Borylative Heterocyclization without Air-Free Techniques

Article abstract of DOI:10.1021/acs.joc.0c01096

In contrast to previously reported borylative heterocyclization methods, a reaction here proceeds without air-free techniques to access synthetically useful borylated thiophenes, benzothiophenes, and isocoumarins. A comparison of stability/decomposition rates in air of several catecholboronic ester (Bcat) compounds derived from different heterocycle cores showed a strong dependence on the heterocycle structure. Lessons learned from this comparison were then harnessed for the development of borylative heterocyclization reactions under ambient-atmosphere conditions and with wet solvent. In contrast to literature reports suggesting general moisture sensitivity, a subset of Bcat products resulting from this technique were chromatography-stable and directly isolable, obviating the requirement for an extra synthetic transformation into more stable boron species, such as pinacolboronic esters (Bpin), for isolation. The isolated Bcat products were amenable to various downstream functionalization reactions, including reactions that were not accessible with their better-known Bpin counterparts, showing the complementarity of Bcat reaction partners and expanding their known chemistry. These results suggest the value of conceptual revisitation of substitution and solvent influence on stability and isolability of organo-Bcat compound classes and lay the groundwork for development of additional practical borylative methods in air.

Full text of DOI:10.1021/acs.joc.0c01096

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Borylative Heterocyclization without Air-Free Techniques
Chao Gao, Shuichi Nakao, and Suzanne A. Blum
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01096 • Publication Date (Web): 16 Jul 2020
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The Journal of Organic Chemistry
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Borylative Heterocyclization without Air-Free Techniques
Chao Gao, Shuichi Nakao†, and Suzanne A. Blum*
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Department of Chemistry, University of California, Irvine, California, 92697-2025, United States
Supporting Information Placeholder
ABSTRACT: In contrast to previously reported borylative heterocyclization methods, a reaction here proceeds without
air-free techniques, to access synthetically useful borylated thiophenes, benzothiophenes, and isocoumarins. A
comparison of stability/decomposition rates in air of several catecholboronic ester (Bcat) compounds derived from
different heterocycle cores showed a strong dependence on heterocycle structure. Lessons learned from this comparison
were then harnessed for the development of borylative heterocyclization reactions under ambient-atmosphere conditions
and with wet solvent. In contrast to literature reports suggesting general moisture sensitivity, a subset of Bcat products
resulting from this technique were chromatography-stable and directly isolable, obviating the requirement for an extra
synthetic transformation into more stable boron species, such as pinacolboronic esters (Bpin) for isolation. The isolated
Bcat products were amenable to various downstream functionalization reactions, including reactions that were not
accessible with their better-known Bpin counterparts, showing the complementarity of Bcat reaction partners and
expanding their known chemistry. These results suggest the value of conceptual revisitation of substitution and solvent
influence on stability and isolability of organo-Bcat compound classes, and lay groundwork for additional practical
borylative methods development in air.
INTRODUCTION
previously reported borlyative heterocyclizations using
BCl318–20 and ClBcat12,13,15,16 (Figure 1a), or for zwitterionic
heterocycles using B(C6F5)321–23. Interestingly, Ingleson
reported one substrate using BCl3 with unpurified solvent
and under ambient atmosphere,20 suggesting the future
possibility of broader use of that reagent under less
stringent conditions as well.
Organoboron reagents, especially those derived from
heterocycles, are versatile building blocks for
pharmaceuticals, natural products, and nanostructured
materials.1–7 Therefore, the development of synthetic
methods for such building blocks is in high demand.
Unlike the traditional synthetic routes for borylated
heterocycles, in which the heterocycles are constructed
first, followed by a subsequent installation of the boron,3,8,9
borylative heterocyclization reactions are synthetically
appealing because both the heterocycle and the boron
core are generated in a single synthetic step. Our
laboratory has developed borylative heterocyclization
reactions under inert atmosphere for synthesizing
1) ClBCat OR BCl3
dry solvent
2) pinacol, Et3N
dry solvent
X
R
With Glovebox or Schlenk
Techniques
Literature Protocols
Bpin
a
b
3
XMe
R
X = S, COO
ClBCat
X
1
benzofurans,10,11
lactones,12
indoles,13
R
wet toluene, 100 oC, 2–24 h
borylated
isoxazoles,14
benzothiophenes,15
dihydrofurans,9
No Air-Free Techniques
This Protocol
Bcat
isochromenes,9 thiophenes,16 and pyrazoles17. In all of the
aforementioned methods, however, the crude products
contained catechol boronic esters (Bcat), and which were
transformed into more stable Bpin products for isolation
(Figure 1a).
2
Figure 1. Comparison of old and new borylative
heterocyclization protocols.
The lack of reports of isolation of Bcat products in the
literature supports the limits of their stability, and has led
to relatively little information about isolation or reactivity
compared to their more common and more stable
congeners (e.g., Bpin). Indeed, in a study of relative
stability of seven bidentate oxygen-based ligands for
organoboron compounds, including the widely prevalent
pinacol, catechol was found to be the least stable towards
We herein develop
a
protocol for borylative
heterocyclization reactions that do not require air-free
techniques for a subset of heterocyclic cores. For some
cores, the full reaction sequences including apparently all
intermediates and reagents (e.g., ClBcat), are amenable
to set up and purification in air and with use of wet
solvents. These conditions starkly contrast with the
stringently air-free conditions required for most of the
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displacement by other hydroxy-based ligands.24 Our
monitored by for up to 336 h (14 d) by periodic acquisition
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current studies include elucidation of a strong substrate
dependence on air stability of borylative heterocyclization
reaction sequences and resulting Bcat products. Isolation
of some of these heterocyclic Bcat products proceed in
high yields by crystallization, or by silica-gel- or reverse-
phase chromatography without air-free techniques.
of H NMR spectra (Figure 2). This type of experiment
provided purely practical stabilty trends as initial
guidance.
The experimental results established that sulfur-
containing benzothiophene 2a and thiophene 2g were the
most stable under these conditions; neither showed
observable decomposition over two weeks (dark blue and
magenta lines, respectively). Isocoumarin 2i also showed
relatively high stability, with >90% remaining after 48 h.
Pyrazoles 6a and 6b were also both relatively stable
(>85% remaining after 48 h). A competition experiment
with 6a and 6b in the same NMR spectroscopy tube
showed little difference in stability from the influence in the
different remote substituents (green and dark purple lines,
respectively), indicating that these remote substituents do
not play a dominant role dispite conjugation with the
pyrazole core.
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Other Bcat heterocycles, however, showed rapid
decomposition. The main decomposition products in
these cases were their respective protodeborylated
product (Bcat substituted with H), through destruction of
the B–C bond. For example, benzofuran 8a had a first
half-life of decomposition of about 20 h. Isochromene 8c
exhibited similar instability. Indole 8b was the least stable
borylated heterocycle to these conditions, with a first half-
life of decomposition of about 10 h. With these
decomposition results indicating promising directions in
synthesis, the generation in wet solvent and subsequent
direct isolation of the most stable of these Bcat-
heterocycles was targeted, without the typical
transesterification step of more stable boron analogues:
Figure 2. Stability of various isolated Bcat-heterocycles in
toluene-d8 in open NMR spectroscopy tubes exposed to air.
a Mbs = 4-methoxybenzenesulfonyl.
RESULTS AND DISCUSSION
We started our investigation upon noticing that
benzothiophene 2a appeared to be bench stable in a
crude product mixture, even when in solvent. We
hypothesized that reactivity/stability trends might be
dictated by the donating ability of the heteroatom (here,
S, N, O), the (related) degree of aromatic stabilization
within the ring, and/or the polarity (and thus hydrolytic
sensitivity) of the resulting carbon–boron bond.
Previously, similar trends have been thoroughly studied
for boronic acids by Lloyd-Jones,25 however, the Bcat
counterparts have remained understudied. Such trends
for Bcat, if understood, are expected to provide predictive
guidance for design of more practical borylative
heterocyclization reactions, e.g., by identifying cases
wherein air-free techniques are most likely to be
avoidable.
given
the
relatively
high
stability
of
Bcat-
benzothiophenes, thiophenes, isocoumarins, and
pyrazoles, we hypothesized that the entire reaction
sequence for the borylative heterocyclization to access
some of these classes might be amenable to synthesis
without air-free conditions. Therefore, we next explored
the viability of air exposure and wet solvent setup for the
reaction
sequence
of
thioboration,15,16,26
carboxyboration,12 and aminoboration13 reactions.
Optimization of reaction conditions without air-free
techniques. Given the highest stability of the sulfur-
containing Bcat heterocycles, the synthesis of compound
2a was the first one targeted.
For robust initial
comparison, the same stoichiometry, time, and
temperature were compaired, with the only variable being
if the reaction was set up in the glovebox or in the air. This
initial experiment employed 1.4 equiv ClBcat at 100 ˚C,
for 4 h, either fully in the glovebox with dry solvents and
oven-dried glassware, or with the alternative open-air/wet
solvent setup.
In order to develop these more practical protocols, we
first focused on determining the simple stability of several
Bcat product classes towards the conditions that they
would face in the laboratory: in organic solvents and open
to air (uncapped). To elucidate trends, initial experiments
examined the relative air-stability of a variety of Bcat-
heterocycles
available
through
borylative
Specifically, the ambient exposure reactions were set
up in air with as-purchased toluene-d8 and off-the-shelf
(i.e., not-oven-dried) glass vials. The glass vials were then
heterocyclization (2, 6, and 8) in toluene-d8, the solvent
optimized for their synthesis. To perform these
experiments, previously isolated Bcat-heterocycles were
dissolved in initially dry toluene-d8 with a nonvolatile
internal standard in NMR spectroscopy tubes inside of the
glovebox. The sample tubes were then transferred out of
the glovebox and onto the bench, and then the caps were
removed and the tubes were opened to air. The stability
of different product classes to diffusion-based
decomposition under these conditions was then
1
capped to prevent solvent evaporation. Crude H NMR
spectroscopy analysis of the test reaction with 1a showed
that the product from borylated heterocyclization was
generated after 4 h, albeit in lower conversion (starting
material remained) than its in-glovebox comparison
reaction (no starting material remained). We
hypothesized that because the reagent ClBcat was
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moisture sensitive,27 a competition between the desired
reaction and decomposition of ClBcat caused by water in
Scheme 1. Synthesis of Borylated Heterocycles
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8
9
the solvent may have resulted in insufficient stoichiometry
of ClBcat. To overcome this problem, the stoichiometry of
ClBcat was increased to 2.0 equiv from 1.4 equiv. Then,
full conversion of the substrate was observed at 4 h, as
determined by 1H NMR spectroscopy.
This increase in ClBcat stoichiometry was found to be
beneficial in extension to other heterocycles. Specifically,
carboxyboration
reactions,
which
synthesized
isocoumarins 2i–2k (100 ˚C, 24 h), also benefited from
increasing the stoichiometry of ClBcat from 1.4 equiv to
2.0 equiv, presumably due to the same competing
process. The stoichiometry of ClBcat in case of 2g,
however, proceeded cleanly with 1.5 equiv—the identical
quantity as used previously in the glovebox preparation.16
The rate of this borylative heterocyclization reaction, the
fastest in the examined set (2 h instead of up to 24 h), was
plausibly faster than the competing decomposition of
ClBcat by water, removing the need for the extra 0.6 equiv
of reagent. The apparent stability of crude Bcat products
2 under these conditions and at these elevated
temperatures was also notable.
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Isolation metods for Bcat compounds in air with wet
solvents. With conditions in hand for synthesis without air-
free conditions, isolation methods in air for the Bcat-
heterocycle products were explored next (Scheme 1). In
order to explore isolation of the materials from the above
syntheses, isolation was performed on the material that
arose from wet-solvent and air-exposure techniques. In
parallel, for comparison with the previous glovebox-then-
transesterification protocol, the synthesis and isolation of
each Bpin product 312,15,16 was also performed in the
glovebox. Scheme 1 shows this direct comparison of
1
isolation of 2 or of 3. H NMR spectroscopy yields of Bcat
products 2 (shown in parentheses), were also compared
inside and outside of the glovebox. This initial in situ
measurement enabled deconvolution of any potential
differences in isolated yields as arising from either the
ambient-exposure reaction itself or the isolation method
(or both).
For the highly stable sulfur heterocycles,
isolated yields of Bcat products were generally similar to
Bpin products, with some specific compounds somewhat
higher or lower. For isocumarines, yields of isolated Bcat
products were somewhat lower than their Bpin analogues,
but moderate yields were still obtained. Individual
compounds and their isolation methods are described in
more detail below.
Catechol boronic ester 2a was purified via silica gel
column chromatography in air in 90% yield. This reaction
could also be scaled up to 1.2 g scale in 82% yield with
longer reaction time (6 h). Compound 2g was also
amenable to purification by silica gel column
chromatography
in
72%
yield.
Alternative
chromatography-free trituration of the crude reaction
mixture with pentane also afforded the pure product
(67%).
a(2) = 1H NMR yield of 2 (reaction wthout air-free techniques).
c
d
b(2) = 1H NMR yield of 2 (glovebox reaction). t = 6 h. t
= 24 h. et = 6 h.
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because protodeborylated product formed during the
course of C18 column chromatography. Assignment of
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8
1
Isocoumarins (2i–2k) were produced in high H NMR
chromatography as the likely cause of protodeborylation
was made because the isolated yields of Bpin derivatives
were significantly higher than that of their Bcat
counterparts; thus, it appeared likely that the significant
quantity of detected protodeborylation occurred during the
course of C18 column chromatography of the Bcat
compounds. These results established a limitation of the
in-air techniques for this heterocycle class.
spectroscopy yields; however, the crude products
decomposed into an unidentifiable mixtures upon
attempted silica gel column chromatography. We
reasoned that this type of product might be more sensitive
to Brønsted acid than its thiophene counterpart, so neutral
alumina was also attempted. Under these conditions,
2i−2k hydrolyzed with loss of the C–B bonds, yielding
their corresponding protodeborylated products. Similarly,
pH 7 buffered (KH2PO4-Na2HPO4) silica gel28 also
resulted in protodeborylation. None of these purifications
were satisfactory. Purification of 2i−2k by reverse phase
(C18) chromatography, was, however, satisfactory
(55−69%).
9
Scheme 2. Synthesis of Borylated Pyrazoles
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Reverse phase chromatography was also a successful
strategy for benzothiophenes 2d, 2e, and 2f (81%, 74%,
and 76% respectively). For the benzothiophenes and
thiophenes
containing
electron
withdrawing
trifluoromethyl groups (2c and 2h), additional
crystallization from hot toluene (~80 ˚C) after reverse-
phase chromatography was required to produce
analytically pure material. Notably, substrate 1f contained
a Lewis and Brønsted acid-sensitive ester group, yet was
amenable to both ambient-condition borylative
heterocyclization with ClBcat and isolation: the
corresponding Bcat product 2f could be isolated in
comparable yield to its Bpin glovebox counterpart 3f (76%
and 75%, respectively).
With techniques for the previous heterocycles in hand,
copper-catalyzed synthesis of Bcat pyrazoles without
using air-free techniques was next attempted. The crude
11B NMR spectrum, however, showed that the precursor
N–B bond in requisite intermediate 5 had already
decomposed under these conditions prior to the
cyclization, likely through hydrolysis of the N–B bond.
Therefore, a “mixed” protocol, in which the borylative
heterocyclization reaction was performed under inert
atmosphere but the isolation was performed open to air,
was attempted (Scheme 2). The isolated yields were low,
aLiterature value on the same reaction scale
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Scheme 3. Downstream Functionalization of Isolated Bcat-heterocycles
1
Bu
2
3
4
5
6
7
8
9
OH
(1.2 equiv)
S
O
P(OPh)3 (5 mol%)
Pd2(dba)3•CHCl3 (5 mol%)
dioxane, 80 ˚C, 2 h
Me
Ph
50%
12
I
O
(1.2 equiv)
S
Bu
O
CsOH•H2O (3.0 equiv)
XPHOS-Pd-G3 (4 mol%)
THF, 75 ˚C, 20 h
Me
Ph
(1.2 equiv)
S
O
Me
68%
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(S)-BINAP (5 mol%)
Rh(acac)(C2H4)2 (3 mol%)
Et3N (5.0 equiv)
Me
73%
13
dioxane/H2O, 100 ˚C, 3 h
Ph
X
(1.2 equiv)
I
Ph
S
R
Ph
Ph
4-nitrobenzonitrile (2.2 equiv)
PhSiH3 (4.0 equiv)
K2CO3 (2.0 equiv)
PdCl2 (10 mol%)
toluene/MeOH/H2O, 80 ˚C, 2 h
Ph
Bcat
45%
10
S
P cat. (15 mol%)
NH
X = S, COO
Isolated
bench-stable
Ph
toluene, 120 ˚C, 4 h
Ph
P
O
67%
S
O
CN
O
14
(6.0 equiv)
OMe
4-nitrobenzonitrile (3.0 equiv)
PhSiH3 (5.0 equiv)
O
Ph
OMe
P cat.
P cat. (50 mol%)
O
DDQ (1.0 equiv)
Pd(OAc)2 (2 mol%)
Ac2O (5.0 equiv)
40%
toluene, 120 ˚C, 4 h
11
Bu
HN
AcOH, air, 90 ˚C, 26 h
CN
79%
15
Isolation of Bcat products enables downstream functionalization NOT accessible to previous Bpin counterparts
O
Ph
O
S
same conditions
same conditions
X
NH
R
Bu
Ph
HN
Bpin
X = S, COO
CN
CN
0%a
14
0%a
15
a Determined by 1H NMR spectroscopy
functionalization demonstrated that Bcat heterocycles
participate in synthetically useful derivitization reactions.
These Bcat heterocycles could access downstream
functionalization reactions that were not accessible to
their better-known Bpin counterparts: Pinacol boronic
ester analogues did not produce 14 or 15 under otherwise
Synthetic utility. Downstream functionalization of
organo-Bcat compounds is relatively underexplored in
comparison to other boron-based groups, with some
notable recent examples.29 Presumably, the limited
reported applications arise in part from the prior limited
reports of isolation of compounds in this class. In order to
explore the synthetic applications of Bcat heterocycles,
diverse representative derivatizations were performed on
selected isolated Bcat products (Scheme 3). A C(sp2)–
C(sp2) bond formation was achieved via Pd-catalyzed
Suzuki cross-coupling reaction to afford 9 in 68% yield.9,29
Cross-coupling of 2g and (iodoethynyl)benzene afforded
10 in 45% yield.30 An oxidative Heck reaction synthesized
11 in 40% yield,31 and a Pd-catalyzed allylation of 2a with
allyl alcohol generated 3-allyl benzothiophene (12) in 50%
yield.32 A Rh-catalyzed 1,4-conjugate addition between
2a and butenone generated 13 in 73% yield.15,33,34
Formation of a C–N bond between Bcat-heterocyles 2g
and 2i and 4-nitrobenzonitrile via organophosphorus
catalyzed aminations35 proceed in 67% and 79% yields,
respectively. This broad scope of downstream
1
identical conditions (0% H NMR spectroscopy yields),
consistent with their lack of amination reactivity reported
by Radosevich.35 It is unlikely that fast conversion from
Bcat to B(OH)2 preceded the C–N coupling due to the
rigorously air- and moisture-free conditions (additional
discussion vida supra). Thus, direct C–N coupling from
the organo-Bcat compound is implicated. These results
demonstrated that the organo-Bcat products were able to
access complementary reactivity, and thus showcased a
value of this new protocol.
Examination of origin of heterocycle core stability
differences. The prior stability comparison with time,
described in Figure 2, was in toluene, which was the
optimal solvent for the borylative heterocyclization
reactions. Yet, under these conditions, decomposition
initiated by water or oxygen in the air is partially limited by
diffusion rates into toluene and into the reaction tube. To
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gain insight into a “purer” origin of the variation in in-air 2a to yield boronic acid 16 and free catechol 17
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2
3
4
5
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7
8
blumstability of Bcat heterocycles observed during these
studies, NMR spectroscopy studies in THF were next
employed, because in this solvent a specific and known
quantity of water could be injected at a specific time into
each sample, due to the miscibility of THF and water. In
these studies, a controlled amount of H2O was added
under inert atmosphere to examine hydrolytic stability
independent of oxygen stability. The two Bcat-
heterocycles that showed the most difference in stability
in toluene were chosen for investigation, namely 2a (the
most persistent compound in Figure 2) and 8b (the least
persistent compound in Figure 2).
(Scheme 4, with the characteristic singlets arising from
the two sets of product hydroxyl groups).7,24,37
Removal of the solvent in vacuo resulted in effective
removal of the water, and the original Bcat compound (2a)
was cleanly regenerated without formation of observable
new or decomposed species. These observations are
consistent with rapid equilibrium between these species
in Scheme 4 under the examined conditions.
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Scheme 4. Hydrolysis of Bcat Heterocycle 2a
An initial control experiment demonstrated that 2a was
stable in dry d8-THF under inert atmosphere (by 1H NMR
spectroscopy, Figure 3a). Yet, upon addition of 10 equiv
of H2O while otherwise maintaining inert atmosphere, the
1H NMR spectrum (Figure 3b) and the 11B NMR spectrum
(see SI) showed an immediate chemical transformation
(< 1 min) to a single new heterocyclic product. The most
distinctive spectroscopic signals from the reacted sample
were two singlets at 8.01 ppm and 7.37 ppm, each
integrating to two protons (red boxes, Figure 3b). No
further transformation was observed over the coures of a
week as determined by periodic monitoring by NMR
spectroscopy.
Indole 8b, in contrast, decomposed into an intractable
mixture in dry d8-THF under inert atmosphere even
without addition of water (>60% decomposed in 22 h).
However, when 10 equiv H2O was added to a freshly
prepared sample of 8b in d8-THF under inert atmosphere,
an immediate clean chemical transformation occurred
similar to that of 2a with H2O (or D2O), and no further
transformation was observed in 24 h. Thus, the addition
of water in the absence of oxygen had a protective effect
on the stability of the boron–carbon bond in THF. The
structure(s) of the product(s) of this transformation could
not be fully determined, because freshly prepared 8b
could not be isolated free of contaminant of
protodeborylated product (see Experimental Section for
details); however, some information could still be obtained
by comparing 1H and 11B NMR spectra from this reaction
with that of prior 2a: There were two similar singlets in the
1H NMR spectrum of 8b with H2O (8.01 ppm and 7.39 ppm
with 8b, comparied to 8.01 ppm and 7.37 ppm with 2a).
Furthermore, the chemical shift in the 11B NMR spectrum
of 8b with H2O was 28.2 ppm (identical to that arising from
2a with H2O). These data are consistent with the
analogous hydrolysis of 8b to the corresponding boronic
acid 8b-B(OH)2, similar to Scheme 4. The stability of this
presumed boronic acid for 24 h at neutral pH is consistent
with previous observations by Lloyd-Jones.25 Stoltz
1
Figure 3. H NMR spectra in THF-d8 of (a) 2a; (b) 2a with
H2O (10 equiv); (c) 2a with D2O (10 equiv); (d) 2H NMR
spectrum of 2a with D2O (10 equiv).
To gain a deeper understanding of the chemical
transformation that had occurred upon addition of this
water, a similar NMR spectroscopy experiment with D2O
instead of H2O was performed (Figure 3c). When D2O was
used, the two singlets at 8.01 ppm and 7.37 ppm were
reported that
a
3-indoleboronic acid synthetic
intermediate in the total synthesis of dragmacidin D was
not stable for isolation,38 seemingly contradictory to the
high stability of 8b-B(OH)2; however, it was not specified
in that report the type of instability encountered (air-
versus water- versus solvent-), and as our experiments
demonstrated, different boron species might possess
different types of stability under these various conditions.
2
absent in the proton spectrum. H NMR spectroscopic
analysis of the sample, however, revealed these two
signals at the same chemical shifts (Figure 3d). These
results indicated that these two distinctive signals
originated from the added water (or heavy water).
11B NMR spectra showed that when either 10 equiv of
either H2O or D2O was added, the 11B chemical shift
changed from 30.3 ppm to 28.2 ppm, indicating the boron
core obtained more electron density, consistent with
better donor ligands,36 and establishing that this shift was
insensitive to the isotope of hydrogen. Signals arising
from free catechol (17) were also identified in this reaction
mixture, as determined by comparison with authentic
samples. These data are consistent with fast hydrolysis of
The conclusion from these experiments in THF is that
different reactions occur in THF upon addition of known
quantities of water than in toluene upon diffusion/bench
stability studies. Some of these reactions produced the
exact opposite effect on the stability of the key C–B bond:
For example, addition of a known quantity of water in THF
actually resulted in an increase in stability of the C–B
bond, by generation of the boronic acid, thereby creating
a longer-lived C–B bond than that established in open-
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The Journal of Organic Chemistry
tube toluene. Specifically, in THF, the stability of 8b-
B(OH)2 was >24 h with the C–B bond remaining intact. In
1
2
3
4
5
6
7
8
Structure–stability trends. As shown in Figure 2,
heterocycles with greater enol ether or enamine character
were observed to be generally more prone to
decomposition in air in toluene. Attenuation of this
character generally resulted in longer persistence of the
C–B bond of the borylated heterocycles. DFT calculations
were also performed to examine additional electronic
properties that might explain the reason for varied
stabilities. Specifically, the ground state electronic
structure and natural bond orbital (NBO)39 of the Bcat
products were calculated in toluene at B3LYP/6-31G(d)
level of theory (see SI for details); however, no additional
clear electronic trend of ground state electron density on
the boron or ipso carbon with experimental C–B bond
persistence could be established through these
calculations.
contrast, in toluene open to air, nearly full
protodeborylation of 8b occurred in 24 h with destruction
of the C–B bond, with less than 20% remaining. Further,
8b decomposed in dry THF (more rapidly than wet THF),
with <40% remaining after 22 h. Therefore, the stability of
the groups on boron towards ligand exchange and the
stability of the C–B bond are distinctly different features.
Both are highly solvent- and condition-dependent. Thus,
one might wish to use the stability measurements most
closely related to the reaction conditions or scientific
questions at hand. For stability of borylated heterocycles
arising from borylative heterocyclization reactions in
toluene, the open-tube stability studies in Figure 2
provided the most useful guide points for practical
handling and reaction development, despite (or perhaps
partially because of) their different behavior than that in
carefully controlled miscible systems.
9
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CONCLUSION
A
protocol
was
developed
for
borylative
Determination of why higher stoichiometry of ClBcat
was required in the absence of air-free techniques during
reaction setup. We revisitied our prior consideration
(during optimization studies) that the extra 0.6 equivalents
of ClBcat may be required in order to act as a drying agent
by eliminating the water in the reaction system. To
examine this hypothesis, first, the stability of ClBcat alone
in wet d8-toluene was examined. This experiment
employed the same batch of (wet) solvent that was used
for measuring 1H NMR spectroscopy yields in Scheme 1,
at the same concentration of ClBcat (2.0 M). At ambient
temperature, neither 1H nor 11B spectra showed
observable change in 24 h; however, a seperate NMR
spectroscopy experiment at the temperature for borylative
heterocyclization (100 ˚C), resulted in substantial
decomposition of ClBcat in 4 h as observed by 11B NMR
spectroscopy.
heterocyclization and isolation of the Bcat heterocyclic
products without using air-free techniques. This study
unexpectedly shows that, for a subset of heterocycles, the
full reaction and isolation sequences with the
commercially available reagent ClBcat are amenable to
in-air conditions with wet solvents. Generally,
heterocycles without substantial enol ether or enamine
character were most amenable to such protocols. Stability
of the protolytically sensitive C–B bond was highly
solvent- and condition-dependent, with some surprises,
such as longer persistence in THF to which water had
been added than in an air-diffusion-limited sample in
toluene, the optimized solvent for borylative
heterocylcization
reactions.
The
isolated
Bcat
heterocycles participated in synthetically useful classes of
downstream functionalization reactions, including
reactions not available to their more-well-studied Bpin
analogs. These results indicate the value of revisiting
assumptions about organo-Bcat stabilities, and open
To examine the thermal stability of ClBcat in dry toluene
instead, an NMR spectroscopy sample in dry d8-toluene
was prepared under inert atmosphere. Upon heating this
potential
avenues
for
additional
borylative
1
sample at 100 ˚C for ca. 17 h, neither the H NMR nor
heterocyclization methods development that do not
require air-free techniques.
11B NMR spectra showed evidence of ClBcat
decomposition, indicating that ClBcat is thermally stable
in this solvent in the absence of water. Thus, some source
of water was indicated as the origin of the consumption of
reagent. To identify the origin of the water, the
concentration of water in the wet toluene was next
measured.
EXPERIMENTAL SECTION
General Information. All reagents and solvents were
used as received from commercial suppliers unless
otherwise
stated.
Tetrahydrofuran
(THF)
and
triethylamine (Et3N) were dried by passing through an
alumina column under argon pressure on a push still
solvent system. Dry toluene-d8 was prepared by drying
over CaH2 at 25 ˚C, degassing using three freeze-pump-
thaw cycles, and vacuum transferring before use. Dry
THF-d8 was prepared by drying over Na at 120 ˚C,
degassing using three freeze-pump-thaw cycles, and
vacuum transferring before use. Dioxane was dried over
CaH2, degassed using three freeze-pump-thaw cycles,
and vacuum transferred before use. Ultrapure water (Milli-
Q H2O) was generated by using Milli-Q Gradient A10
System. Catecholborane (HBcat)9 was degassed using
three freeze-pump-thaw cycles, and vacuum transferred
before use. The catalyst IPrAuTFA was prepared
Karl Fisher titration of the same batches of both toluene
and d8-toluene used in the reactions in Scheme 1,
however, showed very low water concentration
([H2O] = 0.00073 M for toluene and [H2O] = 0.00084 M for
d8-toluene) although both batches of solvents had been
opened and stored in air for months. The water in the
solvent, therefore, was much lower than the concentration
of ClBcat (2.0 M) and thus could not account for a
stoichiometric decomposition reaction that required an
extra 0.6 equiv of ClBcat reagent. Additional water from
the surface of the non-dried glassware and from leakage
through the vial-cap juncture during the course of the
borylative heterocylization reactions are therefore
plausible alternative origins.
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Page 8 of 23
according to a reported procedure.9 Reactions at elevated
temperatures were heated and stirred using preheated
aluminum pie-blocks. Analytical thin layer
chromatography (TLC) was performed using Merck F250
plates and visualized under UV irradiation at 254 nm, or
balloon, which was kept connected to the reaction round-
1
2
3
4
5
6
7
8
bottom flask until the end of the reaction. To the resulting
solution was added Et3N (0.70 mL, 5.0 mmol, 2.0 equiv)
via a syringe. The resulting solution was cooled to 0 °C in
an ice bath. At 0 °C, alkyne (3.8 mmol, 1.5 equiv) was
added dropwise via syringe, followed by warming the
resulting solution to 25 °C. The reaction solution was
stirred at 25 °C under N2 for 18 h or until all aryl iodide
was consumed as shown by TLC. The reaction was
quenched with saturated NH4Cl(aq) (20 mL), and the
resulting organic layer was washed with brine (10 mL).
The aqueous layer was extracted with EtOAc (3 × 10 mL),
and the combined organic layers were dried over MgSO4
and then filtered through a Celite plug (Celite in a medium
glass frit funnel). The filtrate was concentrated in vacuo,
and the crude product was purified by silica gel flash
column chromatography.
using
a
basic aqueous solution of potassium
permanganate. Flash chromatography was conducted
using a Teledyne Isco Combiflash® Rf 200 Automatic
Flash Chromatography System, and Teledyne Isco
Redisep® 35–70 μm silica gel columns or C18 reversed-
phase columns. Karl Fischer titration was performed on a
Mettler Toledo DL37 KF Coulometer. All proton and
carbon nuclear magnetic resonance (1H and 13C NMR)
9
10
11
12
13
14
15
16
17
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60
spectra were recorded on
a
Bruker DRX-400
spectrometer, Bruker DRX-500 spectrometer outfitted
with a cryoprobe, or a Bruker AVANCE-600 spectrometer.
Deuterium nuclear magnetic resonance (2H NMR) spectra
were recorded on a Bruker AVANCE-600 spectrometer.
Boron nuclear magnetic resonance (11B NMR) spectra
were recorded on a Bruker AVANCE-600 spectrometer.
Fluorine nuclear magnetic resonance (19F NMR) spectra
were recorded on a Bruker DRX-400 spectrometer or a
Bruker AVANCE-600 spectrometer. Phosphorus nuclear
magnetic resonance (31P NMR) spectra were recorded on
(2-(hex-1-yn-1-yl)phenyl)(methyl)sulfane (1a): Prepared
according to Procedure A (11.3 g, 45.1 mmol scale) and
purified by flash column chromatography (silica, 0–5%
EtOAc in hexanes) to afford a yellow oil (8.7 g, 86% yield).
1H NMR (500 MHz, CDCl3): δ 7.36 (dd, J = 7.6, 1.4 Hz,
1H), 7.28–7.22 (m, 1H), 7.12 (dd, J = 8.0, 1.1 Hz, 1H),
7.05 (td, J = 7.5, 1.2 Hz, 1H), 2.50 (t, J = 7.0 Hz, 2H), 2.47
(s, 3H), 1.70–1.59 (m, 2H), 1.58–1.64 (m, 2H), 0.96 (t,
J = 7.3 Hz, 3H). This spectrum is in agreement with
previously reported spectral data.15
a
Bruker AVANCE-600 spectrometer. All coupling
constants are reported in Hertz (Hz). Chemical shifts were
reported in ppm and referenced to the residual protiated
solvent peak (δH = 7.26 ppm for CDCl3, δH = 2.08 ppm for
d8-toluene, and δH = 1.72 or 3.58 ppm for d8-THF in
1H NMR spectroscopy experiments; δC = 77.16 ppm for
CDCl3, δC = 20.43 ppm for d8-toluene, and δC = 67.21 or
25.31 ppm for d8-THF in 13C NMR spectroscopy
(2-((4-bromophenyl)ethynyl)phenyl)(methyl)sulfane (1b).
Prepared according to Procedure A (0.625 g, 2.50 mmol)
and purified by flash column chromatography (silica, 0–
9% EtOAc in hexanes) to afford a brown solid (0.82 g,
>99% yield). 1H NMR (500 MHz, CDCl3): δ 7.53–7.45 (m,
3H), 7.45–7.40 (m, 2H), 7.32 (td, J = 7.7, 1.5 Hz, 1H), 7.18
(d, J = 7.9 Hz, 1H), 7.12 (td, J = 7.5, 1.2 Hz, 1H), 2.52 (d,
J = 2.0 Hz, 3H). This spectrum is in agreement with
previously reported spectral data.15
2
experiments); H NMR chemical shifts were reported in
ppm and referenced to the deuterated solvent peak
(δD = 1.72 or 3.58 ppm for d8-THF in 1H NMR
spectroscopy experiments); 11B NMR, 19F NMR, and
31P NMR spectroscopy experiments were referenced to
1
Methyl(2-((4-
the absolute frequency of 0 ppm in the H dimension
(trifluoromethyl)phenyl)ethynyl)phenyl)sulfane
(1c).
according to the Xi scale. High-resolution mass
spectrometry (HRMS) data were obtained at the Mass
Spectrometry Facility of the University of California, Irvine
using ESI, CI, and FI (LIFDI) as ionization techniques with
TOF mass analyzers, and the specific ionization
technique and type of mass analyzer are noted in the
characterization section of each individual compound.
DFT calculations were performed on the Greenplanet
cluster at the University of California, Irvine.
Prepared according to Procedure A (0.625 g, 2.50 mmol)
and purified by flash column chromatography (silica, 0–
5% EtOAc in hexanes) to afford a brown oil (0.63 g, 86%
yield). 1H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 8.4 Hz,
2H), 7.61 (d, J = 8.1 Hz, 2H), 7.50 (dd, J = 7.7, 1.4 Hz,
1H), 7.34 (td, J = 7.7, 1.6 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H),
7.13 (td, J = 7.5, 1.0 Hz, 1H), 2.53 (s, 3H). This spectrum
is in agreement with previously reported spectral data.26
(2-(cyclopropylethynyl)phenyl)(methyl)sulfane
(1d).
General Experimental Procedure A: Sonogashira
reactions for preparation of substrates (1a–1e and 1i–
1k).9 See SI for reaction scheme and product structures.
A flame-dried and septum-capped 100 mL round-bottom
flask was prepared and filled with N2 on a Schlenk line.
Then PdCl2(PPh3)2 (0.0875 g, 0.0125 mmol, 5.00 mol %),
and CuI (0.0475 g, 0.0250 mmol, 10.0 mol %) were
quickly placed, respectively, into the 100 mL round-
bottom flask after the septum was briefly removed. Then
the system was capped with the septum again, followed
by evacuation under high vacuum for ca. 5 min. Then the
system was refilled with N2 on a Schlenk line. Then dry
THF (13 mL) and aryl iodide (2.50 mmol, 1.00 equiv) were
added via syringes under N2 on the Schlenk line,
producing a homogeneous solution. Then the N2 inlet
from the Schlenk line was replaced with a N2-filled
Prepared according to Procedure A (0.625 g, 2.50 mmol)
and purified by flash column chromatography (silica, 0–
25% DCM in hexanes) to afford a yellow oil (0.47 g, >99%
yield). 1H NMR (500 MHz, CDCl3): δ 7.33 (dd, J = 7.6, 1.4
Hz, 1H), 7.23 (t, J = 7.7 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H),
7.03 (td, J = 7.5, 1.2 Hz, 1H), 2.46 (d, J = 1.1 Hz, 3H),
1.55–1.50 (m, 1H), 0.93–0.85 (m, 4H). This spectrum is in
agreement with previously reported spectral data.15
3-((2-(methylthio)phenyl)ethynyl)thiophene
(1e).
Prepared according to Procedure A (0.625 g, 2.50 mmol)
and purified by flash column chromatography (silica, 0–
35% DCM in hexanes) to afford a yellow oil (0.63 g, >99%
yield). 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 3.6 Hz,
1H), 7.36 (d, J = 7.6 Hz, 1H), 7.22–7.17 (m, 2H), 7.12 (d,
J = 5.0 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 8.1,
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The Journal of Organic Chemistry
6.7 Hz, 1H), 2.40 (s, 3H). This spectrum is in agreement
with previously reported spectral data.15
Methyl 2-(hex-1-yn-1-yl)benzoate
line to make a homogeneous solution. Then the N2 inlet
1
2
3
4
5
6
7
8
from the Schlenk line was replaced with a N2-filled
balloon, which was kept connected to the reaction round-
bottom flask until the end of this reaction. The resulting
solution was heated to 80 °C, and the reaction solution
was stirred at 80 °C under N2 for 5 h. The solvent was
partially removed (ca. 40% by volume) in vacuo, followed
by adding saturated NH4Cl(aq) (20 mL), and the resulting
aqueous layer was extracted with DCM (3 × 10 mL). All
organic layers were combined, and the combined organic
layers were dried over MgSO4 and then filtered through a
Celite plug (Celite in a medium glass frit funnel). The
filtrate was concentrated in vacuo. The crude product was
purified by silica gel flash column chromatography (silica,
0–10% DCM in hexanes) to afford a yellow oil that
solidified upon standing (0.89 g, 71% yield). 1H NMR (500
MHz, CDCl3): δ 7.56–7.45 (m, 4H), 7.42–7.30 (m, 6H),
5.98 (s, 1H), 2.17 (s, 3H). This spectrum is in agreement
with previously reported spectral data.16
(1i).
Prepared
according to Procedure A (1.31 g, 5.00 mmol), and
purified by flash column chromatography (silica, 0–9%
EtOAc in hexanes) to afford a yellow oil (1.1 g, >99%
1
yield). H NMR (600 MHz, CDCl3): δ 7.88 (d, J = 7.9 Hz,
1H), 7.51 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.30
(t, J = 7.7 Hz, 1H), 3.91 (s, 3H), 2.48 (t, J = 7.1 Hz, 2H),
1.68–1.57 (m, 2H), 1.55–1.40 (m, 2H), 0.96 (t, J = 7.3 Hz,
1H). This spectrum is in agreement with previously
reported spectral data.12
9
10
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14
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16
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Methyl 2-(cyclopropylethynyl)benzoate (1j). Prepared
according to Procedure A (0.655 g, 2.50 mmol), and
purified by flash column chromatography (silica, 0–9%
EtOAc in hexanes) to afford a yellow oil (0.56 g, >99%
1
yield). H NMR (600 MHz, CDCl3): δ 7.87 (dt, J = 7.8,
0.9 Hz, 1H), 7.48 (dd, J = 7.8, 1.3 Hz, 1H), 7.40 (td,
J = 7.6, 1.4 Hz, 1H), 7.29 (td, J = 7.7, 1.4 Hz, 1H), 3.91 (s,
3H), 1.51 (tt, J = 8.2, 5.0 Hz, 1H), 0.94–0.88 (m, 2H), 0.86
(dq, J = 4.5, 3.0, 2.4 Hz, 2H). This spectrum is in
agreement with previously reported spectral data.40
1,4-bis(4-(trifluoromethyl)phenyl)buta-1,3-diyne (SI-5).
To a 250 mL round bottom flask, CuI (0.095 g, 0.50 mmol,
5.0 mol %) and a stir bar was added. The flask was
capped with a septum, and the system was degassed on
high vacuum for 5 min. The flask was refilled with O2 with
an O2 balloon, and under O2 (ca. 1 atm) at 25 ˚C acetone
(34 mL), 4-(trifluoromethyl)phenylacetylene (SI-4)
(1.6 mL, 10. mmol, 1.0 equiv), TMEDA (0.14 mL,
1.0 equiv, 10. mol %), and Et3N (4.2 mL, 30. mmol,
3.0 equiv) were added via syringes, respectively. The
resulting solution was stirred under O2 for 19 h, followed
by quenching with 50 mL saturated NaHCO3(aq). The
aqueous layer was extracted with DCM (3 × 10 mL), and
the drying agent was then removed via filtration. The
filtrate was concentrated in vacuo to afford the crude
product, which was further purified by a flash column
chromatography (silica, 100% hexanes) to afford a white
Methyl 2-(5-chloropent-1-yn-1-yl)benzoate (1k). Prepared
according to Procedure A (0.655 g, 2.50 mmol), and
purified by flash column chromatography (silica, 0–9%
EtOAc in hexanes) to afford a light orange oil (0.64 g,
>99% yield). 1H NMR (500 MHz, CDCl3): δ 7.89 (d,
J = 7.9 Hz, 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.43 (t, J =
7.6 Hz, 1H), 7.33 (t, J = 7.7 Hz, 1H), 3.92 (s, 3H), 3.78 (t,
J = 6.4 Hz, 2H), 2.68 (t, J = 6.7 Hz, 2H), 2.22–2.02 (m,
2H). This spectrum is in agreement with previously
reported spectral data.41
1,4-diphenylbuta-1,3-diyne (SI-3). Prepared according to
a modified literature procedure.16 To a 250 mL round
bottom flask, CuI (0.19 g, 1.0 mmol, 5.0 mol %), acetone
(68 mL), phenylacetylene (SI-2) (2.2 mL, 20. mmol,
1.0 equiv), TMEDA (0.28 mL, 1.0 equiv, 10. mol %), Et3N
(8.4 mL, 60. mmol, 3.0 equiv), and a stir bar were added,
respectively. The resulting solution was stirred open flask
for 48 h at 25 ˚C. The reaction was quenched with 50 mL
saturated NaHCO3(aq). The aqueous layer was extracted
with DCM (3 × 10 mL), and the drying agent was then
removed via filtration. The filtrate was concentrated in
vacuo to afford the crude product, which was further
purified by a flask column chromatography (silica, 100%
hexanes) to afford a white solid (1.8 g, >99% yield).
1H NMR (600 MHz, CDCl3): δ 7.68–7.49 (m, 4H), 7.42–
7.31 (m, 6H). This spectrum is in agreement with
previously reported spectral data.16
1
solid (1.8 g, >99% yield). H NMR (500 MHz, CDCl3): δ
7.74–7.56 (m, 1H). 13C{1H}NMR (151 MHz, CDCl3) δ
133.0, 131.1 (q, J = 33 Hz), 125.6 (q, J = 4 Hz), 123.8 (d,
J = 272 Hz), 81.1, 75.8. This spectrum is in agreement
with previously reported spectral data.42
(Z)-(1,4-bis(4-(trifluoromethyl)phenyl)but-1-en-3-yn-1-
yl)(methyl)sulfane (1h). Prepared according to a modified
literature procedure.16 A 250 mL round-bottom flask with
a condenser was flame dried and the top of the condenser
was capped with a septum. The system was then filled
with N2 on a Schlenk line. Then SI-5 (1.78 g, 5.27 mmol,
1.0 equiv) and a stir bar were quickly placed into the
250 mL round-bottom flask after the septum was briefly
removed. Then the system was capped with the septum
again, followed by high vacuum for ca. 5 min. Then the
system was refilled with N2 on a Schlenk line. Then EtOH
(55 mL), NaBH4 (0.599 g, 15.8 mmol, 3.0 equiv), and
MeSSMe (0.18 mL, 2.6 mmol, 0.50 equiv) were added
under N2 on the Schlenk line to make a homogeneous
solution. Then the N2 inlet from the Schlenk line was
replaced with a N2-filled balloon, which was kept
connected to the reaction vessel until the end of the
reaction. The resulting solution was heated to 80 °C, and
the reaction solution was stirred at 80 °C under N2 for 5 h.
The solvent was partially removed (ca. 50% by volume) in
vacuo, followed by adding saturated NH4Cl(aq) (20 mL),
and the resulting aqueous layer was extracted with DCM
(Z)-(1,4-diphenylbut-1-en-3-yn-1-yl)(methyl)sulfane (1g).
Prepared according to a modified literature procedure.16
A 250 mL round-bottom flask with a condenser was flame
dried and the top of the condenser was capped with a
septum. The system was then filled with N2 on a Schlenk
line. Then SI-3 (0.891 g, 5.00 mmol, 1.00 equiv) and a stir
bar were quickly placed into the 250 mL round-bottom
flask after the septum was briefly removed. Then the
system was capped with the septum again, followed by
high vacuum for ca. 5 min. Then the system was refilled
with N2 on a Schlenk line. Then EtOH (52 mL), NaBH4
(0.568 g, 15.0 mmol, 3.00 equiv), and MeSSMe (0.44 mL,
5.0 mmol, 1.0 equiv) were added under N2 on the Schlenk
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(3 × 10 mL). All organic layers were combined, and the (E)-4-methyl-N'-(1-(thiophen-2-yl)hept-2-yn-1-
Page 10 of 23
1
2
3
4
5
6
7
8
combined organic layers were dried over MgSO4 and then
filtered through a Celite plug (Celite in a medium glass frit
funnel). The filtrate was concentrated in vacuo. The crude
product was purified by silica gel flash column
chromatography (silica, 100% hexanes). The flash
column chromatography was performed twice to afford a
yellow oil that solidified upon standing (0.46 g, 22% mass
recovery). This resulting product contained some
unidentifiable impurities that were inseparable even even
after two columns. However, the impurities did not
interfere the subsequent borylative heterocyclization
reaction. 1H NMR (600 MHz, CDCl3): δ 7.67 (d, J = 8.1 Hz,
2H), 7.64–7.57 (m, 6H), 6.01 (s, 1H), 2.17 (s, 1H).
13C{1H}NMR (151 MHz, CDCl3): δ 151.2, 141.8, 131.8,
128.5, 125.8 (q, J = 4.0 Hz), 125.4 (q, J = 4.0 Hz), 109.3,
96.9, 89.2, 16.4. 19F{1H}NMR (565 MHz, CDCl3): δ -62.69,
-62.84. HRMS (CI-TOF) m/z calcd for C19H12F6S ([M]+)
386.0564, found 386.0554.
ylidene)benzenesulfonohydrazide (4b). Compound SI-7
(0.192 g, 1.00 mmol, 1.0 equiv), H2NNHTs (0.0204 g, 1.10
mmol, 1.1 equiv), and a stir bar were charged in a 10 dram
vial in air at 25 ˚C, followed by adding EtOH (5 mL) and
H2SO4 (0.060 mL of 98% aqueous solution, 1.1 mmol, 1.1
equiv). The vial was capped and the resulting solution was
stirred at 25 ˚C for 24 h. The resulting white precipitate
was collected by filtration, and the filtration cake was
rinsed with EtOH (3 × 5 mL). The rinsed filtration cake
(white solid) was collected as the final product (0.24 g,
9
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66% yield). H NMR (500 MHz, CDCl3): δ 8.27 (s, 1H),
7.87 (d, J = 8.3 Hz, 2H), 7.37–7.32 (m, 1H), 7.32–7.28 (m,
3H), 6.98 (dd, J = 5.1, 3.6 Hz, 1H), 2.54 (t, J = 7.1 Hz, 2H),
2.41 (s, 3H), 1.73–1.59 (m, 2H), 1.52–1.42 (m, 2H), 0.97
(t, J = 7.4 Hz, 3H). This spectrum is in agreement with
previously reported spectral data.17
2-(phenylethynyl)phenol (SI-9). A 100 mL flame-dried and
septum-capped round-bottom flask was prepared and
filled with N2 on a Schlenk line. Then PdCl2(PPh3)2 (0.175
g, 0.25 mmol, 5.00 mol %), and CuI (0.095 g, 0.50 mmol,
10. mol %) were quickly placed, respectively, into the 100
mL round-bottom flask after the septum was briefly
removed. Then the system was capped with the septum
again, followed by high vacuum for ca. 5 min. Then the
system was refilled with N2 on a Schlenk line. Then dry
THF (25 mL) and 2-iodophenol (1.1 g, 5.0 mmol, 1.0
equiv) were added via syringes under N2 on the Schlenk
line to make a homogeneous solution. Then the N2 inlet
from the Schlenk line was replaced with a N2-filled
balloon, which was kept connected to the reaction round-
bottom flask until the end of this reaction. To the resulting
solution was added Et3N (1.4 mL, 10. mmol, 2.0 equiv) via
a syringe. The resulting solution was cooled to 0 °C in an
ice bath. At 0 °C, phenylacetylene (0.82 mL, 7.5 mmol,
1.5 equiv) was added dropwise via a syringe, followed by
warming the resulting solution to 25 °C. The reaction
solution was stirred at 25 °C under N2 for 18 h or until all
aryl iodide was consumed as shown by TLC. The reaction
was quenched with saturated NH4Cl(aq) (20 mL), and the
resulting organic layer was washed with brine (10 mL).
The aqueous layer was extracted with EtOAc (3 × 10 mL),
and the combined organic layers were dried over MgSO4
and then filtered through a Celite plug (Celite in a medium
glass frit funnel). The filtrate was concentrated in vacuo.
The crude product was purified by silica gel flash column
chromatography (silica, 0–9% EtOAc in hexanes) to
afford a brown oil that solidified upon standing (0.79 g,
(Z)-4-methyl-N'-(1-phenylhept-2-yn-1-
ylidene)benzenesulfonohydrazide
(4a):
Prepared
according to a literature procedure17 (0.186 g, 1.00 mmol)
to afford a white solid (0.27 g, 77% yield). 1H NMR
(600 4aMHz, CDCl3): δ 8.49 (s, 1H), 7.93–7.85 (m, 2H),
7.84–7.76 (m, 2H), 7.41–7.33 (m, 3H), 7.31 (d, J = 8.2 Hz,
2H), 2.57 (dd, J = 7.5, 6.7 Hz, 2H), 2.40 (s, 3H), 1.71–1.61
(m, 2H), 1.49 (dt, J = 14.6, 7.4 Hz, 2H), 0.98 (td, J = 7.4,
0.8 Hz, 3H). This spectrum is in agreement with
previously reported spectral data.17
1-(thiophen-2-yl)hept-2-yn-1-one (SI-7). A 100 mL flame-
dried and septum-capped round-bottom flask was
prepared and filled with N2 on a Schlenk line. Then
PdCl2(PPh3)2 (0.0702 g, 0.100 mmol, 2.00 mol %), and
CuI (0.0308 g, 0.200 mmol, 4.00 mol %) were quickly
placed, respectively, into the 100 mL round-bottom flask
after the septum was briefly removed. Then the system
was capped with the septum again, followed by high
vacuum for ca. 5 min. Then the system was refilled with
N2 on a Schlenk line. Then dry THF (25 mL) and acyl
chloride (SI-6) (0.53 mL, 5.0 mmol, 1.0 equiv) were added
via syringes under N2 on the Schlenk line to make a
homogeneous solution. Then the N2 inlet from the
Schlenk line was replaced with a N2-filled balloon, which
was kept connected to the reaction vessel until the end of
this reaction. To the resulting solution was added Et3N
(0.70 mL, 5.0 mmol, 1.0 equiv) and 1-hexyne (0.60 mL,
5.0 mmol, 1.0 equiv) were added via syringes, and the
resulting solution was stirred at 25 °C under N2 for 1 h.
The reaction was quenched with saturated NH4Cl(aq)
(20 mL), and the resulting organic layer was washed with
brine (10 mL). The aqueous layer was extracted with
EtOAc (3 × 10 mL), and the combined organic layers were
dried over MgSO4 and then filtered through a Celite plug
(Celite in a medium glass frit funnel). The filtrate was
concentrated in vacuo. The crude product was purified by
silica gel flash column chromatography (silica, 0–9%
EtOAc in hexanes) to afford a brown oil that solidified
1
81% yield). H NMR (500, CDCl3): δ 7.55 (ddd, J = 5.5,
3.0, 1.7 Hz, 2H), 7.43 (dd, J = 7.6, 1.7 Hz, 1H), 7.38 (ddd,
J = 4.8, 2.8, 1.5 Hz, 3H), 7.33–7.25 (m, 1H), 6.99 (dd,
J = 8.1, 1.1 Hz, 1H), 6.92 (td, J = 7.5, 1.1 Hz, 1H), 5.82 (s,
1H). This spectrum is in agreement with previously
reported spectral data.11
4-Methoxy-N-(2-
(phenylethynyl)phenyl)benzenesulfonamide (SI-11).
A
50 mL flame-dried and septum-capped round-bottom
flask was prepared and filled with N2 on a Schlenk line.
Compound SI-10 (0.0483 g, 2.50 mmol, 1.0 equiv) and
MbsCl (0.568 g, 2.75 mmol, 1.1 equiv) were added after
the septum was briefly removed. The system was
degassed on high vacuum for 5 min, followed by refilling
the system with N2 via a Schlenk line. Under N2, dry DCM
1
upon standing (0.84 g, 88% yield). H NMR (500 MHz,
CDCl3): δ 7.89 (dt, J = 3.9, 1.1 Hz, 1H), 7.67 (dt, J = 4.9,
1.1 Hz, 1H), 7.14 (t, J = 4.5 Hz, 1H), 2.48 (t, J = 7.1 Hz,
2H), 1.71–1.61 (m, 2H), 1.56–1.45 (m, 2H), 0.96 (t,
J = 7.3 Hz, 3H). This spectrum is in agreement with
previously reported spectral data.17
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The Journal of Organic Chemistry
(12.5 mL) was added, and the resulting solution was 3.0 equiv) was added, and the reaction was stirred at 0 °C
1
2
3
4
5
6
7
8
cooled to 0 ˚C, followed by adding pyridine (0.4 mL,
5.0 mmol, 2.0 equiv). The reaction mixture was warmed
to 25 ˚C, and it was stirred at 25 ˚C for 72 h under N2 (N2
balloon). The reaction was quenched with DI H2O
(10 mL), and the aqueous layer was extracted with DCM
(3 × 10 mL). All organic layers were combined, and the
combined organic layers were dried over MgSO4 and then
filtered through a Celite plug (Celite in a medium glass frit
funnel). The filtrate was concentrated in vacuo. The crude
product was purified by silica gel flash column
chromatography (silica, 0–40% EtOAc in hexanes) to
for 10 min. Then the N2 inlet from the Schlenk line was
replaced with a N2-filled balloon, which was kept
connected to the reaction round- bottom flask until the end
of this reaction. The reaction was then warmed to 25 °C
and stirred at this temperature under N2 18 h before it was
quenched with saturated NH4Cl(aq) (20 mL), and the
resulting organic layer was washed with brine (20 mL).
Then the aqueous layer was extracted with EtOAc
(3 × 10 mL), and the organic layers were combined. The
combined organic layers were then dried over MgSO4 and
then filtered through a Celite plug (Celite in a medium
glass frit funnel), and the filtrate was concentrated in
vacuo to afford the crude product, which was then purified
by flash column chromatography (silica, 0–15% EtOAc in
hexanes) to afford a light yellow oil (0.7 g, 74% yield). 1H
NMR (500 MHz, CDCl3): δ 7.48 (d, J = 7.9 Hz, 1H), 7.38
(d, J = 7.7 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.19 (t, J = 7.6
Hz, 1H), 5.29 (t, J = 5.7 Hz, 1H), 2.46 (t, J = 7.0 Hz, 2H),
2.18 (d, J = 3.9 Hz, 1H), 1.65–1.57 (m, 2H), 1.54–1.44 (m,
5H), 0.96 (t, J = 7.3 Hz, 3H). This spectrum is in
agreement with previously reported spectral data.9
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1
afford a light yellow solid (0.96 g, >99% yield). H NMR
(500 MHz, CDCl3): δ 7.71 (d, J = 8.9 Hz, 2H), 7.62 (d,
J = 8.3 Hz, 1H), 7.51–7.44 (m, 2H), 7.42–7.35 (m, 4H),
7.30 (t, J = 7.9 Hz, 1H), 7.17 (br s, 1H), 7.12–7.04 (m, 1H),
6.90–6.80 (m, 2H), 3.78 (s, 3H). This spectrum is in
agreement with previously reported spectral data.13
1-(2-(hex-1-yn-1-yl)phenyl)ethan-1-one
(SI-13).
A
100 mL flame-dried and septum-capped round-bottom
flask was prepared and filled with N2 on a Schlenk line.
Then 2-iodobenzyl alcohol (SI-12) (1.17 g, 5.00 mmol,
1.0 equiv), PdCl2(PPh3)2 (0.175 g, 0.250 mmol, 5.00 mol
%), and CuI (95.0 mg, 0.500 mmol, 10.0 mol %) were
quickly placed, respectively, into the 100 mL round-
bottom flask after the septum was briefly removed. Then
the system was capped with the septum again, followed
by high vacuum for ca. 5 min. Then the system was
refilled with N2 on a Schlenk line. Then dry THF (25 mL)
was added via a syringe under N2 on the Schlenk line to
make a homogeneous solution. Then the N2 inlet from the
Schlenk line was replaced with a N2-filled balloon, which
was kept connected to the reaction round-bottom flask
until the end of this reaction. To the resulting solution was
added Et3N (1.4 mL, 10. mmol, 2.0 equiv) via a syringe.
The resulting solution was cooled to 0 °C in an ice bath.
At 0 °C, 1-hexyne (0.86 mL, 7.5 mmol, 1.5 equiv) was
added dropwise via a syringe, followed by warming of the
resulting solution to 25 °C. The reaction solution was
stirred at 25 °C under N2 for 18 h. The reaction was
quenched with saturated NH4Cl(aq) (20 mL), and the
resulting organic layer was washed with brine (10 mL).
The aqueous layer was extracted with EtOAc (3 × 10 mL),
and the combined organic layers were dried over MgSO4
and then filtered through a Celite plug (Celite in a medium
glass frit funnel). The filtrate was concentrated in vacuo.
The crude product was purified by silica gel flash column
chromatography (silica, 0–10% EtOAc in hexanes) to
afford a brown oil (1.0 g, >99% yield). 1H NMR (500 MHz,
CDCl3): δ 7.66 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 7.7 Hz,
1H), 7.39 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 2.72
(s, 2H), 2.46 (t, J = 7.1 Hz, 2H), 1.65–1.57 (m, 2H), 1.54–
1.44 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H). This spectrum is in
agreement with previously reported spectral data.9
5-(2-(methylthio)phenyl)pent-4-yn-1-ol (SI-15). Prepared
according to Procedure A (0.625 g, 2.50 mmol), and
purified by flash column chromatography (silica, 0–40%
EtOAc in hexanes) to afford a yellow oil (0.41 g, 79%
1
yield). H NMR (600 MHz, CDCl3): δ 7.45–7.31 (m, 1H),
7.28–7.21 (m, 1H), 7.12 (dq, J = 8.1, 1.3 Hz, 1H), 7.05 (tq,
J = 7.6, 1.3 Hz, 1H), 3.87 (t, J = 6.0 Hz, 2H), 2.62 (tdd,
J = 6.6, 4.8, 2.4 Hz, 2H), 2.50–2.42 (m, 3H), 1.94–1.86
(m, 2H), 1.82 (br s, 1H). 13C NMR (151 MHz, CDCl3): δ
141.3, 132.3, 128.4, 124.3, 123.9, 121.8, 96.3, 78.9, 61.9,
31.3, 16.4, 15.1. HRMS (ESI-TOF) m/z calcd for
C12H14OSNa ([M+Na]+) 229.0663, found 229.0669.
5-(2-(methylthio)phenyl)pent-4-yn-1-yl
acetate
(1f).
Prepared according to a modified literature procedure.43
Compound SI-15 (0.418 g, 1.98 mmol, 1.0 equiv) was
placed into a flame-dried 100 mL round bottomed flask
with a stir bar. Then the round-bottom flask was capped
with a septum followed by high vacuum. Then the system
was refilled with N2 on a Schlenk line. Under dynamic N2,
dry DCM (4.0 mL) and Et3N (0.33 mL, 2.38 mmol,
1.2 equiv) were added via syringes respectively, and the
resulting solution was cooled to 0 ˚C. At 0 ˚C under N2,
acetyl chloride (0.17 mL, 2.38 mmol, 1.2 equiv) was
added dropwise via a syringe, and the resulting
suspension was stirred at 25 ˚C for 3 h before the reaction
was quenched with DI H2O. The resulting aqueous layer
was extracted with DCM (3 × 5 mL), and the organic
layers were combined. The combined organic layers were
then dried over MgSO4 and then filtered through a Celite
plug (Celite in a medium glass frit funnel), and the filtrate
was concentrated in vacuo to afford the crude product,
which was then purified by flash column chromatography
(silica, 0–20% EtOAc in hexanes) to afford a light yellow
oil (0.43 g, 87% yield). 1H NMR (500 MHz, CDCl3): δ 7.35
(dd, J = 7.6, 1.5 Hz, 1H), 7.29–7.22 (m, 1H), 7.12 (dd,
J = 8.0, 1.1 Hz, 1H), 7.05 (td, J = 7.5, 1.2 Hz, 1H), 4.28 (t,
J = 6.3 Hz, 2H), 2.60 (t, J = 7.0 Hz, 2H), 2.47 (s, 3H), 2.06
(s, 3H), 2.02–1.94 (m, 2H). 13C NMR (126 MHz, CDCl3): δ
171.2, 141.4, 132.4, 128.4, 124.2, 123.9, 121.8, 95.6,
79.0, 63.4, 27.9, 21.1, 16.6, 15.1. HRMS (ESI-TOF) m/z
1-(2-(hex-1-yn-1-yl)phenyl)ethan-1-ol
(SI-14).
Compound SI-13 (1.00 g, 5.00 mmol, 1.0 equiv) was
placed into a flame-dried 100 mL round bottomed flask
with a stir bar. Then the round-bottom flask was capped
with a septum followed by high vacuum. Then the system
was refilled with N2 on a Schlenk line. Under N2 on the
Schlenk line, EtOH (50 mL) was added via a syringe to
produce a 0.1 M solution. The resulting solution was
cooled to 0 °C. At 0 °C, NaBH4 (0.568 g, 15.0 mmol,
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calcd for C14H16O2SNa ([M+Na]+) 271.0769, found 5 mL). The resulting solution was concentrated in vacuo
to afford the product (0.063g, 78% yield). 1H NMR
(600 MHz, CDCl3): δ 8.59 (d, J = 8.2 Hz, 1H), 7.90 (d,
J = 8.0 Hz, 1H), 7.65–7.47 (m, 5H), 7.42 (t, J = 7.6 Hz,
1H), 7.32–7.23 (m, 2H), 7.19–7.09 (m, 2H). 13C{1H}NMR
(151 MHz, CDCl3) δ 157.5, 147.9, 144.3, 140.5, 134.0,
131.6, 131.5, 125.6, 125.3, 124.9, 123.6, 123.0, 121.9,
112.8. 11B NMR (193 MHz, CDCl3) δ 30.58. HRMS (FI-
TOF) m/z calcd for C20H12BBrO2S ([M]+) 407.9819, found
407.9781.
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2
3
4
5
6
7
8
271.0776.
General Experimental Procedure B: Synthesis of
Catechol Boronates (2a–2k).
General Remarks: All chemicals were weighed in air.
Vials and stir bars were not dried, and toluene was used
as received from commercial sources without purification.
All reactions were run 1.0 M concentration in substrate. B-
Chlorocatecholborane (ClBcat) was stored in a N2- or Ar-
filled glovebox. For use, the appropriate amount of ClBcat
was removed from glovebox and then weighed in air.
9
2-(2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3-
yl)benzo[d][1,3,2]dioxaborole (2c). Prepared according to
Procedure B (24 h reaction time, 2.0 equiv ClBcat used).
After the reaction was complete, the solvent was removed
in vacuo, and the residue was redissolved in EtOAc (ca.
0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a dark grey solid, and this solid was
further purified by recrystallizing from hot toluene (ca.
80 ˚C) to afford a light grey solid (0.041 g, 52% yield).
1H NMR (600 MHz, CDCl3): δ 8.61 (d, J = 8.2 Hz, 1H),
7.92 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.73 (d,
J = 8.1 Hz, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.5 Hz,
1H), 7.32–7.22 (m, 2H), 7.18–7.06 (m, 2H). 13C{1H}NMR
(151 MHz, CDCl3): δ 156.8, 147.9, 144.2, 140.7, 138.7,
130.5, 125.8, 125.4, 125.3 (q, J = 4 Hz), 125.1, 123.1,
121.9, 112.8. 11B NMR (193 MHz, CDCl3): δ 30.19.
19F NMR (565 MHz, CDCl3): δ -62.58. HRMS (CI-TOF)
m/z calcd for C21H12BF3O2S ([M]+) 396.0607, found
396.0599.
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In air, ClBcat (0.300–0.400 mmol, 1.5–2.0 equiv) was
charged into a one dram vial, followed by addition of
0.1 mL toluene to dissolve the ClBcat. Then, the resulting
solution was transferred to a one dram vial (“reaction vial”)
containing the substrate 1 (S-alkyl ester or O-alkyl ester)
(0.200 mmol, 1.0 equiv) and a stir bar. The ClBcat vial
was rinsed with 0.1 mL of toluene, and this rinse was
added to the reaction vial. The reaction vial was then
capped to avoid loss of solvent upon heating, and the
reaction mixture was heated to 100 ˚C using a preheated
aluminum pie-block, and the reaction mixture was stirred
at this temperature until all substrate was consumed (2.0–
24 h), as determined by TLC monitoring of the reaction
mixture (ca. 30% EtOAc in hexane, UV visualization).
After the completion of the reaction, the crude mixture was
purified by silica gel flash column chromatography,
trituration, or reversed-phase column chromatography;
specific purification methods are described separately for
each product below.
2-(2-cyclopropylbenzo[b]thiophen-3-
2-(2-butylbenzo[b]thiophen-3-
yl)benzo[d][1,3,2]dioxaborole (2d). Prepared according to
Procedure B (4.0 h reaction time, 2.0 equiv ClBcat used).
After the reaction was complete, the solvent was removed
in vacuo, and the residue was redissolved in EtOAC (ca.
0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a white solid (0.047 g, 81% yield).
1H NMR (600 MHz, CDCl3): δ 8.51 (d, J = 8.1 Hz, 1H),
7.78 (d, J = 8.3 Hz, 1H), 7.45 (ddd, J = 8.2, 7.0, 1.2 Hz,
1H), 7.41–7.35 (m, 2H), 7.31 (ddd, J = 8.2, 7.0, 1.2 Hz,
1H), 7.21–7.13 (m, 2H), 3.24 (tt, J = 8.4, 5.0 Hz, 1H),
1.42–1.28 (m, 2H), 1.12–0.94 (m, 2H). 13C{1H}NMR
(151 MHz, CDCl3) δ 167.7, 148.1, 144.2, 137.6, 124.9,
124.3, 123.9, 122.9, 121.9, 112.7, 13.7, 13.0. 11B NMR
(193 MHz, CDCl3): δ 30.66. HRMS (CI-TOF) m/z calcd for
C17H13BO2S ([M]+) 292.0732, found 292.0731.
yl)benzo[d][1,3,2]dioxaborole (2a). Prepared according to
Procedure B (4.0 h reaction time, 2.0 equiv ClBcat used).
The crude reaction mixture was directly loaded on a silica
gel column without removing the reaction solvent, and
was purified by silica gel column chromatography (0–20%
EtOAc in hexanes) to afford a white solid (0.055 g, 90%
yield). 1H NMR (600 MHz, CDCl3):
δ
8.56 (dt,
J = 8.1, 0.9 Hz, 1H), 7.84 (dt, J = 8.0, 0.8 Hz, 1H), 7.47
(td, J = 8.1, 7.6, 1.1 Hz, 1H), 7.41–7.37 (m, 2H), 7.34 (td,
J = 7.6, 7.0, 1.2 Hz, 1H), 7.22–7.15 (m, 2H), 3.44 (t,
J = 6.0 Hz 2H), 1.96–1.78 (m, 2H), 1.61–1.49 (m, 2H),
1.02 (t, J = 7.4 Hz, 3H). 13C{1H}NMR (151 MHz, CDCl3):
δ 164.4, 148.1, 144.0, 139.4, 124.8, 124.7, 123.9, 122.9,
121.8, 112.7, 34.8, 31.0, 22.6, 14.0. 11B NMR (193 MHz,
CDCl3): δ 30.42. 1H NMR (600 MHz, dry THF-d8): δ 8.51
(d, J = 8.1 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.45–7.35 (m,
3H), 7.29 (t, J = 7.5 Hz, 1H), 7.14 (dd, J = 5.8, 3.3 Hz, 2H),
3.45 (t, J = 7.7 Hz, 2H), 1.92–1.78 (m, 2H), 1.60–1.44 (m,
2H), 1.00 (t, J = 7.4 Hz, 3H). 11B NMR (193 MHz, dry THF-
d8): δ 30.27. HRMS (CI-TOF) m/z calcd for C18H1710BO2S
([M]+) 307.1079, found 307.1080.
2-(2-(thiophen-3-yl)benzo[b]thiophen-3-
yl)benzo[d][1,3,2]dioxaborole (2e). Prepared according to
Procedure B (4.0 h reaction time, 2.0 equiv ClBcat used).
After the reaction was complete, the solvent was removed
in vacuo, and the residue was redissolved in EtOAC (ca.
0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a white solid (0.049 g, 74% yield).
1H NMR (600 MHz, CDCl3): δ 8.56 (d, J = 8.1 Hz, 1H),
7.88 (d, J = 8.0 Hz, 1H), 7.74 (dd, J = 2.9, 1.3 Hz, 1H),
7.52–7.45 (m, 2H), 7.43–7.37 (m, 2H), 7.32 (dd, J = 5.8,
3.3 Hz, 2H), 7.15 (dd, J = 5.9, 3.3 Hz, 2H). 13C{1H}NMR
(151 MHz, CDCl3): δ 152.81, 147.97, 144.37, 139.89,
135.32, 129.34, 125.67, 125.50, 125.41, 125.11, 124.63,
122.96, 121.70, 112.75. 11B NMR (193 MHz, CDCl3):
2-(2-(4-bromophenyl)benzo[b]thiophen-3-
yl)benzo[d][1,3,2]dioxaborole (2b). Prepared according to
Procedure B (4.0 h reaction time, 2.0 equiv ClBcat used).
The crude reaction mixture was cooled to 25 ˚C, and
pentane (HPLC grade) was added dropwise (ca. 1 mL) to
the crude reaction mixture until a white precipitate was
observed, then a few more drops of pentane were added.
This precipitate was filtered via the frit in a Poly-Prep®
Chromatography Column and the residue was rinsed with
pentane (3 × 5 mL) and then redissolved in DCM (ca.
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The Journal of Organic Chemistry
δ 30.63. HRMS (CI-TOF) m/z calcd for C18H11BO2S2
([M]+) 334.0297, found 334.0287.
CDCl3): δ 30.33. 19F NMR (565 MHz, CDCl3): δ -62.58, -
62.61. HRMS (CI-TOF) m/z calcd for C24H1310BF6O2S
([M]+) 489.0670, found 489.0689.
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2
3-(3-(benzo[d][1,3,2]dioxaborol-2-yl)benzo[b]thiophen-2-
yl)propyl acetate (2f). Prepared according to Procedure B
(4.0 h reaction time, 2.0 equiv ClBcat used). After the
reaction was complete, the solvent was removed in
vacuo, and the residue was redissolved in EtOAC (ca.
0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a white solid (0.053 g, 76% yield).
1H NMR (600 MHz, CDCl3): δ 8.56 (d, J = 8.0 Hz, 1H),
7.83 (d, J = 7.9 Hz, 1H), 7.47 (ddd, J = 8.2, 7.0, 1.1 Hz,
1H), 7.41–7.32 (m, 3H), 7.21–7.11 (m, 2H), 4.24 (t,
J = 6.4 Hz, 2H), 3.52–3.48 (t, J = 6.0 Hz, 2H), 2.25–2.15
(m, 2H), 2.08 (s, 3H). 13C NMR (151 MHz, CDCl3):
δ 171.2, 162.0, 147.9, 143.8, 139.3, 124.9, 124.8, 124.2,
123.0, 121.8, 112.7, 63.7, 31.2, 29.8, 27.7, 21.0. 11B NMR
(193 MHz, CDCl3): δ 30.31. HRMS (CI-TOF) m/z calcd for
C19H1710BO4SNH4 ([M+NH4]+) 369.1312, found 369.1312.
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4
5
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8
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4-(benzo[d][1,3,2]dioxaborol-2-yl)-3-butyl-1H-
isochromen-1-one (2i). Prepared according to Procedure
B (24 h reaction time, 2.0 equiv ClBcat used). After the
reaction was complete, the solvent was removed in
vacuo, and the residue was redissolved in EtOAC (ca.
0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a white solid (0.043 g, 67% yield).
1H NMR (600 MHz, CDCl3): δ 8.38–8.24 (m, 2H), 7.75 (t,
J = 6.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.36 (dd, J = 5.9,
3.4 Hz, 2H), 7.18 (dd, J = 5.9, 3.3 Hz, 2H), 3.00 (t,
J = 6.0 Hz, 2H), 2.13–1.74 (m, 2H), 1.59–1.28 (m, 2H),
0.97 (t, J = 7.4 Hz, 3H). 13C{1H}NMR (151 MHz, CDCl3): δ
169.6, 162.3, 147.7, 138.8, 135.0, 129.6, 127.8, 126.5,
123.2, 119.9, 112.8, 34.1, 30.9, 22.5, 13.9. 11B NMR (193
MHz, CDCl3): δ 31.97. HRMS (CI-TOF) m/z calcd for
C19H17BO4 ([M]+) 320.1223, found 320.1233.
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2-(2,5-diphenylthiophen-3-yl)benzo[d][1,3,2]dioxaborole
(2g). Prepared according to Procedure B (2.0 h reaction
time, 1.5 equiv ClBcat used). Two different purification
procedures were compared. In the first procedure, the
crude reaction mixture was directly loaded on a silica gel
column without removing the reaction solvent, and the
crude mixture was purified by silica gel column
chromatography (0–1% MeOH in DCM) to afford a white
solid (0.051 g, 72% yield). Alternatively, the crude product
could be purified by trituration, with the following
procedure: after reaction completion, the crude reaction
mixture was cooled to 25 ˚C, and pentane (HPLC grade)
was added dropwise (ca. 1 mL) to the crude reaction
mixture until a white precipitate was observed, then a few
more drops of pentane were added. This precipitate was
filtered via the frit in a Poly-Prep® Chromatography
Column and the residue was rinsed with pentane
(3 × 5 mL) and then redissolved in DCM (ca. 5 mL). The
resulting solution was concentrated in vacuo to afford the
product (0.047g, 67% yield). 1H NMR (600 MHz, CDCl3):
δ 7.89 (s, 1H), 7.80–7.65 (m, 4H), 7.55–7.40 (m, 5H), 7.34
(t, J = 7.5 Hz, 1H), 7.29–7.20 (m, 2H), 7.14–7.03 (m, 2H).
13C{1H}NMR (151 MHz, CDCl3): δ 156.4, 148.3, 144.4,
134.7, 133.9, 130.3, 129.5, 129.1, 128.7, 128.5, 127.9,
126.1, 122.9, 112.7. 11B NMR (193 MHz, CDCl3): δ 30.44.
HRMS (FI-TOF) m/z calcd for C22H15BO2S ([M]+)
354.0890, found 354.0896.
4-(benzo[d][1,3,2]dioxaborol-2-yl)-3-cyclopropyl-1H-
isochromen-1-one (2j). Prepared according to Procedure
B (24 h reaction time, 2.0 equiv ClBcat used). After the
reaction was complete, the solvent was removed in
vacuo, and the residue was redissolved in EtOAC
(ca. 0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a white solid (0.033 g, 55% yield).
1H NMR (600 MHz, CDCl3): δ 8.32 (d, J = 7.9 Hz, 1H),
8.26 (dd, J = 7.9, 1.5 Hz, 1H), 7.73 (dd, J = 8.5, 7.0 Hz,
1H), 7.43 (t, J = 7.6 Hz, 1H), 7.38–7.32 (m, 2H), 7.24–7.10
(m, 2H), 2.90 (tt, J = 8.0, 5.1 Hz, 1H), 1.42–1.31 (m, 2H),
1.14–1.02 (m, 2H). 13C{1H}NMR (151 MHz, CDCl3):
δ 169.0, 161.6, 147.8, 139.4, 135.1, 129.6, 127.2, 126.1,
123.2, 119.7, 112.7, 14.1, 9.3. 11B NMR (193 MHz,
CDCl3): δ 32.66. HRMS (CI-TOF) m/z calcd for C18H13BO4
([M]+) 304.0910, found 304.0913.
4-(benzo[d][1,3,2]dioxaborol-2-yl)-3-(3-chloropropyl)-1H-
isochromen-1-one (2k). Prepared according to Procedure
B (24 h reaction time, 2.0 equiv ClBcat used). After the
reaction was complete, the solvent was removed in
vacuo, and the residue was redissolved in EtOAC
(ca. 0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a white solid (0.047 g, 69% yield).
1H NMR (600 MHz, CDCl3): δ 8.33 (d, J = 9.2 Hz, 2H),
7.78 (td, J = 7.8, 1.5 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H),
7.41–7.33 (m, 2H), 7.23–7.15 (m, 2H), 3.66 (t, J = 6.3 Hz,
2H), 3.33–3.10 (m, 2H), 2.46–2.20 (m, 2H). 13C{1H}NMR
(151 MHz, CDCl3): δ 167.3, 162.0, 147.7, 138.5, 135.3,
129.7, 128.2, 126.7, 123.4, 120.0, 112.9, 44.3, 31.9, 31.1.
11B NMR (193 MHz, CDCl3): δ 32.07. HRMS (CI-TOF) m/z
calcd for C18H14BClO4 ([M]+) 340.0677, found 340.0690.
2-(2,5-bis(4-(trifluoromethyl)phenyl)thiophen-3-
yl)benzo[d][1,3,2]dioxaborole (2h). Prepared according to
Procedure B (5.0 h reaction time, 2.0 equiv ClBcat used).
After the reaction was complete, the solvent was removed
in vacuo, and the residue was redissolved in EtOAc (ca.
0.5 mL), and then loaded onto a C18 reversed-phase
column, and purified by column chromatography (100%
MeCN) to afford a dark green solid, and this solid was
further purified by recrystallizing from hot toluene (ca.
80 ˚C) to afford a white solid (0.065 g, 66% yield). 1H NMR
(600 MHz, CDCl3): δ 7.97 (s, 1H), 7.83 (d, J = 8.1 Hz, 2H),
7.78 (d, J = 8.1 Hz, 2H), 7.73 (d, J = 8.1 Hz, 2H), 7.68 (d,
J = 8.1 Hz, 2H), 7.31–7.23 (m, 2H), 7.17–7.10 (m, 2H).
13C{1H}NMR (151 MHz, CDCl3): δ 155.2, 148.1, 143.5,
137.8, 136.9, 132.0, 129.8, 126.2 (q, J = 4 Hz), 126.2,
125.5 (q, J = 4 Hz), 123.2, 112.8. 11B NMR (193 MHz,
General Experimental Procedure C: Synthesis of
Catechol Boronates 6a–6b. In a N2- or Ar-filled
glovebox, Cu(OTf)2 (0.0036 g, 0.010 mmol, 5.0 mol %)
and a stir bar was put into a one dram vial (“reaction vial”),
and this vial was kept in the glovebox for later use. ClBcat
(0.0308 g, 0.200 mmol, 1.0 equiv) was placed into a one
dram vial, followed by addition of 0.2 mL toluene to
dissolve the ClBcat. Then, the resulting solution was
transferred to a one dram vial (“substrate vial”) containing
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The Journal of Organic Chemistry
Page 14 of 23
hydrazone 4 (0.200 mmol, 1.0 equiv) and a stir bar. The were dried in oven at 120 ˚C for at least 18 h before use.
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ClBcat vial was rinsed with 0.2 mL of toluene, and this
rinse was added to the substrate vial. The resulting
suspension was stirred gently (ca. 150 rpm) to avoid
splashing at 25 ˚C for 20 min in the glovebox. Et3N
(27.8 µL, 0.200 mmol, 1.0 equiv) was added to the
reaction mixture via an airtight syringe at 25 ˚C, and the
resulting mixture was stirred at this temperature for
15 min. The resulting suspension was filtered through a
0.2-μm Target® PTFE syringe filter to remove the
precipitate, and the filtrate was collected directly into the
reaction vial. The filter was rinsed with toluene
(2 × 0.3 mL) and the rinses were collected into the
reaction vial. The reaction vial was capped and the
reaction solution was heated to 40 ˚C using a preheated
aluminum pie-block, and then it was stirred at 40 ˚C for 24
h in the glovebox. The crude mixture was removed from
the glovebox, and the solvent was removed in vacuo in air
to afford a crude oil, and the crude oil was loaded onto a
C18 reversed-phase column, and purified by column
chromatography (100% MeCN) to afford the product.
All other parts and equipment (syringes, solid sample
cartridge, adapters, and etc.) that were used were dried
in the antechamber of the glovebox for 18 h before use. A
solid sample cartridge of 5 g (Catalog No. 69-3873-235),
adjustable solid load cartridge cap (SLCC) (5 gram)
(Catalog No. 60-5237-047), female leur adapter for SLCC
(Catalog No. 209-0094-09), and male leur adapter for
bottom of column (Catalog No. 60-2204-019) were
purchased from Teledyne Isco, Inc (See SI for the photo
of apparatus set-up).
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In an Ar-filled glovebox, oven-dried silica (dehydrated
silica) was packed in a 5 g solid sample cartridge to form
the chromatography column (see picture below for
demonstration of assembly), and the silica was
equilibrated with 20 mL of dry hexanes. Crude reaction
mixture was loaded directly onto the column via a syringe
and then quickly flushed with 10 mL of dry hexanes and
40 mL of eluant (dry Et2O in dry hexanes) (proper ratios
for each product are described separately for each
product below) using syringes. Fractions of eluant were
collected in test tubes and checked by TLC (ca. 30% dry
Et2O in dry hexanes) in the glovebox. All the fractions
containing the target product were combined and
concentrated in vacuo to afford the mixture of desired
catechol boronate 8 and corresponding protodeborylated
product 8′ that was formed during the reaction and/or on
column.
4-(benzo[d][1,3,2]dioxaborol-2-yl)-5-butyl-3-phenyl-1-
tosyl-1H-pyrazole (6a). Prepared and purified according
to Procedure C to afford a yellow oil (0.032 g, of ~95%
purity with 34% mass recovery on average of duplicate
runs). The isolated product contained ca. 5% (determined
1
by H NMR) protodeborylated product that was formed
during purification. 1H NMR (600 MHz, CDCl3): δ 7.98 (d,
J = 8.4 Hz, 2H), 7.76–7.63 (m, 2H), 7.42 (dd, J = 5.2,
1.9 Hz, 3H), 7.34 (d, J = 8.2 Hz, 2H), 7.22 (dd, J = 5.9,
3.4 Hz, 2H), 7.09 (dd, J = 5.9, 3.3 Hz, 2H), 3.66–3.25 (m,
2H), 2.43 (s, 3H), 2.02–1.66 (m, 2H), 1.59–1.44 (m, 2H),
1.01 (t, J = 7.4 Hz, 3H). 13C{1H}NMR (151 MHz, CDCl3): δ
160.2, 159.2, 148.0, 145.9, 135.2, 132.8, 130.1, 129.2,
129.1, 128.4, 128.1, 123.0, 112.7, 33.6, 26.8, 22.9, 21.9,
13.9. 11B NMR (193 MHz, CDCl3): δ 31.12. HRMS (FI-
TOF) m/z calcd for C26H25BN2O4S ([M]+) 472.1633, found
472.1632.
Mixture
yl)benzo[d][1,3,2]dioxaborole
of
2-(2-phenylbenzofuran-3-
(8a) and 2-
phenylbenzofuran (8a′). Prepared by using two modified
reported methods9,11 except the isolation method.
First method: in a N2- or Ar-filled glovebox, SI-9 (0.0388 g,
0.200 mmol, 1.0 equiv) was weighed in a one dram vial,
and 0.1 mL dry toluene was added to make a
homogeneous solution. The resulting solution was
transferred to a one dram vial (“substrate vial”) containing
NaH (0.0052 g of dry powder with 92% purity, 0.20 mmol,
1.0 equiv). The vial of SI-9 was rinsed with 0.1 mL dry
toluene, and the rinse was added to the NaH vial. The
resulting suspension was kept at 25 ˚C without stirring in
the glovebox for 30 min. Compound ClBcat (0.0309 g
0.200 mmol, 1.0 equiv) was weighed in a one dram vial,
and 0.1 mL dry toluene was added to ClBcat to afford a
homogeneous solution, which was transferred to the
substrate vial. The vial of ClBcat was rinsed with 0.1 mL
dry toluene, and the rinse was added to the substrate vial.
The resulting solution was left at 25 ˚C in box without
stirring for 30 min to form the substrate solution. To
another one dram vial (“reaction vial”), IPrAuTFA
(0.0070 g, 0.010 mmol, 5.0 mol %), NaTFA (0.0082 g,
0.060 mmol, 30. mol %), and a stir bar were charged,
followed by adding the substrate solution. The substrate
vial was rinsed with dry toluene (2 × 0.1 mL), and all
rinses were added to the reaction vial. The reaction vial
was capped, and the resulting solution was heated to 60
˚C using a preheated aluminum pie-block, followed by
stirring at 60 ˚C for 24 h in glovebox. The crude product
was purified by General Purification Procedure A (3 g
dehydrated silica, 0% then 20% dry Et2O in dry hexanes)
to afford a pale yellow solid.
4-(benzo[d][1,3,2]dioxaborol-2-yl)-5-butyl-3-(thiophen-2-
yl)-1-tosyl-1H-pyrazole (6b). Prepared and purified
according to General Procedure C to afford a yellow oil
(0.022 g, of ~93% purity with mass recovery of 23%). The
isolated product contained ca. 7% (determined by
1H NMR) protodeborylated product that was formed
during purification. 1H NMR (600 MHz, CDCl3) δ 7.99 (d,
J = 8.1 Hz, 2H), 7.88 (d, J = 3.7 Hz, 1H), 7.35 (t, J =
7.1 Hz, 3H), 7.29 (dd, J = 5.9, 3.4 Hz, 2H), 7.13 (dd,
J = 5.9, 3.3 Hz, 2H), 7.10 (dd, J = 5.1, 3.8 Hz, 1H), 3.50–
3.29 (m, 2H), 2.42 (s, 3H), 1.87–1.70 (m, 2H), 1.56–1.44
(m, 2H), 1.01 (t, J = 7.4 Hz, 3H). 13C{1H}NMR (151 MHz,
CDCl3): δ 159.5, 153.8, 147.9, 145.9, 135.0, 130.0, 128.5,
127.5, 127.0, 123.1, 112.7, 33.5, 26.6, 22.8, 21.9, 13.8.
11B NMR (193 MHz, CDCl3): δ 30.72. HRMS (FI-TOF) m/z
calcd for C24H23BN2O4S2 ([M]+) 478.1197, found
478.1180.
Experimental Procedures for the Synthesis of Catechol
Boronates 8a–8c.
Purification Procedure for Catechol Boronates 8a–8c;
General Remark: All operations were performed in an Ar-
filled glovebox including removing solvents in vacuo.
Solvents (hexanes and Et2O) were purified via a push-still
system before use. Silica gel test tubes, and TLC plates
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The Journal of Organic Chemistry
Second method: in a N2- or Ar-filled glovebox, SI-9 and a stir bar were charged. The suspension generated
in the substrate vial was filtered through a 0.2-μm Target®
PTFE syringe filter to remove the precipitate, and the
filtrate was collected directly into the reaction vial. The
filter was rinsed with dry toluene (2 × 0.2 mL) and the
rinses were collected into the reaction vial. The reaction
vial was capped and the reaction solution was heated to
80 ˚C using a preheated aluminum pie-block, and then it
was stirred at 80 ˚C for 24 h in the glovebox.
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(0.0388 g, 0.200 mmol, 1.0 equiv) was weighed in a one
dram vial (‘substrate vial’), followed by adding HBcat
(21.3 µL, 0.200 mmol, 1.0 equiv) and 0.1 mL dry toluene.
The resulting solution was left in the glovebox at 25 ˚C for
1.5 h to afford the substrate solution. To another one dram
vial (“reaction vial”), IPrAuTFA (0.0070 g, 0.010 mmol,
5.0 mol %), and a stir bar were charged, followed by
adding the substrate solution. The substrate vial was
rinsed with dry toluene (2 × 0.1 mL), and all rinses were
added to the reaction vial. The resulting solution was
heated to 60 ˚C using a preheated aluminum pie-block,
followed by stirring the resulting solution at 60 ˚C for 24 h
in glovebox. The crude product was purified according to
Purification Procedure for Catechol Boronates 8a–8c (3 g
dehydrated silica, 0% then 20% dry Et2O in dry hexanes)
to afford a pale yellow solid.
The crude product was purified according to Purification
9
Procedure for Catechol Boronates 8a–8c (13
g
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dehydrated silica, 0% then 50% dry Et2O in dry hexanes)
to afford a white solid (0.0645 g, 67% mass recovery; ratio
between the desired product and the protodeborylated
product (8b : 8b′) = 7 : 3, which was determined by
1H NMR spectroscopy). After the completion of the
decomposition experiment, the decomposed crude
mixture was purified by silica gel flash column
chromatography (0–15% EtOAc in hexanes) to afford the
On average of two runs (one run for each method), 0.0221
g, 35% mass recovery; ratio between the desired product
and the protodeborylated product (8a : 8a′) = 4 : 6, which
was determined by 1H NMR spectroscopy. After the
completion of the decomposition experiment, the
decomposed crude mixture was purified by silica gel flash
column chromatography (0–10% EtOAc in hexanes) to
afford the purified protodeborylated product, and the
1H NMR and 13C NMR spectra were used as references
to determine the spectroscopic information of 8a′. HRMS
data was taken directly from the purified mixture of 8a and
8a′.
8a: 1H NMR (600 MHz, toluene-d8): δ 8.38 (dd,
J = 7.8, 1.1 Hz, 1H), 8.14 (dd, J = 7.5, 1.5 Hz, 2H), 7.41
(d, J = 8.1 Hz, 1H), 7.38 (d, J = 2.2 Hz, 1H), 7.25 (dt,
J = 15.5, 7.6 Hz, 4H), 7.05–7.03 (m, 2H), 6.81 (dd, J = 5.9,
3.2 Hz, 2H). 13C NMR (151 MHz, toluene-d8): δ 165.6,
148.5, 133.1, 131.5, 129.9, 129.0, 128.6, 125.1, 123.8,
123.7, 123.0, 112.7, 111.1. 11B NMR (193 MHz, toluene-
d8): δ 31.16. HRMS (FI-TOF) m/z calcd for C20H13BO3
([M]+) 312.0948, found 312.0962.
1
purified protodeborylated product, and the H NMR and
13C NMR spectra were used as references to determine
the spectroscopic information of 8b′. HRMS data was
taken directly from the purified mixture of 8b and 8b′.
8b: 1H NMR (600 MHz, toluene-d8): δ 8.72–8.64 (m, 1H),
8.38 (dd, J = 7.7, 1.3 Hz, 1H), 7.39–7.27 (m, 8H), 7.26–
7.16 (m, 3H), 6.84 (dd, J = 5.9, 3.3 Hz, 2H), 6.70 (dd, J =
6.0, 3.3 Hz, 2H), 3.00 (s, 3H). 13C NMR (151 MHz,
toluene-d8): δ 163.8, 151.4, 148.3, 138.5, 133.3, 132.3,
131.1, 129.4, 129.3, 128.5, 127.1, 125.3, 124.6, 123.1,
122.7, 116.1, 114.0, 112.5, 54.9. 11B NMR (193 MHz,
toluene-d8): δ 31.00. HRMS (FI-TOF) m/z calcd for
C27H2010BNO5S ([M]+) 480.1192, found 480.1178.
8b′: 1H NMR (600 MHz, toluene-d8): δ 8.57 (d, J = 8.4 Hz,
1H), 7.63–7.39 (m, 2H), 7.25 (dd, J = 9.5, 2.7 Hz, 2H),
7.22–7.16 (m, 5H), 7.07 (q, J = 7.6, 6.6 Hz, 1H), 6.20 (d,
J = 3.0 Hz, 1H), 6.10 (dd, J = 9.5, 2.7 Hz, 2H), 2.92 (d, J
= 3.2 Hz, 3H). 13C NMR (151 MHz, toluene-d8): δ 163.5,
142.8, 139.2, 133.1, 131.2, 130.8, 130.1, 129.2, 128.7,
127.7, 125.0, 124.5, 121.0, 117.3, 113.8, 113.7, 54.6.
HRMS (FI-TOF) m/z calcd for C21H17NO3S ([M]+)
363.0929, found 363.0923.
8a′: 1H NMR (600 MHz, toluene-d8): δ 7.69 (d, J = 7.9 Hz,
2H), 7.48–7.28 (m, 2H), 7.13 (t, J = 7.6 Hz, 2H), 7.10–6.99
(m, 3H), 6.58 (s, 1H). 13C NMR (151 MHz, toluene-d8): δ
156.3, 155.5, 131.0, 129.8, 128.9, 128.6, 125.2, 124.6,
123.2, 121.2, 111.4, 101.7. HRMS (CI-TOF) m/z calcd for
C14H10O ([M]+) 194.0732, found 194.0729.
Mixture
of
2-(3-butyl-1-methyl-1H-isochromen-4-
yl)benzo[d][1,3,2]dioxaborole (8c) and 3-butyl-1-methyl-
1H-isochromene (8b′). Prepared according to modified
literature procedure9 except the isolation method. In a N2-
or Ar-filled glovebox, SI-14 (0.0405 g, 0.200 mmol,
1.0 equiv) was weighed in a one dram vial (‘substrate
vial’), followed by adding HBcat (21.3 µL, 0.200 mmol,
1.0 equiv) and 0.025 mL dry toluene. The resulting
solution was left in the glovebox at 25 ˚C for 1.5 h to afford
the substrate solution. To another one dram vial (“reaction
vial”), IPrAuTFA (0.0035 g, 0.0050 mmol, 2.5 mol %), and
a stir bar were charged, followed by adding the substrate
solution. The substrate vial was rinsed with 0.175 mL dry
toluene, and all rinses were added to the reaction vial. The
resulting solution was heated to 100 ˚C using a preheated
aluminum pie-block, followed by stirring the resulting
solution at 100 ˚C for 4 h in glovebox. The crude product
was purified according to Purification Procedure for
Catechol Boronates 8a–8c (3 g dehydrated silica, 0%
then 20% dry Et2O in dry hexanes) to afford a transparent
oil (0.0329 g, 51% mass recovery; ratio between the
Mixture
methoxyphenyl)sulfonyl)-2-phenyl-1H-indole (8b) and 1-
((4-methoxyphenyl)sulfonyl)-2-phenyl-1H-indole (8b′).
of
3-(benzo[d][1,3,2]dioxaborol-2-yl)-1-((4-
Prepared according to modified literature procedure13
except the isolation method. In a N2- or Ar-filled glovebox,
SI-11 (0.0727 g, 0.200 mmol, 1.0 equiv) and a stir bar
were weighed in a one dram vial (“substrate vial”), and in
another one dram vial, ClBcat (0.0309 g 0.200 mmol,
1.0 equiv) was weighed, followed by adding 0.2 mL dry
toluene to make a homogeneous solution. This resulting
solution was transferred to the substrate vial. The ClBcat
vial was rinsed with 0.2 mL dry toluene, and the rinse was
added to the substrate vial, followed by adding Et3N
(28 µL, 0.20 mmol, 1.0 equiv) to the reaction mixture. At
25 ˚C, the resulting mixture was gently stirred (ca. 150
rpm) to avoid splashing. To another one dram vial
(“reaction vial”), IPrAuTFA (0.0070 g, 0.010 mmol,
5.0 mol %), NaTFA (0.0054 g, 0.040 mmol, 20. mol %),
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desired product and the protodeborylated product (8c :
spectrum is in agreement with previously reported
8c′)= 8 : 2, which was determined by 1H NMR
spectroscopy). After the completion of the decomposition
experiment, the decomposed crude mixture was purified
by silica gel flash column chromatography (0–20% EtOAc
in hexanes) to afford the purified protodeborylated
product, and the 1H NMR and 13C NMR spectra were used
as references to determine the spectroscopic information
of 8c′. HRMS data was taken directly from the purified
mixture of 8c and 8c′.
spectral data.15
1
2
3
4
5
6
7
8
2-(2-(4-bromophenyl)benzo[b]thiophen-3-yl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (3b). Prepared and
purified according to Procedure D to afford a white solid
(0.046 g, 56% yield, average of two runs). The reaction
was stirred at 100 °C for 4 h using 1.4 equiv of ClBcat and
purified by silica gel flash column chromatography (100%
hexanes). 1H NMR (CDCl3, 500 MHz): δ 8.28 (d,
J = 8.0 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.54–7.49 (m,
4H), 7.42–7.39 (m, 1H), 7.35–7.32 (m, 1H), 1.34 (s, 12H).
This spectrum is in agreement with previously reported
spectral data.15
9
1
8c: H NMR (600 MHz, toluene-d8): δ 8.14 (dd, J = 7.9,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1.1 Hz, 1H), 7.22 (td, J = 7.7, 1.4 Hz, 1H), 7.06–7.00 (m,
3H), 6.81 (tt, J = 4.9, 2.6 Hz, 2H), 6.76 (d, J = 7.2 Hz, 1H),
4.95 (q, J = 6.5 Hz, 1H), 2.92–2.71 (m, 2H), 1.82–1.65 (m,
2H), 1.46–1.36 (m, 5H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR
(151 MHz, toluene-d8): δ 173.2, 148.6, 132.5, 132.1,
128.2, 126.2, 125.9, 123.4, 123.0, 112.4, 74.6, 34.3, 30.9,
23.0, 19.5, 14.1. 11B NMR (193 MHz, toluene-d8): δ 32.63.
HRMS (FI-TOF) m/z calcd for C20H21BO3 ([M]+) 320.1582,
found 320.1588.
4,4,5,5-tetramethyl-2-(2-(4-
(trifluoromethyl)phenyl)benzo[b]thiophen-3-yl)-1,3,2-
dioxaborolane (3c). Prepared and purified according to
Procedure D to afford a white solid (0.046 g, 57% yield)
The reaction was stirred at 100 °C for 4 h using 1.4 equiv
of ClBcat and purified by silica gel flash column
chromatography (100% hexanes). 1H NMR (CDCl3,
600 MHz): δ 8.30 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 7.9 Hz,
1H), 7.73 (d, J = 8.2 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.42
(t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.4 Hz, 1H), 1.33 (s, 12H).
13C{1H} NMR (CDCl3, 151 MHz): δ 153.1, 144.7, 140.7,
139.2, 130.4 (q, J = 33 Hz), 130.4, 125.7, 124.9 (q,
J = 6 Hz), 124.9, 124.6, 124.3 (q, J = 272 Hz), 121.8, 83.9,
24.9. 11B NMR (CDCl3, 193 MHz): δ 30.0. 19F NMR
(CDCl3, 565 MHz): δ –62.4. HRMS (CI-TOF) m/z calcd for
C21H20BF3O2S ([M]+) 404.1229, found 404.1233.
1
8c′: H NMR (600 MHz, toluene-d8): δ 7.03 (td, J = 7.5,
1.2 Hz, 1H), 6.94 (td, J = 7.5, 1.3 Hz, 1H), 6.80 (dd,
J = 7.5, 1.1 Hz, 1H), 6.69 (d, J = 7.5 Hz, 1H), 5.49 (s, 1H),
5.02 (q, J = 6.6 Hz, 1H), 2.12–2.08 (m, 2H), 1.55–1.46 (m,
2H), 1.40 (d, J = 6.5 Hz, 3H), 1.31–1.24 (m, 2H), 0.86 (t,
J = 7.4 Hz, 3H). 13C NMR (151 MHz, toluene-d8): δ 156.8,
131.7, 131.5, 127.5, 125.6, 123.0, 122,6, 100.2, 73.8,
33.6, 29.0, 22.3, 19.5, 13.7. HRMS (FI-TOF) m/z calcd for
C14H18O ([M]+) 202.1358, found 202.1353.
General Experimental Procedure: Synthesis of
Pinacol Boronates (3a–3k). In an N2-filled glovebox, B-
chlorocatecolborane (ClBcat) (43 mg, 0.28 mmol,
1.4 equiv) was dissolved in 0.2 mL of toluene in a 1 dram
vial. A separate 1 dram vial equipped with a stir bar was
charged with alkyne (0.20 mmol, 1.0 equiv). The solution
of the first vial was added to the second vial. The first vial
was rinsed with 0.1 mL of toluene and the rinse was
transferred to the reaction mixture via syringe. The vial
with the resulting solution was capped, and the solution
was stirred and heated using a preheated aluminum pie-
block at 100 °C for the stated time. The reaction vial was
then cooled to room temperature, and a solution of pinacol
(59 mg, 0.50 mmol, 2.5 equiv) in anhydrous Et3N (0.42
mL, 3.0 mmol, 15 equiv) was added. The resulting
solution was stirred at 25 °C for 1 h. The vial containing
the reaction mixture was then removed from the glovebox.
Volatiles were removed in vacuo. The resulting residue
was purified by silica gel chromatography using an elution
gradient from 100% hexanes to approximately 10%
EtOAc in hexanes. (Exact conditions are described
separately for each product below.) Solvent was removed
in vacuo to afford the desired pinacol boronate.
2-(2-cyclopropylbenzo[b]thiophen-3-yl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (3d). Prepared and
purified according to Procedure D to afford a white solid
(0.052 g, 86% yield). The reaction was stirred at 100 °C
for 4 h using 1.4 equiv of ClBcat and purified by silica gel
1
flash column chromatography (100% hexanes). H NMR
(CDCl3, 500 MHz): δ 8.32 (d, J = 8.0 Hz, 1H), 7.74 (d,
J = 7.9 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.25 (t, J = 7.4
Hz, 1H), 3.14–3.09 (m, 1H), 1.43 (s, 12H), 1.23–1.20 (m,
2H), 0.93–0.91 (m, 2H). This spectrum is in agreement
with previously reported spectral data.15
4,4,5,5-tetramethyl-2-(2-(thiophen-3-yl)benzo[b]thiophen-
3-yl)-1,3,2-dioxaborolane (3e). Prepared and purified
according to Procedure D to afford a light yellow oil (0.058
g, 84% yield). The reaction was stirred at 100 °C for 4 h
using 1.4 equiv of ClBcat and purified by silica gel flash
1
column chromatography (0–5% EtOAc in hexanes). H
NMR (500 MHz, CDCl3) δ 8.24 (d, J = 8.1 Hz, 1H), 7.80
(d, J = 8.4 Hz, 1H), 7.68 (dq, J = 3.1, 0.9 Hz, 1H), 7.43
(dd, J = 5.0, 1.2 Hz, 1H), 7.37 (ddd, J = 8.2, 7.1, 1.1 Hz,
1H), 7.34–7.32 (m, 1H), 7.30 (ddd, J = 8.1, 7.0, 1.1 Hz,
1H), 1.38 (s, 12H). This spectrum is in agreement with
previously reported spectral data.15
2-(2-butylbenzo[b]thiophen-3-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (3a). Prepared and purified
according to Procedure D to afford a yellow oil (0.057 g,
90% yield). The reaction was stirred at 100 °C for 4 h
using 1.4 equiv of ClBcat and purified by silica gel flash
column chromatography (0–9% EtOAc in hexanes).
1H NMR (500 MHz, CDCl3): δ 8.34 (d, J = 8.0 Hz, 1H),
7.78 (d, J = 7.9 Hz, 1H), 7.39–7.32 (m, 1H), 7.29–7.22 (m,
1H), 3.26 (t, J = 7.7 Hz, 2H), 1.85–1.69 (m, 2H), 1.50–
1.42 (m, 2H), 1.40 (s, 12H), 0.99 (t, J = 7.4 Hz, 3H). This
3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)benzo[b]thiophen-2-yl)propyl acetate (3f). Prepared
and purified according to Procedure D to afford a light
yellow oil (0.054 g, 75% yield). The reaction was stirred at
100 °C for 4 h using 1.4 equiv of ClBcat and purified by
silica gel flash column chromatography (0–9% EtOAc in
1
hexanes). H NMR (600 MHz, CDCl3): δ 8.37–8.29 (m,
1H), 7.76 (dq, J = 8.0, 1.0 Hz, 1H), 7.34 (ddt, J = 8.1, 7.1,
1.1 Hz, 1H), 7.26 (ddt, J = 8.0, 7.1, 1.1 Hz, 1H), 4.16 (td,
J = 6.6, 0.7 Hz, 2H), 3.35–3.23 (m, 2H), 2.22–1.93 (m,
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The Journal of Organic Chemistry
5H), 1.38 (s, 12H). 13C{1H}NMR (151 MHz, CDCl3): δ
(dd, J = 7.9, 1.0 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.69–
1
2
3
4
5
6
7
8
171.2, 159.4, 144.6, 139.4, 125.2, 124.3, 123.6, 121.6,
83.3, 64.1, 31.5, 27.6, 25.1, 21.1. 11B NMR (193 MHz,
CDCl3): δ 29.28. HRMS (ESI-TOF) m/z calcd for
C19H25BO4SNa ([M+Na]+) 383.1468, found 383.1473.
7.66 (m, 1H), 7.45-7.42 (m, 1H), 3.60 (t, J = 6.4 Hz, 2H),
2.99 (t, J = 7.6 Hz, 2H), 2.22–2.17 (m, 2H), 1.40 (s, 12H)
13C{1H} NMR (CDCl3, 151 MHz): δ 164.6, 162.6, 139.5,
134.8, 129.4, 127.6, 126.8, 120.1, 84.3, 44.5, 31.7, 31.3,
25.0. 11B NMR (CDCl3, 193 MHz): δ 31.2 (s). HRMS (ESI-
TOF) m/z calcd for C18H22BClO4Na ([M+Na]+) 371.1197,
found 371.1201.
2-(2,5-diphenylthiophen-3-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (3g). Prepared and purified according to
Procedure D to afford an orange oil (0.044 g, 60% yield).
The reaction was stirred at 100 °C for 2 h using 1.5 equiv
of ClBcat and purified by silica gel flash column
chromatography (100% hexanes). 1H NMR (CDCl3,
500 MHz): δ 7.65–7.63 (m, 4H), 7.59 (s, 1H), 7.38–7.24
(m, 6H), 1.30 (s, 12H). This spectrum is in agreement with
previously reported spectral data.16
Experimental Procedure for the Synthesis of Pinacol
Boronates 7a: In a N2- or Ar-filled glovebox, Cu(OTf)2
(0.0036 g, 0.010 mmol, 5.0 mol %) and a stir bar was
charged into a one dram vial (“reaction vial”), and this vial
was kept in the glovebox for later use. ClBcat (0.0308 g,
0.200 mmol, 1.0 equiv) was charged into a one dram vial,
followed by addition of 0.2 mL toluene to dissolve the
ClBcat. Then, the resulting solution was transferred to a
one dram vial (“substrate vial”) containing hydrazone 4a
(0.0708 g, 0.200 mmol, 1.0 equiv) and a stir bar. The
ClBcat vial was rinsed with 0.2 mL of toluene, and this
rinse was added to the substrate vial. The resulting
suspension was stirred gently (ca. 150 rpm) to avoid
splashing at 25 ˚C for 20 min in the glovebox. Et3N
(27.8 µL, 0.200 mmol, 1.0 equiv) was added to the
reaction mixture via an airtight syringe at 25 ˚C, and the
resulting mixture was stirred at this temperature for
15 min. The resulting suspension was filtered through a
0.2-μm Target® PTFE syringe filter to remove the
precipitate, and the filtrate was collected directly into the
reaction vial. The filter was rinsed with toluene
(2 × 0.3 mL) and the rinses were collected into the
reaction vial. The reaction vial was capped and the
reaction solution was heated to 40 ˚C using a preheated
aluminum pie-block, and then it was stirred at 40 ˚C for 24
h in the glovebox. The reaction vial was then cooled to
room temperature, and a solution of pinacol (0.059 g,
0.50 mmol, 2.5 equiv) in anhydrous Et3N (0.42 mL,
3.0 mmol, 15 equiv) was added. The resulting solution
was stirred at 25 °C for 1 h. The vial containing the
reaction mixture was then removed from the glovebox.
Volatiles were removed in vacuo. The resulting residue
was purified by silica gel chromatography (0–5% EtOAc
in hexanes) to afford a transparent oil (0.064 g, 67%
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-(2,5-bis(4-(trifluoromethyl)phenyl)thiophen-3-yl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3h). Prepared
and purified according to Procedure D to afford a white
solid (0.037 g, 37% yield). The reaction was stirred at
100 °C for 5 h using 1.5 equiv of ClBcat and purified by
silica gel flash column chromatography (0–1% EtOAc in
1
hexanes). H NMR (CDCl3, 600 MHz): δ 7.76–7.73 (m,
4H), 7.70 (s, 1H), 7.65–7.63 (m, 4H), 1.32 (s, 12H).
13C{1H} NMR (CDCl3, 151 MHz): δ 153.1, 142.7, 138.2,
137.3, 132.2, 130.2 (q, J = 32 Hz), 129.7, 129.5 (q, J = 32
Hz), 126.1, 125.1, 125.1, 124.3 (q, J = 272 Hz), 124.3 (q,
J = 272 Hz), 84.2, 24.9. 11B NMR (CDCl3, 193 MHz): δ
29.4 (s). 19F NMR (CDCl3, 565 MHz): δ –62.5 (s), –62.5
(s). HRMS (CI-TOF) m/z calcd for C24H21BF6O2S ([M]+)
498.1260, found 498.1264.
3-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
1H-isochromen-1-one (3i). Prepared and purified
according to Procedure D to afford a yellow oil (0.050 g,
77% yield). The reaction was stirred at 100 °C for 24 h
using 1.4 equiv of ClBcat and purified by silica gel flash
column chromatography (0–10% EtOAc in hexanes).
1H NMR (CDCl3, 500 MHz): δ 8.26 (d, J = 7.8 Hz, 1H),
8.06 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.43 (t,
J = 7.5 Hz, 1H), 2.82 (t, J = 7.7 Hz, 2H), 1.73–1.67 (m,
2H), 1.43–1.36 (m, 14H), 0.94 (t, J = 7.3 Hz, 3H). This
spectrum is in agreement with previously reported
spectral data.12
1
3-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)-1H-isochromen-1-one (3j). Prepared and purified
according to Procedure D to afford a white solid (0.055 g,
88% yield). The reaction was stirred at 100 °C for 24 h
using 1.4 equiv of ClBcat and purified by silica gel flash
yield). H NMR (500 MHz, CDCl3): δ 7.91 (d, J = 8.2 Hz,
2H), 7.71 (ddd, J = 5.0, 2.4, 1.4 Hz, 2H), 7.41–7.26 (m,
5H), 3.35–3.02 (m, 2H), 2.40 (s, 3H), 1.84–1.58 (m, 2H),
1.51–1.39 (m, 2H), 1.28 (s, 12H), 0.97 (t, J = 7.3 Hz, 3H).
This spectrum is in agreement with previously reported
spectral data.17
1
column chromatography (0–10% EtOAc in hexanes). H
NMR (CDCl3, 600 MHz): δ 8.20 (dd, J = 7.9, 1.1 Hz, 1H),
8.06 (d, J = 8.1 Hz, 1H), 7.64 (td, J = 8.1, 1.1 Hz, 1H), 7.35
(t, J = 7.9 Hz, 1H), 2.69–2.65 (m, 1H), 1.40 (s, 12H), 1.23–
1.20 (m, 2H), 0.94–0.91 (m, 2H). 13C{1H} NMR (CDCl3,
151 MHz): δ 165.9, 162.3, 140.2, 134.7, 129.3, 126.7,
126.2, 119.7, 84.1, 25.0, 13.5, 8.5. 11B NMR (CDCl3, 193
MHz): δ 31.5 (s). HRMS (ESI-TOF) m/z calcd for
C18H21BO4Na ([M+Na]+) 335.1431, found 335.1434.
1-(4-(2,5-diphenylthiophen-3-yl)phenyl)ethan-1-one (9).
Prepared according to a modified literature procedure.9,29
In a N2-filled glovebox, 2f (0.0354 g, 0.100 mmol, 1.00
equiv) and CsOH•H2O (0.0504 g, 0.300 mmol, 3.00 equiv)
were charged into a one dram vial with a stir bar (“reaction
vial”). The cross-coupling partner 1-(4-iodophenyl)ethan-
1-one (0.0295 g, 0.120 mmol, 1.20 equiv) was put in a
separate one dram vial, followed by adding 0.1 ml THF to
dissolve the reagent, and the resulting solution was added
to the reaction vial. In another one dram vial, the catalyst
XPHOS-Pd-G3 (0.003 g, 0.04 mmol, 4 mol %) was
charged, followed by adding 0.2 mL THF, and the
resulting catalyst solution was added to the reaction vial.
Then, the cross-coupling partner vial and catalyst vial
were rinsed with 0.1 mL THF respectively, and all of the
3-(3-chloropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)-1H-isochromen-1-one (3k). Prepared
and purified according to Procedure D to afford a
transparent oil (0.057 g, 82% yield). The reaction was
stirred at 100 °C for 24 h using 1.4 equiv of ClBcat and
purified by silica gel flash column chromatography (0–8%
1
EtOAc in hexanes). H NMR (CDCl3, 600 MHz): δ 8.25
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rinses were added to the reaction vial. The reaction vial followed by removing the drying agent via filtration. The
1
2
3
4
5
6
7
8
was then capped, and following by heating the reaction
mixture to 75 ˚C using a preheated aluminum pie-block,
and the reaction was then stirred at 75 ˚C for 20 h in the
glovebox. The reaction mixture was removed from the
glovebox, and cooled to 25 ˚C, followed by filtering
through a celite plug. The solid was rinsed with DCM (3 ×
2 mL), and all organic phases were combined, and the
solvents was removed in vacuo to afford the crude
product. This crude product was purified by a flash column
chromatography (silica, 0%–12% EtOAc in hexanes) to
afford a white solid (0.024 g, 68% yield). 1H NMR
(600 MHz, CDCl3): δ 7.90 (d, J = 8.4 Hz, 2H), 7.66 (d,
J = 7.0 Hz, 2H), 7.46–7.40 (m, 4H), 7.39 (s, 1H), 7.35–
7.27 (m, 6H), 2.60 (s, 3H). 13C{1H}NMR (151 MHz, CDCl3):
δ 197.8, 143.3, 141.5, 139.5, 137.8, 135.7, 133.9, 133.9,
129.4, 129.3, 129.1, 128.8, 128.7, 128.0, 128.0, 126.01,
125.78, 26.73. HRMS (ESI-TOF) m/z calcd for
C24H18OSNa ([M+Na]+) 377.0976, found 377.0991.
filtrate was concentrated in vacuo to afford the crude
product, which was further purified by a flash column
chromatography (silica, 0–2% EtOAc in hexanes) to
1
afford a light yellow oil (0.015 g, 45% yield). H NMR
(500 MHz, CDCl3): δ 7.97 (dd, J = 7.0, 1.2 Hz, 2H), 7.64
(dd, J = 7.0, 1.2 Hz, 2H), 7.54–7.30 (m, 12H). This
spectrum is in agreement with previously reported
spectral data.45
Methyl (E)-3-(2,5-diphenylthiophen-3-yl)acrylate (11).
Prepared according to a modified literature procedure.31
Under air, 2f (0.0354 g, 0.100 mmol, 1.00 equiv) and
Pd(OAc)2 (0.0004 g, 0.002 mmol, 2 mol %) were weighed
in a one dram vial, followed by adding DDQ (0.0227 g,
0.100 mmol, 1.0 equiv), methyl acrylate (0.05 mL,
0.6 mmol, 6 equiv), Ac2O (0.05 mL, 0.5 mmol, 5.0 equiv),
and AcOH (0.6 mL) to the reaction mixture. The vial was
capped and the resulting solution was heated to 90 ˚C,
and stirred at this temperature for 26 h before it was
diluted with EtOAc (3 mL). The resulting mixture was
washed with DI water (3 mL) and saturated NaHCO3(aq)
(3 mL), and all aqueous layers were combined, followed
by extracting the combined aqueous layers with EtOAc
(3 × 3 mL). All of the organic phases were combined and
dried over MgSO4, and then filtered to remove solids. The
filtrate was concentrated in vacuo to afford the crude
product, which was further purified by a flask column
chromatography (silica, 0–6% EtOAc in pentanes) to
afford a white solid (0.013 g, 40% yield). 1H NMR
(600 MHz, CDCl3): δ 7.72 (d, J = 15.8 Hz, 1H), 7.63 (d,
J = 7.3 Hz, 2H), 7.52 (s, 1H), 7.50–7.39 (m, 7H), 7.34 (t,
J = 7.4 Hz, 1H), 6.37 (d, J = 15.9 Hz, 1H), 3.78 (s, 3H).
13C{1H}NMR (151 MHz, CDCl3): δ 167.9, 146.0, 143.7,
137.8, 133.6, 133.5, 133.1, 129.8, 129.2, 129.0, 128.7,
128.3, 126.0, 121.5, 118.4, 51.8. HRMS (ESI-TOF) m/z
calcd for C20H16O2SH ([M+H]+) 321.0949, found
321.0964.
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(iodoethynyl)benzene (SI-17). To a flame-dried 100 mL
round bottom flask charged with a stir bar and capped with
a septum were added phenylacetylene SI-2 (1.1 mL,
10. mmol, 1.0 equiv) and acetone (34 mL) via syringes
under dynamic N2. Then, the septum was removed,
followed by adding NIS (2.5 g, 11 mmol, 1.1 equiv) and
AgNO3 (0.17, 1.0 mmol, 10 mol %) quickly to the reaction
mixture. Then, the septum was returned, and the reaction
flask was covered with aluminum foil, and the reaction
mixture was stirred at 25 ˚C for 1 h before it was quenched
with saturated NaHCO3(aq), and organic and aqueous
phases were separated. The aqueous phase was
extracted with EtOAc (3 × 10 mL), and all organic phases
were combined. The combined organic phases were then
dried over MgSO4, the drying agent was removed by
vacuum filtration through a Celite plug (Celite in a medium
glass frit funnel), and the filtrate was concentrated in
vacuo to afford the crude product, which was further
purified by a flash column chromatography (silica, 100%
hexanes) to afford a yellow oil (2.0 g, 88% yield). 1H NMR
(600 MHz, CDCl3): δ 7.47–7.40 (m, 2H), 7.36–7.27 (m,
3H). This spectrum is in agreement with previously
reported spectral data.44
3-allyl-2-butylbenzo[b]thiophene
(12).
Prepared
according to a modified literature procedure.32 In a N2-
filled glovebox, 2a (0.0308 g, 0.100 mmol, 1.00 equiv) and
a stir bar were charged into a one dram vial (“reaction
vial”). In another one dram vial, Pd2(dba)3•CHCl3 (0.0052
g 0.0050 mmol, 5.0 mol %) was weighed, followed by
adding 0.15 mL dry dioxane. The resulting solution was
added to the reaction vial. The vial of Pd2(dba)3•CHCl3
was rinsed with 0.15 mL dry dioxane, and this rinse was
added to the reaction vial. The reaction vial was sealed
with a cap with a septum, then it was removed from the
glovebox. Under dynamic N2 on a Schlenk line, P(OPh)3
(1.3 µL, 0.0050 mmol, 0.005 equiv, 5.0 mol %), and allyl
alcohol (8.2 µL, 0.12 mmol, 1.2 equiv) were added to the
reaction mixture with airtight syringes, respectively,
followed by heating the resulting mixture to 80 ˚C using a
preheated aluminum pie-block. This mixture was then
stirred at 80 ˚C for 2 h under dynamic N2. The reaction
was quenched with brine (3 mL), followed by extracting
the mixture with Et2O (3 × 3 mL). All of the organic phases
were combined and dried over MgSO4, followed by
removing the drying agent via filtration. The filtrate was
concentrated in vacuo to afford the crude product, which
was further purified by a flask column chromatography
(silica, 100% pentanes) to afford a colorless oil (0.012 g,
50% yield). 1H NMR (600 MHz, CDCl3): δ 7.77 (dt, J = 7.9,
2,5-diphenyl-3-(phenylethynyl)thiophene (10). Prepared
according to a modified literature procedure.30 In a N2-
filled glovebox, 2f (0.0354 g, 0.100 mmol, 1.00 equiv),
PdCl2 (0.0018 g, 0.010 mmol, 10 mol %), and K2CO3
(0.0276 g, 0.200 mmol, 2.00 equiv.) were weighed in a
one dram vial with a stir bar. (Iodoethynyl)benzene
(0.0274 g, 0.120 mmol, 1.2 equiv) was weighed in another
one dram vial, and it was then dissolved in 0.5 mL dry
toluene, and the resulting solution was added to the
reaction mixture. The vial of (iodoethynyl)benzene was
rinsed with 0.5 mL dry toluene, and the rinse was added
to the reaction mixture. The reaction vial was capped with
a cap with a septum and removed from the glovebox.
Under dynamic N2 via a Schlenk line, MeOH (1.0 mL) and
Milli-Q H2O (0.5 mL) were added via syringes. The
resulting solution was heated to 80 ˚C using a preheated
aluminum pie-block and stirred at 80 ˚C under N2 for 2 h.
The reaction mixture was cooled to 25 ˚C, and the mxiture
was extracted with Et2O (3 × 3 mL). All of the organic
phases were combined, and the combined organic
phases were washed with brine (5 mL), dried over MgSO4,
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The Journal of Organic Chemistry
0.9 Hz, 1H), 7.62 (dt, J = 8.0, 0.9 Hz, 1H), 7.32 (tt, J = 7.0, H2O (5 mL). All aqueous phases were combined, and
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7
8
1.2 Hz, 1H), 7.26 (td, J = 7.6, 1.2 Hz, 1H), 6.02–5.88 (m,
1H), 5.11–5.00 (m, 2H), 3.56 (dt, J = 5.9, 1.7 Hz, 2H), 2.87
(t, J = 6.0 Hz, 2H), 1.78–1.65 (m, 2H), 1.48–1.38 (m, 2H),
0.96 (td, J = 7.4, 1.0 Hz, 3H). 13C{1H}NMR (151 MHz,
CDCl3): δ 141.6, 140.4, 138.5, 135.9, 128.3, 123.9, 123.5,
122.3, 121.6, 115.6, 33.7, 30.7, 28.3, 22.6, 14.0. HRMS
(CI-TOF) m/z calcd for C15H18S ([M]+) 230.1129, found
230.1140.
extracted with DCM (5 mL). The organic phases were
combined and dried over MgSO4, and the drying agent
was then removed via filtration. The filtrate was collected
into a flame-dried 50 mL round bottom flask, and then
concentrated in vacuo to afford SI-19 as a white solid,
which was carried on to the next step without further
1
purification. H NMR (500 MHz, CDCl3): δ 1.86–1.75 (m,
1H), 1.44–1.31 (m, 12H), 0.95 (d, J = 7.0 Hz, 3H).
13C{1H}NMR (125 MHz, CDCl3): δ 56.8 (d, JPC = 57 Hz),
42.3 (s), 25.9 (d, JPC = 7 Hz), 18.1 (d, JPC = 4 Hz), 7.2 (d,
JPC = 31 Hz). 31P NMR (202 MHz, CDCl3): δ 82.12–80.88
(m, major isomer), 80.78–80.02 (m, minor isomer). This
spectrum is in agreement with previously reported
spectral data.46
4-(2-butylbenzo[b]thiophen-3-yl)butan-2-one
Prepared according to modified
(13).
literature
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procedure.15,33,34 In a N2-filled glovebox, 2a (0.0308 g,
0.100 mmol, 1 equiv) and a stir bar were charged into a
one dram vial (“reaction vial”). In another one dram vial
(“catalyst vial”), Rh(acac)(C2H4)2 (0.0008 g 0.003 mmol,
3 mol %) and (S)-BINAP (0.003 g, 0.0050 mmol, 5.0 mol
%) were weighed, followed by adding 0.15 mL dry
dioxane. The resulting solution was transferred to the
reaction vial via a syringe. The catalyst vial was rinsed
with 0.15 mL dry dioxane, and the rinse was transferred
to the reaction vial via the same syringe. The reaction vial
was sealed with a cap with septum and removed from the
glovebox. Under dynamic N2 on a Schlenk line, Et3N
(0.07 mL, 0.5 mmol, 5 equiv), 3-Buten-2-one (0.02 mL,
0.2 mmol, 2 equiv), and 0.015 mL Milli-Q H2O were added
via airtight syringes, followed by heating the resulting
solution to 100 ˚C using a preheated aluminum pie-block.
The reaction mixture was stirred at 100 ˚C for 3 h under
static N2 for 3 h and then cooled to 25 ˚C. Saturate
NaHCO3(aq) (3 mL) were added and the resulting mixture
was extracted with DCM (5 mL). The organic phase was
rinsed with DI H2O (2 × 3 mL), and all aqueous phases
were combined. The combined aqueous phases were
extracted with DCM (3 × 3 mL), followed by combining all
organic phases. The organic phases were dried over
MgSO4 and the drying agent was then removed via
filtration. The filtrate was concentrated in vacuo to afford
the crude product, which was further purified by a flask
column chromatography (silica, 0–12% EtOAc in
pentanes) to afford a light yellow oil (0.019 g, 73% yield).
1H NMR (600 MHz, CDCl3) δ 7.77 (dd, J = 8.1, 1.0 Hz,
1H), 7.58 (dd, J = 8.0, 1.0 Hz, 1H), 7.34 (ddd, J = 8.0, 7.0,
1.1 Hz, 1H), 7.27 (ddd, J = 8.0, 7.1, 1.1 Hz, 1H), 3.08 (t,
J = 7.7 Hz, 2H), 2.90 (t, J = 7.6 Hz, 2H), 2.74 (t, J = 7.7 Hz,
2H), 2.15 (s, 3H), 1.87–1.63 (m, 2H), 1.53–1.40 (m, 2H),
0.97 (t, J = 7.3 Hz, 3H). This spectrum is in agreement
with previously reported spectral data.15
(1R,3R)-1,2,2,3,4,4-hexamethylphosphetane 1-oxide (SI-
20). Prepared according to
a
modified literature
procedure.35,46 A stir bar was added to the 50 mL round
bottom flask containing SI-19, and the flask was
connected to a condenser, and the top of the condenser
was capped with a septum, then degassed on high
vacuum for 5 min. Next, the reaction flask was refilled with
N2 via a Schlenk line, followed by degassing for 5 min.
The pump/purge cycle was repeated was repeated for 3
times before the reaction flask was kept under dynamic
N2 on the Schlenk line. Then, 4 mL dry Et2O was added
to the flask at 25 ˚C under N2, followed by cooling the
reaction mixture to 0 ˚C. At this temperature, MeMgBr
(1.9 mL of a 3.0 M solution in Et2O, 5.8 mmol, 1.1 equiv)
was added dropwise while stirring under N2. Then, the
resulting solution warmed to 25 ˚C, followed by heating to
35 ˚C using a preheated aluminum pie-block under static
N2 (N2 balloon). The reaction mixture was stirred at 35 ˚C
under N2 for 4 h. The mixture was cooled to 0 ˚C, and
quenched by adding saturated NH4Cl(aq) (5 mL)
dropwise. The organic layer was separated (does not
contain product), and the aqueous layer was extracted
with DCM (2 × 5 mL). These newly formed organic layers
were combined, and the combined organic layers were
washed with brine (5 mL). The organic layer was dried
over MgSO4, followed by removing the drying agent by
filtration. The resulting solution was concentrated in vacuo
to afford a white solid (0.064 g, 7% yield over 2 steps). 1H
NMR (600 MHz, CDCl3): δ 1.53 (dd, J = 11.4, 0.8 Hz, 4H),
1.34–1.13 (m, 12H), 0.90 (dd, J = 7.1, 1.7 Hz, 3H).
13C{1H}NMR (151 MHz, CDCl3): δ 45.7 (d, JPC = 60 Hz),
42.9 (d, JPC = 6 Hz), 24.9 (d, JPC = 4 Hz), 17.7 (d, JPC = 4
Hz), 10.1 (d, JPC = 41 Hz), 7.2 (d, JPC = 24 Hz).
31P{1H}NMR (243 MHz, CDCl3): δ 64.23 (minor isomer)
59.10 (major isomer). This spectrum is in agreement with
previously reported spectral data.46
(1S,3S)-1-chloro-2,2,3,4,4-pentamethylphosphetane 1-
oxide (SI-19). Prepared according to a modified literature
procedure.35,46 In a N2-filled glovebox, AlCl3 (0.667 g, 5.00
mmol, 1.0 equiv) and a stir bar were added to a 50 mL
round bottom flask, followed by adding 3 mL dry DCM.
The flask was capped with a septum and removed from
the glovebox. The suspension was cooled to 0 ˚C, and
was stirred at 0 ˚C under dynamic N2 via a Schlenk line.
Then, PCl3 (0.6 mL, 5.0 mmol, 1.0 equiv) was added to
the reaction mixture dropwise via a syringe, followed by
adding SI-18 (0.8 mL, 5.0 mmol, 1.0 equiv) dropwise via
a syringe. Then, the mixture was stirred at 0 ˚C under
static N2 (N2 balloon) for 2 h before it was quenched by
adding DI H2O (5 mL) dropwise at 0 ˚C under static N2.
The organic phase was then separated from the aqueous
phase, and the organic phase was further washed with DI
4-((2,5-diphenylthiophen-3-yl)amino)benzonitrile
(14).
Prepared according to a modified literature procedure.35
In a N2-filled glovebox, 2f (0.0354 g, 0.100 mmol,
1.0 equiv), 4-nitrobenzonitrile (0.0163 g, 0.110 mmol,
1.1 equiv), and SI-20 (0.0026 g, 0.015 mmol, 15 mol %)
were weighed in a one dram vial, and then a stir bar was
added to the vial. Then, 0.2 mL dry toluene was added to
the reaction. To the resulting solution, PhSiH3 (25 µL,
0.20 mmol, 2.0 equiv) was added via an airtight syringe.
Then, the reaction vial was sealed with a cap, and the
reaction mixture was heated to 120 ˚C using a preheated
aluminum pie-block and kept stirring at this temperature
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in the glovebox for 2 h. The reaction mixture was cooled
0.86 (t, J = 7.4 Hz, 3H). 13C{1H}NMR (151 MHz, CDCl3): δ
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3
4
5
6
7
8
to 25 ˚C in the glovebox, and extra 4-nitrobenzonitrile
(0.0163 g, 0.110 mmol, 1.1 equiv) and PhSiH3 (25 µL,
0.20 mmol, 2.0 equiv) were added. The reaction vial was
sealed again with a cap, and the reaction was stirred at
120 ˚C using a preheated aluminum pie-block for another
2 h in the glovebox. Then, the reaction was cooled to
25 ˚C, and removed from the glovebox. Brine (3 mL) was
added to quench the reaction, followed by rinsing the
organic layer with NaOH(aq) (3 mL, 1 M) and brine (3 mL),
respectively. All of the aqueous layers were combined,
and the combined aqueous layer was extracted with
EtOAc (3 × 3 mL), followed by combining all organic
layers. The combined organic layers were dried over
MgSO4, and the drying agent was removed by filtration.
The filtrate was concentrated in vacuo to afford the crude
product, which was further purified by a flask column
chromatography (silica, 0–25% EtOAc in pentanes) to
161.7, 158.9, 150.3, 136.8, 135.3, 134.2, 130.4, 128.4,
122.1, 120.6, 119.9, 114.0, 113.3, 101.3, 29.5, 29.2, 22.5,
13.8. HRMS (ESI-TOF) m/z calcd for C20H18N2O2Na
([M+Na]+) 341.1266, found 341.1278.
Attempted syntheses of 14 and 15 From Bpin
Substrates. The reaction conditions and experimental
operations were the same as in syntheses of 14 and 15
from Bcat substrates, with the exception that the
analogous Bpin substrates were used instead. After
completion of the reaction time, the solvent was removed
in vacuo, and phenanthrene was added to both of the
crude reaction residues as an internal standard. Then, the
crude reaction residues with the internal standards were
dissolved in CDCl3, and 1H NMR spectroscopy was
performed on both crude reaction mixtures. The crude
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1
1
reaction H NMR spectra were compared with H NMR
spectra of authentic isolated 14 and 15 (synthesized using
corresponding Bcat substrates). No signal corresponding
to the spectra of 14 and 15 was observed, indicating
ineffective syntheses of 14 and 15 from Bpin substrates.
1
afford a sticky yellow oil (0.024 g, 67% yield). H NMR
(600 MHz, CDCl3): δ 7.61 (dd, J = 8.0, 1.4 Hz, 2H), 7.52
(dd, J = 8.0, 1.5 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.45–
7.37 (m, 4H), 7.36–7.31 (m, 2H), 7.29 (s, 1H), 6.85 (d,
J = 8.3 Hz, 2H), 5.87 (s, 1H). 13C{1H}NMR (151 MHz,
CDCl3): δ 149.3, 142.2, 134.0, 133.7, 132.7, 132.0, 129.2,
129.2, 128.2, 128.1, 128.0, 125.5, 121.5, 121.3, 120.1,
114.2, 101.2. HRMS (ESI-TOF) m/z calcd for
C23H16N2SNa ([M+Na]+) 375.0932, found 375.0932.
Decomposition Experiments (Figure 2). Compounds
2a, 2g, 2i, 6a, and 6b were prepared according to
previously reported procedures except the isolation
methods.12,15–17 The crude mixtures were purified and
isolated in the same way as in Procedures B and C.
Compounds 8a, 8b, and 8c were prepared according to
the procedures mentioned in Experimental Procedures for
the Synthesis of Catechol Boronates 8a–8c. Each Bcat
compound was stored in –36˚C in the freezer in an Ar-
filled glovebox before use. Each Bcat compounds was
weighed into a one dram vials in the Ar-filled glovebox,
and phenanthrene was added as the internal standard
(allyl acetate was used as the internal standard for 8a
since signals for phenanthrene and 8a overlapped). The
masses of internal standard were carefully measured and
recorded for each sample, followed by adding 0.4 mL dry
d8-toluene to make homogeneous solutions. These
solutions were transferred to J. Young tubes, and the J.
Young tubes were sealed with J. Young tube caps, and
4-((3-butyl-1-oxo-1H-isochromen-4-yl)amino)benzonitrile
(15). Prepared according to
a modified literature
procedure.35 In a N2-filled glovebox, 2h (0.0320 g,
0.100 mmol, 1.0 equiv), 4-nitrobenzonitrile (0.0222 g,
0.150 mmol, 1.5 equiv), and SI-20 (0.0087 g, 0.050 mmol,
50 mol %) were weighed in a one dram vial, and then a
stir bar was added to the vial. Then, 0.2 mL dry toluene
was added to the reaction. To the resulting solution,
PhSiH3 (31.3 µL, 0.250 mmol, 2.5 equiv) was added via
an airtight syringe. Then, the reaction vial was sealed with
a cap, and the reaction mixture was heated to 120 ˚C
using a preheated aluminum pie-block and kept stirring at
this temperature in the glovebox for 2 h. The reaction
mixture was cooled to 25 ˚C in the glovebox, and extra 4-
nitrobenzonitrile (0.0222 g, 0.150 mmol, 1.5 equiv) and
PhSiH3 (31.3 µL, 0.250 mmol, 2.5 equiv) were added. The
reaction vial was sealed again with a cap, and the reaction
was stirred at 120 ˚C using a preheated aluminum pie-
block for another 2 h in the glovebox. Then, the reaction
was cooled to 25 ˚C, and removed from the glovebox.
Brine (3 mL) was added to quench the reaction, followed
by rinsing the organic layer with NaOH(aq) (3 mL, 1 M)
and brine (3 mL), respectively. All of the aqueous layers
were combined, and the combined aqueous layer was
extracted with DCM (3 × 3 mL), followed by combining all
organic layers. The combined organic layers were dried
over MgSO4, and the drying agent was removed by
filtration. The filtrate was concentrated in vacuo to afford
the crude product, which was further purified by a flask
column chromatography (silica, 0–40% EtOAc in
hexanes) to afford a reddish brown oil (0.025 g, 79%
1
removed from the glovebox. H NMR spectra (one scan
for each sample) were taken for each sample. After the
first 1H NMR spectrum (t = 0) was taken for each sample,
the J. Young tube caps were removed to allow air to
1
diffuse into samples. For the first 24 h period, H NMR
spectra were taken for each sample (one scan for each)
in each 2 h. (The J. Young tube caps were temporarily
returned to each J. Young tube when taking the 1H NMR
spectra.) After the first 24 h period, each J. Young tube
was loosely cappaed (partially open to air) with J. Young
tube caps to slow down the evaproration of solvent, and
1H NMR spectra (one scan for each sample) were taken
for all samples every 24 h over a period of two weeks
(selected example orignial 1H NMR spectra were attached
in SI). All samples were run in parallel to restrict variations
that might arise from different conditions. For each type of
Bcat-heterocycles, two samples were prepared so that
duplicate data could be obtained. Each data point in
Figure 2 of the main text was the averaged value of
duplicated data. The percentage of remaining Bcat
product (%Bcatrem.) was calculated with the following
formula:
1
yield). H NMR (600 MHz, CDCl3): δ 8.30 (dd, J = 7.9,
1.3 Hz, 1H), 7.67 (td, J = 7.7, 1.3 Hz, 1H), 7.50 (td, J = 7.7,
1.1 Hz, 1H), 7.44 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 7.6 Hz,
1H), 6.63 (d, J = 8.3 Hz, 2H), 5.56 (s, 1H), 2.59 (d,
J = 9.0 Hz, 2H), 1.80–1.47 (m, 2H), 1.41–1.23 (m, 2H),
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The Journal of Organic Chemistry
(internal standard) was added to the same vial, and the
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3
4
5
6
7
8
9
weight of phenanthrene was carefully measured and
recorded. For spectra without internal standard,
phenanthrene was not added. Then, 0.25 mL dry d8-THF
was added to the sample to make a homogeneous
solution, followed by transferring the resulting solution to
a J. Young tube. The original sample vial was rinsed with
0.20 mL dry d8-THF and the rinse was transferred to the
J. Young tube. The J. Young tube was then sealed with a
J. Young tube cap and removed from the govebox.
The first 1H and 11B NMR spectra were taken immediately
after the sealed tube was removed from the glovebox. To
add H2O (or D2O) to the anhydrous samples, the J. Young
tube was connected to a N2 Schlenk line on top to the J.
Young tube cap. Under dynamic N2, the cap was carefully
partially opened, followed by addition of H2O (or D2O) into
the J. Young tube via an gas-tight syringe, followed by
quickly re-closing the cap under dynamic N2. In this
process, the J. Young tube cap was opened just enough
for the needle to go into the J. Young tube, to avoid
introduction of air into the sample. When adding H2O or
D2O, the droplet was deliberately kept on the wall of the
J. Young tube, and not mixed with the otherwise
anhydrous sample. Then, the H2O (or D2O) droplet was
mixed with the anhydrous sample by shaking the J. Young
tube right before the NMR spectroscopy sample was
injected into the NMR spectrometer. Then, spectra were
acquired within one min after H2O or D2O was mixed with
the anhydrous sample.
1
General Procedure for H NMR Yields Using Internal
Standards
a) 1H NMR Yields for Reactions Without Air-free
Techniques: Each Bcat product was prepared according
to Procedure B except the isolation procedures were not
performed. Instead, after each reported reaction time was
completed, the crude mixtures were cooled to 25 ˚C.
Then, internal standard (phenanthrene) was added, and
the mass of the added phenanthrene was carefully
measured and recorded. To the resulting mixtures,
additional wet d8-toluene (or wet d6-DMSO if precipitate
formed after the crude reaction mixture cooled to 25 ˚C)
was added until the total volume of each sample reached
0.4 mL. Each sample was carefully shaken until a
homogeneous solution formed. The homogeneous
solutions were transferred to NMR tubes. 1H NMR spectra
(one scan for each sample) were taken to calculate the
1H NMR spectroscopy yields. The results and NMR
solvents were summarized in Table S1 (See SI for
details).
b) 1H NMR Yields for Reactions Run in Glovebox: In a N2-
or Ar-filled glovebox, each Bcat product was prepared
according to previously reported protocols12,15,16 with the
following modifications from reported protocols: reaction
scales were all modified to be 0.2 mmol in substrate, dry
d8-toluene was used as solvent, and all reactions were
performed in one dram vials with a stir bar. Further, the
isolation procedures were not performed. Instead, after
each reported reaction time was completed, the crude
mixtures were cooled to 25 ˚C in the glovebox. Then, an
internal standard (phenanthrene) was added, and the
mass of the added phenanthrene was carefully measured
and recorded. To the resulting mixtures, additional dry d8-
toluene (or dry d6-DMSO if precipitate formed after the
crude reaction mixture cooled to 25 ˚C) was added until
the total volume of each sample reached 0.4 mL. Each
sample was carefully shaken until a homogeneous
solutions was formed. The homogeneous solutions were
transferred to J. Young tubes, which were then capped.
1H NMR spectra (one scan for each sample) were taken
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Evidence for reversibility of catechol ligand exchange.
After all NMR spectra were taken, the sample of 2a and
H2O (containing phenanthrene) was concentrated on high
vacuum for ca. 10 h, and the resulting residue was
dissolved in CDCl3, followed by acquisition of a new
1H NMR spectrum. The resulting spectrum was in
agreement with the spectral data for authentic 2a reported
above. Further, the catechol signals in this spectrum (and
the one of 2a reported above) did not match the previously
reported spectral data for free catechol in CDCl3,47
allowing conclusion that concentration in vacuo of the
sample of 16 and 17 in wet THF regenerated 2a, upon the
removal of water.
1
Mixture of 16 and 17 (formed upon treatment of 2a with
H2O): 1H NMR (500 MHz, THF-d8:): δ 8.03 (d, J = 12.6 Hz,
3H), 7.71 (d, J = 7.9 Hz, 1H), 7.37 (s, 2H), 7.21 (ddd,
J = 8.1, 7.1, 1.3 Hz, 1H), 7.15 (td, J = 7.5, 1.3 Hz, 1H),
6.70 (dd, J = 5.9, 3.6 Hz, 2H), 6.57 (dd, J = 5.9, 3.6 Hz,
2H), 3.14 (t, J = 7.7 Hz, 2H), 1.82–1.66 (m, 2H), 1.49–1.38
(m, 2H), 0.94 (t, J = 7.4 Hz, 3H). 11B NMR (160 MHz, THF-
d8): δ 28.16.
for each sample to calculate the H NMR spectroscopy
yields. The results and NMR solvents were summarized
in Table S2 (See SI for details).
General Procedures for taking 1H NMR spectra or
2H NMR spectra with a controlled amount of H2O (or D2O)
under innert atmosphere. General Remarks: All
anhydrous NMR spectroscopy samples were prepared in
a N2-filled glovebox. All substrates (2a and 8b) were
prepared and isolated according to protocols shown
above. Isolated 2a was dried on high vacuum for at least
12 h before taken into a N2-filled glovebox. Compound 8b
was purified inside a either Ar- or N2- filled glovebox, and
kept in glovebox at –35 ˚C until usage. THF-d8 was dried
over Na at 120 ˚C for 12 h, and vacuum transferred before
use. J. Young tubes were dried in oven (120 ˚C) for at
least 12 h before transferred into a N2-filled glovebox. J.
Young tube caps were dried on high vacuum for at least
12 h before transferred into a N2-filled glovebox.
Mixture of 16-d2 and 17-d2 (formed upon treatment of 2a
with D2O): 1H NMR (600 MHz, THF-d8): δ 8.01 (d, J = 8.2
Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.21 (t, J = 7.8 Hz, 1H),
7.15 (t, J = 7.8 Hz, 1H), 6.78–6.65 (m, 2H), 6.62–6.50 (m,
2H), 3.24–2.77 (m, 2H), 1.97–1.59 (m, 2H), 1.42 (ddt, J =
14.9, 7.6, 4.3 Hz, 2H), 0.94 (td, J = 7.5, 2.4 Hz, 3H). 11B
2
NMR (193 MHz, THF-d8): δ 28.26. H NMR (92 MHz,
THF-d8): δ 8.00 (s, 2D), 7.39 (s, 2D).
Pure 17 (wet solvent): 1H NMR (400 MHz, wet THF-d8): δ
8.18 (s, 2H), 6.78–6.65 (m, 2H), 6.62–6.47 (m, 2H).
13C NMR (99 MHz, wet THF-d8): δ 146.6, 120.2, 116.0.
In a N2-filled glovebox, substrate (2a or 8b) were weighed
in a one dram vial (oven dried), and phenanthrene
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Pure 17 (dry solvent): 1H NMR (400 MHz, dry THF-d8): δ
7.85 (s, 2H), 6.72–6.64 (m, 2H), 6.62–6.52 (m, 2H).
13C NMR (99 MHz, dry THF-d8): δ 146.5, 120.3, 116.0.
(1)
(2)
Godula, K. C-H Bond Functionalization in Complex Organic
Synthesis. Science 2006, 312, 67–72.
Cheng, F.; Jäkle, F. Boron-containing polymers as versatile
building blocks for functional nanostructured materials.
Polym. Chem. 2011, 2, 2122.
Issaian, A.; Tu, K. N.; Blum, S. A. Boron–Heteroatom
Addition Reactions via Borylative Heterocyclization:
Oxyboration, Aminoboration, and Thioboration. Acc. Chem.
Res. 2017, 50, 2598–2609.
Burkhardt, E. R.; Matos, K. Boron Reagents in Process
Chemistry: Excellent Tools for Selective Reductions.
Chem. Rev. 2006, 106, 2617–2650.
Boron Reagents in Synthesis; Coca, A., Ed.; ACS
Symposium Series; American Chemical Society:
Washington, DC, 2016; Vol. 1236.
Fyfe, J. W. B.; Watson, A. J. B. Recent Developments in
Organoboron Chemistry: Old Dogs, New Tricks. Chem
2017, 3, 31–55.
1
2
3
4
5
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7
8
General Procedure for ClBcat decomposition
experiments in undried d8-toluene. NMR spectroscopy
samples for ClBcat decomposition experiments were
prepared in the same way as described in General
Experimental Procedure B, with the exception that
phenanthrene was added prior to the start of the
experiment as an internal standard, and no substrate was
added.
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General Procedure for Karl Fischer titration. Wet
toluene or d8-toluene (0.2 mL) was taken up in a syringe
of the same type used in synthetic reactions, and the
weight of syringe with solvent was measured and
recorded. Then, Karl Fischer titration was performed on
the KF coulometer, followed by measurment of the
residual weight of the syringe. The mass of the titrated
solvent was calculated by taking the difference between
the weight of syringe with solvent and without solvent, and
the actual volume of titrated solvent was then calculated
based on the mass of titrated solvent.
(7)
(8)
Hall, D. G. Boronic acid catalysis. Chem. Soc. Rev. 2019,
48, 3475–3496.
Larsen, M. A.; Hartwig, J. F. Iridium-Catalyzed C–H
Borylation of Heteroarenes: Scope, Regioselectivity,
Application to Late-Stage Functionalization, and
Mechanism. J. Am. Chem. Soc. 2014, 136, 4287–4299.
Tu, K. N.; Gao, C.; Blum, S. A. An Oxyboration Route to a
Single Regioisomer of Borylated Dihydrofurans and
Isochromenes. J. Org. Chem. 2018, 83, 11204–11217.
Hirner, J. J.; Faizi, D. J.; Blum, S. A. Alkoxyboration: Ring-
Closing Addition of B–O σ Bonds across Alkynes. J. Am.
Chem. Soc. 2014, 136, 4740–4745.
Faizi, D. Oxyboration: Synthesis of Borylated Benzofurans.
Org. Synth. 2016, 93, 228–244.
Faizi, D. J.; Issaian, A.; Davis, A. J.; Blum, S. A. Catalyst-
Free Synthesis of Borylated Lactones from Esters via
Electrophilic Oxyboration. J. Am. Chem. Soc. 2016, 138,
2126–2129.
Chong, E.; Blum, S. A. Aminoboration: Addition of B–N σ
Bonds across C–C π Bonds. J. Am. Chem. Soc. 2015, 137,
10144–10147.
Tu, K. N.; Hirner, J. J.; Blum, S. A. Oxyboration with and
without a Catalyst: Borylated Isoxazoles via B–O σ-Bond
Addition. Org. Lett. 2016, 18, 480–483.
Faizi, D. J.; Davis, A. J.; Meany, F. B.; Blum, S. A. Catalyst-
Free Formal Thioboration to Synthesize Borylated
Benzothiophenes and Dihydrothiophenes. Angew. Chem.,
Int. Ed. 2016, 55, 14286–14290.
Bel Abed, H.; Blum, S. A. Transition-Metal-Free Synthesis
of Borylated Thiophenes via Formal Thioboration. Org. Lett.
2018, 20, 6673–6677.
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ASSOCIATED CONTENT
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Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
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Reaction
schemes
for
Experimental
Section,
characterization data, DFT calculation data, and 1H, 2H, 11B,
13C, and 19F NMR spectra (PDF).
AUTHOR INFORMATION
Corresponding Author
*E-mail: blums@uci.edu
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ORCID
Suzanne A. Blum: 0000-0002-8055-1405
Chao Gao: 0000-0003-3662-6518
Shuichi Nakao: 0000-0001-5920-5797
Tu, K. N.; Kim, S.; Blum, S. A. Copper-Catalyzed
Aminoboration from Hydrazones To Generate Borylated
Pyrazoles. Org. Lett. 2019, 21, 1283–1286.
Yang, C.-H.; Zhang, Y.-S.; Fan, W.-W.; Liu, G.-Q.; Li, Y.-M.
Intramolecular Aminoboration of Unfunctionalized Olefins.
Angew. Chem., Int. Ed. 2015, 54, 12636–12639.
Lv, J.; Zhao, B.; Liu, L.; Han, Y.; Yuan, Y.; Shi, Z. Boron
Trichloride‐Mediated Synthesis of Indoles via the
Aminoboration of Alkynes. Adv. Synth. Catal. 2018, 360,
4054–4059.
Present Addresses
†Department of Applied Chemistry, Graduate School of
Engineering, Osaka University, 2-1 Yamadaoka, Suita,
Osaka 565-0871, Japan.
Notes
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Warner, A. J.; Churn, A.; McGough, J. S.; Ingleson, M. J.
BCl3-Induced Annulative Oxo- and Thioboration for the
The authors declare no competing financial interest.
Formation
of
C3-Borylated
Benzofurans
and
ACKNOWLEDGMENT
Benzothiophenes. Angew. Chem., Int. Ed. 2017, 56, 354–
358.
Lawson, J. R.; Melen, R. L. Tris(pentafluorophenyl)borane
and Beyond: Modern Advances in Borylation Chemistry.
Inorg. Chem. 2017, 56, 8627–8643.
Melen, R. L.; Hansmann, M. M.; Lough, A. J.; Hashmi, A. S.
K.; Stephan, D. W. Cyclisation versus 1,1-Carboboration:
Reactions of B(C6F5)3 with Propargyl Amides. Chem. Eur.
J. 2013, 19, 11928–11938.
Yuan, K.; Wang, S. trans-Aminoboration across Internal
Alkynes Catalyzed by B(C6F5)3 for the Synthesis of
Borylated Indoles. Org. Lett. 2017, 19, 1462–1465.
Lennox, A. J. J.; Lloyd-Jones, G. C. Selection of boron
We thank the National Science Foundation (CHE-1665202)
and the University of California, Irvine (UCI) for funding. We
thank Dr. Nathan R. M. Crawford (UCI) for assisting DFT
calculations. C. G. thanks Drs. Hassen Bel Abed, Joshua J.
Hirner, Darius Faizi, Kim Ngan Tu, and Adena Issaian for
helpful discussions and providing substrates. S. N. thanks
Uomoto Foundation for Co-operation in the Area of University
Education for a scholarship.
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REFERENCES
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1
2
3
The Journal of Organic Chemistry
reagents for Suzuki–Miyaura coupling. Chem. Soc. Rev.
15200–15205.
2014, 43, 412–443.
(36)
(37)
Ashe III, A. J. In Comprehensive Heterocyclic Chemistry III;
Elsevier, 2008; pp 1189–1224.
(25)
Cox, P. A.; Leach, A. G.; Campbell, A. D.; Lloyd-Jones, G.
C. Protodeboronation of Heteroaromatic, Vinyl, and
Furikado, Y.; Nagahata, T.; Okamoto, T.; Sugaya, T.;
Iwatsuki, S.; Inamo, M.; Takagi, H. D.; Odani, A.; Ishihara,
K. Universal Reaction Mechanism of Boronic Acids with
Diols in Aqueous Solution: Kinetics and the Basic Concept
of a Conditional Formation Constant. Chem. Eur. J. 2014,
20, 13194–13202.
Garg, N. K.; Sarpong, R.; Stoltz, B. M. The First Total
Synthesis of Dragmacidin D. J. Am. Chem. Soc. 2002, 124,
13179–13184.
Weinhold, F. Natural bond orbital analysis: A critical
overview of relationships to alternative bonding
perspectives. J. Comput. Chem. 2012, 33, 2363–2379.
Hattori, H.; Hoff, L. V.; Gademann, K. Total Synthesis and
Structural Revision of Mangrolide D. Org. Lett. 2019, 21,
3456–3459.
Cyclopropyl
Boronic
Acids:
pH–Rate
Profiles,
Autocatalysis, and Disproportionation. J. Am. Chem. Soc.
2016, 138, 9145–9157.
Issaian, A.; Faizi, D. J.; Bailey, J. O.; Mayer, P.; Berionni,
G.; Singleton, D. A.; Blum, S. A. Mechanistic Studies of
Formal Thioboration Reactions of Alkynes. J. Org. Chem.
2017, 82, 8165–8178.
B-Chlorocatecholborane. B-Chlorocatecholborane; SDS
C1669; TCI America: Portland, OR, Nov 18, 2019.
Coffey, D. S.; Overman, L. E.; Stappenbeck, F.
4
5
6
(26)
(38)
(39)
(40)
7
8
9
(27)
(28)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Enantioselective
Total
Syntheses
of
13,14,15-
Isocrambescidin 800 and 13,14,15-Isocrambescidin 657. J.
Am. Chem. Soc. 2000, 122, 4904–4914.
(29)
(30)
(31)
(32)
(33)
(34)
(35)
Thomas, A. A.; Zahrt, A. F.; Delaney, C. P.; Denmark, S. E.
Elucidating the Role of the Boronic Esters in the Suzuki–
Miyaura Reaction: Structural, Kinetic, and Computational
Investigations. J. Am. Chem. Soc. 2018, 140, 4401–4416.
Mound, W. R.; Scutt, J. N.; Slater, M.; Willetts, N. J.
Herbicidally active cyclic dione compounds, or derivatives
therefor, substituted by a phenyl which has an alkynyl-
containing substituent. WO/2014/096289, 2014.
(41)
(42)
Fürstner, A.; Mathes, C. Alkyne Cross Metathesis
Reactions of Extended Scope. Org. Lett. 2001, 3, 221–223.
Xu, H.; Wu, K.; Tian, J.; Zhu, L.; Yao, X. Recyclable
Cu/C3N4 composite catalysed homo- and cross-coupling of
terminal alkynes under mild conditions. Green Chem. 2018,
20, 793–797.
Nakatani, A.; Hirano, K.; Satoh, T.; Miura, M. Nickel-
Catalyzed Direct Alkylation of Heterocycles with α-Bromo
Carbonyl Compounds: C3-Selective Functionalization of 2-
Pyridones. Chem. Eur. J. 2013, 19, 7691–7695.
Usanov, D. L.; Yamamoto, H. Enantioselective Alkynylation
of Aldehydes with 1-Haloalkynes Catalyzed by Tethered
Bis(8-quinolinato) Chromium Complex. J. Am. Chem. Soc.
2011, 133, 1286–1289.
Santana, A. S.; Carvalho, D. B.; Cassemiro, N. S.; Viana,
L. H.; Hurtado, G. R.; Amaral, M. S.; Kassab, N. M.;
Guerrero, P. G.; Barbosa, S. L.; Dabdoub, M. J.; Baroni, A.
C. M. Synthesis of 3-iodothiophenes via iodocyclization of
(Z)-thiobutenynes. Tetrahedron Lett. 2014, 55, 52–55.
Nykaza, T. V.; Harrison, T. S.; Ghosh, A.; Putnik, R. A.;
Radosevich, A. T. A Biphilic Phosphetane Catalyzes N–N
Bond-Forming Cadogan Heterocyclization via PIII/PV═O
Redox Cycling. J. Am. Chem. Soc. 2017, 139, 6839–6842.
Chen, S.; Foss, F. W. Aerobic Organocatalytic Oxidation of
Aryl Aldehydes: Flavin Catalyst Turnover by Hantzsch’s
Ester. Org. Lett. 2012, 14, 5150–5153.
(43)
(44)
(45)
Sun, P.; Zhu, Y.; Yang, H.; Yan, H.; Lu, L.; Zhang, X.; Mao,
J. The ligand and base-free Pd-catalyzed oxidative Heck
reaction of arylboronic acids and olefins. Org. Biomol.
Chem. 2012, 10, 4512–4515.
Kayaki, Y.; Koda, T.; Ikariya, T.
(Triphenyl phosphite)palladium Catalyst for
A
Highly Effective
Cross-
a
coupling Reaction of Allylic Alcohols with Organoboronic
Acids. Eur. J. Org. Chem. 2004, 4989–4993.
Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.;
Hayashi, T. Rhodium-catalyzed asymmetric 1,4-addition of
arylboron reagents to α,β-unsaturated esters. Tetrahedron:
Asymmetry 1999, 10, 4047–4056.
Takaya, Y.; Ogasawara, M.; Hayashi, T. Rhodium-
catalyzed asymmetric 1,4-addition of 2-alkenyl-1,3,2-
(46)
(47)
benzodioxaboroles
to
α,β-unsaturated
ketones.
Tetrahedron Lett. 1998, 39, 8479–8482.
Nykaza, T. V.; Cooper, J. C.; Li, G.; Mahieu, N.; Ramirez,
A.; Luzung, M. R.; Radosevich, A. T. Intermolecular
Reductive C–N Cross Coupling of Nitroarenes and Boronic
Acids by PIII/PV═O Catalysis. J. Am. Chem. Soc. 2018, 140,
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