chem.
Soc. 2014, 136, 14349−14352.
(3) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457−2483.
(b) Petasis, N. A.; Akritopoulou, I. Tetrahedron Lett. 1993, 34, 583−
586.
(11) For Ir-catalyzed borylation of alkenes, see: (a) Sasaki, I.; Doi,
H.; Hashimoto, T.; Kikuchi, T.; Ito, H.; Ishiyama, T. Chem. Commun.
́
2013, 49, 7546−7548. (b) Olsson, V. J.; Szabo, K. J. J. Org. Chem.
2009, 74, 7715−7723.
(12) For Pt-catalyzed borylation of alkenes, see: Ohmura, T.;
Takasaki, Y.; Furukawa, H.; Suginome, M. Angew. Chem., Int. Ed.
2009, 48, 2372−2375.
(13) For Ru-catalyzed borylation of alkenes, see: (a) Blackwell, H.
E.; O’Leary, D. J.; Chatterjee, A. K.; Washenfelder, R. A.; Bussmann,
D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 58−71. (b) Funk,
T. W.; Efskind, J.; Grubbs, R. H. Org. Lett. 2005, 7, 187−190.
(c) Marciniec, B.; Jankowska, M.; Pietraszuk, C. Chem. Commun.
2005, 41, 663−665.
(14) For Fe-catalyzed borylation of alkenes, see: Wang, C.; Wu, C.
Z.; Ge, S. ACS Catal. 2016, 6, 7585−7589.
(15) For Co-catalyzed borylation of alkenes, see: (a) Wen, H.;
Zhang, L.; Zhu, S.; Liu, G.; Huang, Z. ACS Catal. 2017, 7, 6419−
6425. (b) Zhang, L.; Huang, Z. J. Am. Chem. Soc. 2015, 137, 15600−
15603.
(4) (a) Gridnev, I. D.; Miyaura, N.; Suzuki, A. Organometallics 1993,
12, 589−592. (b) Pereira, S.; Srebnik, M. Organometallics 1995, 14,
3127−3128. (c) Ohmura, T.; Yamamoto, Y.; Miyaura, M. J. Am.
̌
̌
́
Chem. Soc. 2000, 122, 4990−4991. (d) Lipshutz, B. H.; Boskovic, Z.
V.; Aue, D. H. Angew. Chem., Int. Ed. 2008, 47, 10183−10186.
(e) Molander, G. A.; Ellis, N. M. J. Org. Chem. 2008, 73, 6841−6844.
́
́
(f) Cid, J.; Carbo, J. J.; Fernandez, E. Chem. - Eur. J. 2012, 18, 1512−
1521. (g) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Chem. - Eur. J.
̈
2012, 18, 4179−4184. (h) Gunanathan, C.; Holscher, M.; Pan, F.;
Leitner, W. J. Am. Chem. Soc. 2012, 134, 14349−14352.
(i) Kiesewetter, E. T.; O’Brien, R. V.; Yu, E. C.; Meek, S. J.;
Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2013, 135, 6026−
6029. (j) Greenhalgh, M. D.; Thomas, S. P. Chem. Commun. 2013, 49,
11230−11232. (k) Obligacion, J. V.; Neely, J. M.; Yazdani, A. N.;
Pappas, I.; Chirik, P. J. J. Am. Chem. Soc. 2015, 137, 5855−5858.
(l) Jang, W. J.; Lee, W. L.; Moon, J. H.; Lee, J. Y.; Yun, J. Org. Lett.
2016, 18, 1390−1394. (m) Yang, Z.; Zhong, M.; Ma, X.; Nijesh, K.;
De, S.; Parameswaran, P.; Roesky, H. W. J. Am. Chem. Soc. 2016, 138,
(16) For Cu-catalyzed borylation of alkenes, see: Mazzacano, T. J.;
Mankad, N. P. ACS Catal. 2017, 7, 146−149.
(17) (a) Mankad, N. P.; Laitar, D. S.; Sadighi, J. P. Organometallics
2004, 23, 3369−3371. (b) Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P.
Organometallics 2006, 25, 2405−2408. (c) Dang, L.; Zhao, H.; Lin,
Z.; Marder, T. B. Organometallics 2007, 26, 2824−2832. (d) Jordan,
A. J.; Lalic, G.; Sadighi, J. P. Chem. Rev. 2016, 116, 8318−8372.
(18) (a) Li, L.; Yu, Z.; Shen, Z. Adv. Synth. Catal. 2015, 357, 3495−
3500. (b) Zhao, M.; Zhang, W.; Shen, Z. J. Org. Chem. 2015, 80,
8868−8873. (c) Zhu, Y.; Zhao, M.; Lu, W.; Li, L.; Shen, Z. Org. Lett.
2015, 17, 2602−2605. (d) Zhu, Y.; Li, L.; Shen, Z. Chem. - Eur. J.
2015, 21, 13246−13252.
̈
2548−2551. (n) Gorgas, N.; Alves, L. G.; Stoger, B.; Martins, A. M.;
Veiros, L. F.; Kirchner, K. J. Am. Chem. Soc. 2017, 139, 8130−8133.
(o) Nakajima, K.; Kato, T.; Nishibayashi, Y. Org. Lett. 2017, 19,
4323−4326.
(19) See the Supporting Information for details.
(5) (a) Lee, Y.; Jang, H.; Hoveyda, A. H. J. Am. Chem. Soc. 2009,
131, 18234−18235. (b) Jang, H.; Zhugralin, A. R.; Lee, Y.; Hoveyda,
A. H. J. Am. Chem. Soc. 2011, 133, 7859−7871. (c) Moure, A. L.;
́
(20) Di Giuseppe, A.; Castarlenas, R.; Perez-Torrente, J. J.; Lahoz, F.
J.; Polo, V.; Oro, L. Angew. Chem., Int. Ed. 2011, 50, 3938−3942.
(21) Itoh, T.; Matsueda, T.; Shimizu, Y.; Kanai, M. Chem. - Eur. J.
2015, 21, 15955−15959.
́
́
Gomez Arrayas, R.; Cardenas, D. J.; Alonso, I.; Carretero, J. C. J. Am.
́
Chem. Soc. 2012, 134, 7219−7222. (d) Moure, A. L.; Mauleon, P.;
́
(22) If a strong electron-rich group is attached at the para position
of phenyl ring, the insertion step becomes sluggish, resulting in low
yield, for example, substrate 1g (Table 1, entry 7). On the other hand,
strong electron-deficient aromatic groups (R) are prone to leading to
competitive protonation of alkyl copper complex B to form
Gomez Arrayas, R.; Carretero, J. C. Org. Lett. 2013, 15, 2054−2057.
(e) Ojha, D. P.; Prabhu, K. R. Org. Lett. 2016, 18, 432−435.
(6) (a) Yun, J. Asian J. Org. Chem. 2013, 2, 1016−1025.
(b) Barbeyron, R.; Benedetti, E.; Cossy, J.; Vasseur, J.-J.;
Arseniyadis, S.; Smietana, M. Tetrahedron 2014, 70, 8431−8452.
D
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hydroborylation side-product 4a, in which a small amount of water in
solvent probably provides the proton source. Substrates 1m−1o and
1v−1w verify this phenomenon (Table 1, entries 13−15, 22, 23).
(23) (a) Buchanan, H. S.; Pauff, S. M.; Kosmidis, T. D.; Taladriz-
Sender, A.; Rutherford, O. I.; Hatit, M. Z. C.; Fenner, S.; Watson, A. J.
B.; Burley, G. A. Org. Lett. 2017, 19, 3759−3762. (b) Stephens, T. C.;
Pattison, G. Org. Lett. 2017, 19, 3498−3501. (c) Hemelaere, R.;
Caijo, F.; Mauduit, M.; Carreaux, F.; Carboni, B. Eur. J. Org. Chem.
2014, 2014, 3328−3333.
E
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