Cobalt- or copper-catalyzed synthesis of gem-difluoroallyl MIDA boronates from α-trifluoromethyl alkenes

Article abstract of DOI:10.1016/j.tetlet.2020.151940

A novel two-step synthesis of gem-difluoroallyl MIDA boronates, which are air- and moisture-stable fluorine-containing building blocks for potential applications in iterative cross-couplings, was developed. The first step involves cobalt- or copper-cataly

Full text of DOI:10.1016/j.tetlet.2020.151940

Journal Pre-proofs
Cobalt- or copper-catalyzed synthesis of gem-difluoroallyl MIDA boronates
from α-trifluoromethyl alkenes
Yisen Liu, Chunmei Li, Chuan Liu, Jingjing He, Xianghu Zhao, Song Cao
PII:
DOI:
Reference:
S0040-4039(20)30383-X
https://doi.org/10.1016/j.tetlet.2020.151940
TETL 151940
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
5 February 2020
9 April 2020
13 April 2020
Please cite this article as: Liu, Y., Li, C., Liu, C., He, J., Zhao, X., Cao, S., Cobalt- or copper-catalyzed synthesis
of gem-difluoroallyl MIDA boronates from α-trifluoromethyl alkenes, Tetrahedron Letters (2020), doi: https://
doi.org/10.1016/j.tetlet.2020.151940
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover
page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version
will undergo additional copyediting, typesetting and review before it is published in its final form, but we are
providing this version to give early visibility of the article. Please note that, during the production process, errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2020 Published by Elsevier Ltd.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Cobalt- or copper-catalyzed synthesis of
gem-difluoroallyl MIDA boronates from -
trifluoromethyl alkenes
Leave this area blank for abstract info.
Yisen Liu, Chunmei Li, Chuan Liu, Jingjing He, Xianghu Zhao, and Song Cao*
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology (ECUST),
Shanghai 200237, China
O
O
N
HO
MIDA
OH
Co(acac)
2 (5 mol%), THF
MeN
B
CF3
F
F
LiOtBu (3 equiv), 80 oC, 6 h, Ar
(
, 6.0 equiv)
B2pin2
+
O
O
Ar
O
O
or CuCN
LiOtBu (1 equiv), 60 oC, 6 h, Ar
(5 mol%), THF
DMSO (10 mL)
110 oC, 12 h
Ar
 Ligand-free Good FG tolerance Facile product isolation and purification

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Cobalt- or copper-catalyzed synthesis of gem-difluoroallyl MIDA boronates from
-trifluoromethyl alkenes
Yisen Liu, Chunmei Li, Chuan Liu, Jingjing He, Xianghu Zhao, and Song Cao
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology (ECUST), Shanghai 200237, China
———
ARTICLE INFO
ABSTRACT
*Corresponding author. E-mail address: scao@ecust.edu.cn
Article history:
Received
Received in revised form
Accepted
A novel two-step synthesis of gem-difluoroallyl MIDA boronates, which are air- and moisture-
stable fluorine-containing building blocks for potential applications in iterative cross-couplings,
was developed. The first step involves cobalt- or copper-catalyzed defluoroborylation of -
trifluoromethyl alkenes with B2pin2 in the absence of ligand. Next, without further purification,
the resulting gem-difluroallylboronic acid pinacol ester was converted to gem-difluoroallyl
MIDA boronates by heating in the presence of MIDA.
Available online
2019 Elsevier Ltd. All rights reserved.
Keywords:
cobalt- or copper-catalyzed
gem-difluoroallyl MIDA boronates
-trifluoromethyl alkenes
gem-Difluoroalkenes are recognized as important architectural
units widely found in agrochemicals, pharmaceuticals as well as
organic materials.1 Furthermore, they are useful synthetic
intermediates for the synthesis of a variety of fluorine-containing
or non-fluorinated organic molecules due to their high
polarization of the carbon–carbon double bond and the good
leaving-group ability of the fluoride ion.2 Therefore, the synthesis
of various gem-difluoroalkenes has attracted increasing attention
in recent years.3 Numerous methods have been developed thus
far for the synthesis of gem-difluoroalkene derivatives.4 One of
the most commonly used method for the synthesis of
functionalized gem-difluoroalkenes involves the SN2′ reaction of
2-trifluoromethyl-1-alkenes with oxygen, sulfur, nitrogen
nucleophiles and organometallic reagents.5
of column chromatography.10 As a consequence, increasing
efforts have been devoted to the synthesis of structurally diverse
MIDA boronates in recent years.11
MeN
F
K
R
O
OH
OH
O
O
R
B
R
B
B F
B
O
O
R
O
F
RB(OH)2
sp2
RBpin
RBF3K
sp3
RBMIDA
sp3
hybridized boron
species:
sp2
Reacitivity: High
Stability: Low
Low
High
High
Selectivity: Low
Scheme 1 The comparison of various organoboron reagents
gem-Difluoroallylboronates are useful precursors for further
transformation into various difluorinated compounds.12
Nowadays, the highly efficient copper or iron-catalyzed synthesis
of -substituted-,-difluoroallylboronic acid pinacol ester from
trifluoromethyl alkenes and B2pin2 has received significant
growing interests. In 2011, Hoveyda′ group disclosed the first
example of Cu-catalyzed defluoroborylation of CF3-substituted
alkenes with B2pin2 in the presence of chiral or achiral
imidazolinium salt. However, only one borylated gem-
difluoroalkene was obtained (yields 54 and 20 %, respectively).13
In 2017, Zhou and co-workers have reported the synthesis of
gem-difluoroallylboronates via FeCl2-catalyzed defluorobor-
ylation of trifluoromethyl alkenes.14 In 2018, Shi and Ito
independently developed a novel approach for the synthesis of
enantioenriched gem-difluoroallylboronates via the copper(I)-
Boronic acids (RB(OH)2), boronate esters such as pinacol
boronates (RBpin), potassium organotrifluoroborates (RBF3K)
and N-methyliminodiacetic acid (MIDA) boronates are four main
organoboron reagents (Scheme 1).6 They are indispensable and
versatile coupling partners in transition-metal-catalyzed C−C and
C−heteroatom bond formation.7 Among the various available
organoboron compounds, MIDA boronates are especially
attractive because they have found wide applications in the
synthesis of small-molecule natural products through the iterative
cross-coupling (ICC) strategy.8 The MIDA boronates are stable
towards many types of chemical transformations and also stable
to storage on the bench top under air without noticeable
decomposition for several months.9 Furthermore, they are
generally highly crystalline, free-flowing solids and could be
easily purified by recrystallization from solvent without the use
Table 1. Optimization of reaction conditions.a

Tetrahedron
F
F
CF3
1a
MeN
B
DMSO (10 mL), 110 oC, 12 h
F
F
Catalyst, Base
Temp, 6 h, Ar
Bpin
B2pin2
+
O
O
O
O
O
O
O
O
N
HO
OH
, 6.0 equiv)
2a
(without purification)
O
3a
MIDA
(
Entry
Catalyst (x mol%)
Base (x equiv)
Solvent
Temp (oC)
2a (%)b
1
2
3
4
none
Co(OAc)2 (10)
CoF2 (10)
CoCl2(PPh3)4 (10)
CoBr2 (10)
LiOtBu (1)
LiOtBu (1)
LiOtBu (1)
LiOtBu (1)
LiOtBu (1)
LiOtBu (1)
None
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
CH3CN
toluene
DMF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
80
80
80
rt
0
7
10
16
22
50
0
13
16
22
30
7
5
6
7
8
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac) 2 (10)
Co(acac) 2 (10)
Co(acac) 2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (10)
Co(acac)2 (5)
Co(acac)2 (3)
CuOAc (10)
CuOAc (10)
CuI (10)
CH3ONa (1)
C2H5ONa (1)
KOtBu (1)
NaOtBu (1)
LiOtBu (1)
LiOtBu (1)
LiOtBu (1)
LiOtBu (1)
LiOtBu (2)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (3)
LiOtBu (1)
LiOtBu (0.5)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
13
24
42
61
70
90
89
60
10
80
88
87
89
95
95
95
20
60
60
60
60
60
60
60
60
CuBr (10)
CuSCN (10)
CuCN (10)
CuCN (5)
CuCN (5)
CuCN (5)
aReaction conditions: 1a (0.1 mmol), B2pin2 (0.12 mmol), solvent (1 mL).
bYields are determined by GC analysis based on 1a.
catalyzed asymmetric defluoroborylation of CF3-substituted
alkenes using (R,S)-Josiphos as the chiral ligand.15 More recently,
our group also reported an efficient method for the synthesis of
gem-difluoroallylboronates via CuOAc-catalyzed defluorinative
borylation of -trifluoromethyl alkenes with B2pin2 using
Xantphos as ligand and NaOtBu as base.16
the absence of ligand.16 Encouraged by these preliminary results,
we carried out this reaction without any additional ligand in the
following investigation. We began our experiment by using the
reaction of 1-methoxy-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene
1a with B2pin2 as the model reaction to optimize the reaction
conditions (Table 1). No desired product 2a was detected in the
absence of a metal catalyst (entry 1). The effect of the Co catalyst
on the reaction was then examined. Among the various Co salts
tested (entries 2–6), Co(acac)2 was the most suitable for the
reaction, giving the expected product 2a in moderate yield, while
other cobalt salts such as Co(OAc)2, CoF2, CoCl2(PPh3)4 and
CoBr2 gave lower yields. Screening of different bases exhibited
that LiOtBu was effective for this reaction (entries 7–11), while
small amounts of the borylated gem-difluoroalkenes were formed
when CH3ONa, C2H5ONa, KOtBu or NaOtBu was used as the
base. Subsequently, the influence of solvent was investigated
(entries 12–15). The results indicated that both THF and DMF
could afford moderate yields of 2a, whereas the yields were
reduced when Et2O, CH3CN and toluene were used as solvent.
Furthermore, an excess of LiOtBu and higher temperature were
found to be favorable for the reaction and afforded 2a in high
yield (entries 16–18). To our delight, decreasing the amount of
Co(acac)2 from 10 mol % to 5 mol % would also provide 2a in
good yield (entry 19). Further decreasing the amount of
Co(acac)2 led to significant decrease in the yield (60%, entry 20).
Although the above-mentioned approaches to the synthesis of
gem-difluoroallylboronates are efficient and useful, these
methods still suffer one or more drawbacks such as the use of
complex and expensive ligands, limited substrate scope and
tedious and time-consuming chromatographic separation.
Therefore, there is a growing demand for more simple and
efficient new catalytic system. Cobalt-catalyzed couplings are of
interest in organic synthesis because cobalt catalysts are stable,
inexpensive and low toxic.17 To the best of our knowledge,
defluoroborylation of trifluoromethyl alkenes employing Co-
based catalysts have not been previously reported. In this letter,
we reported a novel method for the synthesis of gem-difluoroallyl
MIDA boronates through cobalt- or copper-catalyzed defluor-
oborylation of trifluoromethyl alkenes with B2pin2 in the absence
of ligand, followed by treatment of the crude borylation products
with N-methyliminodiacetic acid (MIDA).
We previously reported a copper-catalyzed synthesis of gem-
difluoroallylboronates from -trifluoromethyl alkenes and B2pin2
in the presence of Xantphos and NaOtBu. During the course of
our investigation on Cu-catalyzed defluoroborylation of
trifluoromethyl alkenes, we found that the reaction could also
provide the expected gem-difluoroallylboronate in 37% yield in
Inspired by the success in the Co-catalyzed defluoroborylation
of -trifluoromethyl alkenes, we focused on the
defluoroborylation of trifluoromethyl alkenes using various Cu(I)

3
catalysts in the absence of ligand. After careful screening a
number of reaction conditions, such as the type of Cu(I) salt,
catalyst and base amount, and reaction temperatures (entries 21–
29). We found that the defluoroborylation of -trifluoromethyl
alkenes could proceed smoothly in the presence of 5 mol %
CuCN and 1.0 equiv of LiOtBu using THF as the solvent at 60
°C for 6 h (entry 28). When the amount of LiOtBu was reduced
from 1.0 to 0.5 equiv, the yield decreased sharply and only 20%
of 3a was obtained (entry 29).
Table 2 Co-catalyzed synthesis of gem-difluoroallyl MIDA
boronates from -trifluoromethyl alkenes.a,b
CF3
F
F
F
F
MIDA
(6 equiv)
Co(acac)2 (5 mol%)
B2pin2
+
Ar
BMIDA
LiOtBu (3 equiv)
THF, 80 oC, 6 h, Ar
Bpin
DMSO, 12 h
Ar
Ar
110 o
, 8595% (GC)
(without isolation)
C
1a s

2a
s

3a

s
F
F
F
F
F
F
F
F
BMIDA
BMIDA
O
BMIDA
BMIDA
On the basis of our previous experimental observations, we
found some gem-difluoroallylboronates are unstable during
aqueous work-up and storage. Furthermore, some of them are
sensitive or incompatible with silica gel chromatography and
susceptible to decomposition during chromatographic isolation.
To overcome these limitations, we next tried to convert pinacol
boronic ester 2a to MIDA-protected boronate 3a. Delightfully,
MIDA boronate 3a could be synthesized by the reaction of
trifluoromethyl alkene 1a with B2pin2, followed by the addition
of MIDA without the isolation of the intermediate gem-
difluoroallylboronate 2a. The gem-difluoroallyl MIDA boronates
3a could be easily purified by recrystallization with Et2O without
the use of column chromatography.
O
O
O
O
O
3a
3b
, 70%
3c
3d
, 71%
, 71%
, 68%
F
F
F
F
F
F
F
F
BMIDA
BMIDA
BMIDA
BMIDA
O
O
S
3e
F
3f
3g
3h
, 70%
, 67%
, 66%
, 65%
F
F
F
F
F
F
F
BMIDA
BMIDA
BMIDA
F3CO
BMIDA
Ph
3i
3j
, 63%
3k
, 72%
3l
, 60%
, 58%
F
F
F
F
F
F
F
F
BMIDA
BMIDA
F3C
BMIDA
BMIDA
With the optimized reaction conditions in hand (Table 1, entry
19), the scope and limitations of the Co-catalyzed synthesis of
gem-difluoroallyl MIDA boronates was investigated. As shown
in Table 2, in all cases, gem-difluroallylboronic acid pinacol
esters 2a−s could be obtained in high yields (85−95%, GC-MS).
Both strong electron-donating (OMe, 3a) and strong electron-
withdrawing (NO2, 3r and CN, 3s) groups attached to the
aromatic ring of -trifluoromethyl alkenes are compatible with
the reaction conditions. This reaction exhibited a broad substrate
scope and a variety of functional groups such as methoxy,
methylthio, tert-butyl, trifluoromethoxy, chloro, bromo,
trifluoromethyl, ester, nitro and cyano, groups were well tolerated
under the optimized reaction conditions. The tolerance of the
chloro, bromo, ester, nitro and cyano groups was particularly
useful, which offered synthetic opportunities for further
transformation. Notably, substrates bearing ester (1q), nitro (1r)
or cyano (1s) groups worked well under the standard conditions.
However, trifluoromethyl alkene 1q failed to provide the
expected product under our previously reported reaction
conditions.16 Meanwhile, defluorinative borylation of substrates
1r and 1s hardly proceeded under Zhou’s reaction conditions.14
Cl
Br
Cl
3m
, 68%
3n
3o
3p
, 58%
, 61%
, 68%
F
F
F
F
F
F
BMIDA
BMIDA
BMIDA
O2N
O
NC
O
3q
, 64%
3r
3s
, 63%
, 60%
a
Reaction conditions: 1) 1a−s (1.0 mmol), B2pin2 (1.2 mmol), Co(acac)2 (5
mol%), LiOtBu (3 equiv), THF (5 mL), 80 °C, 6 h, Ar. 2) MIDA (6 equiv),
DMSO (10 mL), 12 h, 110 °C, Ar.
b Isolated yields.
Table 3 Cu-catalyzed synthesis of gem-difluoroallyl MIDA
boronates from -trifluoromethyl alkenes.a,b
CF3
F
F
F
F
MIDA
(6 equiv)
CuCN (5 mol%)
B
2pin2
+
Ar
LiOtBu (1 equiv)
THF, 60 oC, 6 h, Ar
BMIDA
BMIDA
Bpin
DMSO, 12 h
110 o
Ar
Ar
C
1as
2as

3as
, 85 98% (GC)
(without isolation)
F
F
F
F
F
F
F
F
BMIDA
O
BMIDA
BMIDA
O
O
O
O
O
Without purification of the pinacol boronic esters 2a−s, N-
methyliminodiacetic acid (MIDA) was then directly added to the
crude pinacol boronic esters.18 To our delight, MIDA-protected
boronates 3a−s were obtained in moderate to good yields. All
these gem-difluoroallyl MIDA boronates 3a−s could be
conveniently isolated in excellent purity by recrystallization with
Et2O and no chromatography was necessary. In addition, MIDA
boronates 3a−s are air-stable crystalline solids that can be stored
on the bench top in air for more than three months without any
detectable decomposition.
3a
3b
3c
3d
, 70%
, 70%
, 70%
, 72%
F
F
F
F
F
F
F
F
BMIDA
BMIDA
BMIDA
BMIDA
O
O
S
3e
F
3f
3g
3h
, 68%
, 71%
, 70%
, 75%
F
F
F
F
F
F
F
BMIDA
BMIDA
F3CO
BMIDA
BMIDA
Ph
3i
3j
3k
3l
, 60%
, 62%
, 65%
, 70%
F
F
F
F
F
F
F
F
BMIDA
BMIDA
Br
BMIDA
F3C
BMIDA
After the successful synthesis of a series of gem-difluoroallyl
MIDA boronates under cobalt-catalyzed conditions, we next
carried out the defluoroborylation of trifluoromethyl alkenes
1a−s under the reaction conditions described for Table 1, entry
28 (5 mol% CuCN and 1.0 equiv of LiOtBu), and sequential
addition of MIDA without purification of the pinacol boronic
esters 2a−s. We were delighted to find that this copper-catalyzed
two-step reaction also proceeded efficiently and afforded the
corresponding products 3a−s in comparable yields (Table 3).
Cl
Cl
3m
3n
3o
3p
, 62%
, 65%
, 60%
, 65%
F
F
F
F
F
F
BMIDA
O2N
BMIDA
BMIDA
O
NC
O
3q
3r
3s
, 67%
, 68%
, 58%
a
Reaction conditions: 1) 1a−s (1.0 mmol), B2pin2 (1.2 mmol), CuCN (5
mol%), LiOtBu (1 equiv), THF (5 mL), 60 °C, 6 h, Ar. 2) MIDA (6 equiv),
DMSO (10 mL), 110 °C, 12 h, Ar. b Isolated yields.
In summary, we have developed a novel two-step strategy for
the synthesis of gem-difluoroallyl MIDA boronates through

Tetrahedron
Chem. 77 (2012) 5956−5964;
cobalt- or copper-catalyzed defluoroborylation of trifluoromethyl
(d) G.A. Molander, J. Org. Chem. 80 (2015) 7837−7848.
[7] (a) C.M. Crudden, C. Ziebenhaus, J.P.G. Rygus, K. Ghozati, P.J.
Unsworth, M. Nambo, S. Voth, M. Hutchinson, V.S. Laberge, Y.
Maekawa, D. Imao, Nat. Commun. 7 (2016) 11065;
(b) L. Xu, S. Zhang, P. Li, Chem. Soc. Rev. 44 (2015) 8848−8858;
(c) C.P. Seath, J.W.B. Fyfe, J.J. Molloy, A.J.B. Watson, Angew.
Chem. Int. Ed. 54 (2015) 9976−9979;
(d) E.C. Neeve, S.J. Geier, I.A.I. Mkhalid, S.A. Westcott, T.B. Marder,
Chem. Rev. 116 (2016) 9091−9161.
[8] (a) J. Li, S.G. Ballmer, E.P. Gillis, S. Fujii, M.J. Schmidt, A.M.E.
Palazzolo, J.W. Lehmann, G.F. Morehouse, M.D. Burke, Science 347
(2015) 1221−1226;
(b) E.M. Woerly, A.H. Cherney, E.K. Davis, M.D. Burke, J. Am.
Chem. Soc. 132 (2010) 6941−6943.
[9] E.P. Gillis, M.D. Burke, Aldrichimica Acta 42 (2009) 17−27.
[10] (a) J. Nakhla, ChemFiles 9 (2009) 1−10;
(b) G.A. Molander, B. Canturk, Angew. Chem. Int. Ed. 48 (2009)
9240−9261.
[11] (a) R.D. Dewhurst, E.C. Neeve, H. Braunschweig, T.B. Marder, Chem.
Commun. 51 (2015) 9594−9607;
alkenes with B2pin2 in the absence of ligand, followed by the
addition of N-methyliminodiacetic acid (MIDA) without
purification of the crude pinacol boronic esters. The
difluoroallylation reaction exhibits good functional group
compatibility and a variety of air- and moisture-stable gem-
difluoroallyl MIDA boronates were obtained in moderate to good
yields via this two-step procedure. Compared with the known
protocols available, one of the notable advantages of this method
is that the reaction is compatible with ester, nitro and cyano
groups. Therefore, this method represents an efficient and
valuable option for the synthesis of the important gem-
difluoroallylboronates and gem-difluoroallyl MIDA boronates
from -trifluoromethyl alkenes. Further efforts to extend the
applications of these fluorine-containing MIDA boronates in
coupling reaction are underway in our laboratory.
Acknowledgments
(b) H. Yoshida, M. Seki, I. Kageyuki, I. Osaka, S. Hatano, M. Abe,
ACS Omega 2 (2017) 5911−5916;
(c) C.F. Lee, A. Holownia, J.M. Bennett, J.M. Elkins, J.D.St. Denis, S.
Adachi, A.K. Yudin, Angew. Chem. Int. Ed. 56 (2017) 6264−6267;
(d) W.X. Lv, Q. Li, J.L. Li, Z. Li, E Lin, D.H. Tan, Y.H. Cai, W.X.
Fan, H. Wang, Angew. Chem. Int. Ed. 57 (2018) 16544−16548.
[12] (a) B. Zhang, X. Zhang, Chin. J. Chem. 34 (2016) 477−480;
(b) P.V. Ramachandran, A. Tafelska-Kaczmarek, K. Sakavuyi, Org.
Lett. 13 (2011) 4044−4047;
We are grateful for financial support from the National Key
Research and Development Program of China (No.
2017YFD0200505).
References
(c) P.V. Ramachandran, A. Tafelska-Kaczmarek, A. Chatterjee, J. Org.
Chem. 77 (2012) 9329−9333.
[13] R. Corberán, N.W. Mszar, A.H. Hoveyda, Angew. Chem. Int. Ed. 50
(2011) 7079−7082.
[14] Y. Liu, Y. Zhou, Y. Zhao, J. Qu, Org. Lett. 19 (2017) 946−949.
[15] (a) P. Gao, C. Yuan, Y. Zhao, Z. Shi, Chem. 4 (2018) 2201−2211;
(b) R. Kojima, S. Akiyama, H. Ito, Angew. Chem. Int. Ed. 57 (2018)
7196−7199;
[16] X. Zhao, C. Li, B. Wang, S. Cao, Tetrahedron Lett. 60 (2019)
129−132.
[17] (a) C. Gosmini, J.M. Bégouin, A. Moncomble, Chem. Commun.
(2008) 3221−3233;
(b) G. Cahiez, A. Moyeux, Chem. Rev. 110 (2010) 1435−1462;
(c) W. Hess, J. Treutwein, G. Hilt, Synthesis 22 (2008) 3537−3562.
[18] E.M. Woerly, A.H. Cherney, E.K. Davis, M.D. Burke, J. Am. Chem.
Soc. 132 (2010) 6941−6943.
[1] (a) S. Messaoudi, B. Tréguier, A. Hamze, O. Provot, J.F. Peyrat, J.R.D.
Losada, J.M. Liu, J. Bignon, J. Wdzieczak-Bakala, S. Thoret, J.
Dubois, J.D. Brion, M. Alami, J. Med. Chem. 52 (2009) 4538−4542;
(b) B. Malo-Forest, G. Landelle, J.A. Roy, J. Lacroix, R.C. Gaudreault,
J.F. Paquin, Bioorg. Med. Chem. 23 (2013) 1712−1715;
(c) A.B. Frost, M. Brambilla, R.M. Exner, M. Tredwell, Angew.
Chem. Int. Ed. 58 (2019) 472−476;
(d) T. Fujita, K. Fuchibe, J. Ichikawa, Angew. Chem. Int. Ed. 58
(2019) 390−402.
[2] (a) H. Amii, K. Uneyama, Chem. Rev. 109 (2009) 2119−2183;
(b) J. Ichikawa, Y. Wada, M. Fujiwara, K. Sakoda, Synthesis 13 (2002)
1917−1936;
(c) T. Fujita, M. Takazawa, K. Sugiyama, N. Suzuki, J. Ichikawa, Org.
Lett. 19 (2017) 588−591;
(d) X. Liu, E.E. Lin, G. Chen, J.L. Li, P. Liu, H. Wang, Org. Lett. 21
(2019) 8454−8458;
(e) J. Zhang, W. Dai, Q. Liu, S. Cao, Org. Lett. 19 (2017) 3283−3286;
(f) Q.Q. Zhang, S.Y. Chen, E. Lin, H. Wang, Q. Li, Org. Lett. 21
(2019) 3123−3126;
(g) S.S. Yan, D.S. Wu, J.H. Ye, L. Gong, X. Zeng, C.K. Ran, Y.Y.
Gui, J. Li, D.G. Yu, ACS Catal. 9 (2019) 6987−6992;
(h) H.J. Tang, Y.F. Zhang, Y.W. Jiang, C. Feng, Org. Lett. 20 (2018)
5190−5193;
Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at
(i) L.F. Jiang, B.T. Ren, B. Li, G.Y. Zhang, Y. Peng, Z.Y. Guan, Q.H.
Deng, J. Org. Chem. 84 (2019) 6557−6564.
[3] (a) X. Zhang, S. Cao, Tetrahedron Lett. 58 (2017) 375−392;
(b) X. Lu, X.X. Wang, T.J. Gong, J.J. Pi, S.J. He, Y. Fu, Chem. Sci. 10
(2019) 809−814;
(c) Y. He, D. Anand, Z. Sun, L. Zhou, Org. Lett. 21 (2019)
3769−3773.
Declaration of interests
[4] (a) T. Ichitsuka, T. Fujita, J. Ichikawa, ACS Catal.
5947−5950;
5 (2015)
(b) F. Jaroschik, Chem. Eur. J. 24 (2018) 14572−14582;
☒ The authors declare that they have no known
competing financial interests or personal
relationships that could have appeared to influence
the work reported in this paper.
(c) D. Ding, Y. Lan, Z. Lin, C. Wang, Org. Lett. 21 (2019) 2723−2730.
[5] (a) G. Chelucci, Chem. Rev. 112 (2012) 1344−1462;
(b) H. Chen, T. Xiao, L. Li, D. Anand, Y. He, L. Zhou, Adv. Synth.
Catal. 359 (2017) 3642−3647;
(c) W. Dai, Y. Lin, Y. Wan, S. Cao, Org. Chem. Front. 5 (2018)
55−58;
(d) J. Yang, X. Zhou, Y. Zeng, C. Huang, Y. Xiao, J. Zhang, Chem.
Commun. 52 (2016) 4922−4925;
(e) Z. Zhang, Q. Zhou, W. Yu, T. Li, G. Wu, Y. Zhang, J. Wang, Org.
Lett. 17 (2015) 2474−2477;
(f) X.Wu, F. Xie, I.D. Gridnev, W. Zhang, Org. Lett. 20 (2018)
1638−1642.
☐The authors declare the following financial
interests/personal relationships which may be
considered as potential competing interests:
[6] (a) A.J.J. Lennox, G.C. Lloyd-Jones, Chem. Soc. Rev. 43 (2014)
412−443;
(b) A.J.J. Lennox, G.C. Lloyd-Jones, Isr. J. Chem. 50 (2010) 667−674;
(c) N. Zhang, D.J. Hoffman, N. Gutsche, J. Gupta, V. Percec, J. Org.

5
Highlights:




MIDA boronates are versatile building blocks for
organic synthesis.
The functionalized gem-difluoroalkenes are valuable
synthetic intermediates.
Co- or Cu-catalyzed borylation of -trifluoromethyl
alkenes.
Synthesis of gem-difluoroallyl MIDA boronates.
Graphical Abstract
O
O
N
HO
MIDA
OH
Co(acac)
2 (5 mol%), THF
MeN
B
CF3
F
F
LiOtBu (3 equiv), 80 oC, 6 h, Ar
(
, 6.0 equiv)
B2pin2
+
O
O
Ar
O
O
or CuCN
LiOtBu (1 equiv), 60 oC, 6 h, Ar
(5 mol%), THF
DMSO (10 mL)
110 oC, 12 h
Ar
 Ligand-free Good FG tolerance Facile product isolation and purification