Borinic Acid-Catalyzed Regioselective Ring-Opening of 3,4- and 2,3-Epoxy Alcohols with Halides

Article abstract of DOI:10.1002/adsc.201901268

Methods for the regioselective ring-opening of 3,4-epoxy alcohols and 2,3-epoxy alcohols with halide nucleophiles, using a diarylborinic acid catalyst, are disclosed. Ring-opening occurs at the position proximal to the OH group, an effect ascribed to a catalytic tethering mechanism whereby coordination to the substrate OH group positions the diarylborinic acid to deliver a coordinated halide nucleophile. These methods provide access to halohydrin substitution patterns that were not previously accessible through catalytic epoxide ring-opening reactions. (Figure presented.).

Full text of DOI:10.1002/adsc.201901268

Title: Borinic Acid-Catalyzed Regioselective Ring-Opening of 3,4- and
2,3-Epoxy Alcohols with Halides
Authors: Grace Wang and Mark Taylor
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Borinic Acid-Catalyzed Regioselective Ring-Opening of 3,4- and
2,3-Epoxy Alcohols with Halides
Grace Wanga and Mark S. Taylora*
a
Department of Chemistry, University of Toronto, 80 St. George St., Toronto ON M5S 3H6 CANADA
Phone: (+1) 416-946-0571. E-mail: mtaylor@chem.utoronto.ca
Received: ((will be filled in by the editorial staff))
Dedicated to Professor Eric N. Jacobsen on the occasion of his 60th birthday.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Our group has investigated diarylborinic acids as
Abstract. Methods for the regioselective ring-opening of
3,4-epoxy alcohols and 2,3-epoxy alcohols with halide catalysts for regioselective ring-opening[ 10 ] and
rearrangement reactions[11] of epoxy alcohols. In the
nucleophiles, using a diarylborinic acid catalyst, are
disclosed. Ring-opening occurs at the position proximal to
the OH group, an effect ascribed to a catalytic tethering
mechanism whereby coordination to the substrate OH group
positions the diarylborinic acid to deliver a coordinated
halide nucleophile. These methods provide access to
halohydrin substitution patterns that were not previously
accessible through catalytic epoxide ring-opening reactions.
case of 3,4-epoxy alcohols with amine or thiol
nucleophiles, the use of diarylborinic acid catalysis
resulted
in
C3-selective
ring-opening,
a
complementary outcome to that achieved using the
transition metal or lanthanide-based Lewis acids
described above (Scheme 1).[12] We proposed that the
regiochemical outcome arose from a catalytic
tethering mechanism[13] in which the boron compound
interacted simultaneously with the nucleophile and the
electrophile (via the pendant hydroxyl group).[ 14 ]
Related methods employing electron-deficient
arylboronic acids as catalysts were reported by Wang
and co-workers.[ 15 ] Considering the importance of
halohydrin motifs in synthetic intermediates and
bioactive natural products,[ 16 ] we sought to apply
organoboron catalysis to ring-openings of 3,4-epoxy
alcohols with halide nucleophiles. (In an earlier study
of chloroacylations and chlorosulfonylations of 2,3-
epoxy alcohols,[10a] we noted that the only 3,4-epoxy
alcohol substrate examined gave an unexpected
regiochemical outcome; it was this observation that
motivated our efforts to explore such substrates for
catalytic tethering using diarylborinic acids.) Here, we
describe the development of protocols for the
regioselective synthesis of chlorohydrins and
bromohydrins by diarylborinic acid-catalyzed epoxide
ring-opening. Consistent with our earlier work, and in
contrast to existing catalytic methods for halohydrin
Keywords: boron; halides; homogeneous catalysis;
regioselectivity.
Introduction
Regioselective ring-openings of epoxides are useful
and versatile methods for the construction of
functionalized, enantio- and/or diasteromerically
enriched organic compounds.[1] Despite the synthetic
utility of epoxide ring-opening reactions, protocols
that provide reliable regioselectivity and broad scope
of application are available for only a few substrate
2
]
classes (e.g., 2,3-epoxy alcohols,[
2,3-
epoxypropionic acid derivatives,[3] glycal epoxides[4]).
In recent years, important advances have been made in
the development of catalytic protocols for epoxide
ring-opening and their extension to new substrate
classes. Yamamoto and co-workers have explored
W(VI), Mo(VI), Ce(III), and Gd(III) complexes for
enantioselective and/or regioselective ring-openings
of 2,3-epoxy alcohols and 2,3-epoxy sulfonamides,[5]
as well as Ni(II)-based catalysts for aminolysis of 3,4-
epoxy alcohols.[ 6 ] These protocols give rise to
outcomes consistent with chelation-based mechanisms
(C3-selectivity for ring-openings of 2,3-epoxy
alcohols and sulfonamides and C4-selectivity for 3,4-
epoxy alcohols).[7] Similar patterns of regioselectivity
have been obtained using the erbium(III) and
lanthanum(III) trifluoromethanesulfonate-catalyzed
methods developed by Iwabuchi and co-workers.[8],[9]
O
OH
OH
Ar2BOH
(cat)
O
R
R
Ar
B
OH
+
R
O
Nu
Nu–H
Nu
Ar
(NuH = R1R2NH, R3SH)
Ar2BOH
(cat)
OH
O
OH
base•HX
+
OH
R
R
X = F, Cl, Br or I
X
Scheme 1. Diarylborinic acid-catalyzed ring-opening of
3,4-epoxy alcohols with amine and thiol nucleophiles, and
proposed extension to regioselective halohydrin formation.
1
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
synthesis, these reactions result in C3-selective ring-
opening of 3,4-epoxy alcohols. Extensions to C2-
selective openings of 2,3-epoxy alcohols are also
demonstrated, providing access to a regiochemical
outcome complementing that of existing catalytic
methods.[5c]
than catalyst 1a, and roughly similar results were
obtained using substituted diarylborinic acid catalysts
1c and 1d. In contrast, the less Lewis acidic
oxaboraanthrancene 1e[17] resulted in only a modest
enhancement in C3:C4 regioselectivity relative to the
uncatalyzed reaction. Low regioselectivities were also
obtained using arylboronic acid catalysts 1f–1g.[15b]
Applications of 1a to hydrochlorinations of other 3,4-
epoxy alcohol substrates were investigated (Scheme 2).
By using pyridinium bromide in place of the chloride
salt, regioselective hydrobrominations were also
achieved. The yields and C3:C4 ratios for reactions
conducted in the absence of the organoboron catalyst
are also shown for each substrate combination. Overall,
the results show that diarylborinic acid catalysis
enables C3-selective halohydrin formation from
substituted epoxy alcohols that would otherwise lead
to mixtures of regioisomers. Catalytic tethering was
Results and Discussion
For ring-openings of 3,4-epoxy alcohols with amine
and thiol nucleophiles, nucleophiles having pKa values
of roughly 5–6 gave rise to the highest reaction rates
in the presence of the diarylborinic acid catalyst. While
the mechanistic basis for this observation is not clear
at this stage, we hoped to use it as a rough guideline
for selecting appropriate nucleophilic partners. In the
context of ring-openings by halide anions, this could
be achieved by employing an acidic counterion.
Consistent with this hypothesis, the reaction of epoxy
alcohol 2a with pyridinium chloride in the presence of
10 mol % of bis(4-fluorophenyl)borinic acid (1a)
resulted in >19:1 regioselectivity for the formation of
chlorohydrin diol 3a (Table 1, entry 1). In the absence
of catalyst, the ring-opened product was formed in
quantitative yield (overnight reaction time), but as a
1.8:1 mixture of isomers. These results indicate that
the diaryborinic acid-catalyzed process outcompetes a
poorly selective background reaction and gives rise to
the outcome consistent with a catalytic tethering
R2
OH
F
OH
R3 R4
R1
X
R2
OH
R3 R4
pyr•HX
(3 equiv)
O
3a–3p (X = Cl, Br)
B
OH
1a
R1
+
1a (10 mol %)
MeCN, 35 °C
16 h
R2
X
2a–2h
OH
R3 R4
R1
F
HO
3a’–3p’
Me
O
O
O
OH
Ph
OH
Me Me
R1
CH3(CH2)4
2a: R1 = Bn 2d: R1 = (CH2)2OAc
2b: R1 = Et 2e: R1 = (CH2)2OCPh3
2c: R1 = iPr 2f: R1 = (CH2)2OTBS
OH
2g
2h
mechanism.
The
use
of
La(III)
OH
OH
OH
OH
trifluoromethanesulfonate (La(OTf)3) or Cu(OTf)2 in
place of 1a resulted in mixtures of regioisomers
(entries 3 and 4). The parent diphenylborinic acid (1b)
gave similar regioselectivity but slightly lower activity
OH
OH
Bn
Et
iPr
X
X
X
3a (X = Cl)
92% yield, >19:1 3a:3a’
(67% yield, 1.8:1 3a:3a’)
3c (X = Cl)
70% yield, >19:1 3c:3c’
(92% yield, 1.2:1 3c:3c’) (73% yield, 1.9:1 3e:3e’)
3e (X = Cl)
91% yield, >19:1 3e:3e’
3b (X = Br)
87% yield, >19:1 3b:3b’
(96% yield, 2.0:1 3b:3b’)
3d (X = Br)
72% yield, >19:1 3d:3d’
(65% yield, 1.1:1 3d:3d’)
3f (X = Br)
82% yield, >19:1 3f:3f’
(92% yield, 2.3:1 3f:3f’)
Table 1. Evaluation of catalysts for regioselective
hydrochlorination of 3,4-epoxy alcohol 2a.
OH
OH
OH
OH
OH
OH
Cl
pyr•HCl
OH
AcO
(3 equiv)
OH
Ph3CO
O
TBSO
OH
+
Bn
OH
Bn
X
X
X
Bn
catalyst (10 mol %)
MeCN, 35 °C
1 h
Cl
OH
3g (X = Cl)
79% yield, >19:1 3g:3g’)
(91% yield, 2.0:1 3g:3g’)
3i (X = Cl)
88% yield, >19:1 3i:3i’
(87% yield, 1.9:1 3i:3i’)
3k (X = Cl)
79% yield, >19:1 3k:3k’
(83% yield, 1.5:1 3k:3k’)
2a
3a (C3-Cl)
3a’ (C4-Cl)
OH
B
OH
Catalyst structures:
O
3h (X = Br)
85% yield, >19:1 3h:3h’
(83% yield, 1.9:1 3h:3h’)
3j (X = Br)
80% yield, >19:1 3j:3j’
(89% yield, 1.8:1 3j:3j’)
3l (X = Br)
79% yield, >19:1 3l:3l’
(80% yield, 1.5:1 3l:3l’)
Ar
1a (Ar = 4-FC6H4)
Ar
Ar
1b (Ar = Ph)
B
OH
B
1f (Ar = Ph)
1g (Ar = 4-MeOC6H4)
1h (Ar = 3,5-(CF3)2C6H3)
1c (Ar = 3,4-(MeO)2C6H3)
1d (Ar = 3,5-Me2C6H3)
OH
1e
Me
OH
Ph
OH
HO
CH3(CH2)4
entry
1
2
3
4
5
6
7
8
catalyst
yielda
80%
67%
>95%
>95%
65%
86%
80%
72%
66%
80%
70%
3a:3a’b
>19:1
1.8:1
2.1:1
2.2:1
>19:1
13:1
>19:1
2.4:1
1.7:1
2.0:1
Me Me
X
OH
X
1a
none
La(OTf)3
Cu(OTf)2
1b
3m (X = Cl)
84% yield, 4.4:1 3m:3m’
(80% yield, 1:1.3 3m:3m’)
3o (X = Cl)
85% yield, 2.8:1 3o:3o’
(88% yield, 1:14 3o:3o’)
3n (X = Br)
85% yield, 10:1 3n:3n’
(83% yield, 1.1:1 3n:3n’)
3p (X = Br)
80% yield, 2.0:1 3p:3p’
(93% yield, 1:17 3p:3p’)
1c
1d
1e
1f
1g
1h
Scheme 2. Diarylborinic acid-catalyzed hydrochlorinations
and hydrobrominations of 3,4-epoxy alcohols. Combined
yields of the two regioisomers (0.2 mmol scale) after
purification by silica gel chromatography are reported.
Regioselectivities were determined by 1H NMR
spectroscopy. Yields and regioselectivities for reactions
carried out in the absence of catalyst (0.1 mmol scale,
determined by 1H NMR spectroscopy with 1,3,5-
trimethoxybenzene as a quantitative internal standard) are
shown in parentheses.
9
10
11
2.5:1
a
1
Yields (0.1 mmol scale) were determined by H NMR
spectroscopy using 1,3,5-trimethoxybenzene as
a
b
quantitative internal standard.
Regioselectivities were
determined by 1H NMR spectroscopy.
2
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
also possible in the case of a tertiary alcohol substrate
(products 3m and 3n). The lower regioselectivies
obtained in these cases presumably reflect impaired
catalyst–substrate binding due to steric hindrance.
Ring-opening of a terminal epoxide at the secondary
carbon was also achieved (products 3o and 3p). In this
instance, the organoboron catalyst was in competition
with a background reaction that displayed high
selectivity for opening at the less hindered, primary
position. More generally, the relatively high rate of
uncatalyzed hydrochlorination and hydrobromination
of epoxides under the optimized conditions has
presented a challenge for generating the products of
‘contrasteric’ ring-openings at the levels that were
possible for our previously reported couplings with
amine and thiol nucleophiles.[12]
diarylborinic
reaction, perhaps due to the strong B–F interaction.
Likewise, diarylborinic acid-catalyzed
hydroiodination proved to be challenging, with no
appreciable rate acceleration or change in
regioselectivity relative to the background reaction.
We speculate that the iodide affinity of the
organoboron complex may be too low for efficient
catalysis relative to the uncatalyzed ring-opening in
this case.
As noted above, we documented a single example of
C3-selective chloroacylation of a 3,4-epoxy alcohol
while exploring the scope and limitations of the
diarylborinic acid-catalyzed coupling of acid chlorides
with 2,3-epoxy alcohol substrates.[10a] Consistent with
this result, chlorobenzoylation of substrate 3a was
achieved in 90% yield (6.2:1 C3:C4-Cl
regioselectivity) using a combination of 1a and
Bu4N+Cl– as co-catalysts (Scheme 4).[10b] In the
acid-catalyzed
hydrochlorination
Limitations of the organoboron-catalyzed halohydrin
formation from 3,4-epoxy alcohols are depicted in
Scheme 3. Styrene-derived epoxy alcohol 2i
underwent hydrochlorination with low regioselectivity, absence of the organoboron catalyst, the yield and
presumably due to the activated nature of the benzylic
position. Competing cyclization to tetrahydropyran
derivative 4 was also observed from this substrate; in
the absence of catalyst, only the latter product was
observed. A drop in regioselectivity was observed
using cis-configured epoxy alcohol 2j and
trisubstituted 2k. A similar dependence on epoxy
alcohol configuration was observed previously for
reactions with amine and thiol nucleophiles,[12] and
was ascribed to unfavorable steric interactions in the
chairlike transition state for boron-tethered ring-
opening of the cis-isomer. Extension of the protocol to
hydrofluorination of 3,4-epoxy alcohols was
unsuccessful; ring-opening was not observed, and the
addition of fluoride salts caused inhibition of the
regioselectivity
of
chlorobenzoylation
were
considerably lower. Similarly chloroacetylation of 2a
was accomplished in 84% yield (5.2:1 5b:5b’) using
diphenylborinic acid-derived pre-catalyst 1i. The rate
of the uncatalyzed reaction was higher in this case, but
a significant difference in regioselectivity was again
evident (2.0:1 5b:5b’ in the absence of the
organoboron catalyst). In contrast to the successful
chloroacylations of 2a, coupling with para-
toluenesulfonyl chloride (TsCl) under the previously
reported conditions for chlorosulfonylsulfonylation of
2,3-epoxy alcohols[10a] resulted in a low yield of 5c,
along with several unidentified side products. Whereas
monoester 5a was accessible via chlorobenzoylation
OH
Cl
BzCl (3 equiv)
O
OH
OH
OBz
OBz
+
Bn
Bn
Bn
OH
Ph
1a (5 mol %)
Cl
5a
OH
5a’
Bu4N+Cl– (30 mol %)
iPr2NEt (0.55 equiv)
MeCN, 35 °C
2a
pyr•HCl
(3 equiv)
O
Cl
3q
Ph
O
OH
+
90% yield, 6.2:1 5a:5a’
25% yield, 1:1.7 5a:5a’
Ph
1a (10 mol %)
MeCN, 35 °C
16 h
16 h
Cl
Without 1a:
HO
2i
OH
4
OH
Cl
Ph
AcCl (1.5 equiv)
O
OAc
+
OAc
OH
OH
3q’
47% yield, 1.2:1 3q:3q’ 46% yield
Bn
Bn
Cl
Bn
H2
N
Ph
Ph
OH
5b’
2a
(1i, 10 mol %)
B
5b
Without catalyst:
0% yield
94% yield
O
84% yield, 5.2:1 5b:5b’
91% yield, 2.0:1 5b:5b’
Proton-sponge®
(0.2 equiv)
Without 1i:
pyr•HCl
(3 equiv)
Et
OH
Cl
OH
CH2Cl2, 25 °C, 5 h
OH
+
OH
Et
O
Et
1a (20 mol %)
MeCN, 35 °C
16 h
OH
TsCl (3 equiv)
O
Cl
3r
OH
3r’
unidentified
side products
OTs
OH
+
2j
Bn
Bn
Bn
Cl
1i (10 mol %)
2a
99% yield, 1.0:1 3r:3r’
63% yield, 1.6:1 3r:3r’
iPr2NEt (1.5 equiv)
MeCN, 35 °C
16 h
Without catalyst:
5c
10% yield
OH
OH
OH
OH
OBz
OH
OH
pyr•HCl
(3 equiv)
BzCl (1.5 equiv)
O
OH
OH
OBz
OBz
+
Bn
Cl
Bn
Cl
Cl
+
1i (5 mol %)
iPr2NEt (1.5 equiv)
MeCN, 25 °C
5 h
Cl
3a
1a (20 mol %)
MeCN, 35 °C
16 h
Cl
5a
44% yield
5d
2k
3s
3s’
37% yield, 1:2.6 3s:3s’
Without catalyst: 48% yield, 1:2.7 3s:3s’
12% yield
Scheme 4. Reactions of 3,4-epoxy alcohol 1a with BzCl,
AcCl and TsCl, and attempted monoesterifications of diol
3a. Yields after purification by silica gel chromatography,
unless otherwise noted. Regioselectivities were determined
Scheme 3. Limitations of the diarylborinic acid-catalyzed
hydrochlorination of 3,4-epoxy alcohols. Yields and
regioselectivities were determined by 1H NMR
a
by 1H NMR spectroscopy. Yields were determined by 1H
spectroscopy with 1,3,5-trimethoxybenzene as
a
quantitative internal standard, unless otherwise noted.
NMR spectroscopy with 1,3,5-trimethoxybenzene as a
quantitative internal standard.
aYield after purification by silica gel chromatography.
3
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
of 2a, its synthesis by diarylborinic acid-catalyzed
acylation of 3a[ 18 ] was less successful, due to the
competitive formation of dibenzoate 5d. Considering
that 1,2- and 1,3-diols have been employed
successfully in such regioselective functionalizations,
we propose that the affinity of the 1,4-diol group for
the diarylborinic acid catalyst is not suffiently high to
enable efficient activation of ring-opened products
such as 3a. It is noteworthy that the chloroacylation
protocol provides accesso derivatives that are not
OH
F
F
R
OH
X
pyr•HX
(3 equiv)
O
7a–7h (X = Cl, Br)
B
OH
1a
R
OH
1a (10 mol %)
MeCN, 35 °C
16 h
X
6a: R = CH2OBz
6b: R = CH2OCPh3
6c: R = CH2OTBS
6d: R = (CH2)2Ph
R
OH
OH
7a’–7h’
OH
OH
Ph3CO
BzO
OH
OH
X
readily
opening/monofunctionalization.
Finally, diarylborinic
available
by
sequential
ring-
X
7a (X = Cl)
91% yield, >19:1 7a:7a’
(81% yield, 5.1:1 7a:7a’)
7c (X = Cl)
94% yield, >19:1 7c:7c’
(97% yield, 3.1:1 7c:7c’)
acid-catalyzed
hydrochlorinations and hydrobrominations of 2,3-
epoxy alcohols[19] were also investigated. A variety of
protocols for halohydrin formation from such
substrates have been developed.[20] The majority of
them give rise to C3-selectivity and require a
stoichiometric amount of Lewis acid promoter,
presumably because the 1,2-diol product can act as a
chelating ligand. Transition metal-catalyzed, C3-
selective openings of 2,3-epoxy alcohols and
sulfonamides with chloride, bromide and iodide were
developed by Yamamoto and Wang.[5c] Particularly
relevant precedent was established by the group of
Miyashita, who demonstrated that phenylboronic acid
and trialkylborates act as stoichiometric promoters for
C2-selective ring-openings of 2,3-epoxy alcohols with
halide, azide, thiolate and cyanide nucleophiles.[21]
The authors proposed that an unusual endo-mode ring-
opening of a boron chelate was responsible for the
regiochemical outcome. Using diarylborinic acid
catalyst 1a, the reaction of 2,3-epoxy alcohol 6a with
pyridinium chloride resulted in C2-selective ring-
opening in 91% yield and >19:1 regioselectivity
(Scheme 5). Hydrochlorination and hydrobromination
reactions of other trans-disubstituted 2,3-epoxy
alcohols were accomplished using this protocol. For
substrates 6a–6c, the uncatalyzed ring-openings by
pyridinium chloride and bromide took place with
modest to good levels of C2-selectivity (results shown
in parentheses in Scheme 3). In the case of substrate
6d, the uncatalyzed hydrochlorination and
hydrobromination reactions were unselective, while
modest levels of C2-selectivity were achieved using
catalyst 1a.
7b (X = Br)
80% yield, >19:1 7b:7b’
(91% yield, 4.7:1 7b:7b’)
7d (X = Br)
89% yield, 10:1 7d:7d’
(99% yield, 2.5:1 7d:7d’)
OH
OH
TBSO
OH
Ph
OH
X
X
7e (X = Cl)
77% yield, >19:1 7e:7e’
(99% yield, 3.6:1 7e:7e’)
7g (X = Cl)
67% yield, 2.8:1 7g:7g’)
(88% yield, 1.1:1 7g:7g’)
7f (X = Br)
77% yield, >19:1 7f:7f’
(99% yield, 4.0:1 7f:7f’)
7h (X = Br)
98% yield, 2.9:1 7h:7h’
(98% yield, 1.5:1 7h:7h’)
Scheme 5. Diarylborinic acid-catalyzed hydrochlorinations
and hydrobrominations of 2,3-epoxy alcohols. Combined
yields of the two regioisomers (0.2 mmol scale) after
purification by silica gel chromatography are reported.
Regioselectivities were determined by 1H NMR
spectroscopy. Yields and regioselectivities for reactions
carried out in the absence of catalyst (0.1 mmol scale,
determined by 1H NMR spectroscopy with 1,3,5-
trimethoxybenzene as a quantitative internal standard) are
shown in parentheses.
Conclusion
In conclusion, the catalytic tethering strategy based on
interactions of diarylborinic acids with epoxy alcohols
has been successfully extended to halides as
nucleophiles. The method enables C3-selective ring-
openings of 3,4-epoxy alcohols and C2-selective
openings of trans-disubstituted 2,3-epoxy alcohols,
using chloride and bromide as nucleophiles. For both
epoxy alcohol substrate classes, catalytic protocols for
halide ring-opening with this sense of regioselectivity
had not been reported previously. Consistent with our
previous work on ring-openings with amine and thiol
nucleophiles, the presence of a mild Brønsted acid (in
this case, the pyridinium counterion) was important for
high catalytic reactivity. Detailed mechanistic studies
of the ring-openings of epoxy alcohols, as well as
extensions of the diarylborinic acid-based catalytic
tethering approach to other transformations, are among
our goals for future work.
The scope of the diarylborinic acid-catalyzed ring-
opening of 2,3-epoxy alcohols with halides proved to
be somewhat limited, with cis-disubstituted,
trisubstituted and terminal epoxides giving rise to
lower levels of regioselectivity. In this regard, the
transformation is complementary to our previously
reported chloroacylation of 2,3-epoxy alcohols, which
favoured ring-opening at the C3-position and was most
efficient for cis-configured epoxy alcohols.
4
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
Experimental Section
Chlorobenzoylation
Procedure was adapted from the reported chloroacylation
protocol.[10a] Under ambient atmosphere, a one dram vial
equipped with a magnetic stirbar is charged with 3,4-epoxy
Typical Procedure for the Halide Ring-Opening of 3,4-
Epoxy Alcohols
alcohol
(0.2
mmol,
1.0
equiv.),
bis(para-
Under ambient atmosphere, a one dram vial equipped with
a magnetic stirbar is charged with 3,4-epoxy alcohol (0.2
mmol, 1.0 equiv.), bis(para-fluorophenyl)borinic acid 1a
(10 mol %), and 0.80 mL acetonitrile. To the resulting
homogeneous mixture, pyridinium halide (0.6 mmol, 3.0
equiv.) is added. The reaction vial is sealed with a screw cap,
fluorophenyl)borinic acid 1a (5 mol %), and 1.00 mL
acetonitrile. To the resulting homogeneous mixture, benzoyl
chloride (0.6 mmol, 3.0 equiv.), tetrabutylammonium
chloride (0.06 mmol, 30 mol %) and N,N-
diisopropylethylamine (0.11 mmol, 0.55 equiv.) are
subsequently added. The reaction vial is sealed with a screw
cap, taped with PTFE and stirred at 35 ᵒC for 16 hours. The
reaction mixture is then concentrated in vacuo to remove
solvent and then purified by flash chromatography on silica
gel, eluting with a hexanes-EtOAc gradient system to afford
the product as a mixture of regioisomers.
ᵒ
taped with PTFE and stirred at 35 C for 16 hours. The
reaction mixture is then concentrated in vacuo to remove
solvent and then treated with aqueous NaBO3 (0.05 M, 2.0
mL, 0.10 mmol)[4a] to facilitate subsequent product isolation
by column chromatography by oxidative removal of the
borinic acid catalyst 1a. After 5 minutes of stirring, the
mixture is diluted with saturated aqueous NH4Cl and
extracted three times with EtOAc. The combined organic
layers are washed with brine, dried over anhydrous MgSO4,
filtered, and concentrated in vacuo. The crude residue is
purified by flash chromatography on silica gel, eluting with
a hexanes-EtOAc gradient system to afford the product as a
mixture of regioisomers.
Chloroacetylation
Procedure was adapted from the reported chloroacylation
protocol.[10a] Under ambient atmosphere, a one dram vial
equipped with a magnetic stirbar is charged with 3,4-epoxy
alcohol (0.2 mmol, 1.0 equiv.), 2-aminoethyl
diphenylborinate (10 mol %), and 1.00 mL dichloromethane.
To the resulting homogeneous mixture, acetyl chloride (0.3
mmol, 1.5 equiv.), and proton sponge (0.04 mmol, 0.2
equiv.) are subsequently added. The reaction vial is sealed
with a screw cap, taped with PTFE and stirred at 25 ᵒC for 5
hours. The reaction mixture is then concentrated in vacuo to
remove solvent and then purified by flash chromatography
on silica gel, eluting with a hexanes-EtOAc gradient system
to afford the product as a mixture of regioisomers.
Typical Procedure for the Halide Ring-Opening of 2,3-
Epoxy Alcohols
Under ambient atmosphere, a one dram vial equipped with
a magnetic stirbar is charged with 2,3-epoxy alcohol (0.2
mmol, 1.0 equiv.), bis(para-fluorophenyl)borinic acid 1a
(10 mol %), and 0.80 mL acetonitrile. To the resulting
homogeneous mixture, pyridinium halide (0.6 mmol, 3.0
equiv.) is added. The reaction vial is sealed with a screw
cap, taped with PTFE and stirred at 35 ᵒC for 16 hours
before concentrating in vacuo to remove solvent. The
crude residue is purified by flash chromatography on silica
gel, eluting with a hexanes-EtOAc gradient system to
afford the product as a mixture of regioisomers.
Acknowledgements
This work was funded by NSERC, the Canada Foundation for
Innovation (Projects #t17545 and #19119), the Province of
Ontario and the McLean Foundation.
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
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10.1002/adsc.201901268
Advanced Synthesis & Catalysis
COMMUNICATION
Borinic Acid-Catalyzed Regioselective Ring-
Opening of 3,4- and 2,3-Epoxy Alcohols with
Halides
X–
OH
R
O
N
O
Ar
B
H
OH
OH
R
R
(X = Cl, Br)
Ar2BOH
(cat)
O
X
Adv. Synth. Catal. Year, Volume, Page – Page
Ar
X
Grace Wang and Mark S. Taylor*
7
This article is protected by copyright. All rights reserved.