Tetrahydroxydiboron-initiated atom-transfer radical cyclization

Article abstract of DOI:10.1055/a-1485-4956

In this work, the first diboron reagent initiated atom-transfer radical cyclization was reported, in which the boryl radicals were generated by the homolytic cleavage of a B-B single bond weakened by the coordination of Lewis base. To clarify the role of

Full text of DOI:10.1055/a-1485-4956

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–I
feature
A
en
P. Wang et al.
Feature
Synthesis
Tetrahydroxydiboron-Initiated Atom-Transfer Radical Cyclization
R2
Pengfei Wang◊
Yuli Li◊
I
R1
2–
O
O
H
N
HO
O
O
N
R3
Guangwei Wang*
0
0
0
0
-
0
0
0
3
-
4
4
6
6
-
9
8
0
9
HO
HO
OH
OH
B
K2CO3, DMF
B
B
Tianjin Key Laboratory of Molecular Optoelectronic Science,
Department of Chemistry, School of Science, Tianjin University,
Tianjin 300072, P. R. China
O
R2 R1
I
R2
R1
O
base
O
O
wanggw@tju.edu.cn
N
R3
N
R3
◊These authors contributed equally
eGTMiuaananjiCilgnowwrKareeniysgWpgLowanbn@dogitrnjaugt.oeArduyuto.hcfonMr olecular Optoelectronic Science, Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, P. R. China
Received: 01.03.2021
Bu3SnH/AIBN
Accepted after revision: 19.04.2021
Published online: 19.04.2021
DOI: 10.1055/a-1485-4956; Art ID: ss-2021-g0094-fa
X
transition metal
(SET reagents)
X
O
O
Y
Y
Et3B/O2
Abstract In this work, the first diboron reagent initiated atom-trans-
fer radical cyclization was reported, in which the boryl radicals were
generated by the homolytic cleavage of a B–B single bond weakened by
the coordination of Lewis base. To clarify the role of carbonate and DMF
in the cleavage of B–B bond, we calculated the free energy diagram of
two pathways by density functional theory (DFT) investigations. The
DFT calculation showed that the presence of carbonate facilitates the
B–B bond cleavage to form boron radicals, which can be further stabi-
lized by DMF. Subsequent atom-transfer cyclization initiated by stabi-
lized dihydroxyboron radical is also energetically favored.
Y = C, O, N; X = Cl, Br, I
Scheme 1 Atom-transfer radical cyclization by various initiators
Since the advent of Miyaura borylation reaction, various
tetraalkoxydiboron compounds such as bis(pinacolato)di-
boron (B2pin2) and bis(catecholato)diboron (B2cat2), which
are highly stable and easy to handle, have been increasingly
utilized in organic synthesis.6 Due to the high bond energy
of B–B bond (297 KJ/mol), the cleavage of B–B bond requires
external activation by transition metal or Lewis base. In
2016, Li et al. found that when two sp2 hybridized boron at-
oms of bis(pinacolato)diboron were coordinated with Lewis
base 4-cyanopyridine, the B(sp3)–B(sp3) bonds would be
weakened by the synergistic activation and undergo ho-
molysis to form boryl radicals.7 Besides 4-cyanopyridine,
other Lewis bases, such as DMA and N-hydroxyphthalimide
ester, can also serve as activators inducing homocleavage of
B–B bonds through coordination with boron center. This
strategy of boryl radical formation was immediately
Key words tetrahydroxydiboron, homolytic cleavage, atom-transfer
radical cyclization, radical initiator, density functional theory
Radical chemistry has made significant progress in the
past 100 years, and various radical initiators have been de-
veloped (Scheme 1).1 So far, Bu3SnH has been commonly
used as a mediator with azo compounds (R–N=N–R) as initi-
ators in radical reactions.2 However, Bu3SnH is highly toxic
and very difficult to remove completely, which limits its ap-
plication on many fields, especially in pharmaceutical in-
dustry. Various transition metals have also been developed
as single electron transfer (SET) reagents to delicately con-
trol various radical reactions.3 However, it is still necessary
to develop novel metal-free, nontoxic, atom-economic,
mild, and practical radical initiator to meet the requirement
of green chemistry. Boron-containing compounds have
been considered as ideal candidates for green chemistry
due to their nontoxicity and environmental friendliness.
Since 1967, organoboranes have played a key role as radical
initiators and precursors in radical processes through the
cleavage of carbon–boron bonds.4 Currently, Et3B/O2 serves
as a common radical initiator in organic synthesis.5 Howev-
er, the vigorous reactivity is an inherent drawback of
organoboranes, making it necessary to develop mild boron
compounds as radical initiators.
A. Homolytic cleavage of diboron reagents for borylation.
Lewis base
R
(LB)
R
B
B
LB
B
B
LB = pyridine, DMA, etc.
B. Our previous work: B2(OH)4-promoted radical addition.
R'
R'
B2(OH)4
X
R
+
Ar
O
OH
with or
without Ni cat.
R
Ar
C. Current work: B2(OH)4-initiated radical cyclization.
I
I
B2(OH)4
or
O
O
K2CO3/DMF
O
N
N
N
Ts
Ts
Ts
Scheme 2 Tetrahydroxydiboron and its derivatives involved radical re-
actions
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
P. Wang et al.
Feature
Synthesis
applied to the synthesis of organoboron compounds
(Scheme 2A).8
groups, the solvent may coordinate with B2(OH)4 through
additional hydrogen bond to facilitate the B–B bond break
to form boron radical.
However, in previously reported reactions, stoichiomet-
ric amount of tetraalkoxydiborons were necessary, and the
corresponding catalytic amount of diboron initiated radical
reaction has seldom been realized.9 Besides, the commonly
used tetraalkoxydiboron such as B2pin2 and B2cat2 are mol-
ecules with low atom-economy from the perspective of
green chemistry, in which the protective group accounts for
more than 60% of the total weight. We have been wonder-
ing if the atom-economic tetrahydroxydiboron [B2(OH)4]
could serve as a radical precursor. Compared with the wide-
ly used tetraalkoxydiboron, the application of B2(OH)4 is far
behind, and it is sporadically used as a borylation regent10
and a reducing reagent.11 The crystal structure shows that
B2(OH)4 molecules form a network structure through hy-
drogen bonding.12 Due to the presence of four hydroxyl
With this idea in mind, our group recently developed a
novel B2(OH)4-promoted radical addition of internal
alkynes followed by 1,5-HAT process (Scheme 2B).13 In this
reaction, stoichiometric amount of B2(OH)4 is necessary in
the absence of nickel catalyst, which indicates that B2(OH)4
was consumed during the process of reaction. Here, we dis-
close a novel radical cyclization process initiated by sub-
stoichiometric B2(OH)4 in the presence of carbonate salt
and DMF. Monocylic or bicyclic compounds can be obtained
depending on the reaction temperature and amount of base
(Scheme 2C). In this process, DMF has been considered to
play a key role in weakening B–B bond through coordina-
tion. Meanwhile, carbonate, which was previously thought
to serve as the proton scavenger in the process of reaction,
can also serve as activator due to the presence of two oxy-
Biographical Sketches
Guangwei Wang obtained his
Ph.D. in organic chemistry from
Purdue University under the su-
pervision of Prof. Ei-ichi Negishi
in 2009. Then he worked in the
same group as a postdoctoral
associate for two years. After
working for three years at Uni-
Tris Biopharma Co. Ltd., Shang-
hai as Director (2011–2014) in
the R & D department of phar-
maceuticals, he joined the
School of Science at Tianjin Uni-
versity as Professor of Chemis-
try in 2014. His research
interests are focused in the field
of organometallic chemistry
and synthesis of biologically ac-
tive molecules.
Pengfei Wang obtained her
Bachelor’s degree in chemistry
from the University of Weifang
in 2018. Since September 2018,
she has been a M.S. student un-
der the supervision of Prof.
Guangwei Wang. Her research
interests include the radical re-
action initiated by tetrahydroxy-
diboron and difluoroalkylation
of unsaturated hydrocarbons.
Yuli Li has been an undergradu-
ate student in Tianjin University
since 2018 under the supervi-
sion of Prof. Guangwei Wang
and Prof. Yanfeng Dang. He has
also been a summer student in
UCLA under the supervision of
Prof. Kendall Houk since 2020.
His research interests include
organic synthesis and solving
problems in organic and bio-
organic chemistry using theo-
retical
and
computational
methods and programs.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

C
P. Wang et al.
Feature
Synthesis
gen anions, thus endow it with good electron donating ca-
pacity. Therefore, we also performed DFT calculation to elu-
cidate the role of carbonate and DMF.
With the optimized conditions in hand, the reaction
scope was explored (Scheme 3). The isolated yield was 88%
for substrate 1a. When R1 was methyl, the product 2b was
obtained in a yield of 68%. When R2 was methyl, the prod-
uct 2c was obtained in 82% yield. Besides R1 and R2, various
substitutions on nitrogen atom have also been attempted.
When R3 was ethylsulfonyl, 2d was obtained in 80% yield.
When R3 is a benzenesulfonyl group, the products 2e–h can
Initially, we selected N-allyl-2-iodo-N-tosylacetamide as
the bench substrate in the presence of B2(OH)4 (0.5 equiv)
and K2CO3 (2.0 equiv) in DMF at 60 °C for 12 hours. To our
delight, the bicyclic product 3a (Table 1, entry 1) was ob-
tained in 97% yield. When the reaction was performed in
DMSO, the yield decreased to 67%. Other solvents such as
DCM, CH3CN, and THF were also tested and no product 3a
(entries 2–5) was observed. Then we screened the amount
of B2(OH)4. It was found that increasing or decreasing the
amount of B2(OH)4 had little effect on the yield of the prod-
uct 3a (entries 6 and 7). However, in the absence of B2(OH)4,
no expected product 3a (entry 8) was observed. Then vari-
ous bases have been evaluated with DMF as solvent in the
presence of 0.2 equivalent of B2(OH)4. In the case of Na2CO3,
NaHCO3, KHCO3, Et3N as base, which are weaker than potas-
sium carbonate, product 2a was obtained as the dominant
product in moderate yields (entries 9–13). However, when
Cs2CO3 and DBU are used as bases, product 3a was obtained
as the leading product with moderate yield due to the
stronger alkaline strength (entries 10 and 15). When potas-
sium tert-butoxide was used as base, neither 2a or 3a can
be resulted (entry 14). Then we went on to study the effect
of temperature and found that when the reaction tempera-
ture was lowered to room temperature or even to 0 °C, 2a
was obtained in 92–95% yield in one hour (entries 16, 17).
At room temperature, the amount of K2CO3 could be re-
duced to 0.5 equivalent, and the yield of 2a was still 93%
(entry 18). However, the conversion from 2a to 3a could be
promoted with the increase of reaction temperature. When
the temperature was 60 °C, only 3a was formed (entry 6).
When the temperature was 40 °C, both 2a and 3a were
formed as non-discriminatory products after 12 hours (en-
try 19). With the extension of reaction time, 2a was gradu-
ally converted to 3a. After 36 hours, 3a was formed as the
dominating product (entry 20). It is noteworthy that in the
absence of K2CO3, no expected product 2a was detected (en-
try 21). We tested other diboron reagents, and when B2pin2
was used, no expected product was detected. When B2cat2
was used, only 29% 2a was detected (entries 22, 23).14
Therefore, the choice of the boron source is critical for the
reaction to proceed smoothly. Whether the final product is
the monocyclic 2a or bicyclic 3a depends on the reaction
temperature and the amount of base.
Table 1 Optimization of Reaction Conditionsa
I
I
B2(OH)4 (0.2 equiv)
+
O
O
O
N
N
N
base, solvent, T
Ts
1a
Ts
3a
Ts
2a
Entry
Solvent
Base
Temp (°C) Yield (%)b Yield (%)b
2a 3a
1c
2c
DMF
DMSO
DCM
CH3CN
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
NaHCO3
KHCO3
Et3N
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
rt
<5
97
<5
67
3c
n.d.
11
n.d.
n.d.
n.d.
93 (88)
95
4c
5c
n.d.
<5
6
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
7d
<5
8e
n.d.
59
n.d.
12
9
10
11
12
13
14
15
16
17
18f
19
20g
21
22h
23i
n.d.
56
26
<5
58
<5
46
19
KOtBu
DBU
n.d.
n.d.
95
n.d.
46
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
–
<5
0
92
7
rt
93(85)
52
6
40
40
rt
43
<5
84
n.d.
n.d.
29
n.d.
n.d.
<5
K2CO3
K2CO3
rt
rt
a Unless otherwise noted, all reactions were performed with 1a (0.2 mmol,
1.0 equiv), B2(OH)4 (0.04 mmol, 0.2 equiv), base (0.4 mmol, 2.0 equiv) in a
solvent (1.0 mL) at 60 °C under argon for 12 h.
b Yields were determined by GC. The values in parentheses are isolated
yields. n.d.: not detected.
In the presence of excessive amount of base, the -hy-
drogen of 2a was deprotonated, thus facilitating the intra-
molecular SN2 reaction that leads to the formation of 3a. In-
creasing the reaction temperature is also beneficial to the
formation of bicyclic 3a. According to the above screening
results, we chose the reaction conditions in entry 6 as the
best conditions for product 3a and conditions in entry 18 as
the best conditions for product 2a.
c B2(OH)4 (0.5 equiv).
d B2(OH)4 (1.0 equiv).
e Without B2(OH)4.
f B2(OH)4 (0.2 equiv), K2CO3 (0.5 equiv), rt, 1 h.
g At 40 °C, 36 h.
h B2pin2 (0.2 equiv) was used instead of B2(OH)4, K2CO3 (0.5 equiv), rt, 1 h.
i B2cat2 (0.2 equiv) was used instead of B2(OH)4, K2CO3 (0.5 equiv), rt, 1 h.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

D
P. Wang et al.
Feature
Synthesis
be obtained in moderate yields, regardless of whether there
is an electron-withdrawing group or an electron-donating
group on the benzene ring. When R3 is benzylsulfonyl, 2i
can be obtained in 78% yield. Here, the sulfonyl group pro-
tected amide is crucial to the success of the reaction. This
result may be attributed to the lower energy barrier to rota-
tion of the N–CO bond caused by the strong electron-with-
drawing effect of the sulfonyl group.15 When R3 is alkyl,
benzyl, or phenyl groups, the reaction is messy without iso-
lation of desired products. When the iodo group was re-
placed by bromo or chloro group, no cyclization occurred
due to the low reactivity of C–Br or C–Cl compared with C–I
bond. When allyl 2-iodoacetate was subjected to the condi-
tions, the reaction is messy without the isolation of cyclic
product. We have tried N-propargyl-2-iodo-N-tosylacet-
amide, but no cyclization product was observed at the room
temperature.
R2
I
R1
R2
R1
B2(OH)4 (0.2 equiv)
O
N
R3
O
K2CO3 (2.0 equiv)
DMF, 60 °C,12 h
N
R3
1
3
Me
O
O
N
S
N
O
O
O
O
N
N
O
O
O
S
O
Ts
Ts
Ph
3a, 85%
3b, 65%
3e, 68%
OMe
3f, 85%
N
O
N
N
O
S O
O
S O
O
S O
NO2
MeO2C
3i, 76%
NO2
3g, 77%
3h, 73%
Scheme 4 Scope of bicyclic products. Reagents and conditions: 1 (1.0
mmol, 1.0 equiv), B2(OH)4 (0.2 mmol, 0.2 equiv), K2CO3 (2.0 mmol, 2.0
equiv), and DMF (5.0 mL) at 60 °C for 12 h. Isolated yields are shown.
R2
R2 R1
I
I
R1
B2(OH)4 (0.2 equiv)
O
O
N
R3
K2CO3 (0.5 equiv)
DMF, rt, 1 h
N
R3
1
2
B–B bond homolysis induced by coordination of DMF with
B2(OH)4. The resulted boryl radicals can be stabilized by
complexation with Lewis base, in which the boryl radical
might equilibrate to a carbon-centered radical. First, we op-
timized the structure of the hypothetical radical intermedi-
ate generated after DMF coordination. We also calculated
the Gibbs free energy variation of the reaction and com-
pared with that of the reactions with non-hydrogen bond-
ing B2pin2 and B2cat2 replacing B2(OH)4 under the otherwise
I
I
I
Me
N
I
Me
I
O
O
N
N
O
O
O
O
N
N
O
S
O
O
S
O
Ts
Ts
Ts
Et
Ph
2a, 88%
2b, 68%
2c, 82%
2d, 80%
2e, 66%
I
I
I
I
O
N
N
S
O
O
N
N
O
S
O
O
O
O
S
O
O
S
O
NO2
OH
MeO2C
2i, 78%
OMe
2f, 84%
NO2
2g, 81%
O
B
HO
HO
OH
OH
O
O
H
2h, 81%
B
B
+
2
2
2
2
H
H
N
N
+19.0 kcal/mol
+23.4 kcal/mol
Scheme 3 Scope of monocyclic products. Reagents and conditions: 1
(1.0 mmol, 1.0 equiv), B2(OH)4 (0.2 mmol, 0.2 equiv), K2CO3 (0.5 mmol,
0.5 equiv), and DMF (5.0 mL) at rt for 1 h. Isolated yields are shown.
B2(OH)4
DMF
INT 1
O
B
O
N
O
O
O
O
O
O
Reaction scope for product 3 was also investigated with
the optimized conditions (Scheme 4). When R1 was methyl
group, the bicyclic product 3b was obtained in 65% yield.
Various substituents on R3 such as substituted benzenesul-
fonyl groups and benzylsulfonyl group can be well tolerat-
ed, leading to bicyclic products 3e–i in medium to high
yields. However, for substrate 1c, no bicyclic product was
resulted even with the extension of reaction time and in-
crease of temperature. This may be due to the steric hin-
drance in -position, which renders the intramolecular SN2
reaction difficult to proceed.
B
B
+
N
B2pin2
DMF
INT 1'
O
B
O
N
O
O
O
O
O
O
B
B
+
2
2
H
+29.0 kcal/mol
N
B2cat2
DMF
INT 1''
The pyrrolidine derivatives were produced by the 5-exo-
trig radical cyclization iodine atom transfer reaction in
which the generation of a reactive radical is the key to the
reaction. In order to elucidate the mechanism for the for-
mation of the radical, we performed DFT calculation for the
B2(OH)4
B2pin2
B2cat2
Scheme 5 Variations of free energy for reactions of DMF with different
diboron reagents leading to different boron radicals
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

E
P. Wang et al.
Feature
Synthesis
same conditions (Scheme 5). We found that the Gibbs free
energy variation for B2(OH)4 was the lowest, which might
be due to the presence of hydrogen bond. The B-B single
bond lengths of B2(OH)4, B2pin2 and B2cat2 were also calcu-
lated respectively, and the results showed that the bond
length of B-B in B2(OH)4 is the longest among them. These
calculated results are consistent with the experimental re-
sults that this reaction can proceed conveniently with
B2(OH)4 as a diboron reagent, instead of B2pin2 and B2cat2.
Then, we calculated the Gibbs free energy profile ac-
cording to the above process (Figure 1). Based on the calcu-
lated free energy changes of the whole potential energy
surface, the rate-determining step is the B-B bond homolyt-
ic cleavage via TS1 with an overall barrier of 50.9 kcal/mol.
This overall barrier indicates that the reaction is quite unfa-
vorable under the experimental conditions. Therefore, the
possibility of producing boryl radical through this process is
very low.
Therefore, we need to reexamine the activation mecha-
nism for B–B bond cleavage. It is noteworthy that carbonate
has much better coordination capability than DMF due to
the presence of two oxygen anions. Therefore, we suspect-
ed that the carbonate, which was previously believed to
serve as alkali to neutralize the proton in the intermediate
in the system, might play a crucial role for the activation of
B–B bond. In order to verify this assumption, a control ex-
periment was performed. The experimental results (Table
1, entries 18 and 19) show that the yield of the reaction was
very high in the presence of even catalytic amount of car-
bonate. However, no product was afforded in the absence of
potassium carbonate. Based on these results, we hypothe-
sized that carbonate might coordinate with B2(OH)4, leading
ΔG (kcal/mol)
+50.9
M06-2X/ma-def2TZVP, SMD(DMF)
TS1
H
O
N
HO
B
OH
O
HO
B
N
OH
H
0.0
B2(OH)4
+ DMF
Figure 1 Calculated Gibbs free energy (in kcal/mol) profile for the DMF
catalyzed homolytic B–B bond cleavage in B2(OH)4. The distances be-
tween atoms are in Å.
2–
2–
O
O
H
N
HO
O
O
O
H
OH
DMF
B
B
2–
B2(OH)4
+ CO3
O
O
O
O
ΔG (kcal/mol)
M06-2X/ma-def2TZVP, SMD(DMF)
INT5
INT6
+38.0
O
H
O
H
B2(OH)4
+
O
O
O
O
O
H
2–
H
O
2 CO3
O
B
B
HO
O
OH
O
O
O
H
O
B
B
HO
O
O
+21.8
O
TS2
O
H
+16.3
O
H
INT3
O
O
O
H
O
B
B
O
O
HO
O
+0.7
INT4
0.0
O
O
H
OH
B
2–
INT2 + CO3
O
O
O
O
H
N
HO
O
O
O
–11.1
B
H
O
O
INT5
O
OH
O
O
O
B
B
O
OH
HO
–23.2
INT6
DMF
INT2
INT3
TS2
INT4
INT5
INT6
Figure 2 Calculated Gibbs free energy (in kcal/mol) profile for the carbonate catalyzed homolytic B–B bond cleavage in B2(OH)4 in the solvent (DMF).
Distances between atoms are in Å.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

F
P. Wang et al.
Feature
Synthesis
to the formation of two sp3 hybridized boron. Then the
cleavage of B–B bond produces boryl radical intermediate.
The Gibbs free energy profile for carbonate catalyzed ho-
molytic B–B bond cleavage in B2(OH)4 is calculated and
shown in Figure 2.
tiated the 5-exo-trig radical cyclization iodine atom transfer
reaction to produce pyrrolidine derivatives 2. Then in the
presence of base, the intramolecular SN2 reaction took place
after the deprotonation at -position of carbonyl, leading to
bicyclic compound 3.
First, the coordination of carbonate to one boron atom
of B2(OH)4 generates the sp2–sp3 intermediate (INT2). Then,
a second carbonate ion binds to the sp2 boron atom of INT2
to form a possible sp3–sp3 diboron (INT3). Both INT2 and
INT3 are stabilized by intramolecular six-membered hydro-
gen bonding ring. Then, the homolytic cleavage of the B–B
bond in INT3 occurs via TS2 with a potential barrier of 21.8
In conclusion, we have developed a novel tetrahydroxy-
diboron-initiated radical cyclization process. This process
provides a convenient strategy for monocyclic compounds
or bicyclic pyrrolidine compounds. The current research
opens up the application of B2(OH)4 as a mild, low-toxicity
radical initiator in organic transformations. DFT calculation
has been performed to elucidate the role of DMF and potas-
sium carbonate. The computational results showed that po-
tassium carbonate serves as Lewis bases to coordinate with
boron atoms and promotes homolytic cleavage of a B–B sin-
gle bond to generate boryl radical stabilized by DMF. Fur-
ther application of B2(OH)4 as an environment-friendly and
convenient radical initiator is still in progress in our group.
2–
kcal/mol (relative to the intermediate INT2 + CO3 with
lowest energy), which leads to a diradical intermediate
(INT4). The rate-determining step in this process is the ho-
molytic cleavage of B–B bond. Two radicals are weakly
bound through the intermolecular hydrogen bond. Finally,
this diradical species may dissociate into two boryl radicals
(INT5).
It is obvious that the B–B bond coordinated by carbon-
ate is easy to cleave and form boryl radical intermediate.
Furthermore, DMF can interact with the boron radical in-
termediate to form INT6, which will reduce the energy of
the intermediate by 12.1 kcal/mol. This explains why DMF
is the best solvent.
Then we calculated the variation of free energy for the
subsequent reaction initiated by the boryl radical (Scheme
6). Since the B–I bond is not easy to form according to the
calculation, the most stable byproducts are the iodide and
trivalent boron species 4. This reaction has a much negative
free energy change (–59.0 kcal/mol), which can explain that
it is energetically favored to initiate the carbon radicals
from the boryl radical. Spin population analysis showed
that 20% of the carbon radicals were delocalized on the car-
bonyl oxygen, making the radical more stable.
All experiments were conducted under argon atmosphere. MeCN,
DMF, DMSO, THF, and DCM were dried and distilled by standard
methods. Flash chromatographic separations were carried out on
200–300 mesh silica gel. Reactions were monitored by TLC and GC
analysis of reaction aliquots. GC analysis was performed on an Agilent
7890 Gas Chromatography using a HP-5 capillary column (30 m ×
0.32 mm, 0.5 m film) with appropriate hydrocarbons as internal
standards. 1H and 13C NMR spectra were recorded in CDCl3 on a
Bruker AVANCE III spectrometer and JNM-ECZ600R spectrometer and
calibrated using residual undeuterated solvent (CDCl3 at 7.26 ppm 1H
NMR, 77.16 ppm 13C NMR). Chemical shifts () are reported in ppm,
and coupling constants (J) are in hertz (Hz). Standard abbreviations
were used to explain the multiplicities. High-resolution mass spec-
trometry (HRMS) were recorded on a QTOF mass analyzer with elec-
trospray ionization (ESI) by Waters G2-XS QTOF. Melting points were
measured in an X-6 Micro Melting Point Apparatus purchased from
Beijing TECH Instrumental Company.
Geometry optimizations were performed with the M06-2X functional
theory16 and the standard ma-def2-TZVP basis17,18 set for all the at-
oms in the solvent phase with default convergence criteria. Because
the M06-2X functional can give refined energies for organocatalyzed
reactions, and it is a more vigorous theoretical treatment of longer-
range interactions, so it could deal well with the system of formed hy-
drogen bonds between B2(OH)4 and carbonate. The vibrational fre-
quencies were computed at the same level of theory as for the geome-
try optimizations to confirm whether each optimized structure is an
energy minimum (with all real frequencies) or a transition state
(with only one imaginary frequency). The solvation effects were also
evaluated at the M06-2X/ma-def2-TZVP level of theory with Truhlar’s
SMD method19 with DMF ( = 37.219) used as a solvent. All the calcu-
lations were performed with Gaussian 09 soft package.20 Additional
computational results are given in the Supporting Information.
2–
O
O
H
N
HO
O
O
O
OH
1a
B
B
+ I– + DMF
O
O
–59.0 kcal/mol
O
N
Ts
H
O
O
4
INT6
INT7
Scheme 6 Variation of free energy for the boryl radical induced reac-
tion
Monocyclic Products 2; General Procedure
Based on above DFT calculation for the energy of vari-
ous intermediates and Gibbs free energy profile of several
key steps, possible mechanism was proposed as below. In
the presence of DMF and K2CO3, tetrahydroxydiboron disso-
ciated to form stabilized dihydroxyboron radical, which ini-
An oven-dried 25 mL of Schlenk tube equipped with a magnetic stir-
ring bar and charged with 1 (1.0 mmol, 1.0 equiv), B2(OH)4 (0.2 mmol,
0.2 equiv), K2CO3 (0.5 mmol, 0.5 equiv), and DMF (5 mL) under argon
atmosphere. The reaction mixture was stirred at rt for 1 h. The mix-
ture was then quenched with H2O (30 mL) and extracted with EtOAc
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

G
P. Wang et al.
Feature
Synthesis
(3 × 30 mL). The combined organic extracts were washed with brine
(40 mL), dried (anhyd Na2SO4), filtered, and concentrated. The crude
product was purified by silica gel chromatography to give the desired
product 2.
4-(Iodomethyl)-1-((4-methoxyphenyl)sulfonyl)pyrrolidin-2-one
(2f)
Yield: 332 mg (84%); white solid; mp 100.0–102.3 °C.
1H NMR (600 MHz, CDCl3):  = 7.93 (d, J = 8.9 Hz, 2 H), 6.97 (d, J = 8.9
Hz, 2 H), 4.03 (dd, J = 10.3, 7.5 Hz, 1 H), 3.84 (s, 3 H), 3.53 (dd, J = 10.4,
6.4 Hz, 1 H), 3.18 (dd, J = 10.2, 5.8 Hz, 1 H), 3.13 (dd, J = 10.2, 6.9 Hz, 1
H), 2.67–2.56 (m, 2 H), 2.26–2.20 (m, 1 H).
4-(Iodomethyl)-1-tosylpyrrolidin-2-one (2a)
Yield: 333 mg (88%); white solid; mp 129.5–130 °C.
1H NMR (400 MHz, CDCl3):  = 7.92 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 8.0
Hz, 2 H), 4.08 (dd, J = 10.4, 7.3 Hz, 1 H), 3.57 (dd, J = 10.3, 6.1 Hz, 1 H),
3.23–3.09 (m, 2 H), 2.70–2.56 (m, 2 H), 2.44 (s, 3 H), 2.32–2.20 (m, 1
H).
13C NMR (151 MHz, CDCl3):  = 171.4, 164.2, 130.4, 129.2, 114.3, 55.8,
52.9, 39.5, 33.6, 7.7.
HRMS (ESI): m/z [M + H+] calcd for C12H15INO4S+: 395.9761; found:
395.9767.
13C NMR (101 MHz, CDCl3):  = 171.4, 145.6, 135.0, 129.9, 128.3, 53.0,
39.7, 33.9, 21.8, 7.3.
All analytical data were in good accordance with the reported data.21
4-(Iodomethyl)-1-[(4-nitrophenyl)sulfonyl]pyrrolidin-2-one (2g)
Yield: 334 mg (81%); white solid; mp 143.8–145.1 °C.
1H NMR (600 MHz, CDCl3):  = 8.40 (d, J = 8.9 Hz, 2 H), 8.27 (d, J = 8.9
Hz, 2 H), 4.13 (dd, J = 10.3, 7.9 Hz, 1 H), 3.62 (dd, J = 10.3, 6.3 Hz, 1 H),
3.24 (dd, J = 10.4, 5.4 Hz, 1 H), 3.17 (dd, J = 10.4, 6.6 Hz, 1 H), 2.71–
2.64 (m, 2 H), 2.35–2.28 (m 1 H).
13C NMR (151 MHz, CDCl3):  =171.6, 151.2,143.3, 129.9, 124.5, 53.2,
39.4, 33.6, 7.3.
4-(Iodomethyl)-4-methyl-1-tosylpyrrolidin-2-one (2b)
Yield: 266 mg (68%); white solid; mp 156.3–158.6 °C.
1H NMR (600 MHz, CDCl3):  = 7.91 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 7.8
Hz, 2 H), 3.77 (d, J = 10.4 Hz, 1 H), 3.65 (d, J = 10.3 Hz, 1 H), 3.19 (d, J =
1.1 Hz, 2 H), 2.52 (d, J = 17.3 Hz, 1 H), 2.44 (s, 3 H), 2.32 (d, J = 17.3 Hz,
1 H), 1.24 (s, 3 H).
HRMS (ESI): m/z [M+ H+] calcd for C11H12INO4S+: 410.9506, found:
410.9510.
13C NMR (151 MHz, CDCl3):  = 172.1, 145.4, 135.3, 129.8, 128.3,
116.8, 51.2, 36.9, 21.8, 21.0, 19.6
All analytical data were in good accordance with the reported data.22
4-(Iodomethyl)-1-[(2-nitrophenyl)sulfonyl]pyrrolidin-2-one (2h)
Yield: 334 mg (81%); white solid; mp 116.1–120.0 °C.
4-(Iodomethyl)-3-methyl-1-tosylpyrrolidin-2-one (2c)
1H NMR (600 MHz, CDCl3):  = 8.47–8.43 (m, 1 H), 7.83–7.78 (m, 2 H),
7.78–7.75 (m, 1 H), 4.20 (dd, J = 10.4, 7.8 Hz, 1 H), 3.77 (dd, J = 10.4,
7.0 Hz, 1 H), 3.33–3.25 (m, 2 H), 2.86–2.78 (m, 1 H), 2.71–2.65 (m, 1
H), 2.46–2.38 (m, 1 H).
13C NMR (151 MHz, CDCl3):  = 171.8, 148.2, 135.3, 134.7, 132.3,
131.4, 124.5, 52.9, 39.5, 34.8, 6.8.
Yield: 324 mg (82%); white solid; mp 155.4–157.7 °C.
1H NMR (400 MHz, CDCl3):  = 7.93 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 8.0
Hz, 2 H), 4.10 (dd, J = 10.1, 7.6 Hz, 1 H), 3.43–3.34 (m, 2 H), 3.10 (dd,
J = 10.4, 8.2 Hz, 1 H), 2.44 (s, 3 H), 2.28–2.18 (m, 1 H), 2.14–2.02 (m, 1
H), 1.16 (d, J = 7.0 Hz, 3 H).
13C NMR (151 MHz, CDCl3):  = 174.3, 145.5, 135.1, 129.9, 128.2, 51.8,
HRMS (ESI): m/z [M + H+] calcd for C11H12INO4S+: 410.9506; found:
45.0, 42.0, 21.8, 13.4, 5.9.
410.9513.
HRMS (ESI): m/z [M + H+] calcd for C13H17INO3S+: 393.9968; found:
393.9974.
Methyl 2-({[4-(Iodomethyl)-2-oxopyrrolidin-1-yl]sulfonyl}meth-
yl)benzoate (2i)
1-(Ethylsulfonyl)-4-(iodomethyl)pyrrolidin-2-one (2d)
Yield: 342 mg (78%); white solid; mp 84.2–87.1 °C.
1H NMR (600 MHz, CDCl3):  = 7.94 (d, J = 7.8 Hz, 1 H), 7.53 (t, J = 7.5
Hz, 1 H), 7.47 (t, J = 7.6 Hz, 1 H), 7.40 (d, J = 7.6 Hz, 1 H), 5.24 (s, 2 H),
3.91 (s, 3 H), 3.51 (dd, J = 10.2, 7.8 Hz, 1 H), 3.07 (dd, J = 10.3, 6.3 Hz, 1
H), 3.05–2.99 (m, 2 H), 2.68–2.62 (m, 1 H), 2.51–2.43 (m, 1 H), 2.38–
2.32 (m, 1 H).
13C NMR (151 MHz, CDCl3):  = 172.7, 167.5, 132.9, 132.3, 131.8,
131.2, 129.5, 128.1, 55.7, 53.3, 52.7, 39.5, 33.8, 7.3.
Yield: 253 mg (80%); white solid; mp 63.7–64.9 °C.
1H NMR (600 MHz, CDCl3):  = 3.99 (dd, J = 10.3, 7.9 Hz, 1 H), 3.51 (dd,
J = 10.3, 6.7 Hz, 1 H), 3.43 (q, J = 7.4 Hz, 2 H), 3.28–3.20 (m, 2 H), 2.75–
2.65 (m, 2 H), 2.45–2.37 (m, 1 H), 1.34 (t, J = 7.4 Hz, 3 H).
13C NMR (151 MHz, CDCl3):  = 172.7, 52.8, 47.7, 39.5, 33.6, 7.9, 7.6.
HRMS (ESI): m/z [M + H+] calcd for C7H13INO3S+: 317.9655; found:
317.9667.
HRMS (ESI): m/z [M + H+] calcd for C14H17INO4S+: 437.9867; found:
437.9868.
4-(Iodomethyl)-1-(phenylsulfonyl)pyrrolidin-2-one (2e)
Yield: 241 mg (66%); white solid; mp 135.8–139.4 °C.
Bicyclic Products 3; General Procedure
1H NMR (600 MHz, CDCl3):  = 8.04 (d, J = 7.3 Hz, 2 H), 7.66 (t, J = 7.5
Hz, 1 H), 7.56 (t, J = 7.9 Hz, 2 H), 4.09 (dd, J = 10.3, 7.7 Hz, 1 H), 3.58
(dd, J = 10.3, 6.4 Hz, 1 H), 3.22–3.11 (m, 2 H), 2.69–2.60 (m, 2 H), 2.31–
2.23 (m, 1 H).
13C NMR (151 MHz, CDCl3):  = 171.4, 138.0, 134.4, 129.3, 128.2, 53.0,
39.6, 33.8, 7.4.
An oven-dried 25 mL of Schlenk tube equipped with a magnetic stir-
ring bar was charged with 1 (1.0 mmol, 1.0 equiv), B2(OH)4 (0.2 mmol,
0.2 equiv), K2CO3 (2.0 mmol, 2.0 equiv), and DMF (5 mL) under argon
atmosphere. The reaction mixture was stirred at 60 °C for 12 h. The
mixture was then quenched with H2O (30 mL) and extracted with
EtOAc (3 × 30 mL). The combined organic extracts were washed with
brine (40 mL), dried (anhyd Na2SO4), filtered, and concentrated. The
crude product was purified by silica gel chromatography to give the
desired product 3.
HRMS (ESI): m/z [M + H+] calcd for C11H13INO3S+: 365.9655; found:
365.9664.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

H
P. Wang et al.
Feature
Synthesis
3-Tosyl-3-azabicyclo[3.1.0]hexan-2-one (3a)
1H NMR (400 MHz, CDCl3):  = 8.45–8.39 (m, 1 H), 7.81–7.69 (m, 3 H),
4.14 (dd, J = 10.2, 5.6 Hz, 1 H), 4.03 (d, J = 10.2 Hz, 1 H), 2.12–2.03 (m,
1 H), 1.99–1.92 (m, 1 H), 1.31–1.22 (m, 1 H), 1.03–0.97 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.1, 148.1, 135.1, 134.6, 132.1,
131.2, 124.2, 48.8, 20.6, 12.9, 11.9.
Yield: 214 mg (85%); white solid; mp 120.6–123.8 °C.
1HNMR (400 MHz, CDCl3):  = 7.89 (d, J = 8.4 Hz, 2 H), 7.33 (d, J = 8.1
Hz, 2 H), 3.94 (d, J = 10.2 Hz, 1 H), 3.84 (dd, J = 10.2, 5.5 Hz, 1 H), 2.43
(s, 3 H), 1.98–1.84 (m, 2 H), 1.23–1.16 (m, 1 H), 0.79–0.73 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 173.0, 145.2, 135.2, 129.8, 128.1, 48.8,
21.8, 20.9, 12.7, 12.2.
HRMS (ESI): m/z [M + H+] calcd for C12H12NO5S+: 282.0431; found:
282.0436.
All analytical data were in good accordance with the reported data.23
Methyl 2-{[(2-oxo-3-azabicyclo[3.1.0]hexan-3-yl)sulfonyl]meth-
yl}benzoate (3i)
5-Methyl-3-tosyl-3-azabicyclo[3.1.0]hexan-2-one (3b)
Yield: 236 mg (76%); white solid; mp 106.7–107.2 °C.
Yield: 173 mg (65%); white solid; mp 166–168 °C.
1H NMR (400 MHz, CDCl3):  = 7.95 (d, J = 7.6 Hz, 1 H), 7.53 (t, J = 7.4
Hz, 1 H), 7.47 (t, J = 7.5 Hz, 1 H), 7.40 (d, J = 7.5 Hz, 1 H), 5.27 (d, J = 2.9
Hz, 2 H), 3.92 (s, 3 H), 3.52 (d, J = 10.2 Hz, 1 H), 3.23 (dd, J = 10.2, 5.7
Hz, 1 H), 2.03–1.95 (m, 1 H), 1.89–181 (m, 1 H), 1.25–1.16 (m, 1 H),
0.76–0.71 (m, 1 H).
13C NMR (101 MHz, CDCl3):  = 174.2, 167.6, 132.9, 132.2, 131.9,
131.3, 129.4, 128.5, 55.5, 52.6, 49.2, 20.9, 13.0, 12.3.
1H NMR (400 MHz, CDCl3):  = 7.89 (d, J = 8.3 Hz, 2 H), 7.33 (d, J = 8.3
Hz, 2 H), 3.96 (d, J = 9.9 Hz, 1 H), 3.56 (d, J = 9.9 Hz, 1 H), 2.43 (s, 3 H),
1.68–1.65 (m, 1 H), 1.30 (s, 3 H), 1.12–1.08 (m, 1 H), 0.94–0.90 (m, 1
H).
13C NMR (101 MHz, CDCl3):  = 173.3, 145.2, 135.2, 129.8, 128.1, 53.4,
27.3, 21.8, 20.5, 19.2, 18.6.
HRMS (ESI): m/z [M + H+] calcd for C14H17O3S+: 265.0893; found:
265.0898.
HRMS (ESI): m/z [M + H+] calcd for C15H17O5S+: 309.0791; found:
309.0793.
3-(Phenylsulfonyl)-3-azabicyclo[3.1.0]hexan-2-one (3e)
Yield: 161 mg (68%); white solid; mp 93.3–96.8 °C.
Conflict of Interest
1H NMR (400 MHz, CDCl3):  = 7.99 (d, J = 8.0 Hz, 2 H), 7.63 (t, J = 7.4
Hz, 1 H), 7.52 (t, J = 7.7 Hz, 2 H), 3.93 (d, J = 10.2 Hz, 1 H), 3.83 (dd, J =
10.2, 5.5 Hz, 1 H), 1.98–1.91 (m, 1 H), 1.90–1.83 (m, 1 H), 1.22–1.16
(m, 1 H), 0.77–0.70 (m, 1 H).
The authors declare no conflict of interest.
Funding Information
13C NMR (101 MHz, CDCl3):  = 172.9, 138.0, 134.1, 129.1, 127.9, 48.8,
20.8, 12.7, 12.2.
The authors are grateful for the financial support from the Major Na-
tional Science and Technology Projects of water pollution control and
treatment (2017ZX07402003). The authors also thank the Natural
Science Foundation of Tianjin (19JCYBJC20200) for support of this re-
HRMS (ESI): m/z [M + H+] calcd for C11H12NO3S+: 238.0532; found:
238.0536.
search.
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3-[(4-Methoxyphenyl)sulfonyl]-3-azabicyclo[3.1.0]hexan-2-one
(3f)
Yield: 228 mg (85%); white solid; mp 159.4–164.7 °C.
Supporting Information
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 8.9 Hz, 2 H), 6.98 (d, J = 8.9
Hz, 2 H), 3.93 (d, J = 10.2 Hz, 1 H), 3.87 (s, 3 H), 3.83 (dd, J = 10.2, 5.6
Hz, 1 H), 1.99–1.91 (m, 1 H), 1.91–1.84 (m, 1 H), 1.23–1.16 (m, 1 H),
0.78–0.73 (m, 1 H).
Supporting information for this article is available online at
https://doi.org/10.1055/a-1485-4956.
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13C NMR (101 MHz, CDCl3):  = 173.0, 164.0, 130.4, 129.5, 114.3, 55.8,
48.8, 20.9, 12.7, 12.2.
References
HRMS (ESI): m/z [M + H+] calcd for C12H14NO4S+: 268.0638; found:
268.0642.
(1) (a) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91,
1237. (b) Sibi, M. P.; Manyem, S.; Zimmerman, J. Chem. Rev.
2003, 103, 3263. (c) Rowlands, G. J. Tetrahedron 2009, 65, 8603.
(d) Rowlands, G. J. Tetrahedron 2010, 66, 1593. (e) Studer, A.;
Curran, D. P. Angew. Chem. Int. Ed. 2016, 55, 58. (f) Yan, M.; Lo, J.
C.; Edwards, J. T.; Baran, P. S. J. Am. Chem. Soc. 2016, 138, 12692.
(2) (a) Curran, D. P. Synthesis 1988, 417. (b) Curran, D. P.; Seong, C.
M. J. Am. Chem. Soc. 1990, 112, 9401. (c) Curran, D. P.; Tamine, J.
J. Org. Chem. 1991, 56, 2746.
(3) (a) Gansäuer, A.; Bluhm, H. Chem. Rev. 2000, 100, 2771.
(b) Crossley, S. W. M.; Obradors, C.; Martinez, R. M.; Shenvi, R. A.
Chem. Rev. 2016, 116, 8912. (c) Clark, A. J. Chem. Soc. Rev. 2002,
31, 1. (d) Wang, F.; Chen, P.; Liu, G. Acc. Chem. Res. 2018, 51,
2036. (e) Snider, B. B. Chem. Rev. 1996, 96, 339. (f) Nicolaou, K.
C.; Ellery, S. P.; Chen, J. S. Angew. Chem. Int. Ed. 2009, 48, 7140.
(g) Edmonds, D. J.; Johnston, D.; Procter, D. J. Chem. Rev. 2004,
104, 3371.
3-[(4-Nitrophenyl)sulfonyl]-3-azabicyclo[3.1.0]hexan-2-one (3g)
Yield: 218 mg (77%); yellow solid; mp 154.7–156.2 °C.
1H NMR (400 MHz, CDCl3):  = 8.38 (d, J = 8.9 Hz, 2 H), 8.23 (d, J = 8.9
Hz, 2 H), 4.01 (d, J = 10.1 Hz, 1 H), 3.86 (dd, J = 10.1, 5.6 Hz, 1 H), 2.07–
1.99 (m, 1 H), 1.96–1.90 (m, 1 H), 1.32–1.26 (m, 1 H), 0.89–0.84 (m, 1
H).
13C NMR (101 MHz, CDCl3):  = 173.0, 150.9, 143.4, 129.7, 124.4, 48.9,
20.8, 13.1, 12.5.
HRMS (ESI): m/z [M + H+] calcd for C12H12NO5S+: 282.0431; found:
282.0435.
3-[(2-Nitrophenyl)sulfonyl]-3-azabicyclo[3.1.0]hexan-2-one (3h)
Yield: 206 mg (73%); yellow solid; mp 147.5–150.4 °C.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

I
P. Wang et al.
Feature
Synthesis
(4) (a) Ollivier, C.; Renaud, P. Chem. Rev. 2001, 101, 3415.
(b) Renaud, P.; Beauseigneur, A.; Brecht-Forster, A.; Becattini,
B.; Darmency, V.; Kandhasamy, S.; Montermini, F.; Ollivier, C.;
Panchaud, P.; Pozzi, D.; Scanlan, E. M.; Schaffner, A.-P.; Weber,
V. Pure Appl. Chem. 2007, 79, 223. (c) Curran, D. P.; Solovyev, A.;
Brahmi, M. M.; Fensterbank, L.; Malacria, M.; Lacôte, E. Angew.
Chem. Int. Ed. 2011, 50, 10294. (d) Xu, A.-Q.; Zhang, F.-L.; Ye, T.;
Yu, Z.-X.; Wang, Y.-F. CCS Chem. 2019, 1, 504. (e) Guo, A.; Han, J.-
B.; Tang, X.-Y. Org. Lett. 2018, 20, 2351.
(5) (a) Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima, K.
J. Org. Chem. 1998, 63, 8604. (b) Yorimitsu, H.; Nakamura, T.;
Shinokubo, H.; Oshima, K.; Omoto, K.; Fujimoto, H. J. Am. Chem.
Soc. 2000, 122, 11041. (c) Yorimitsu, H.; Shinokubo, H.;
Matsubara, S.; Oshima, K.; Omoto, K.; Fujimoto, H. J. Org. Chem.
2001, 66, 7776.
Eur. J. 2014, 20, 6608. (f) Mfuh, A. M.; Doyle, J. D.; Chhetri, B.;
Arman, H. D.; Larionov, O. V. J. Am. Chem. Soc. 2016, 138, 2985.
(g) Hu, D.; Wang, L.; Li, P. Org. Lett. 2017, 19, 2770. (h) Zhang, J.-
J.; Duan, X.-H.; Wu, Y.; Yang, J.-C.; Guo, L.-N. Chem. Sci. 2019, 10,
161.
(11) (a) Londregan, A. T.; Piotrowski, D. W.; Xiao, J. Synlett 2013, 24,
2695. (b) Xia, Y.-T.; Sun, X.-T.; Zhang, L.; Luo, K.; Wu, L. Chem.
Eur. J. 2016, 22, 17151. (c) Cummings, S. P.; Le, T.-N.; Fernandez,
G. E.; Quiambao, L. G.; Stokes, B. J. J. Am. Chem. Soc. 2016, 138,
6107. (d) Chen, D.; Zhou, Y.; Zhou, H.; Liu, S.; Liu, Q.; Zhang, K.;
Uozumi, Y. Synlett 2018, 29, 1765.
(12) Baber, R. A.; Norman, N. C.; Orpen, A. G.; Rossi, J. New J. Chem.
2003, 27, 773.
(13) Sun, Z.-Y.; Zhou, S.; Yang, K.; Guo, M.; Zhao, W.; Tang, X.; Wang,
G. Org. Lett. 2020, 22, 6214.
(6) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60,
7508. (b) Ishiyama, T.; Itoh, Y.; Kitano, T.; Miyaura, N. Tetrahe-
dron Lett. 1997, 38, 3447. (c) Wang, M.; Shi, Z. Chem. Rev. 2020,
120, 7348. (d) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott,
S. A.; Marder, T. B. Chem. Rev. 2016, 116, 9091. (e) Kuang, Z.;
Yang, K.; Zhou, Y.; Song, Q. Chem. Commun. 2020, 56, 6469.
(7) (a) Wang, G.; Zhang, H.; Zhao, J.; Li, W.; Cao, J.; Zhu, C.; Li, S.
Angew. Chem. Int. Ed. 2016, 55, 5985. (b) Wang, G.; Zhang, H.;
Zhao, J.; Li, W.; Cao, J.; Zhu, C.; Li, S. Angew. Chem. Int. Ed. 2016,
128, 6089. (c) Wang, G.; Cao, J.; Gao, L.; Chen, W.; Huang, W.;
Cheng, X.; Li, S. J. Am. Chem. Soc. 2017, 139, 3904. (d) Cao, J.;
Wang, G.; Gao, L.; Cheng, X.; Li, S. Chem. Sci. 2018, 9, 3664.
(e) Gao, L.; Wang, G.; Cheng, X.; Ma, J.; Li, S. ACS Catal. 2019, 9,
10142.
(8) (a) Fawcett, A.; Pradeilles, J.; Wang, Y.; Mutsuga, T.; Myers, E. L.;
Aggarwal, V. K. Science 2017, 357, 283. (b) Zhang, L.; Jiao, L.
J. Am. Chem. Soc. 2017, 139, 607. (c) Zhang, L.; Jiao, L. Chem. Sci.
2018, 9, 2711. (d) Zhang, L.; Jiao, L. J. Am. Chem. Soc. 2019, 141,
9124. (e) Cheng, Y.; Mück-Lichtenfeld, C.; Studer, A. Angew.
Chem. Int. Ed. 2018, 57, 16832. (f) Cheng, Y.; Mück-Lichtenfeld,
C.; Studer, A. J. Am. Chem. Soc. 2018, 140, 6221. (g) Friese, F. W.;
Studer, A. Angew. Chem. Int. Ed. 2019, 58, 9561.
(14) For the slow hydrolysis of B2cat2 to B2(OH)4, see: Li, J.; Wang, H.;
Qiu, Z.; Huang, C.-Y.; Li, C.-J. J. Am. Chem. Soc. 2020, 142, 13011.
(15) Ikeda, M.; Teranishi, H.; Nozaki, K.; Ishibashi, H. J. Chem. Soc.,
Perkin Trans. 1 1998, 10, 1691.
(16) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215.
(17) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297.
(18) Zheng, J.; Xu, X.; Truhlar, D. G. Theor. Chem. Acc. 2010, 128, 295.
(19) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B
2009, 113, 6378.
(20) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.;
Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Montgomery, J. A. Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.;
Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;
Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.;
Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam,
N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin,
A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09;
Gaussian Inc: Wallingford CT, 2009.
(9) Cao, J.; Wang, G.; Gao, L.; Chen, H.; Liu, X.; Cheng, X.; Li, S. Chem.
Sci. 2019, 10, 2767.
(10) (a) Sebelius, S.; Olsson, V. J.; Szabó, K. J. J. Am. Chem. Soc. 2005,
127, 10478. (b) Olsson, V. J.; Sebelius, S.; Selander, N.; Szabó, K. J.
J. Am. Chem. Soc. 2006, 128, 4588. (c) Molander, G. A.; Trice, S. L.
J.; Dreher, S. D. J. Am. Chem. Soc. 2010, 132, 17701. (d) Zhao, C.-
J.; Xue, D.; Jia, Z.-H.; Wang, C.; Xiao, J. Synlett 2014, 25, 1577.
(e) Erb, W.; Hellal, A.; Albini, M.; Rouden, J.; Blanchet, J. Chem.
(21) Cao, L.; Li, C. Tetrahedron Lett. 2008, 49, 7380.
(22) Liu, Q.; Chen, C.; Tong, X. Tetrahedron Lett. 2015, 56, 4483.
(23) Wang, K.-B.; Ran, R.-Q.; Xiu, S.-D.; Li, C.-Y. Org. Lett. 2013, 15,
2374.
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