Iron-Based Catalyst for Borylation of Unactivated Alkyl Halides without Using Highly Basic Organometallic Reagents

Article abstract of DOI:10.1021/acs.joc.0c02364

The mild borylation of alkyl bromides and chlorides with bis(neopentylglycolato)diborane (B2neop2) mediated by iron-bis amide is described. The reaction proceeds with a broad substrate scope and good functional group compatibility. Moreover, sufficient ca

Full text of DOI:10.1021/acs.joc.0c02364

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Iron-Based Catalyst for Borylation of Unactivated Alkyl Halides
without Using Highly Basic Organometallic Reagents
Sheema Siddiqui, Ramesh Bhawar, and K. Geetharani*
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ABSTRACT: The mild borylation of alkyl bromides and chlorides with
bis(neopentylglycolato)diborane (B2neop2) mediated by iron-bis amide is
described. The reaction proceeds with a broad substrate scope and good functional
group compatibility. Moreover, sufficient catalytic activity was obtained for primary
and secondary alkyl halides. Mechanistic studies indicate that the reaction proceeds
through a radical pathway.
ncreasing attention has been devoted to the development of
earth-abundant elements in catalysis for various cross-
alkyl halides with bis(pinacolato)diboron, catalyzed by iron
salts. These methods need a reactive organometallic reagent,
EtMgBr and tBuLi, respectively, to facilitate this transformation
(Scheme 1). Our campaign to study the C-X borylation
revealed that the use of NHC-Co catalyst was effective to
cleave the C−X bond of both aryl20 as well as alkyl halides.15
Moreover, we have also shown iron-catalyzed hydroboration of
carbonyls21 using HBpin, where Fe[N(Si(CH3)3)2]2 (A)
proved to be an effective pre-catalyst. Thus, we speculated
that there is an opportunity to extend the catalytic efficiency of
Fe[N(Si(CH3)3)2]2 to C−X (X = Cl, Br) bond activation. We
herein report an iron amide catalyzed borylation of primary,
secondary, and some tertiary alkyl halides with bis-
(neopentylglycolato)diborane (B2neop2) as borylating agent
to produce alkylboronic esters from bromides and chlorides.
At first, we examined the reaction of Fe(II)amide (A)-
catalyzed borylation reaction with 5 mol % of catalyst loading
using primary alkyl bromide 1a with B2neop2 (2a) in the
presence of a base; the reaction proceeded in MTBE at 85 °C
for 16 h to produce 63% of desired borylated product (3a),
along with the formation of 16% protodehalogenated (B), and
5% homocoupled byproducts (C) (Table 1; entry 1). When
the base was changed from LiOtBu to KOtBu, NaOtBu
produced 3a in merely comparable yields (entries 2 and 3),
I
coupling reactions in recent years.1 The importance of iron has
been recognized for the functionalization and transformation
of organic/inorganic substrates, because of the high efficiency,
low cost, and minimal environmental impact.2 Following
seminal work by Hartwig and co-workers,3a iron has received
greater attention for the facile C-H activation;3b,c however, its
application in catalytic borylation reaction remains an elusive
challenge in this field.4 Alkylboronic acids and esters are
imperative reagents in synthetic chemistry, pharmaceutical
production, and other scientific fields because of their exclusive
reactivity. They are also indispensable units used in carbon−
carbon and carbon−heteroatom bond forming transforma-
tions.5 For the synthesis of alkylboronic esters, the direct C-H
borylation using alkanes was found to be more advantageous.6
However, the product selectivity of this method is mainly
controlled by steric factors.7 An alternative method, employing
an alkyl halide as starting material was developed using
organolithium/magnesium reagents. This procedure has
substantial limitations and low functional group tolerance.
Along this line, the nucleophile substitution reaction of boryl
species with alkyl electrophiles, mainly alkyl halides, emerged
as a complementary and distinct synthetic strategy for the
synthesis of alkylboronic esters.8 Several transition metal
complexes containing Ir,9 Pd,10 Zn,11 Cu,12 Ni,13 Mn,14 and
Co15 elements have emerged as key players to catalyze this
process. Although a recent report of iron catalysis yielding
alkylboronic esters through hydroborylative cyclization16 has
been an interesting pathway, the reports of Fe catalysts for
alkyl halide activation have been scarce.17 In 2014, Cook18 and
Bedford19 independently reported a direct cross-coupling of
Received: October 6, 2020
https://dx.doi.org/10.1021/acs.joc.0c02364
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

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Further optimization was focused on the catalyst loading. We
were pleased to observe that the catalyst loading of 10 mol %
gave 3a in 88% yield (entry 12). Use of B2pin2 as diboron
reagent instead of B2neop2 led to a noticeable decrease in the
yield of 3a (66%) (see Supporting Information; Table S5,
entry 6).
Scheme 1. Iron-Catalyzed Borylation of Unactivated Alkyl
Halides
Encouraged by these results, we further screened various
iron sources for the catalytic borylation reaction of our interest.
This comprised commercially available ferrous and ferric salts,
such as FeCl2, FeCl3, and Fe(acac)3 (Table 1, entries 13−15).
All of these choices of catalyst did not prove to be efficient as
that of Fe(II)amide catalyst A. Conducting the reaction with
20 mol % of Li[N(Si(CH3)3)2] as catalyst caused the yield of
3a to be 6% (entry 16). During the development of an iron
based catalyst for the borylation of alkyl halides, Cook and co-
workers observed that using iron(III) acetoacetate as a catalyst
enables the direct cross-coupling of alkyl halides with a
diboron reagent.18 Hence, we also examined Fe(III)
compound (D) as a catalyst. Intriguingly, compound D is as
effective as catalyst A, but only with higher catalyst loading
(Table 1, entries 17 and 18).
With the optimized conditions in hand, we investigated the
reaction scope of this catalyst system using a variety of
commercially and noncommercially available alkyl halides
including alkyl chlorides (Schemes 2 and 3). Several acyclic
Table 1. Optimization of Reaction Conditions for the
Borylation of 1-Bromo-3-phenyl Propane (1a) Catalyzed by
Iron Complex
a
Scheme 2. Substrate Scope of Fe-Catalyzed Borylation of
a
Unactivated Alkyl Bromides
b
entry
catalyst (mol %)
base
solvent
yield
63
65
67
16
40
trace
50
55
31
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
A (5)
A (5)
A (5)
A (5)
A (5)
A (10)
A (10)
A (10)
A (10)
A (10)
A (10)
A (10)
FeCl2(10)
FeCl3(10)
Fe(acac)3 (10)
Li[N(TMS)2] (20)
D (10)
LiOtBu
KOtBu
NaOtBu
LiOMe
NaOEt
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
THF
CPME
hexane
toluene
benzene
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
44
48
c
95 (88)
23
45
46
6
67
c
D (15)
98 (87)
a
Conditions: 1a (0.1 mmol), 2a (0.18 mmol), base (0.18 mmol), and
Fe catalyst (5−10 mol %) were used at 75 °C in 750 μL of solvent.
a
Conditions: alkyl halide (0.1 mmol), 2a (1.8 equiv), NaOEt (1.8
b
c
Yields were determined by 1H NMR. Isolated yield (A =
equiv), and Fe catalyst (10 mol %) were used at 75 °C in 750 μL of
b
solvent. 1H NMR yields are given in parentheses. exo-2-
Fe[N(Si(CH3)3)2]2; D = Fe(N(Si(CH3)3)2)2Cl(THF).
c
Bromonorbornane was used. (A) (15 mol %) and the reaction was
carried out for 22 h.
and the yield reduced to 16% when LiOMe was used as a base
(entry 4). When NaOEt was employed as a base, the desired
ester (3a) was obtained in comparatively higher yield of 40%
(entry 5) with less amount of protodehalogenated product
(see Supporting Information (SI); Table S5). Importantly, in
the absence of base, the reaction does not proceed (entry 6).
Reactions in a more polar solvent like THF or less polar
solvents such as CPME (cyclopentyl methyl ether), hexane,
toluene, and benzene were less effective (entries 7−11).
primary alkyl bromides worked efficiently, leading to high
reaction yields (1a−1c, 90−95% yield). Alkyl bromides
bearing ether groups, such as (2-bromoethoxy)benzene (1d),
1-(3-bromopropyl)-4-methoxybenzene (1e), and 2-(2-bro-
moethyl)-1,3-dioxane (1f), afforded excellent yields of the
corresponding products (3d−3f). p-Trifluoromethyl benzyl
bromide (1g) was also suitable for this reaction, affording the
B
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To probe the involvement of the radical, substrate 1a was
subjected to the standard reaction conditions in the presence
of TEMPO; the reaction proceeded to give only a trace
amount of borylated product 3a and 11% of TEMPO coupled
product. The catalytic borylation reactions of 1a in standard
reaction conditions in the presence of 9,10-dihyroanthracene
also suppressed the formation of borylated product signifi-
cantly and produced anthracene as side product, further
verifying the radical mechanism (Scheme 4). Moreover, when
Scheme 3. Substrate Scope of Fe-Catalyzed Borylation of
Unactivated Alkyl Chlorides
a
Scheme 4. Mechanistic Investigations of Fe-Catalyzed
Borylation of Unactivated Alkyl Halides on a Radical
Mediated Process via Scavenger Experiments
a
Conditions: alkyl chlorides (0.1 mmol), 2 (1.8 equiv), NaOEt (1.8
equiv), and A (12 mol %) in MTBE as a solvent at 80 °C for 22 h. 1H
NMR yields are given in parentheses. (A) 15 mol % and the reaction
b
was carried out for 25 h at 80 °C.
corresponding borylated product, 3g, in moderate yield.
Noticeably, when cyclic and acyclic secondary alkyl bromides
were used as substrates (1h−1k), relevant alkylboronates were
obtained in moderate to good yields. The tertiary bromide
substrate required higher catalyst loading and reaction
temperature (see SI). Reaction with 1-bromo adamantane
(1l), gave the desired product (3l) in moderate yield (54%).
Since the previous reports18,19 showed limitation toward
alkyl chlorides, we were interested in investigating the scope of
this reaction to the inexpensive and easily accessible alkyl
chlorides, using 3-phenylpropyl chloride (1m) as model
reacting partner. A better result was obtained with 12 mol %
of A, 1.8 equiv of 2a and NaOEt, using MTBE as the solvent at
80 °C for 22 h (3a, 82%; see SI). As shown in Scheme 3, both
primary and secondary alkyl chlorides gave the corresponding
alkyl boronates in moderate to good yields. The alkyl chlorides
bearing acyclic substituents (1n−1o) reacted well to afford the
desired products 3n−3o in good yields. Cyclohexyl chloride
(1p) was also suitable for this reaction, giving the desired
product in moderate yield. Tertiary alkyl chloride, 1q, also
worked by using a higher amount of catalyst, albeit with lower
yield (3q = 44%).
a radical clock experiment was conducted using 1r as a
substrate, the isolation of ring opening product (3r) suggests
the radical-mediated process. Further, the formation of the
cyclized product, cyclopentylmethyl-boronate (3s), from the
borylation reaction of 6-bromohex-1-ene (1s) also confirms
that the reaction proceeds via a radical-based mechanism
(Scheme 5). However, detailed mechanistic studies are
required to confirm the existence of the C-center radical in
these reaction conditions.
Scheme 5. Radical Clock Experiments for Fe-Catalyzed
Borylation of Unactivated Alkyl Halides on a Radical
Mediated Process
To gain some mechanistic understanding on this trans-
formation, several control experiments were carried out.
Bedford and co-workers have shown that the combination of
activated borate ion and the phosphine ligated iron(I) boryl
complex induces the borylation of alkyl halides. Consequently,
we probed whether this catalytic reaction mechanism involved
any iron boryl intermediate; reaction between an equimolar
mixture of Fe-catalyst A and diborane on 75 °C led to a rapid
change from a dark green suspension to a deep red solution.
Monitoring the reaction by 11B{1H} NMR spectroscopy
showed that the (Me3Si)2N-Bneop is the major by product,
along with the formation of an Fe-boryl complex and other
boron containing species. However, this experiment proved
largely uninformative, due to the paramagnetic nature of the
metal center, and all our attempts to isolate an Fe-boryl
complex failed due to the lack of stabilization by the labile
ligand as well as their extreme sensitivity toward air and
moisture.
The scope of boron protecting groups was examined using
1,8-diaminonaphthalene (DAN)28 and trifluoroborate salt.29
Alkyl-Bneop compound 3a can be efficiently converted into
the corresponding alkyl-Bdan and alkyl-BF3K (82% and 99%
conversion, respectively, Experiment S2 a, SI). Next, we exhibit
synthetic transformations of 3a, as the reactivity of alkyl-Bneop
is not well-known, while transformations of alkyl-Bpin are very
well-established. Reactions of 3a with 0.66 equiv of alkyl halide
was performed in the presence of 5 mol % of Pd(OAc)2 as a
catalyst30 with 3 equiv of KOtBu as base. The coupling product
was obtained in moderate yield after the mixture was refluxed
at 70 °C for 24 h (Experiment S2 b, SI)
In conclusion, we have developed an Fe(II)-bis amide
catalyzed borylation of alkyl halides, achieving high yields for a
variety of derivatives bearing different functional groups. The
methodology enables the borylation of alkyl halides, without
C
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substrates (1 mmol) was added, followed by addition of 5 mL of
solvent MTBE. The reaction was performed in an oil bath installed at
the desired temperature for the optimized reaction time for various
substrates. After completion, the reaction was quenched by exposing
the mixture to air, and the mixture was diluted with the addition of 20
mL of hexane (or pentane). The mixture was filtered with paddings of
Celite-silica (2:1) and washed with diethyl ether (2 × 3 mL). Solvent
was evaporated under reduced pressure not more than a temperature
of 55 °C. The borylated product was further purified by silica gel
chromatography mostly eluted with a 2:98 solution of EtOAc and
hexane.
the use of reductive organometallic reagents. The reaction
conditions are mild, and all the reagents are readily available
and inexpensive. Unlike other previous methods, the system
was also efficient for alkyl chloride substrates. Radical clock
experiments demonstrated the involvement of a radical
mechanism. Future work will focus on more detailed
mechanistic studies and to find a next generation iron catalyst
with improved scope and activity.
EXPERIMENTAL SECTION
■
Experimental Procedures and Characterization Data. 5,5-
Dimethyl-2-(3-phenylpropyl)-1,3,2-dioxaborinane (3a and 3m).10b
Compounds 3a and 3m were obtained following general procedure B
as colorless oils in 88% yield (204 mg) from 1a (199 mg, 1.0 mmol)
and also in 72% yield (167 mg) with 1m (155 mg, 1.0 mmol).
Product was purified by silica gel column chromatography eluted with
General Information. Unless otherwise mentioned, all the
reactions are performed in a nitrogen filled MBraun glovebox or
using the standard Schlenk technique. All chemicals are purchased
from either Sigma-Aldrich, Alfa Aesar, or Avra-chemicals and used
without further purification. Bis(neopentylglycolato)diborane
(B2neop2) and bis(pinacolato)diborane (B2pin2) were obtained
from AllyChem Co. Ltd., China, and were used after further
purification by a sublimation process. Reagent grade solvents are
purchased from SD Fine Chemicals (India), distilled according to a
standard procedure, degassed by a freeze pump thaw cycle (three to
four times), and stored under molecular sieves before using. MTBE
was further passed through activated alumina in a nitrogen
atmosphere and stored in molecular sieves. CDCl3 and C6D6 were
purchased from either Cambridge Isotope Laboratories or Sigma-
Aldrich and deoxygenated by a freeze pump thaw cycle and stored
over molecular sieves before use. NMR spectra [1H (400 MHz),
13C{1H} (100 MHz), and 11B{1H} (128 MHz) were recorded by a
Bruker Avance 400 MHz NMR spectrometer at an ambient
1
an EtOAc:hexane (2:98) mixture. H NMR (400 MHz, CDCl3) δ
7.31−7.28 (m, 2H), 7.23−7.17 (m, 3H), 3.60 (s, 4H), 2.65 (t, J = 7.6
Hz, 2H), 1.76 (p, J = 7.8 Hz, 2H), 0.98 (s, 6H), 0.81 (t, J = 7.8 Hz,
2H). 11B{1H} NMR (128 MHz, CDCl3) δ 30.3. 13C{1H} NMR (100
MHz, CDCl3) δ 143.1, 128.7, 128.2, 125.6, 72.0, 38.9, 31.7, 26.3, 21.8,
14.7 (C-B). GC−MS m/z: (M)+ 232.
5,5-Dimethyl-2-octyl-1,3,2-dioxaborinane (3b and 3n).23 Com-
pounds 3b and 3n were obtained following general procedure B as
colorless oils in 78% yield (177 mg) from 1b (192 mg, 1.0 mmol) and
also in 60% yield (136 mg) with 1n (149 mg, 1.0 mmol). Product was
purified by silica gel column chromatography eluted with an
1
EtOAc:hexane (2:98) mixture. H NMR (400 MHz, CDCl3) δ 3.52
(s, 4H), 1.29−1.21 (m, 11H), 0.89 (s, 6H), 0.82 (m, 4H), 0.64 (t, J =
7.8 Hz, 2H). 11B{1H} NMR (128 MHz, CDCl3) δ 30.5. 13C{1H}
NMR (100 MHz, CDCl3) δ 72.0, 32.7, 32.0, 29.6, 29.4, 24.2, 22.8,
21.9, 14.1. The carbon directly attached to the boron atom was not
detected, likely due to quadrupolar broadening. GC−MS m/z: (M)+
226.
1
temperature. H NMR chemical shifts are reported relative to TMS
and were referenced via residual proton resonances of the
corresponding deuterated solvent (CDCl3: 7.26 ppm, C6D6: 7.16
ppm), whereas 13C{1H} NMR spectra are reported relative to TMS
using the carbon signals of the deuterated solvent (CDCl3: 77.16
ppm). 11B{1H} NMR signals are quoted relative to BF3. H NMR
5,5-Dimethyl-2-phenethyl-1,3,2-dioxaborinane (3c).24 Com-
pound 3c was obtained following general procedure B as a colorless
oil in 86% yield (187 mg) from 1c (184 mg, 1.0 mmol). Product was
purified by silica gel column chromatography eluted with an
EtOAc:hexane (2:98) mixture. 1H NMR (400 MHz, CDCl3) δ
7.35−7.30 (m, 4H), 7.28−7.19 (m, 1H), 3.65 (s, 4H), 2.80 (t, J = 8
Hz, 2H) 1.17 (t, J = 8.2 Hz, 2H), 0.98 (s, 6H). 11B{1H} NMR (128
MHz, CDCl3) δ 30.3. 13C{1H} NMR (100 MHz, CDCl3) δ 145.1,
128.2, 128.1, 125.4, 71.9, 31.7, 30.2, 21.9. The carbon directly
attached to the boron atom was not detected, likely due to
quadrupolar broadening. GC−MS m/z: (M)+ 218.
1
yield was calculated as CH3NO2 (nitromethane) as an internal
standard. GC−MS data were acquired using a GCMS-QP2010 SE
SHIMADZU system. Commercially available, precoated TLC sheets
ALUGRAM Xtra Sil G/UV254 were purchased from MACHEREY-
NAGEL GmbH & Co. KG. The removal of solvent was performed on
a rotary evaporator in vacuo at a maximum temperature of 55 °C. N-
Heterocyclic carbene IMes (1,3-bis(2,4,6-trimethylphenyl)midazole-
2-ylidene)22a and iron complexes Fe(N(Si(CH3)3)2)2 and Fe(N(Si-
(CH3)3)2)2Cl(THF) were synthesized similar to the reported
literature procedure.21,22b
General Procedure A. For Small Scale Catalytic Reactions. In a
glass vial equipped with a magnetic stirring bar, a catalytic amount of
stock solution (0.38 M) of Fe-catalyst in hexane as x mol % (x = 10
for R-Br, x = 12 for R-Cl, x = 15 for tertiary alkylhalides) in hexane
was taken; then NaOEt (1.8 equiv, 0.018 mmol, 12.3 mg) and
diborane B2neop2 (1.8 equiv, 0.018 mmol, 40.5 mg) were added. To
this, alkyl halide substrate (0.01 mmol) and MTBE (750 μL) were
added. The vials were properly capped with an aluminum based
septum before bringing out of the glovebox, further wrapped with
Teflon-tape to secure the septum, and left for stirring on an oil bath at
75 °C for 16−22 h. After the completion, the reaction was quenched
by being exposed to air and 3 mL of a hexane and ether mixture (7:3)
was added. Further workup was done by passing the reaction mixture
with a Celite and silica mixture (2:1), followed by washing the
mixture with diethyl ether. The solvent was removed in vacuo, and the
product was dried using reduced pressure. The NMR sample was
prepared in CDCl3 using nitromethane as internal standard.
2-(2-Methoxyethyl)-5,5-dimethyl-1,3,2-dioxaborinane (3d).
Compound 3d was obtained following general procedure B, using
pentane and diethyl ether solution for chromatography, as a colorless
oil in 70% yield (120 mg) from 1d (139 mg, 1.0 mmol) in a 5:95
Et2O and pentane solution. Product was purified by silica gel column
chromatography eluted with a Et2O:pentane (10:90) mixture. 1H
NMR (400 MHz, CDCl3) δ 3.52 (s, 4H), 3.43 (m, 2H), 3.26 (s, 3H),
0.89 (s, 6H), 0.69 (m, 2H). 11B{1H} NMR (128 MHz, CDCl3) δ
30.7. 13C{1H} NMR (100 MHz, CDCl3) δ 72.2, 58.3, 34.3, 31.8, 22.5.
The carbon directly attached to the boron atom was not detected,
likely due to quadrupolar broadening. HRMS (ESI) m/z (M + Na)+
calc for C8H17BNaO3 195.1168, found 195.1155.
2-(3-(4-Methoxyphenyl)propyl)-5,5-dimethyl-1,3,2-dioxabori-
nane (3e). Compound 3e was obtained following general procedure
B as a colorless oil in 85% yield (222.7 mg) from 1e (228 mg, 1.0
mmol). Product was purified by silica gel column chromatography
1
eluted with an EtOAc:hexane (2:98) mixture. H NMR (400 MHz,
CDCl3) δ 7.10−7.08 (m, 2H), 6.82−6.80 (m, 2H), 3.78 (s, 3H), 3.57
(s, 4H), 2.54 (t, J = 7.6 Hz, 2H), 1.67 (p, J = 7.8 Hz, 2H), 0.95 (s,
6H), 0.75 (t, J = 7.9, 2H). 11B{1H} NMR (128 MHz, CDCl3) δ 30.7.
13C{1H} NMR (100 MHz, CDCl3) δ 157.7, 135.3, 129.6, 113.7, 72.1,
55.4, 37.9, 22.0, 14.2. The carbon directly attached to the boron atom
was not detected, likely due to quadrupolar broadening. HRMS (ESI)
m/z (M + H)+ calc for C15H24BO3 263.1819, found 263.1798.
General Procedure B. For Larger Scale Catalytic Reactions. In a
50 mL airtight Teflon tube equipped with a magnetic stirring bar,
Fe(N(Si(CH3)3)2)2 catalyst, in the form of a homogeneous stock
solution (0.38M) in hexane was taken in an amount as x mol % (x =
10 for R-Br, x = 12 for R-Cl, x = 15 for tertiary alkylhalides). To this,
1.8 equiv of base NaOEt (1.8 mmol, 123 mg) and diborane B2neop2
(1.8 mmol, 405 mg) were added; then 1 equiv of alkyl halides
D
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2-(2-(1,3-Dioxan-2-yl)ethyl)-5,5-dimethyl-1,3,2-dioxaborinane
(3f). Compound 3f was obtained following general procedure B as a
colorless oil in 88% yield (201 mg) from 1f (194 mg, 1.0 mmol) in an
8:92 EtOAc and hexane solution. 1H NMR (400 MHz, CDCl3) δ 4.44
(t, J = 5.2 Hz, 1H), 4.06 (dd, J = 5.0 Hz, 10.7 Hz, 2H), 3.73 (dt, J =
2.1 Hz, 12.4 Hz, 2H), 3.55 (s, 4H), 2.10−1.99 (m, 1H), 1.68−1.62
(m, 2H), 1.30−1.23 (m, 1H), 0.92 (s, 6H), 0.73 (t, J = 7.8 Hz, 2H).
11B{1H} NMR (128 MHz, CDCl3) δ 30.4. 13C{1H} NMR (100 MHz,
CDCl3) δ 103.7, 72.1, 67.0, 31.7, 29.7, 26.0, 22.0. The carbon directly
attached to the boron atom was not detected, likely due to
quadrupolar broadening. HRMS (ESI) m/z (M + Na)+ calc for
C11H21BNaO4 251.1431, found 251.1455.
mmol). Product was purified by flash column chromatography eluted
1
with hexane. H NMR (400 MHz, CDCl3) δ 3.57 (s, 4H), 1.85(m,
3H) 1.75−1.72 (m, 12H), 0.93 (s, 6H). 11B{1H} NMR (128 MHz,
CDCl3) δ 29.5. 13C{1H} NMR (100 MHz, CDCl3) δ 72.1, 38.4, 37.8,
31.7, 28.1, 27.8, 21.8. The carbon directly attached to the boron atom
was not detected, likely due to quadrupolar broadening. HRMS (ESI)
m/z (M + Na)+ calc for C15H25BNaO2 271.1845, found 271.1863.
GC−MS m/z: (M)+ 248.
2-(2-Ethylhexyl)-5,5-dimethyl-1,3,2-dioxaborinane (3o).15 Com-
pound 3o was obtained following general procedure B as a colorless
oil in 70% yield (158 mg) from 1o (148 mg, 1.0 mmol). Product was
purified by silica gel column chromatography eluted with an
1
EtOAc:hexane (2:98) mixture. H NMR (400 MHz, CDCl3) δ 3.57
5,5-Dimethyl-2-(4-(trifluoromethyl)benzyl)-1,3,2-dioxaborinane
(3g). Compound 3g was obtained following general procedure B as a
yellowish liquid in 27% yield (73 mg) from 1g (239 mg, 1.0 mmol).
Product was purified by flash column chromatography eluted with an
EtOAc:hexane (1:99) mixture. 1H NMR (400 MHz, CDCl3) δ 7.39−
7.38 (m, 2H), 7.17−7.16 (m, 2H), 3.51 (s, 4H), 2.19 (s, 2H) 0.84 (s,
6H). 11B{1H} NMR (128 MHz, CDCl3) δ 30.3. 13C{1H} NMR (100
MHz, CDCl3): δ 144.5, 129.2, 125.1, 72.4, 31.8, 21.9. The carbon
directly attached to the boron atom was not detected, likely due to
quadrupolar broadening. HRMS (ESI) m/z (M)+ calc for
C13H16BF3O2 272.1195, found 272.1208. GC−MS m/z: (M)+ 272.
2-Cyclopentyl-5,5-dimethyl-1,3,2-dioxaborinane (3h).25 Com-
pound 3h was obtained following general procedure B as a colorless
oil in 83% yield (151 mg) from 1h (151 mg, 1.0 mmol. Product was
purified by silica gel column chromatography eluted with an
(s, 4H), 1.51−1.42 (m, 1H), 1.32−1.15 (m, 8H), 0.91 (s, 6H), 0.91−
0.82 (m, 7H), 0.65 (m, 1H). 11B{1H} NMR (128 MHz, CDCl3) δ
30.7. 13C{1H} NMR (100 MHz, CDCl3) δ 72.1, 36.0, 35.7, 29.4, 23.2,
22.1, 22.0, 14.3. The carbon directly attached to the boron atom was
not detected, likely due to quadrupolar broadening. GC−MS m/z:
(M − CH3)+ 211.
Radical Clock Experiment. 2-(But-3-en-1-yl)-5,5-dimethyl-
1,3,2-dioxaborinane (3r).27 In a glass vial equipped with a magnetic
stirring bar, a catalytic amount of a stock solution of Fe-catalyst (10
mol %; 0.38 M) in hexane was taken; then NaOEt (1.8 equiv, 0.018
mmol, 12.3 mg) and diborane B2neop2 (1.8 equiv, 0.018 mmol, 40.5
mg) were added. Following that, the substrate (bromomethyl)-
cyclopropane and solvent MTBE (750 μL) were added. The vials
were properly capped with an aluminum based septum before
bringing out of the glovebox and left for stirring on an oil bath at 75
°C for 16 h. The reaction mixture was quenched while exposing it to
air, and 3 mL of pentane was added. The mixture was further passed
through a Celite and silica mixture (1:1), followed by washing with a
solution of 30% ether in pentane (2 × 3 mL). Solvent was evaporated
under reduced pressure, and the NMR sample was made in CDCl3
using nitromethane as internal standard. Borylated product 3r was
obtained as a colorless oil in 39% yield (65 mg) from 1r (135 mg, 1.0
mmol). Product was purified by silica gel column chromatography
1
EtOAc:hexane (2:98) mixture. H NMR (400 MHz, CDCl3) δ 3.59
(s, 4H), 1.74−1.68 (m, 2H), 1.57−1.48 (m, 7H), 0.95 (s, 6H).
11B{1H} NMR (128 MHz, CDCl3) δ 30.8. 13C{1H} NMR (100 MHz,
CDCl3) δ 72.2, 31.8, 29.8, 28.8, 27.0, 21.9. GC−MS m/z: (M −
CH3)+ 167.
2-(sec-Butyl)-5,5-dimethyl-1,3,2-dioxaborinane (3i).26 Com-
pound 3i was obtained following general procedure B as a colorless
oil in 79% yield (134.2 mg) from 1i (136 mg, 1.0 mmol. Product was
purified by silica gel column chromatography eluted with an
1
1
eluted with a Et2O:pentane (2:98) mixture. H NMR (400 MHz,
EtOAc:hexane (2:98) mixture. H NMR (400 MHz, CDCl3) δ 3.58
CDCl3) δ 5.90 (m, 1H), 5.02−4.97(m, 1H), 4.91−4.87(m, 1H), 3.59
(s, 4H), 2.05−2.04 (m, 2H), 0.95 (s, 6H), 0.86−0.84 (m, 2H).
11B{1H} NMR (128 MHz, CDCl3) δ 30.4. 13C{1H} NMR (100 MHz,
CDCl3) δ 141.5, 112.9, 72.2, 32.4, 28.2, 23.58, 22.0. GC−MS m/z:
(M)+ 168.
(s, 4H), 1.47−1.42 (m, 1H), 1.32−1.28 (m, 2H), 0.95 (s, 6H), 0.93−
0.89 (m, 3H). 11B{1H} NMR (128 MHz, CDCl3) δ 30.7. 13C{1H}
NMR (100 MHz, CDCl3) δ 72.1, 31.8, 27.5, 26.2, 15.6, 13.8. The
carbon directly attached to the boron atom was not detected, likely
due to quadrupolar broadening. GC−MS m/z: (M)+ 170.
2-Cyclohexyl-5,5-dimethyl-1,3,2-dioxaborinane (3j and 3p).25
Compounds 3j and 3p were obtained following general procedure B
as colorless oils in 80% yield (156 mg) from 1j (162 mg, 1.0 mmol)
and also in 67% yield (131 mg) with 1p (118 mg, 1.0 mmol). Product
was purified by silica gel column chromatography eluted with an
2-(Cyclopentylmethyl)-5,5-dimethyl-1,3,2-dioxaborinane (3s). In
a glass vial equipped with a magnetic stirring bar, a catalytic amount of
a stock solution of Fe catalyst (10 mol %; 0.38 M) in hexane was
taken; then NaOEt (1.8 equiv, 0.018 mmol, 12.3 mg) and diborane
B2neop2 (1.8 equiv, 0.018 mmol, 40.5 mg) were added. Following
that, the substrate 6-bromohex-1-ene and solvent MTBE (750 μL)
were added. The vials were properly capped with an aluminum based
septum before bringing out of the glovebox and left for stirring on an
oil bath at 75 °C for 16 h. The reaction mixture was quenched while
exposing it to air, and 3 mL of pentane was added. The mixture was
further passed through a Celite and silica mixture (2:1), followed by
washing with a solution of 30% ether in pentane (2 × 3 mL). Solvent
was evaporated under reduced pressure, and the NMR sample was
made in CDCl3 using nitromethane as internal standard. Borylated
product 3s was obtained as a colorless oil in 61% yield (120 mg) from
1s (163 mg, 1.0 mmol). Product was purified by silica gel column
chromatography eluted with a Et2O:pentane (2:98) mixture. 1H
NMR (400 MHz, CDCl3) δ 3.57 (s, 4H), 1.55 (m, 5H), 1.36−1.33
(m, 1H), 1.26−1.24 (m, 2H), 0.95 (s, 6H), 0.72−0.72 (d, J = 7.8 Hz,
2H). 11B{1H} NMR (128 MHz, CDCl3) δ 30.3. 13C{1H} NMR (100
MHz, CDCl3) δ 72.1, 31.8, 31.0, 27.3, 27.0, 22.0. HRMS (ESI) m/z
(M)+ calc for C11H21BO2 196.1635, found 196.1644.
1
EtOAc:hexane (2:98) mixture. H NMR (400 MHz, CDCl3) δ 3.57
(s, 4H), 1.72−1.49 (m, 9H), 1.28−1.26 (m, 2H), 0.94 (s, 6H).
11B{1H} NMR (128 MHz, CDCl3) δ 30.2. 13C{1H} NMR (100 MHz,
CDCl3) δ 72.1, 32.8, 28.4, 27.6, 27.1, 21.9. The carbon directly
attached to the boron atom was not detected, likely due to
quadrupolar broadening. GC−MS m/z: (M)+ 196.
2-((1R,2R,4R)-Bicyclo[2.2.1]heptan-2-yl)-5,5-dimethyl-1,3,2-diox-
aborinane (3k). Compound 3k was obtained following general
procedure B as a colorless oil in 76% yield (158 mg) from 1k (174
mg, 1.0 mmol). Product was purified by silica gel column
chromatography eluted with an EtOAc:hexane (2:98) mixture. 1H
NMR (400 MHz, CDCl3) δ 3.57 (s, 4H), 2.27−2.12 (m, 1H), 1.62−
1.47 (m, 6H), 1.28−1.24 (m, 4H), 0.93 (s, 6H). 11B{1H} NMR (128
MHz, CDCl3) δ 30.4. 13C{1H} NMR (100 MHz, CDCl3) δ 72.2,
38.9, 38.2, 36.8, 32.5, 32.3, 29.5, 23.5, 21.9. The carbon directly
attached to the boron atom was not detected, likely due to
quadrupolar broadening. HRMS (ESI) m/z (M + CH3OH + Na)+
calc for C13H25BNaO3 263.1794, found 263.1775. GC−MS m/z: (M
− CH3)+ 181.
ASSOCIATED CONTENT
■
2-((3r,5r,7r)-Adamantan-1-yl)-5,5-dimethyl-1,3,2-dioxaborinane
(3l and 3q). Compounds 3l and 3q were obtained following general
procedure B as white solids in 54% yield (134 mg) from 1l (214 mg,
1.0 mmol) and also in 44% yield (75 mg) with 1q (170 mg, 1.0
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02364.
E
https://dx.doi.org/10.1021/acs.joc.0c02364
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Experimental and spectroscopic data, copies of 1H,
13C{1H}, and 11B{1H} NMR spectra (PDF)
Construction of C-B Bonds. Chem. Rev. 2010, 110, 890−931.
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AUTHOR INFORMATION
Corresponding Author
K. Geetharani − Department of Inorganic and Physical
Chemistry, Indian Institute of Science, Bangalore 560012,
India; orcid.org/0000-0003-2064-1297;
Email: geetharani@iisc.ac.in
■
Authors
Sheema Siddiqui − Department of Inorganic and Physical
Chemistry, Indian Institute of Science, Bangalore 560012,
India
Ramesh Bhawar − Department of Inorganic and Physical
Chemistry, Indian Institute of Science, Bangalore 560012,
India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02364
(6) Ishiyama, T.; Miyaura, N. Transition metal-catalysed borylation
of alkanes and arenes via C-H activation. J. Organomet. Chem. 2003,
680, 3−11.
Notes
The authors declare no competing financial interest.
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Isolation, Characterisation, and Reactivity as a Boryl Anion. Science
2006, 314, 113−115. (b) Lu, X.; Zhang, Z.-Q.; Yu, L.; Zhang, B.;
Wang, B.; Gong, T.-J.; Tian, C.-L.; Xiao, B.; Fu, Y. Free Radical
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ACKNOWLEDGMENTS
■
K.G. thanks the SERB (CRG/2019/002319), DST inspire
faculty award (DST/INSPIRE/04/2015/000785), and Indian
Institute of Science (IISc) start-up research grant, for funding.
S.S. thanks IISc Bangalore for a research fellowship. We also
thank Prof. S. Ramakrishnan, IISc Bangalore, for the GC−MS
analysis and the AllyChem Co. Ltd., China, for a gift of B2pin2
and B2neop2. The authors thank Dr. A. Baishya for his help.
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