Aliphatic α-Boryl-α-bromoketones: Synthesis and Reactivity

Article abstract of DOI:10.1002/ejoc.202000078

A protocol for the preparation of α-boryl-α-bromoketones from alkenyl MIDA boronates was developed and applied to functionalized aliphatic derivatives. The reaction sequence included regioselective hydroxybromination of olefin moiety, followed by oxidation of alcohol group with Dess–Martin periodinane. The target trifunctional boronate-containing derivatives were obtained in up to 94 % yield over two steps starting from alkenyl MIDA boronates. In some cases, functional groups present in the substrate participated in the bromohydroxylation step via intramolecular nucleophilic attack at the bromonium cation leading to cyclic products. Additionally, the reactivity of aliphatic α-boryl-α-bromoketones was illustrated by nucleophilic substitution at the α-C atom and heterocyclization reactions.

Full text of DOI:10.1002/ejoc.202000078

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Title: Aliphatic α-Boryl-α-bromoketones: Synthesis and Reactivity
Authors: Yevhen M. Ivon, Yuliya O. Kuchkovska, Zoya V. Voitenko,
and Oleksandr O Grygorenko
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000078
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10.1002/ejoc.202000078
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Aliphatic -Boryl--bromoketones: Synthesis and Reactivity
Yevhen M. Ivon,[a,b] Yuliya O. Kuchkovska,[a,b] Prof. Dr. Zoya V. Voitenko,[b] and Dr. Oleksandr O.
Grygorenko*[a,b]
Abstract: A protocol for the preparation of -boryl--bromoketones
from alkenyl MIDA boronates was developed and applied to
functionalized aliphatic derivatives. The reaction sequence included
regioselective hydroxybromination of olefin moiety, followed by
oxidation of alcohol group with Dess–Martin periodinane. The target
trifunctional boronate-containing derivatives were obtained in up to
94% yield over two steps starting from alkenyl MIDA boronates. In
some cases, functional groups present in the substrate participated
in the bromoxydroxylation step via intramolecular nucleophilic attack
at the bromonium cation leading to cyclic products. Additionally, the
reactivity of aliphatic -boryl--bromoketones was illustrated by
nucleophilic substitution at the -C atom and heterocyclization
reactions.
-borylcarbonyl compounds 1 deserve particular attention.[18,29]
For long, attempts to access this structural motif were
unsuccessful due to kinetically and thermodynamically
favourable rearrangement of -borylcarbonyl compounds 1 into
boryl enolates 2 (Scheme 1, B). This issue was overcome by
replacement of the sp2-hybridized boron atom in 1 by sp3-
hybridized one, for example by selection of MIDA ligand for
boronates 3. Further introduction of heteroatomic substituents to
the -C atom of 3 can lead to other unusual structural motifs.
Representatives of the substitution pattern 4 included 2-oxoacyl-
boronates 5,[20,21] -heteroatom-substituted -boryl aldehydes
and ketones 6 and 7 (Scheme 1, C),[19,27,28,30] which were
recently reported by Yudin’s and Wang’s research groups. The
utility of these trifunctional building blocks was demonstrated by
synthesis of several heteroaromatic derivatives, including
imidazole-based kinase inhibitors, quinoxalines, thiazoles, and
furans.[31]
Introduction
The Suzuki–Miyaura cross-coupling reaction has become one of
the most frequently used methods for the C–C bond formation.[1–
3]
A great variety of boronic acid derived reagents has emerged
in order to tune the nucleophilicity of C–B bond and to ensure
substantial stability towards possible side reactions at boron
centre.[4,5] An important breakthrough in this field was
elaboration of N-methyliminodiacetic acid (MIDA) boronates
(Scheme 1, A).[6,7] These derivatives provided a convenient
alternative to conventional boronic acid esters bearing
a
tricoordinated boron atom, and were successfully used for
automated preparations of diverse scaffolds by iterative Suzuki–
Miyaura reaction.[8–10]
Although synthetic methods for introduction of the boronate
group to pre-synthesized scaffolds are well-known in the
literature,[11] a number of recent publications were focused on an
alternative approach – the construction of molecular frameworks
from small molecule building blocks bearing the MIDA boronate
moiety.[12–24] A huge variety of chemotypes can be constructed
from these flexible platforms provided that functional groups with
orthogonal reactivity have been incorporated at the - and -
positions to the MIDA boronate group.[21,24–28]
Among the aforementioned boronate-containing derivatives,
Scheme 1. Structural types of discussed -borylcarbonyl derivatives.
[a]
[b]
Yevhen M. Ivon, Yuliya O. Kuchkovska, Dr. Oleksandr O.
Grygorenko
Enamine Ltd. (www.enamine.net)
Chervonotkatska Street 78, Kyiv 02094, Ukraine
Yevhen M. Ivon, Yuliya O. Kuchkovska, Prof. Dr. Zoya V. Voitenko,
Dr. Oleksandr O. Grygorenko
Taras Shevchenko National University of Kyiv
Volodymyrska Street 60, Kyiv 01601, Ukraine
E-mail: gregor@univ.kiev.ua
Despite the uncommon combination of chemical functionalities
in proximity to each other, a potential of these reagents is still
not fully disclosed. One of the current gaps in regard to the
derivatives 7 is limited structural scope achievable by the known
synthetic methods. The only reported approach towards -halo-
ketones 7 relied on one-pot oxidative halogenation of alkenyl-
boronates 8 with NBS and 2-iodoxybenzoic acid (IBX), and was
limited by preparation of several 1-aryl-substituted derivatives
URL: https://orcid.org/0000-0002-6036-5859
Supporting information for this article is given via a link at the end of
the document.
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(Scheme 2).[27] Yet, a possibility to obtain compounds 7 with
saturated and functionalized substituents remained unclear.
did not occur, and the reaction yielded intermediate 11a as a
single product (Scheme 3, B). Nonetheless, when alcohol 11a
was isolated prior to the next step and the oxidation was carried
out in anhydrous CH3CN, the target -bromoketone 10a was
obtained with an excellent yield of 94% over two steps (Scheme
3, C). Importantly, this method also worked well on scale-up,
thus up to 11 g of 10a were prepared in a single run without
significant change in the reaction outcome.
Scheme 2. Synthetic approaches towards -bromoketones 7 and 10.
In this work, we describe a modified approach towards -
brominated -boryl ketones, which enabled preparation of
products with non-aromatic substituents. The scope of the
discussed method was studied for acyclic aliphatic and alicyclic
substituents in 9 and included examples bearing ether, ester,
and Boc-protected amino functional groups. Additionally,
illustrative transformations at the -C atom and carbonyl group
were performed with one of the synthesized trifunctional building
blocks 10, including heterocyclization reactions with 1,3-dinuc-
leophiles.
Scheme 3. Optimization of the reaction conditions for the preparation of 10a.
Relative configuration is shown for 11a.
Results and Discussion
Our initial attempts to prepare aliphatic MIDA boronates 10a
relied on the one-pot procedure reported previously for their aryl
counterparts[27] and appeared to be unfruitful. A complex mixture
of products was obtained from the model substrate 9a, which
contained less than 40% of the target compound 10a in a crude
sample (according to 1H NMR analysis) (Scheme 3, A). All
attempts to isolate 10a from this mixture in pure form were
unsuccessful. This result has prompted us to undertake
optimization of the oxidative bromination procedure for the
aliphatic derivatives.
Scheme 4. Preparation of alkenyl MIDA boronates 9.
Since the reaction was heterogeneous because of the poor
solubility of 9a in toluene, we have switched to polar organic
solvents. In addition, IBX was replaced by milder Dess–Martin
periodinane (DMP), which is known to be compatible with MIDA
boronates.[21,32] The initial one-pot procedure included an
overnight reaction of the alkene 9a with NBS in the presence of
H2O, followed by addition of DMP and stirring for an additional
night. Under these conditions, oxidation of the alcohol to ketone
Next, the scope and limitations of the developed method were
studied for a series of aliphatic substrates 9. The starting MIDA
boronates 9 were obtained from either terminal alkynes 12 (by
addition of pinacolborane)[33] or from aldehydes 13 (by the
boron-Wittig reaction with bis[(pinacolato)boryl]methane 14)[34,35]
(Scheme 4). The obtained pinacolates 15 were further subjected
to transesterefication with MIDAH2 to give 9 with up to 54% yield
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10.1002/ejoc.202000078
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for two steps. The transformation of pinacolates into MIDA
boronates was essential for the following hydroxybromination
step because of the susceptibility of the C–Bpin bond towards
electrophilic attack upon action of NBS.
9c appeared to be an exception and gave 11c as ca. 1:1 mixture
of diastereomers. This effect might be explained by participation
of the corresponding cyclopropylmethyl carbocation as
a
possible intermediate. Noteworthy, the proven stereochemistry
Application of the newly developed protocol to alkenylboronates
9a–f gave products 11a–f as single regioisomers in 63–96%
yield (Table 1). It should be noted that boronic moiety remained
intact, and possible competitive bromination at the phenyl ring
was not observed. Radical bromination at both allylic and
benzylic (for 9d) sites was prevented by applying mild reaction
conditions (dark; ambient temperature).
On the basis of X-Ray diffraction studies, which were performed
with derivative 11e (Figure 1), we assume that anti addition of
H2O to the cyclic bromonium cation 16 took place and led to the
formation of diastereomerically pure products 11 in most cases
(Scheme 5, A). However, hydroxybromination of the compound
of compound 11e was opposite to stereochemistry of adduct 9p
which was previously indicated as
a
product of
hydroxychlorination reaction of phenylalkenyl MIDA boronate
11p by Wang and colleagues (Scheme 5, B).[15] One of the
possible explanations to this observation is that unlike
bromination of alkene moiety via bridged bromonium ion 16,
chlorination is more likely to proceed via freely-rotating open
carbocation which can adapt the favourable conformation prior
to nucleophilic attack by H2O. Therefore, although adducts of the
type 11 are expected to have configuration similar to 11e (anti-
addition products), the assignment of stereochemistry for
hydroxyhalogentation adducts should be done with caution.
Table 1. Preparation of compounds 10.
Method used for the
preparation of 9 [a]
Entry
R
9
11
Yield (%)
10
Yield (%)
9a
9b
9c
11a
11b
11c
96
63
–
10a
10b
10c
1
2
3
A
B
98[b]
79
CH3
A
B
52[c]
9d
9e
11d
11e
72
93
10d
10e
4
5
84
85
B
A
9f
11f
65
10f
6
93
9g
9h
9i
11g
11h
11i
N/A[d]
69
10g
10h
10i
7
8
9
A
A
A
N/A
84
27
N/A
59[c]
9j
11j
72[e]
10j
10
A
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81[c]
9k
11k
86[e]
10k
11
A
9l
11l
N/A[d]
10l
12
13
A
B
N/A
N/A
9m
11m
0
10m
9n
9o
11n
11o
0
10n
10o
14
15
A
B
N/A
96
32
[a] See Scheme 4
[b] Yield for 11.2 g scale
[c] Yield after two steps
[d] The products 17g or 17l were obtained (see Scheme 6)
[e] As a mixture with ca. 20% of 17j or ca. 25% mol. of 17k
place (94% yield, with 5–10% of 11g). To the best of our
knowledge, such transformation is unprecedented in the
literature. Probably, tetrahydrofuran ring closure occurred
through nucleophilic attack of the ether oxygen atom at the
bromonium cation centre of 18g. Whereas the pure analytical
sample of 17g was obtained after repeated recrystallization,
isolation of the target compound 11g was not successful due to
its low content in the starting crude mixture.
Scheme 5. Hydroxybromination (A) and hydroxychlorination (B) of the
compounds 9.
Figure 1. Molecular structure of the compound 11e (ellipsoids are shown at
50% probability level).
An unexpected reaction pathway was observed when the
compound 9g was subjected to hydroxybromination (Scheme 6).
Instead of the predominant conversion of 9g to the target
product 11g, cyclization to tetrahydrofuran derivative 17g took
Scheme 6. Hydroxybromination of compounds 9g–l (relative configurations
are shown)
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Since the trifunctional compounds 10 were envisaged as
convenient synthetic platforms for the construction of diverse
small-molecule building blocks containing MIDA boronate moiety,
reactivity of the electrophilic -C centre and the carbonyl group
was studied using 10a as a model substrate. In particular,
nucleophilic substitution of bromide with acetate anion led to the
product 20 in 84% yield (Scheme 8). Similarly, derivative 21 was
formed in 92% yield when 10a was subjected to the reaction
with NaN3 in anhydrous DMSO. It should be noted that the same
reaction proceeded quite slowly when it was carried out in
CH3CN; addition of H2O resulted in protodeboronation.
This unusual result prompted us to study other functionalized
substrates 9h–l in the hydroxybromination reaction. It was found
that homologous benzyloxy-substituted derivative 9h gave acyc-
lic adduct 11h exclusively in 72% yield; no traces of ether 17h
was observed.
With methyl ether 9i, a complex mixture was formed; the target
product 11i could be isolated in 27% yield; again, no cyclic ether
17g was detected. It is possible that in this case, transition state
18i does not result in the cleavage of O–CH3 bond. Instead,
other C–O bonds are cleaved, which leads to decomposition
products.
Ester 9j also gave the product 11j after the hydroxybromination
reaction (72% yield); however, its partial cyclization into lactone
17j (up to 20%) was observed upon chromatographic purification.
Notably, the product 17j was not present in the crude reaction
mixture. Analogously, ester 9k led to mixture of 11k and 17k (ca.
3:1, 86% yield); in this case, both products were present in the
crude reaction mixture, and a small fraction of 17k with ca. 90–
95% purity could be obtained. Finally, N-Boc protected primary
amine derivative 9l gave oxazolidone 17l (61% yield); less than
20% of acyclic product 11l was likely present in the crude
reaction mixture, but it was not isolated.
Scheme 8. Nucleophilic substitution at the -C atom of 10a.
The presence of strong electron-withdrawing groups adjacent to
the alkene moiety in 9m and significant steric hindrance of t-Bu
group in 9n were unfavourable for the hydroxybromination
reaction. When 9m was treated with NBS, compound 19 was
formed as ca. 5:1 mixture of E/Z isomers in 83% yield (Scheme
7). A possible explanation of this result might include lowered
electronic density at the double bond, so that halodeboronation
occurred instead of the hydroxybromination. On the contrary, the
substrate 9i was unreactive even at heating under reflux, and
the starting material was recovered.
To assess reactivity of the carbonyl group, Wittig and Horner–
Wadsworth–Emmons olefinations were attempted. Whilst a
complex mixture of unidentified products was formed when the
starting compound 10a reacted with Ph3P+–CH2 , no reaction
–
occurred when 10a was subjected to the olefination with triethyl
phosphonoacetate anion. These results show that reactivity of
the carbonyl group in the substrates of the type 10 does not
always resemble the properties of usual ketones and should be
considered with caution when designing the synthetic route.
Scheme 7. Reaction of the compound 9m with NBS.
The next oxidation step allowed preparation of the compounds
10a,b, 10d–f, and 10h in 79–98% yield. In the case of
cyclopropyl- and ester-containing derivatives, the compounds
10c, 10j, and 10k were obtained in 52–81% yield over two steps.
The elaborated synthetic protocol was also applied to the
preparation of ketone 10o starting from alkene 9o bearing an
electron-rich aromatic ring. For this substrate, the yield on the
hydroxybromination step appeared to be lower (32%) as
compared to the aliphatic derivatives, which was probably
caused by competing bromination at the aryl moiety.
Nevertheless, further oxidation proceeded smoothly and gave
the target compound 10o in 96% yield.
Scheme 9. Heterocyclization reactions of 10a.
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These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
In order to investigate the utility of reagents 10 for
heterocyclization reactions, we aimed to construct imidazole,
thiazole, and furan-based scaffolds. Unfortunately, the
attempted condensations of 10a with benzamidine, 2-amino-
pyridine and ethyl acetoacetate were not successful; the starting
materials were recovered. Nevertheless, thiazole derivatives 22
and 23 were obtained in 86% and 33% yield, respectively, by
reaction of 10a with thiourea and benzothioamide (Scheme 9).
Moreover, 2-amino-3-furonitrile 24 was synthesized from 10a
and malononitrile with 55% yield. These chemical properties of
10a are similar to that reported for its aryl counterparts.[27]
General procedure for the preparation of MIDA boronates 9 via
hydroboration (Method A).[33] Alkyne 12 (100 mmol) and pinacolborane
(16 mL, 110 mmol, prepared according to the procedure by Knochel et
al.[37] and distilled prior the usage) were mixed under argon atmosphere.
BH3·THF complex (1 M in THF, 10 mL, 10.0 mmol) was added to the
mixture, and the reaction was heated to 60 C overnight. After cooling to
rt, the reaction mixture was quenched carefully with MeOH (10 mL),
stirred for 20 min and evaporated under reduced pressure to give crude
alkenylboronic acid pinacol ester 15 (ca. 40 mmol), which was subjected
to the next transesterefication with N-methyliminodiacetic acid without
additional purification. It was dissolved in DMSO (160 mL). N-
methyliminodiacetic acid (35.3 g, 240 mmol) and triethyl orthoformate
(26.6 mL, 160 mmol) were sequentially added to the solution, and the
mixture was stirred at 100–110 C for 48 h. After colling to rt, the
resulting mixture was quenched with H2O (700 mL), and extracted with
EtOAc (2×400 mL). The combined organic layers were washed with half-
saturated aq NaCl (2×400 mL), dried over anhydrous Na2SO4 and
evaporated in vacuo. The residue was triturated with Et2O and filtered.
Conclusions
The hydroxybromination of alkenyl MIDA boronates followed by
oxidation of alcohol moiety was applied for the synthesis of -
boryl--bromoketones bearing aliphatic and functionalized
substituents for the first time. This method allowed to obtain
target trifunctional compounds with 52–94% yield over two steps
on up to 11.2 g scale. It was shown that ether, carboxylic acid
ester, and Boc-protected amine groups were typically
compatible with the reaction conditions. For some substrates,
participation of nucleophilic functional groups in the
hydroxybromination via intramolecular nucleophilic attack at the
bromonium ion was observed, resulting in cyclization products
instead of the target bromohydrines. These processes were
especially important if five-membered rings could be formed.
Limitations of the procedure included substrates with strong
electron-withdrawing or sterically hindered substituents adjacent
to the C=C bond of the starting alkenyl MIDA boronate. In
addition, the presence of electron-rich aromatic substituents was
found to decrease the methods efficiency, possibly due to
competing bromination into the ring. The utility of synthesized
building blocks was illustrated by nucleophilic substitution of
bromide by acetate and azide anions, as well as by
heterocyclization to thiazol and furan-based derivatives.
General procedure for the preparation of MIDA boronates 9 (Method
A) via the boron-Wittig reaction (Method B). A solution of 2,2,6,6-
tetramethylpiperidine (8.2 mL, 48.0 mmol) in THF (160 mL) was cooled to
0 C under argon atmosphere. n-BuLi (2.5 M in hexanes, 18.4 mL, 46.0
mmol) was added dropwise at this temperature and the solution was
stirred for 20 minutes. Bis[(pinacolato)boryl]methane 14 (10.7 g, 40.0
mmol) was added dropwise at 0 C, and the solution was stirred for 10
min at the same temperature. After cooling to –80 C, a solution of
aldehyde 13 (46.0 mmol) was added dropwise and the mixture was
stirred at –80 – –60 C for 2 h. Then, the reaction was quenched with
saturated aq NH4Cl (100 mL), and was allowed to warm to rt. THF was
evaporated under reduced pressure, and the residue was extracted with
t-BuOMe (2×200 mL). The combined organic layers were dried over
anhydrous Na2SO4 and concentrated in vacuo to give crude
alkenylboronic acid pinacol ester 15, which was subjected to the next
transesterefication with N-methyliminodiacetic acid as described above
for Method A without additional purification.
(E)-2-(Hex-1-en-1-yl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione
(9a). The compound was obtained by the method A and purified by
recrystallization from EtOAc – t-BuOMe. Yield 9.28 g (49%) from 6.50 g
of 12a. White crystalline solid, mp = 95–97 C. 1H NMR (400 MHz,
DMSO-d6) δ 5.94 (dt, J = 17.6, 6.4 Hz, 1H), 5.37 (d, J = 17.6 Hz, 1H),
4.17 (d, J = 17.1 Hz, 2H), 3.95 (d, J = 17.1 Hz, 2H), 2.72 (s, 3H), 2.07 (q,
J = 6.8 Hz, 2H), 1.41 – 1.22 (m, 4H), 0.87 (t, J = 7.0 Hz, 3H) ppm. 13C
NMR (126 MHz, DMSO-d6) δ 169.2, 144.1, 125.9, 61.2, 46.7, 34.5, 30.5,
21.7, 13.8 ppm. MS (APCI): m/z = 240 [M+H]+. Anal. Calcd. for
C11H18BNO4: C 55.26; H 7.59; N 5.86. Found: C 55.38; H 7.39; N 5.47.
Experimental Section
General. The solvents were purified according to the standard
procedures.[36] All starting materials were purchased from Enamine and
UORSY. Melting points were measured on MPA100 OptiMelt automated
melting point system. Analytical TLC was performed using Polychrom SI
F254 plates. Column chromatography was performed using Kieselgel
Merck 60 (230–400 mesh) as the stationary phase. 1H and 13C NMR
spectra were recorded on a Bruker 170 Avance 500 spectrometer (at
499.9 MHz for Protons and 124.9 MHz for Carbon-13) and Varian Unity
Plus 400 spectrometer (at 400.4 MHz for protons and 100.7 MHz for
Carbon-13). Chemical shifts are reported in ppm with solvent residual
signal used as an internal standard. Elemental analyses were performed
at the Laboratory of Organic Analysis, Department of Chemistry, Taras
Shevchenko National University of Kyiv. Mass spectra were recorded on
an Agilent 1100 LCMSD SL instrument (chemical ionization (APCI),
electrospray ionization (ESI)) and Agilent 5890 Series II 5972 GCMS
instrument (electron impact ionization (EI)). CCDC 1977977 contains the
supplementary crystallographic data for this paper (compound 11e).
(E)-6-Methyl-2-(prop-1-en-1-yl)-1,3,6,2-dioxazaborocane-4,8-dione
(9b). The compound was obtained by the method B and purified by
recrystallization from EtOAc. Yield 1.25 g (28%) from 1.00 g of 13b.
White crystalline solid, mp = 125–127 C. 1H NMR (400 MHz, DMSO-d6)
δ 5.94 (dq, J = 17.5, 6.2 Hz, 1H), 5.39 (d, J = 17.5 Hz, 1H), 4.17 (d, J =
17.1 Hz, 2H), 3.95 (d, J = 17.1 Hz, 2H), 2.72 (s, 3H), 1.75 (d, J = 6.2 Hz,
3H) ppm. 13C NMR (101 MHz, DMSO-d6) δ 169.2, 139.0, 127.5, 61.2,
46.6, 21.1 ppm. MS (APCI): m/z = 198 [M+H]+. Anal. Calcd. for
C8H12BNO4: C 48.78; H 6.14; N 7.11. Found: C 48.52; H 6.08; N 7.30.
(E)-2-(2-Cyclopropylvinyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-
dione (9c).[38] The compound was obtained by the method A and purified
by trituration with t-BuOMe. Yield 1.42 g (42%) from 1.00 g of 12c. Beige
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10.1002/ejoc.202000078
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crystalline solid, mp = 85–86 C. 1H NMR (500 MHz, DMSO-d6) δ 5.48 –
5.37 (m, 2H), 4.15 (d, J = 17.0 Hz, 2H), 3.94 (d, J = 17.0 Hz, 2H), 2.73 (s,
3H), 1.48 – 1.39 (m, 1H), 0.74 – 0.66 (m, 2H), 0.44 – 0.36 (m, 2H) ppm.
13C NMR (126 MHz, DMSO-d6) δ 169.1, 148.0, 122.5, 61.2, 46.6, 16.1,
7.0 ppm. MS (APCI): m/z = 224 [M+H]+. Anal. Calcd. for C10H14BNO4: C
53.85; H 6.33; N 6.28. Found: C 54.24; H 6.12; N 6.08.
(m, 2H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 169.6, 144.6, 139.2,
128.7, 127.84, 127.76, 126.6, 72.3, 70.0, 61.7, 47.1, 35.1, 29.2, 25.5
ppm. MS (APCI): m/z = 368 [M+Na]+. Anal. Calcd. for C18H24BNO5: C,
62.63; H, 7.01; N, 4.06. Found: C, 62.45; H, 7.13; N, 4.12.
(E)-2-(5-Methoxypent-1-en-1-yl)-6-methyl-1,3,6,2-dioxazaborocane-
4,8-dione (9i). The compound was obtained by the method A and
purified by column chromatography (EtOAc as eluent, Rf = 0.30). Yield
2.64 g (22%) from 4.70 g of 12i. Yellowish oil. 1H NMR (400 MHz,
DMSO-d6) δ 5.91 (dt, J = 17.6, 6.3 Hz, 1H), 5.35 (d, J = 17.6 Hz, 1H),
4.14 (d, J = 17.4 Hz, 2H), 3.92 (d, J=17.4 Hz, 2H), 3.26 (t, J = 6.4 Hz, 2H),
3.17 (s, 3H), 2.68 (s, 3H), 2.12 – 1.99 (m, 2H), 1.62 – 1.50 (m, 2H) ppm.
13C NMR (101 MHz, DMSO-d6) δ 168.2, 142.6, 125.1, 70.3, 60.2, 56.8,
45.6, 30.39, 27.2 ppm. MS (APCI): m/z = 278 [M+Na]+. Anal. Calcd. for
C11H18BNO5: C, 51.80; H, 7.11; N, 5.49. Found: C, 51.74; H, 7.15; N,
5.38.
(E)-6-Methyl-2-(3-phenylprop-1-en-1-yl)-1,3,6,2-dioxazaborocane-4,8-
dione (9d). The compound was obtained by the method B and purified
by trituration with t-BuOMe. Yield 0.619 g (31%) from 1.00 g of 13d.
Beige crystalline solid, mp = 138–140 C. 1H NMR (400 MHz, DMSO-d6)
δ 7.33 – 7.26 (m, 2H), 7.22 – 7.14 (m, 3H), 6.08 (dt, J = 17.5, 6.4 Hz, 1H),
5.45 (d, J = 17.5 Hz, 1H), 4.19 (d, J = 17.1 Hz, 2H), 3.97 (d, J = 17.1 Hz,
2H), 3.41 (d, J = 6.4 Hz, 2H), 2.75 (s, 3H) ppm. 13C NMR (126 MHz,
DMSO-d6) δ 169.1, 142.9, 140.0, 128.5, 128.4, 127.2, 125.9, 61.3, 46.8,
41.3 ppm. MS (APCI): m/z = 296 [M+Na]+. Anal. Calcd. for C14H16BNO4:
C 61.57; H 5.91; N 5.13. Found: C 61.66; H 5.89; N 5.24.
(E)-Ethyl
6-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)hex-5-
(E)-tert-Butyl
4-(2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-
enoate (9j). The compound was obtained by the method A and purified
by column chromatography (EtOAc as eluent, Rf = 0.42). Yield 2.37 g
(22%) from 5.00 g of 12j. Colourless oil. 1H NMR (400 MHz, DMSO-d6) δ
5.92 (dt, J = 17.2, 5.2 Hz, 1H), 5.39 (d, J = 17.2 Hz, 1H), 4.18 (d, J = 17.0
Hz, 2H), 4.04 (q, J = 6.8 Hz, 2H), 3.96 (d, J = 17.0 Hz, 2H), 2.74 (s, 3H),
2.27 (t, J = 6.5 Hz, 2H), 2.14 – 2.01 (m, 2H), 1.70 – 1.57 (m, 2H), 1.17 (t,
J = 6.8 Hz, 3H) ppm. 13C NMR (101 MHz, DMSO-d6) δ 171.6, 168.0,
142.1, 125.8, 60.0, 58.5, 45.5, 32.9, 31.7, 22.4, 12.9 ppm. MS (APCI):
m/z = 298 [M+H]+. Anal. Calcd. for C13H20BNO6: C, 52.55; H, 6.79; N,
4.71. Found: C, 52.48; H, 6.67; N, 4.59.
yl)vinyl)piperidine-1-carboxylate (9e). The compound was obtained by
the method B and purified by trituration with t-BuOMe. Yield 0.620 g
(36%) from 1.00 g of 13e. Beige crystalline solid, mp = 204–205 C. 1H
NMR (500 MHz, DMSO-d6) δ 5.91 (dd, J = 17.8, 5.9 Hz, 1H), 5.37 (d, J =
17.8 Hz, 1H), 4.18 (d, J = 17.2 Hz, 2H), 3.97 (d, J = 17.2 Hz, 2H), 3.92 –
3.87 (m, 2H), 2.89 – 2.73 (m, 2H), 2.71 (s, 3H), 2.19 – 2.08 (m, 1H), 1.65
(d, J = 13.0 Hz, 2H), 1.38 (s, 9H), 1.21 – 1.11 (m, 2H) ppm. 13C NMR
(126 MHz, DMSO-d6) δ 169.1, 153.9, 147.8, 124.0, 78.4, 61.2, 46.7, 43.4,
39.9, 31.0, 28.1 ppm. MS (APCI): m/z = 267 [M–CO2–CH2C(CH3)2+H]+.
Anal. Calcd. for C17H27BN2O6: C 55.76; H 7.43; N 7.65. Found: C 55.80;
H 7.25; N 7.98.
(E)-Benzyl 2,2-dimethyl-5-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaboro-
can-2-yl)pent-4-enoate (9k). The compound was obtained by the
method A and purified by column chromatography (EtOAc as eluent, Rf =
0.41). Yield 1.09 g (21%) from 3.00 g of 12k. Colourless oil. 1H NMR (400
MHz, DMSO-d6) δ 1H NMR (500 MHz, DMSO) δ = 7.46 – 7.28 (m, 5H),
5.93 – 5.82 (m, 1H), 5.43 (d, J = 17.4 Hz, 1H), 5.08 (s, 2H), 4.19 (d,
J = 17.6 Hz, 2H), 3.93 (d, J = 17.6 Hz, 2H), 2.70 (s, 3H), 2.32 (d, J = 5.9
Hz, 2H), 1.14 (s, 6H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 175.0,
167.8, 138.0, 135.1, 129.0, 127.2, 126.6, 126.2, 64.2, 60.0, 45.5, 44.6,
40.7, 23.4 ppm. MS (APCI): m/z = 374 [M+H]+. Anal. Calcd. for
C19H24BNO6: C, 61.15; H, 6.48; N, 3.75. Found: C, 61.49; H, 6.82; N,
3.50.
(E)-5-(6-Methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)pent-4-en-1-yl
benzoate (9f). The compound was obtained by the method A and
purified by column chromatography (EtOAc as eluent, Rf = 0.31). Yield
0.702 g (38%) from 1.00 g of 12f. Colourless oil. 1H NMR (400 MHz,
DMSO-d6) δ 7.97 (d, J = 7.6 Hz, 2H), 7.65 (d, J = 7.6 Hz, 1H), 7.52 (t, J =
7.6 Hz, 2H), 6.02 (dt, J = 17.6, 6.3 Hz, 1H), 5.46 (d, J = 17.6 Hz, 1H),
4.27 (t, J = 6.5 Hz, 2H), 4.20 (d, J = 17.1 Hz, 2H), 3.97 (d, J = 17.1 Hz,
2H), 2.75 (s, 3H), 2.23 (q, J = 7.0 Hz, 2H), 1.83 (quint, J = 6.9 Hz, 2H)
ppm. 13C NMR (101 MHz, DMSO-d6) δ 169.2, 165.7, 143.1, 133.2, 129.8,
129.1, 128.7, 126.8, 64.1, 61.2, 46.7, 31.2, 27.3 ppm. MS (APCI): m/z =
346 [M+H]+. Anal. Calcd. for C17H20BNO6: C 59.16; H 5.84; N 4.06.
Found: C 59.05; H 6.07; N 3.74.
(E)-tert-Butyl (3-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)al-
lyl)carbamate (9l). The compound was obtained by the method A and
purified by column chromatography (gradient EtOAc to EtOAc – CH3CN
(8:1), Rf = 0.38 (EtOAc – CH3CN (8:1))), followed by recrystallization from
EtOAc – t-BuOMe. Yield 5.90 g (29%) from 10.0 g of 12l. White solid. Mp
121–123 C. 1H NMR (500 MHz, DMSO-d6) δ 6.95 (br s, 1H), 5.91 – 5.78
(m, 1H), 5.46 (d, J = 17.4 Hz, 1H), 4.18 (d, J = 17.0 Hz, 2H), 3.94 (d,
J = 17.0 Hz, 2H), 3.32 (s, 3H), 2.72 (br s, 2H), 1.37 (s, 9H) ppm. 13C
NMR (126 MHz, DMSO-d6) δ 169.6, 156.0, 141.5, 126.0, 78.1, 61.7, 47.2,
44.1, 28.7 ppm. MS (APCI): m/z = 335 [M+Na]+, 257 [M+H–C4H8]+, 213
[M+H–C4H8–CO2] Anal. Calcd. for Anal. Calcd. for C13H21BN2O6: C,
50.02; H, 6.78; N, 8.98. Found: C, 50.28; H, 7.07; N, 9.29.
(E)-2-(5-(Benzyloxy)pent-1-en-1-yl)-6-methyl-1,3,6,2-dioxazaboro-
cane-4,8-dione (9g). The compound was obtained by the method A and
purified by column chromatography (EtOAc as eluent, Rf = 0.36). Yield
0.440 g (23%) from 1.00 g of 12g. Colourless oil. 1H NMR (400 MHz,
DMSO-d6) δ 7.39 – 7.22 (m, 5H), 5.97 (dt, J = 17.4, 6.4 Hz, 1H), 5.39 (d,
J = 17.4 Hz, 1H), 4.44 (s, 2H), 4.18 (d, J = 17.1 Hz, 2H), 3.94 (d, J = 17.1
Hz, 2H), 3.42 (t, J = 6.5 Hz, 2H), 2.70 (s, 3H), 2.14 (q, J = 7.1 Hz, 2H),
1.65 (quint, J = 6.9 Hz, 2H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 169.1,
143.7, 138.7, 128.2, 127.4, 127.3, 126.2, 71.8, 69.1, 61.2, 46.6, 31.5,
28.4 ppm. MS (APCI): m/z = 354 [M+Na]+. Anal. Calcd. for C17H22BNO5:
C 61.65; H 6.70; N 4.23. Found: C 61.57; H 6.90; N 4.09.
(E)-2-(3,3-Dimethylbut-1-en-1-yl)-6-methyl-1,3,6,2-dioxazaborocane-
4,8-dione (9m). The compound was obtained by the method A and
purified by recrystallization from EtOAc. Yield 1.57 g (54%) from 1.00 g of
12m. White crystalline solid, mp = 237–240 C. 1H NMR (500 MHz,
DMSO-d6) δ 5.98 (d, J = 18.0 Hz, 1H), 5.27 (d, J = 18.0 Hz, 1H), 4.17 (d,
J = 17.1 Hz, 2H), 3.95 (d, J = 17.1 Hz, 2H), 2.70 (s, 3H), 0.99 (s, 9H)
ppm. 13C NMR (101 MHz, DMSO-d6) δ 169.2, 154.5, 119.2, 61.3, 46.7,
34.0, 29.2 ppm. MS (APCI): m/z = 240 [M+H]+. Anal. Calcd. for
C11H18BNO4: C 55.26; H 7.59; N 5.86. Found: C 54.97; H 7.77; N 6.26.
(E)-2-(6-(Benzyloxy)hex-1-en-1-yl)-6-methyl-1,3,6,2-dioxazaboroca-
ne-4,8-dione (9h). The compound was obtained by the method A and
purified by column chromatography (EtOAc as eluent, Rf = 0.34). Yield
6.36 g (50%) from 7.00 g of 12h. Colourless oil, which crystallized upon
standing, mp = 58–59˚C. 1H NMR (400 MHz, DMSO-d6) δ 7.44 – 7.17 (m,
5H), 5.93 (dt, J = 17.5, 6.1 Hz, 1H), 5.36 (d, J = 17.5 Hz, 1H), 4.40 (s,
2H), 4.15 (d, J = 17.0 Hz, 2H), 3.92 (d, J = 17.0 Hz, 2H), 3.45 – 3.31 (m,
2H), 2.70 (s, 3H), 2.13 – 1.93 (m, 2H), 1.61 – 1.44 (m, 2H), 1.44 – 1.33
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000078
European Journal of Organic Chemistry
FULL PAPER
(E)-Ethyl 3-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)acrylate
(9n). The compound was obtained by the method B and purified by
trituration with t-BuOMe. Yield 0.953 g (38%) from 1.00 g of 13n. White
crystalline solid, mp = 165–167 C. 1H NMR (500 MHz, DMSO-d6) δ 6.92
(d, J = 17.9 Hz, 1H), 6.16 (d, J = 17.9 Hz, 1H), 4.27 (d, J = 17.1 Hz, 2H),
4.13 (q, J = 7.0 Hz, 2H), 4.07 (d, J = 17.1 Hz, 2H), 2.80 (s, 3H), 1.22 (t, J
= 7.0 Hz, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 168.9, 165.4, 144.6,
131.8, 61.7, 60.0, 46.8, 14.1 ppm. MS (APCI): m/z = 256 [M+H]+. Anal.
Calcd. for C10H14BNO6: C 47.10; H 5.53; N 5.49. Found: C 47.15; H 5.35;
N 5.69.
2H), 7.19 (t, J = 7.2 Hz, 1H), 4.35 (d, J = 17.2 Hz, 1H), 4.28 (d, J = 17.1
Hz, 1H), 4.03 (d, J = 17.2 Hz, 1H), 4.03 (d, J = 17.1 Hz, 1H), 3.97 – 3.89
(m, 1H), 3.72 (d, J = 4.1 Hz, 1H), 3.35 (br s, 1H), 3.03 (s, 3H), 2.93 (dd, J
= 14.1, 2.2 Hz, 1H), 2.67 (dd, J = 14.1, 9.1 Hz, 1H) ppm. 13C NMR (126
MHz, DMSO-d6) δ 168.7, 168.3, 139.8, 129.3, 128.0, 125.8, 72.2, 63.0,
62.6, 51.8, 45.9, 40.6 ppm. MS (APCI): m/z = 368/370 [M–H]+. Anal.
Calcd. for C14H17BBrNO5: C 45.45; H 4.63; N 3.79; Br 21.60. Found: C
45.85; H 4.47; N 3.88; Br 21.53.
tert-Butyl
4-((1R*,2S*)-2-bromo-1-hydroxy-2-(6-methyl-4,8-dioxo-
(11e).
1,3,6,2-dioxazaborocan-2-yl)ethyl)piperidine-1-carboxylate
(E)-2-(4-Methoxystyryl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione
(9o).[27] The compound was obtained by the method B and purified by
recrystallization from EtOAc. Yield 0.451 g (21%) from 1.00 g of 13o.
White crystalline solid, mp = 220–222 C. 1H NMR (500 MHz, DMSO-d6)
δ 7.42 (d, J = 7.5 Hz, 2H), 6.91 (d, J = 7.5 Hz, 2H), 6.75 (d, J = 18.1 Hz,
1H), 6.08 (d, J = 18.1 Hz, 1H), 4.23 (d, J = 17.1 Hz, 2H), 4.03 (d, J = 17.1
Hz, 2H), 3.75 (s, 3H), 2.78 (s, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ
171.5, 169.2, 159.1, 140.6, 130.6, 127.7, 114.0, 61.3, 55.1, 46.7 ppm.
MS (APCI): m/z = 290 [M+H]+. Anal. Calcd. for C14H16BNO5: C 58.17; H
5.58; N 4.85. Found: C 58.43; H 5.82; N 4.78.
The compound was purified by recrystallization from EtOAc. Yield 0.588
g (93%) from 0.50 g of 9e. White crystalline solid, mp = 202–203 C. 1H
NMR (500 MHz, DMSO-d6) δ 5.19 (s, 1H), 4.36 (d, J = 17.3 Hz, 1H), 4.15
(d, J = 16.7 Hz, 1H), 4.03 (d, J = 17.3 Hz, 1H), 4.00 – 3.94 (m, 2H), 3.93
(d, J = 16.7 Hz, 1H), 3.66 – 3.60 (m, 1H), 3.59 – 3.52 (m, 1H), 3.02 (s,
3H), 2.72 – 2.55 (m, 2H), 1.99 – 1.92 (m, 1H), 1.64 (d, J = 12.9 Hz, 1H),
1.38 (s, 9H), 1.36 – 1.24 (m, 1H), 1.19 – 1.11 (m, 1H) ppm. 13C NMR
(126 MHz, DMSO-d6) δ 168.6 (2C), 153.7, 78.4, 75.0, 63.7, 62.6, 46.3,
44.3, 43.0 (2C), 38.8, 29.2, 28.1, 24.4 ppm. MS (APCI): m/z = 461/463
[M–H]+. Anal. Calcd. for C17H28BBrN2O7: C 44.09; H 6.09; N 6.05; Br
17.25. Found: C 44.45; H 5.85; N 6.22; Br 17.36.
General procedure for the preparation of the compounds 11. Alkenyl
MIDA boronate 9 (20.0 mmol) was dissolved in THF–H2O (2:1) (200–600
mL, depending on solubility of 9). The reaction flask was covered with
aluminum foil to protect the reaction mixture from light, and N-bromosuc-
cinimide (4.27 g, 24.0 mmol) was added in one portion. The solution was
stirred at rt overnight, and then aq Na2S2O3 (10%, 100 mL) was added.
THF was evaporated under reduced pressure, and the residue was
extracted with EtOAc (3×100 mL). The combined organic layers were
dried over anhydrous Na2SO4 and concentrated in vacuo to give crude
bromohydrins 11 which were purified by either recrystallization, or by
column chromatography on silica. Visualization of TLC was carried out
with KMnO4.
(4R*,5S*)-5-Bromo-4-hydroxy-5-(6-methyl-4,8-dioxo-1,3,6,2-dioxaza-
borocan-2-yl)pentyl benzoate (11f). The compound was purified by
column chromatography (EtOAc as eluent, Rf = 0.22). Yield 0.458 g
(65%) from 0.550 g of 9f. White amorphous solid, mp = 65–68 C. 1H
NMR (400 MHz, DMSO-d6) δ 7.98 (d, J = 7.7 Hz, 2H), 7.64 (t, J = 7.4 Hz,
1H), 7.51 (t, J = 7.6 Hz, 2H), 5.01 (s, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.31
– 4.19 (m, 3H), 4.02 (d, J = 17.3 Hz, 1H), 4.00 (d, J = 16.9 Hz, 1H), 3.81
– 3.67 (m, 2H), 3.04 (s, 3H), 1.99 – 1.83 (m, 1H), 1.83 – 1.66 (m, 2H),
1.66 – 1.48 (m, 1H) ppm. 13C NMR (101 MHz, DMSO-d6) δ 168.8, 168.4,
165.9, 133.3, 130.0, 129.2, 128.8, 70.2, 64.8, 62.9, 62.6, 52.7, 45.9, 30.5,
25.0 ppm. MS (APCI): m/z
=
440/442 [M–H]+. Anal. Calcd. for
C17H21BBrNO7: C 46.19; H 4.79; N 3.17; Br 18.07. Found: C 46.25; H
4.41; N 3.25; Br 17.86.
2-((1R*,2S*)-1-Bromo-2-hydroxyhexyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (11a). The compound was purified by
column chromatography (EtOAc as eluent, Rf = 0.33). Yield 11.9 g (96%)
from 8.82 g of 9a. White amorphous solid, mp = 58–61 C. 1H NMR (400
MHz, DMSO-d6) δ 4.32 (d, J = 17.3 Hz, 1H), 4.22 (d, J = 17.0 Hz, 1H),
4.00 (d, J = 17.3 Hz, 1H), 3.98 (d, J = 17.0 Hz, 1H), 3.70 (d, J = 3.7 Hz,
1H), 3.68 – 3.61 (m, 1H), 3.44 (br s, 1H), 3.03 (s, 3H), 1.60 – 1.48 (m,
1H), 1.48 – 1.36 (m, 2H), 1.34 – 1.20 (m, 3H), 0.87 (t, J = 6.7 Hz, 3H)
ppm. 13C NMR (126 MHz, DMSO-d6) δ 168.7, 168.3, 70.4, 62.9, 62.5,
52.9, 45.8, 33.6, 27.7, 22.2, 14.0 ppm. MS (APCI): m/z = 334/336 [M–H]+.
Anal. Calcd. for C11H19BBrNO5: C 39.32; H 5.70; N 4.17; Br 23.78.
Found: C 39.07; H 5.55; N 3.93; Br 23.46.
2-((1R*,2S*)-6-(Benzyloxy)-1-bromo-2-hydroxyhexyl)-6-methyl-
1,3,6,2-dioxazaborocane-4,8-dione (11h). The compound was purified
by column chromatography (gradient EtOAc to EtOAc – CH3CN (8:1) as
eluent, Rf = 0.47 (CH3CN (8:1) as eluent)). Yield 2.31 g (67%) from 2.70
g of 9h. Colourless amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ
7.37 – 7.25 (m, 4H), 7.27 – 7.17 (m, 1H), 4.80 (br s, 1H), 4.41 (s, 2H),
4.35 – 4.26 (d, J = 17.1 Hz, 1H), 4.19 (d, J = 17.1 Hz, 1H), 3.96 (dd,
J = 17.1, 6.5 Hz, 2H), 3.64 (dd, J = 17.1, 5.4 Hz, 2H), 3.43 – 3.34 (m, 2H),
2.99 (s, 3H), 1.62 – 1.35 (m, 5H), 1.41 – 1.21 (m, 1H) ppm. 13C NMR
(126 MHz, DMSO-d6) δ 173.9, 173.5, 144.0, 133.4, 132.6, 132.5, 77.0,
75.6, 75.0, 68.1, 67.7, 58.0, 51.0, 39.0, 34.5, 27.5 ppm. MS (APCI): m/z
= 440/442 [M–H]–. Anal. Calcd. for C18H25BBrNO6: C, 48.90; H, 5.70; N,
3.17. Found: C, 48.66; H, 5.78; N, 3.56.
2-((1R*,2S*)-1-Bromo-2-hydroxypropyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (11b). The compound was purified by
recrystallization from EtOAc. Yield 1.03 g (63%) from 1.10 g of 9b. White
crystalline solid, mp = 167–169 C. 1H NMR (500 MHz, DMSO-d6) δ 4.80
(br s, 1H), 4.33 (d, J = 17.2 Hz, 1H), 4.22 (d, J = 16.9 Hz, 1H), 4.01 (d, J
= 17.2 Hz, 1H), 3.99 (d, J = 16.9 Hz, 1H), 3.88 – 3.81 (m, 1H), 3.76 –
3.66 (m, 1H), 3.03 (s, 3H), 1.15 – 1.06 (m, 3H) ppm. 13C NMR (126 MHz,
DMSO-d6) δ 168.7, 168.3, 66.4, 62.9, 62.5, 53.6, 45.8, 20.8 ppm. MS
(APCI): m/z = 292/294 [M–H]+. Anal. Calcd. for C8H13BBrNO5: C 32.69; H
4.46; N 4.77; Br 27.19. Found: C 32.72; H 4.67; N 4.85; Br 27.37.
2-((1R*,2S*)-1-Bromo-2-hydroxy-5-methoxypentyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (11i). The compound was purified by
column chromatography (gradient EtOAc to EtOAc – CH3CN (8:1) as
eluent, Rf = 0.32 (CH3CN (8:1) as eluent)), followed by recrystallization
from EtOAc. Yield 0.23 g (27%) from 0.61 g of 9i. White solid. 1H NMR
(400 MHz, DMSO-d6) δ 4.39 (d, J = 17.2 Hz, 1H), 4.38 (br s, 1H), 4.22 (d,
J = 17.2 Hz, 1H), 4.09 – 3.96 (m, 3H), 3.43 – 3.35 (m, 3H), 3.25 (s, 3H),
3.07 (s, 3H), 1.68 – 1.36 (m, 4H) ppm. 13C NMR (126 MHz, DMSO-d6) δ
167.5, 167.1, 79.3, 61.6, 61.3, 59.8, 56.6, 54.7, 44.8, 27.9, 27.7 ppm. MS
(APCI): m/z = 352/354 [M+H]+. Anal. Calcd. for C11H19BBrNO6: C, 37.54;
H, 5.44; N, 3.98; Br, 22.70. Found: C, 37.22; H, 5.54; N, 4.25; Br, 22.90.
2-((1R*,2S*)-1-Bromo-2-hydroxy-3-phenylpropyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (11d). The compound was purified by
column chromatography (EtOAc as eluent, Rf = 0.37). Yield 0.488 g
(72%) from 0.50 g of 9d. Beige crystalline solid, mp = 197–200 C. 1H
NMR (500 MHz, DMSO-d6) δ 7.28 (t, J = 7.5 Hz, 2H), 7.23 (d, J = 7.0 Hz,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000078
European Journal of Organic Chemistry
FULL PAPER
(5S*,6R*)-Ethyl 6-bromo-5-hydroxy-6-(6-methyl-4,8-dioxo-1,3,6,2-dio-
xazaborocan-2-yl)hexanoate (11j). The compound was used in the next
step without chromatographic purification. Column chromatography
(gradient EtOAc to EtOAc – CH3CN (8:1) as eluent, Rf = 0.40 (CH3CN
(8:1))) led to a mixture of 11j with lactone 17j (according to 1H NMR and
LC-MS, 11j : 17j = ca. 4:1), which was not present in the crude product.
Yield 0.88 g (72%) from 0.93 g of 9j. Colourless amorphous solid. 1H
NMR (500 MHz, DMSO-d6) δ 4.88 (br s, 1H), 4.33 (d, J = 17.2 Hz, 1H),
4.22 (d, J = 17.2 Hz, 1H), 4.12 – 3.95 (m, 4H), 3.72 – 3.61 (m, 2H), 3.03
(s, 3H), 2.38 – 2.20 (m, 2H), 1.92 – 1.37 (m, 4H), 1.18 (t, J = 7.1 Hz, 3H)
ppm. 13C NMR (126 MHz, DMSO-d6) δ 173.4, 169.2, 168.7, 70.6, 63.3,
63.0, 60.1, 53.1, 46.3, 34.1, 33.8, 21.7, 14.6 ppm. MS (APCI): m/z =
376/378 [M+H–H2O]+ (11j), 348/350 [M+H]+ (17j).
2-(1-Bromo-2-oxopropyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-
dione (10b). The compound was purified by column chromatography
(EtOAc as eluent, Rf = 0.30). Yield 0.659 g (79%) from 0.840 g of 11b.
1
White crystalline solid. H NMR (500 MHz, DMSO-d6) δ 4.43 (d, J = 17.2
Hz, 1H), 4.33 (s, 1H), 4.32 (d, J = 17.2 Hz, 1H), 4.10 (d, J = 17.2 Hz, 1H),
4.09 (d, J = 17.2 Hz, 1H), 3.05 (s, 3H), 2.28 (s, 3H) ppm. 13C NMR (101
MHz, DMSO-d6) δ 202.8, 168.1, 168.1, 62.9, 62.8, 46.2, 46.1, 28.1 ppm.
MS (APCI): m/z = 290/292 [M–H]+. Anal. Calcd. for C8H11BBrNO5: C
32.92; H 3.80; N 4.80; Br 27.37. Found: C 32.54; H 4.18; N 4.53; Br
27.74.
2-(1-Bromo-2-cyclopropyl-2-oxoethyl)-6-methyl-1,3,6,2-dioxazaboro-
cane-4,8-dione (10c). The compound was prepared from the alkene 9c
(1.25 g, 5.61 mmol), which was converted to 2-(1-bromo-2-cyclopropyl-2-
hydroxyethyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (11c) by the
general procedure for the preparation of the compounds 11. Purification
of the obtained product by column chromatography resulted in ca. 1:1
diastereomeric mixture of the compound 11c with 90–95% purity. Thus,
the crude 11c was subjected to the next oxidation according to general
procedure for the preparation of the compounds 10 without additional
purification. The title compound 10c was purified by column
chromatography (EtOAc as eluent, Rf = 0.35). Yield 927 mg (52 %) from
1.25 g of 9c. White amorphous solid, mp = 88–89 C. 1H NMR (400 MHz,
DMSO-d6) δ 4.41 (s, 1H), 4.40 (d, J = 17.2 Hz, 1H), 4.34 (d, J = 17.2 Hz,
1H), 4.10 (d, J = 17.2 Hz, 1H), 4.08 (d, J = 17.2 Hz, 1H), 3.04 (s, 3H),
2.40 – 2.32 (m, 1H), 1.00 – 0.91 (m, 2H), 0.90 – 0.83 (m, 2H) ppm. 13C
NMR (126 MHz, DMSO-d6) δ 205.1, 168.2 (2C), 62.9, 62.7, 46.2, 45.6,
19.1, 11.9, 11.5 ppm. MS (APCI): m/z = 318/320 [M+H]+. Anal. Calcd. for
C10H13BBrNO5: C 37.78; H 4.12; N 4.41; Br 25.13. Found: C 37.96; H
3.94; N 4.64; Br 25.18.
(4S*,5R*)-Benzyl 5-bromo-4-hydroxy-2,2-dimethyl-5-(6-methyl-4,8-di-
oxo-1,3,6,2-dioxazaborocan-2-yl)pentanoate (11k). The compound
was used in the next step without chromatographic purification. Column
chromatography (gradient EtOAc to EtOAc – CH3CN (8:1) as eluent, Rf =
0.59 (CH3CN (8:1))) led to a mixture of 11k with lactone 17k (11k : 17k =
ca. 3:1), which was present in the crude product. Yield 0.37 g (86%) from
0.34 g of 9h. Colourless amorphous solid. 1H NMR (500 MHz, DMSO-d6)
δ 7.40 (d, J = 6.8 Hz, 2H), 7.35 (t, J = 6.9 Hz, 2H), 7.30 (t, J = 6.8 Hz, 1H),
5.06 (d, J = 12.8 Hz, 1H), 4.99 (d, J = 12.8 Hz, 1H), 4.69 (br s, 1H), 4.37
(d, J = 17.1 Hz, 1H), 4.20 (d, J = 17.1 Hz, 1H), 4.02 (d, J =17.1 Hz, 1H),
3.98 (d, J = 17.1 Hz, 1H), 3.90 (br s, 1H), 3.70 (s, 1H), 3.01 (s, 3H), 2.00
– 1.91 (m, 1H), 1.63 (d, J=14.2 Hz, 1H), 1.17 (s, 6H) ppm. 13C NMR (126
MHz, DMSO-d6) δ 176.0, 167.8, 167.2, 135.8, 127.4, 126.7, 126.6, 66.4,
64.4, 61.8, 61.6, 53.6, 44.8, 43.1, 28.6, 26.0, 23.2 ppm. MS (APCI): m/z
= 452/454 [M+H–H2O]+ (11k), 362/364 [M+H]+ (17k).
2-(1-Bromo-2-hydroxy-2-(4-methoxyphenyl)ethyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (11o). The compound was purified by
recrystallization from EtOAc. Yield 0.141 g (32%) from 0.330 g of 9o.
White crystalline solid, mp = 168–169 C. 1H NMR (400 MHz, DMSO-d6)
δ 7.28 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 5.30 (d, J = 5.1 Hz,
1H), 4.94 (s, 1H), 4.41 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 16.8 Hz, 1H),
4.06 (d, J = 17.4 Hz, 1H), 3.97 (d, J = 16.8 Hz, 1H), 3.77 – 3.69 (m, 4H),
3.08 (s, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 168.9, 168.4, 157.9,
137.0, 127.0, 112.8, 71.0, 62.7, 62.5, 55.0, 52.9, 46.2 ppm. MS (APCI):
m/z = 384/386 [M–H]+. Anal. Calcd. for C14H17BBrNO6: C 43.56; H 4.44;
N 3.63; Br 20.70. Found: C 43.93; H 4.12; N 3.87; Br 20.32.
2-(1-Bromo-2-oxo-3-phenylpropyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (10d). The compound was purified by
recrystallization from EtOAc. Yield 0.272 g (84%) from 0.325 g of 11d.
Beige crystalline solid, mp = 217–218 C (dec). 1H NMR (400 MHz,
DMSO-d6) δ 7.36 – 7.22 (m, 3H), 7.20 (d, J = 6.9 Hz, 2H), 4.52 (s, 1H),
4.45 (d, J = 17.3 Hz, 1H), 4.35 (d, J = 17.2 Hz, 1H), 4.17 – 4.03 (m, 3H),
3.91 (d, J = 16.8 Hz, 1H), 3.09 (s, 3H) ppm. 13C NMR (126 MHz, DMSO-
d6) δ 202.6, 168.2, 168.1, 134.8, 129.7, 128.2, 126.6, 63.0, 62.9, 46.5,
46.3, 45.7 ppm. MS (APCI): m/z = 366/368 [M–H]+. Anal. Calcd. for
C14H15BBrNO5: C 45.70; H 4.11; N 3.81; Br 21.71. Found: C 45.44; H
3.99; N 3.69; Br 21.57.
General procedure for the preparation of the compounds 10.
Bromohydrin 11 (10.0 mmol) was dissolved in CH3CN (100 mL), and
Dess-Martin periodinane (12.0 mmol) was added in one portion (NOTE:
the reaction is slightly exothermic; thus on 40.0 mmol scale reaction
mixture was cooled to 0 C, and the oxidant was added in two portions).
The mixture was stirred overnight and concentrated under reduced
pressure. The residue was triturated with EtOAc – CHCl3 and filtered.
The obtained crude product was purified by either recrystallization or
column chromatography on silica. Visualization of TLC was carried out
with p-methoxybenzaldehyde/H2SO4 stain.
tert-Butyl 4-(2-bromo-2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-
2-yl)acetyl)piperidine-1-carboxylate (10e). The compound was purified
by column chromatography (EtOAc as eluent, Rf = 0.36). Yield 0.390 g
(85%) from 0.460 g of 11f. White amorphous solid, mp = 125–128 C
(dec). 1H NMR (400 MHz, DMSO-d6) δ 4.50 (s, 1H), 4.46 – 4.37 (m, 1H),
4.31 (d, J = 17.1 Hz, 1H), 4.09 (d, J = 17.3 Hz, 1H), 4.08 (d, J = 17.1 Hz,
1H), 4.01 – 3.91 (m, 2H), 3.32 (s, 1H), 3.06 (s, 3H), 3.04 – 2.97 (m, 1H),
2.81 – 2.64 (m, 2H), 1.81 (d, J = 13.0 Hz, 1H), 1.69 (d, J = 13.3 Hz, 1H),
1.39 (s, 9H), 1.27 – 1.16 (m, 1H) ppm. 13C NMR (126 MHz, DMSO-d6) δ
207.0, 168.1, 168.1, 153.7, 78.7, 62.9, 62.7, 46.3, 46.0, 43.7, 42.8 (2C),
28.3, 28.1, 27.3 ppm. MS (APCI): m/z
CH2C(CH3)2+H]+. Anal. Calcd. for C17H26BBrN2O7: C 44.28; H 5.68; N
6.08; Br 17.33. Found: C 44.36; H 5.69; N 6.22; Br 17.08.
=
361/363 [M–CO2–
2-(1-Bromo-2-oxohexyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione
(10a). The compound was purified by column chromatography (EtOAc as
eluent, Rf = 0.47). Yield 11.2 g (98%) from 11.5 g of 11a. White
crystalline solid, mp = 98–99 C. 1H NMR (400 MHz, DMSO-d6) δ 4.40 (d,
J = 17.3 Hz, 1H), 4.32 (s, 1H), 4.31 (d, J = 17.2 Hz, 1H), 4.09 (d, J = 17.3
Hz, 1H), 4.08 (d, J = 17.2 Hz, 1H), 3.05 (s, 3H), 2.82 – 2.70 (m, 1H), 2.62
– 2.52 (m, 1H), 1.47 (quint, J = 7.4 Hz, 2H), 1.26 (sext, J = 7.4 Hz, 2H),
0.86 (t, J = 7.3 Hz, 3H) ppm. 13C NMR (101 MHz, DMSO-d6) δ 205.0,
168.1 (2C), 62.9, 62.7, 46.2, 45.5, 39.6, 25.7, 21.6, 13.7 ppm. MS
(APCI): m/z = 332/334 [M–H]+. Anal. Calcd. for C11H17BBrNO5: C 39.56;
H 5.13; N 4.19; Br 23.93. Found: C 39.16; H 5.26; N 4.30; Br 23.96.
5-Bromo-5-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)-4-
oxopentyl benzoate (10f). The compound was purified by column
chromatography (EtOAc as eluent, Rf = 0.39). Yield 0.287 g (93%) from
0.310 g of 11g. White crystalline solid, mp = 93–95 C. 1H NMR (400
MHz, DMSO-d6) δ 7.98 (d, J = 7.6 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51
(t, J = 7.6 Hz, 2H), 4.42 (d, J = 17.4 Hz, 1H), 4.40 (s, 1H), 4.32 (d, J =
17.3 Hz, 1H), 4.25 (t, J = 6.4 Hz, 2H), 4.10 (d, J = 17.4 Hz, 1H), 4.09 (d, J
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000078
European Journal of Organic Chemistry
FULL PAPER
= 17.3 Hz, 1H), 3.06 (s, 3H), 2.99 (dt, J = 17.8, 7.2 Hz, 1H), 2.75 (dt, J =
17.8, 7.1 Hz, 1H), 1.94 (quint, J = 7.0 Hz, 2H) ppm. 13C NMR (101 MHz,
DMSO-d6) δ 204.5, 168.1 (2С), 165.7, 133.3, 129.8, 129.2, 128.7, 63.9,
63.0, 62.8, 46.3, 45.7, 36.6, 23.0 ppm. MS (APCI): m/z = 438/440 [M–H]+.
Anal. Calcd. for C17H19BBrNO7: C 46.40; H 4.35; N 3.18; Br 18.16.
Found: C 46.14; H 4.64; N 2.94; Br 18.55.
17.1 Hz, 1H), 4.06 – 3.94 (m, 3H), 3.88 (d, J = 4.2 Hz, 1H), 3.78 (q, J =
6.8 Hz, 1H), 3.68 – 3.58 (m, 1H), 3.03 (s, 3H), 1.96 – 1.64 (m, 4H) ppm.
13C NMR (126 MHz, DMSO-d6) δ 168.5, 168.3, 78.7, 67.8, 63.0, 62.5,
48.1, 45.9, 28.9, 25.8 ppm. MS(APCI): m/z = 320/321 [M+H]+. Anal.
Calcd. for C10H15BBrNO5: C 37.54; H 4.73; N 4.38; Br 24.97. Found: C
37.34; H 4.72; N 4.28; Br 24.60.
2-(6-(Benzyloxy)-1-bromo-2-oxohexyl)-6-methyl-1,3,6,2-dioxazaboro-
cane-4,8-dione (10h). The compound was purified by column
chromatography (EtOAc as eluent, Rf = 0.43). Yield 1.81 g (84%) from
2.16 g of 11h. Colourless amorphous solid. 1H NMR (400 MHz, DMSO-
d6) δ 7.41 – 7.24 (m, 5H), 4.49 – 4.25 (m, 5H), 4.09 (dd, J = 17.2, 4.0 Hz,
2H), 3.42 (t, J = 5.5 Hz, 2H), 3.05 (s, 3H), 2.84 – 2.74 (m, 1H), 2.64 –
2.53 (m, 1H), 1.62 – 1.47 (m, 4H) ppm. 13C NMR (101 MHz, DMSO-d6) δ
205.5, 168.6, 139.1, 128.7, 127.9, 127.8, 72.2, 69.8, 63.4, 63.2, 46.7,
46.0, 40.1, 29.0, 21.0 ppm. MS (APCI): m/z = 440/442 [M+H]+. Anal.
Calcd. for C18H23BBrNO6: C, 49.12; H, 5.27; N, 3.18; Br, 18.16. Found: C,
49.33; H, 5.14; N, 3.54; Br, 18.47.
2-((R*)-Bromo-((S*)-4,4-dimethyl-5-oxotetrahydrofuran-2-yl)methyl)-
6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (17k). A small fraction (55
mg) of the compound with ca. 90–95% purity was isolated upon column
chromatography of 11k. Colourless oil. 1H NMR (500 MHz, DMSO-d6) δ
4.74 (td, J = 8.0, 2.8 Hz, 1H), 4.44 (d, J = 17.2 Hz, 1H), 4.30 – 4.20 (m,
2H), 4.07 (dd, J=17.2, 14.8 Hz, 2H), 3.09 (s, 3H), 2.08 – 2.04 (m, 2H),
1.23 (s, 3H), 1.18 (s, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 13C
NMR (101 MHz, DMSO) δ 179.7, 167.3, 167.0, 74.8, 61.6, 61.4, 53.7,
44.9 (2C), 44.5, 23.8, 23.2 ppm. MS (APCI): m/z = 362/364 [M+H]+.
2-((S*)-Bromo-((R*)-2-oxooxazolidin-5-yl)methyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (17l). The compound was obtained analo-
gously to 17g, but avoiding extractive work-up due to hydrophilic nature
of product. The reaction mixture was evaporated and triturated with
EtOAc. The unsoluble residue was purified by recrystallization from EtOH.
Yield 0.509 g (61%) from 0.791 g of 9l. White solid. Mp > 250C. 1H NMR
(400 MHz, DMSO-d6) δ 7.49 (s, 1H), 4.82 (t, J = 8.7 Hz, 1H), 4.44 (d, J =
17.2 Hz, 1H), 4.27 (d, J = 17.2 Hz, 1H), 4.09 (s, 2H), 4.07 (d, J = 17.2,
1H), 3.50 (t, J = 8.7, 1H), 3.39 – 3.34 (m, 1H), 3.08 (s, 3H) ppm. 13C
NMR (126 MHz, DMSO-d6) δ 168.3, 168.0, 158.3, 75.1, 62.7, 62.6, 46.0,
Ethyl 6-bromo-6-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)-5-
oxohexanoate (10j). The compound was purified by column
chromatography (EtOAc as eluent, Rf = 0.34). Yield 0.561 g (59%) from
0.720 g of 9j. Colourless amorphous solid. 1H NMR (400 MHz, DMSO-d6)
δ 4.43 – 4.22 (m, 3H), 4.12 – 3.96 (m, 4H), 3.00 (s, 3H), 2.84 – 2.72 (m,
1H), 2.64 – 2.49 (m, 1H), 2.23 (t, J = 7.4 Hz, 2H), 1.77 – 1.62 (m, 2H),
1.14 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 205.2,
172.9, 168.5, 63.4, 63.2, 60.2, 46.7, 45.8, 39.4, 33.0, 19.5, 14.5 ppm. MS
(APCI): m/z = 392/394 [M+H]+. Anal. Calcd. for C13H19BBrNO7: C, 39.83;
H, 4.89; N, 3.57; Br, 20.38. Found: C, 39.69; H, 5.11; N, 3.79; Br, 20.44.
42.7 ppm. MS (APCI): m/z
=
333/335 [M–H]–. Anal. Calcd. for
C9H12BBrN2O6: C, 32.28; H, 3.61; N, 8.36; Br, 23.86. Found: C, 32.56; H,
3.63; N, 8.44; Br, 23.97.
Benzyl 5-bromo-2,2-dimethyl-5-(6-methyl-4,8-dioxo-1,3,6,2-dioxaza-
borocan-2-yl)-4-oxopentanoate (10k). The compound was purified by
column chromatography (EtOAc as eluent, Rf = 0.43). Yield 0.301 g
(81%) from 0.303 g of 9k. White solid, mp = 86–88 C. 1H NMR (500
MHz, DMSO-d6) δ 7.41 – 7.28 (m, 5H), 5.06 (s, 2H), 4.41 (d, J = 17.1 Hz,
1H), 4.33 (s, H), 4.33 (d, J = 17.1 Hz, 1H), 4.07 (d, J = 17.1, 1H), 4.06 (d,
J = 17.1, 1H), 3.16 (d, J = 18.4 Hz, 1H), 3.02 (s, 3H), 2.95 (d, J = 18.4 Hz,
1H), 1.16 (s, 3H), 1.16 (s, 3H) ppm. 13C NMR (126 MHz, DMSO-d6)
202.0, 175.0, 166.9, 166.9, 135.2, 127.2, 126.6, 126.3, 64.3, 61.7, 61.6,
48.7, 45.0, 43.8, 38.4, 23.9, 23.8. ppm. MS (APCI): m/z = 360/362 [M–
OBn]+. Anal. Calcd. for C19H23BBrNO7: C, 48.75; H, 4.95; N, 2.99; Br,
17.07. Found: C, 48.64; H, 4.76; N, 2.74; Br, 17.30.
1-(6-Methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)-2-oxohexyl
acetate (20). To a solution of bromide 10a (500 mg, 1.50 mmol) in
CH3CN (10 mL), KOAc (590 mg, 6.02 mmol) and small crystal of
18-crown-6 ether were added, and the mixture was refluxed for 6 h. After
cooling to rt, the resulting solution was filtered through a silica plug. The
filtrate was concentrated under reduce pressure. The title compound was
purified by recrystallization from EtOAc. Yield 390 mg (84%). White
crystalline solid, mp = 197–200 C. 1H NMR (400 MHz, DMSO-d6) δ 4.95
(s, 1H), 4.40 (d, J = 17.3 Hz, 1H), 4.26 (d, J = 17.1 Hz, 1H), 4.06 (d, J =
17.3 Hz, 1H), 4.03 (d, J = 17.1 Hz, 1H), 2.92 (s, 3H), 2.43 (t, J = 7.3 Hz,
2H), 2.07 (s, 3H), 1.45 (quint, J = 7.3 Hz, 2H), 1.25 (sext, J = 7.4 Hz, 2H),
0.86 (t, J = 7.3 Hz, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 206.1,
170.0, 168.6, 168.1, 73.8, 62.2, 62.1, 46.0, 38.4, 25.3, 21.6, 20.5, 13.8
ppm. MS (APCI): m/z = 314 [M+H]+. Anal. Calcd. for C13H20BNO7: C
49.87; H 6.44; N 4.47. Found: C 49.91; H 6.11; N 4.83.
2-(1-Bromo-2-(4-methoxyphenyl)-2-oxoethyl)-6-methyl-1,3,6,2-
dioxazaborocane-4,8-dione (10o). The compound was purified by
recrystallization from EtOAc. Yield 0.091 g (96%) from 0.095 g of 11o.
White crystalline solid, mp = 152–154 C. 1H NMR (500 MHz, DMSO-d6)
δ 8.02 (d, J = 9.0 Hz, 2H), 7.04 (d, J = 9.0 Hz, 2H), 5.20 (s, 1H), 4.36 (d,
J = 17.0 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.10 (d, J = 17.0 Hz, 1H),
4.08 (d, J = 17.3 Hz, 1H), 3.85 (s, 3H), 3.07 (s, 3H) ppm. 13C NMR (126
MHz, DMSO-d6) δ 194.2, 168.3, 168.3, 163.4, 131.5, 128.2, 113.9, 63.0,
62.9, 55.6, 46.5, 38.1 ppm. MS (APCI): m/z = 384/386 [M+H]+. Anal.
Calcd. for C14H15BBrNO6: C 43.79; H 3.94; N 3.65; Br 20.81. Found: C
43.62; H 4.05; N 3.27; Br 21.20.
2-(1-Azido-2-oxohexyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione
(21). To a solution of bromide 10a (300 mg, 0.898 mmol) in DMSO (2
mL), NaN3 (0.18 g, 2.77 mmol) was added and the mixture was stirred at
rt overnight. The reaction was quenched with H2O (20 mL) and extracted
with EtOAc (2×20 mL). The combined organic layers were washed with
half-saturated aq. NaCl (2×20 mL), dried over anhydrous Na2SO4 and
concentrated in vacuo. Yield 180 mg (67%). Yellow solid, mp = 89–91 C
(dec). 1H NMR (400 MHz, DMSO-d6) δ 4.38 (d, J = 17.2 Hz, 1H), 4.24 (d,
J = 17.0 Hz, 1H), 4.19 (s, 1H), 4.06 (d, J = 17.2 Hz, 2H), 3.01 (s, 3H),
2.64 – 2.40 (m, 2H), 1.48 (quint, J = 7.3 Hz, 2H), 1.26 (sext, J = 7.2 Hz,
2H), 0.86 (t, J = 7.3 Hz, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 207.8,
168.4, 167.8, 62.4, 62.2, 61.5, 46.2, 39.9, 25.5, 21.7, 13.8 ppm. MS
(APCI): m/z = 269 [M–N2+H]+. Anal. Calcd. for C11H17BN4O5: C 44.62; H
5.79; N 18.92. Found: C 44.94; H 6.04; N 19.23.
2-(Bromo(tetrahydrofuran-2-yl)methyl)-6-methyl-1,3,6,2-dioxazabo-
rocane-4,8-dione (17g). (E)-2-(5-(Benzyloxy)pent-1-en-1-yl)-6-methyl-
1,3,6,2-dioxazaborocane-4,8-dione (9g) (0.380 g, 1.15 mmol) was
subjected to hydroxybromination by the general procedure for the
preparation of the compounds 11. Product 17g was obtained with 94%
yield (0.355 g, 90–95% purity) in a mixture with -bromoketone 10g. The
analytical sample was isolated from the mixture by repeated
recrystallization from EtOAc. White crystalline solid, mp = 208–211 C.
1H NMR (400 MHz, DMSO-d6) δ 4.32 (d, J = 17.2 Hz, 1H), 4.25 (d, J =
2-(2-Amino-4-butylthiazol-5-yl)-6-methyl-1,3,6,2-dioxazaborocane-
4,8-dione (22). To a solution of 2-(1-bromo-2-oxohexyl)-6-methyl-1,3,6,2-
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10.1002/ejoc.202000078
European Journal of Organic Chemistry
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dioxazaborocane-4,8-dione (10a) (450 mg, 1.35 mmol) in CH3CN (10
mL), thiourea (120 mg, 1.62 mmol) and NEt3 (0.23 mL, 1.62 mmol) were
added, and the mixture was refluxed for 3 days. The resulting mixture
was concentrated under reduced pressure and H2O (20 mL) was added
to the residue. The compound was extracted with EtOAc (2×20 mL). The
combined organic layers were dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude product was purified by
recrystallization from EtOAc. Yield 360 mg (86%). Beige solid solid, mp =
219–220 C. 1H NMR (500 MHz, DMSO-d6) δ 7.33 (s, 1H), 6.18 (s, 1H),
4.31 (d, J = 16.9 Hz, 2H), 4.09 (d, J = 16.8 Hz, 2H), 2.80 (s, 3H), 2.36 (t,
J = 7.5 Hz, 2H), 1.48 (quint, J = 7.6 Hz, 2H), 1.24 (sext, J = 7.4 Hz, 2H),
0.86 (t, J = 7.3 Hz, 3H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 168.5,
167.3, 152.1, 63.0, 45.6, 30.8, 30.3, 21.7, 13.7 ppm (the boron-caring C-
5 signal was not registered due to its low intensity). MS (APCI): m/z =
312 [M+H]+. Anal. Calcd. for C12H18BN3O4S: C 46.32; H 5.83; N 13.50; S
10.30. Found: C 46.56; H 5.89; N 13.69; S 10.40.
Keywords: MIDA boronate • boron • ketone • bromide • building
blocks
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(500 MHz, DMSO-d6) δ 7.92 (d, J = 7.0 Hz, 2H), 7.52 – 7.42 (m, 3H),
4.42 (d, J = 17.4 Hz, 2H), 4.19 (d, J = 17.4 Hz, 2H), 2.73 – 2.65 (m, 5H),
1.68 (quint, J = 7.7 Hz, 2H), 1.34 (sext, J = 7.4 Hz, 2H), 0.90 (t, J = 7.4
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and molononitrile (180 mg, 2.70 mmol) in CH3CN (9 mL), NHEt2 (0.28 mL,
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6.99 (s, 2H), 4.30 (d, J = 17.2 Hz, 2H), 4.00 (d, J = 17.2 Hz, 2H), 2.70 (s,
3H), 2.41 (t, J = 7.6 Hz, 2H), 1.42 (quint, J = 7.5 Hz, 2H), 1.22 (sext, J =
7.3 Hz, 2H), 0.83 (t, J = 7.4 Hz, 3H) ppm. 13C NMR (151 MHz, DMSO-d6)
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Acknowledgments
The work was funded by Enamine Ltd. O.O.G. and Z.V.V. were
also funded by Ministry of Education and Science of Ukraine
(Grants No. 19BF037-03 and 19BF037-06, respectively). The
authors thank Prof. Andrey A. Tolmachev for his encouragement
and support, and Dr. Andriy V. Tymtsunik for helpful discussions
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10.1002/ejoc.202000078
European Journal of Organic Chemistry
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000078
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
MIDA boronates
Yevhen M. Ivon, Yuliya O. Kuchkovska,
Zoya V. Voitenko, Oleksandr O.
Grygorenko *
Page No. – Page No.
Preparation of -boryl--bromoketones from alkenyl MIDA boronates bearing
functionalized aliphatic derivatives is described. 10 examples of the target
trifunctional boronate-containing derivatives were obtained in up to 94% yield over
two steps.
Aliphatic -Boryl--bromoketones:
Synthesis and Reactivity
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