The Boron-Wittig Olefination of Aldehydes and Ketones with Bis[(pinacolato)boryl]methane: an Extended Reaction Scope

Article abstract of DOI:10.1002/ejoc.201900648

Preparation of 2,2-disubstituted and 2-monosubstituted alkenylboronic acid esters from aliphatic and aromatic ketones and aldehydes by the boron-Wittig olefination with bis[(pinacolato)boryl]methane was examined and applied on the multigram scale. The influence of the substrate steric and electronic features on the overall efficiency and stereochemical outcome of the reaction was studied. Additionally, a series of diversely functionalized (hetera)cycloalkylidenemethyl and (hetera)cycloalkyl boronic acid-derived building blocks was synthesized.

Full text of DOI:10.1002/ejoc.201900648

A Journal of
Accepted Article
Title: The boron-Wittig olefination of aldehydes and ketones with
bis[(pinacolato)boryl]methane: an extended reaction scope
Authors: Maksym Kovalenko, Dmytro V. Yarmoliuk, Dmytro Serhiichuk,
Daria Chernenko, Vladyslav Smyrnov, Artur Breslavskyi,
Oleksandr V. Hryshchuk, Ihor Kleban, Yuliya Rassukana,
Andriy V. Tymtsunik, Andrey A. Tolmachev, Yuliya O.
Kuchkovska, and Oleksandr O Grygorenko
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900648
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900648
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10.1002/ejoc.201900648
European Journal of Organic Chemistry
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The boron-Wittig olefination of aldehydes and ketones with
bis[(pinacolato)boryl]methane: an extended reaction scope
Maksym Kovalenko,[a] Dmytro V. Yarmoliuk,[a,b] Dmytro Serhiichuk,[a] Daria Chernenko,[a,d] Vladyslav
Smyrnov,[a,b] Artur Breslavskyi,[a] Oleksandr V. Hryshchuk,[a,b] Ihor Kleban,[a,c] Dr. Yuliya Rassukana,[c,d]
Dr. Andriy V. Tymtsunik,[a,d] Prof. Dr. Andrey A. Tolmachev,[a,b] Yuliya O. Kuchkovska[a,b] and
Dr. Oleksandr O. Grygorenko*[a,b]
Abstract: Preparation of 2,2-disubstituted and 2-monosubstituted
alkenylboronic acid esters from aliphatic and aromatic ketones and
aldehydes by the boron-Wittig olefination with bis[(pinacolato)boryl]-
methane was examined and applied on the multigram scale. The
influence of substrate steric and electronic features on the overall
efficiency and stereochemical outcome of the reaction was studied.
lead-oriented synthesis.[10]
Additionally,
a series of diversely functionalized (hetera)cyclo-
alkylidenemethyl and (hetera)cycloalkyl boronic acid-derived building
blocks was synthesized.
Introduction
The Suzuki – Miyaura cross-coupling of boronic acid derivatives
and organic halides became one of the top reactions in organic
and medicinal chemist`s toolbox.[1,2] The rapid advancement of
this method resulted in its efficient application for the late-stage
modification of biologically active substrates and construction of
combinatorial libraries.[3–6] However, the overuse of arylhalides
and arylboronic coupling reagents became one of the reasons
behind the prevalence of linear and flattened structures in the
compound collections, and, consequently, resulted in under-
representation of the three-dimensional chemical space in drug
discovery projects.[1,7] One of the recent trends in the field of
organoboron reagents and C–C bond-forming reactions using
them is related to the shift from aromatic compounds towards
cyclic sp3-enriched structures,[8,9] which comply with criteria of
[a]
Maksym Kovalenko, Dmytro V. Yarmoliuk, Dmytro Serhiichuk, Daria
Chernenko, Vladyslav Smyrnov, Artur Breslavskyi, Oleksandr V.
Hryshchuk, Ihor Kleban, Dr. Andriy V. Tymtsunik, Prof. Dr. Andrey
A. Tolmachev, Yuliya O. Kuchkovska, Dr. Oleksandr O. Grygorenko
Enamine Ltd. (www.enamine.net)
Scheme 1. Boron-Wittig reactions with gem-diborylalkanes.
Chervonotkatska Street 78, Kyiv 02094, Ukraine
Although numerous methods for the synthesis of alkyl- and
alkenylboronates are known in the literature,[11] some recent
approaches may provide more efficient alternatives and expand
the scope of suitable substrates.[12] One of these new
opportunities is application of gem-diborylalkanes – stable,
accessible, and convenient reagents for various C–C bond-
forming reactions.[13,14] In particular, their reaction with carbonyl
compounds has attracted much attention over the past decade
(Scheme 1).[15–20] In contrast to the classical boron-Wittig
reaction, which involves monoborylated derivatives and
resembles Wittig and Peterson olefinations,[21] transformations
of gem-diborylated compounds remains far from being studied
comprehensively. This method was first applied by Matteson
[b]
Dmytro V. Yarmoliuk, Vladyslav Smyrnov, Oleksandr V. Hryshchuk,
Ihor Kleban, Prof. Dr. Andrey A. Tolmachev, Yuliya O. Kuchkovska,
Dr. Oleksandr O. Grygorenko
Taras Shevchenko National University of Kyiv
Volodymyrska Street 60, Kyiv 01601, Ukraine
E-mail: gregor@univ.kiev.ua
URL: https://orcid.org/0000-0002-6036-5859
Ihor Kleban, Dr. Yuliya Rassukana
Institute of Organic Chemistry, National Academy of Sciences of
Ukraine, Murmanska Street 5, Kyiv 02660, Ukraine
Daria Chernenko, Dr. Yuliya Rassukana, Dr. Andriy V. Tymtsunik
National Technical University of Ukraine ‘Igor Sikorsky Kyiv
Polytechnic Institute’, Prospect Peremogy 37, Kyiv 03056, Ukraine
[c]
[d]
Supporting information for this article is given via a link at the end of
the document.
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Figure 1. (Hetera)cycloalkylidenemethyl boronates 3a–p obtained in this work.
and
co-workers
to
hardly
accessible
tris-
and
Our initial efforts were put into the synthesis of a series of
tetrakis(dialkoxyboryl)methanes in 1970s,[22–25] and later – to
ethyleneglycol- and 1,3-propanediol-protected gem-diborylalka-
nes lacking sufficient hydrolytical stability.[26]
(hetera)cycloalkylidenemethyl boronates 3a–r (Table 1). A
slightly modified procedure developed by Morken and co-
workers[18] was used. Typically, a solution of 1.5–3-fold excess
of the starting ketone was added dropwise to the anion of 1
(generated by action of LiTMP) in THF at –78 C, the mixture
was warmed to rt overnight and then subjected to work-up.
Under these conditions, non-functionalized cycloalkanones 4a,
4b, and 4c led to the corresponding cycloalkylidenemethyl
boronates 3a–c in 82–85% yield. However, in the case of cyclic
ketones 4d–r, the yields of the corresponding olefins were lower
due to the steric and/or electronic effects of the functional
groups present. In particular, the carboxylates 3d–f were
obtained in 35–90% yield, the Boc-protected endocyclic amines
3g–j – in 48–80% yield, and the cyclic ethers 3k–m – in 23–65%
yield. The lowest yield observed for the oxetane derivative 3k
(23%) was related to limited stability of the corresponding boron
pinacolate 5k; therefore, the product was isolated as the
trifluoroborate 3k instead (Scheme 2). Derivatives 3n and 3o
bearing sulfone and cyclic ketal moieties were synthesized in
67% and 79% yields, respectively. Additionally, this reaction was
evaluated for bicyclic ketones 4p and 4r. The derivative 3p was
obtained in 71% yield, whereas synthesis of the compound 3r
could not be accomplished due to substantial steric hindrance
from the methylene bridge at the α position to the carbonyl group,
even if a 10-fold excess of the deprotonated reagent 1 was used.
It should be noted that of the (hetera)cycloalkylidenemethyl-
boronates 3a–p, only 3b and 3c were reported in the
literature.[27,28]
The preparative versions of the method were reported only in
the last decade (Scheme 1). Methods A, B, and D included
synthesis of tetrasubstituted alkenes by boron-Wittig reaction of
alkyl-, benzyl-, phenyl- and TMS-substituted bis[(pinacolato)-
boryl]methane derivatives with ketones.[15–17,19] In reactions with
aldehydes, both unsubstituted and monosubstituted bis[(pina-
colato)boryl]methane reagents were studied (C), which allowed
for the preparation of 1,2-disubstituted and 1,1,2-trisubstituted
derivatives, respectively.[18] The only work describing boron-
Wittig reaction of the parent bis[(pinacolato)boryl]methane (1)
with ketones was published by Pattison and co-workers (E);[20]
however, the corresponding products 2 were not isolated and
characterized. Meanwhile, ketones might be more accessible
starting materials for the preparation of 2 as compared to those
used in other approaches, e.g. alkynes (for hydroboration),
alkenylhalides (for transition metal-catalyzed coupling with
diboryl reagents) or terminal alkenes (for methatesis with
vinylboronic reagents).
This opportunity urged us to extend the utility of the boron-Wittig
reaction for the preparation of 1,2,2-trisubstituted alkene
derivatives 2 using commercially available bis[(pinacolato)bor-
yl]methane (1). Because the previous reports studied this
method only for non-functionalized carbonyl compounds (except
the work of Pattison and co-workers[20] describing reactions of
ketones bearing additional heteroatoms), in this work, we have
focused mainly on various functionalized substrates. A special
subset of boronic acid derivatives obtained in this work included
sp3-enriched
(hetera)cycloalkylidenemethylboronates
3a–p
(Figure 1), as well as their hydrogenated and deprotected
derivatives, which represent promising building-blocks for
organic and medicinal chemistry. Special attention was also paid
to stereochemical outcome of the boron-Wittig reaction in the
case of non-symmetrical carbonyl compounds.
Scheme 2. Synthesis of the compound 3k.
Results and Discussion
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The stereochemical outcome of the boron-Wittig reaction applied
to unsymmetrical ketones 4e, 4h, 4i, and 4l is worth special
attention. It was found that products 3e, 3i, and 3l were obtained
with high diastereoselectivity, whereas the compound 3h was
formed as ca. 1:1 mixture of E- and Z-isomers. A possible
explanation of Z-stereoselectivity observed for the three out of
four products might be related to coordination of the
pinacolatoboron moiety to the corresponding oxygen-containing
groups in the transitions 6e, 6i, and 6l (Scheme 3). In the case
of 6h, such coordination is not possible due to the nearly planar
geometry of carbamate moiety, and hence the remote location of
CO2t-Bu group from the Bpin fragment. It should be noted that
similar transformations of acyclic substrates where the
stereoselectivity was induced by CH2NMe2 or CH2OMe moieties
were reported previously.[15]
Table 1. Synthesis of (hetera)cycloalkylidenemethyl boronates 3a–r.
Yield, %
(E : Z ratio)
Entry
1
R1 / R2
4
3
4a
3a
84
82
2
3
4
4b
4c
4d
3b
3c
3d
85
90
63
(0 : 100)
5
6
4e
4f
3e
3f
35
72
7
8
4g
4h
3g
3h
48
(50 : 50)
50
(0 : 100)
9
4i
3i
10
11
12
4j
4k
4l
3j
3k
3l
80
23
74
(5 : 95)
13
14
4m
4n
3m
3n
65
67
Scheme 3. Structures of 6e, 6h, 6i, and 6l
15
4o
3o
79
Stereoselectivity of the boron-Wittig olefination was additionally
studied for reaction of ketones 4i and 4l with substituted
bis[(pinacolato)boryl]methane 7. Reagent 7 was synthesized by
a previously reported procedure.[29] As a result, compound 8i
was obtained as a single isomer (E)-8i, with carbamate and Bpin
moieties at the same side of the double bond (48% yield,
Scheme 4). Similarly, reaction of 4l with 7 also led to a single
isomer (E)-8l. However, the purification of the resulting mixture
16
17
4p
4r
3p
3r
71
0
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10.1002/ejoc.201900648
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containing 8l was challenging, and the configuration of the
compound was proven by NOE experiment with a crude mixture.
unreactive under similar conditions, whereas increasing the
amount of deprotonated reagent 1 up to 8-fold excess led to
complex mixtures of products.
Diastereomeric ratios of the products were determined both in
purified samples and in the crude mixtures prior to
chromatography. It was found that in the case of ketones 9a and
9b, the products were obtained as nearly equimolar mixture of
E/Z stereoisomers. For ketones 9c and 9d bearing electron-
withdrawing
pyridinyl
and
p-nitrophenyl
substituents,
respectively, formation of E-isomers was favoured over Z-iso-
mers. However, an opposite stereochemical outcome was
noticed in the case of ketones 9e and 9f with p-methoxyphenyl
and o-chlorophenyl groups – the Z-isomers were identified as
the major products. In order to check whether electronic
properties of the aryl substituents define the stereochemistry of
the boron-Wittig reaction, the same transformation was carried
out with ketone 9i bearing both electron-withdrawing 4-pyridyl
and electron-donating p-methoxyphenyl substituents. In this
case, the E- and Z-isomers were formed in nearly equal ratio.
Besides the aforementioned ketones, the boron-Wittig
olefination was also carried out with 2,2,2-trifluoroacetophenone
9j, which gave (E)-10j and (Z)-10j as ca. 2 : 3 mixture in 56%
yield.
Scheme 4. Preparation of 8i and 8l.
Apart from the ketones 4a–r, the boron-Wittig reaction with
anion of 1 was carried out with non-symmetric (hetero)aromatic
and (hetero)aliphatic carbonyl compounds 9a–r (Table 2).
(Het)aryl methyl ketones 9a–f gave the corresponding
alkenylboronates in 43–61% yield. Thiazole- and pyrazine-
derived ketones 9g and 9h, respectively, appeared to be
Table 2. Synthesis of 10a–r.
E : Z ratio
for isolated product
E : Z ratio
for crude mixture
Entry
1
R1
R2
9
10
Yield, %
43
CH3
9a
10a
50 : 50
58 : 42
60 : 40
44 : 56
2
CH3
9b
10b
50
3
4
5
CH3
CH3
CH3
9c
9d
9e
10c
10d
10e
61
43
50
99 : 1
80 : 20
25 : 75
90 : 10
83 : 17
22 : 78
6
7
CH3
CH3
9f
10f
48
0
0 : 100
13 : 87
9g
10g
–
–
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8
CH3
9h
9i
10h
10i
10j
10k
10l
0
–
–
9
45
56
62
42
52 : 48
40 : 60
100 : 0
100 : 0
43 : 57
40 : 60
100 : 0
ND
10
11
12
CF3
H
9j
9k
9l
H
13
H
9m
10m
42
100 : 0
ND
9n
(X = TMS)
10n
(X = H)
37 (over 2
steps)
14
15
H
97 : 3
ND
CH3
9o
9p
10o
10p
63
78
84 : 16
76 : 24
16
CH3
4 : 96
ND
17
18
H
H
9q
9r
10q
10r
55
52
85 : 15
90 : 10
ND
ND
Unlike aryl ketones 9a–f, aryl aldehydes 9k–m were converted
to the corresponding (E)-alkenes 10k–m, isolated as single
stereoisomers, with 42–62% yield; this result is in accordance
with the literature data.[18] Alkenylboronate 10n bearing a free
phenolic OH group was obtained by sequential boron-Wittig
reaction of aldehyde 9n, and TMS-deprotection with 37% overall
yield (Scheme 5).
In the previous works, stereoselectivity of the boron-Wittig
reaction was rationalized by formation of cyclic intermediates of
the type 11, where lithium cation was coordinated to the oxygen
atom in the pinacol residue, and of type 12 (Scheme 6, A).[15,16]
The DFT computational study proposed that in the case of
monosubstituted bis[(pinacolato)boryl]methane reagents, forma-
tion of the six-membered intermediates 11 was more consistent
with experimental results than four-membered adducts of the
type 12.[16] Nevertheless, because the formation of 1,2-
oxaboretanide complexes 12 by the boron-Wittig reaction was
confirmed by X-ray diffraction studies for analogous species with
B(Mes)2[30,31] and B(C6F5)[32] moieties, the latter reaction pathway
should not be completely omitted from the consideration. These
models provide straightforward explanation for the E-
stereoselectivity observed in the reactions of aldehydes 9k–n
and 1, since the corresponding conformations 13a are
favourable over 13b when R1 = H (Scheme 6, B). Their
application to ketones 9a–f becomes less explicit since the
Scheme 5. Synthesis of the compound 10n.
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10.1002/ejoc.201900648
European Journal of Organic Chemistry
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difference between the conformations 13a and 13b is not so
unambiguous. The precise steric and/or electronic factors
contributing to the prevalence of Z or E isomer in 10c–f remain
unclear.
the case of 10o, prevalent formation of E isomer was observed.
Z-Stereoselectivity observed in the case of 10p can be
addressed to coordination of one of the boron atoms in the
bis[(pinacolato)boryl]methane reagent to one of the oxygen
atoms in the ketone 9p side chain. It should be noted that such
stereochemical effect was previously observed only for
ketones;[15] its possibility for aliphatic aldehydes with hetero-
atom-containing substituents was not clear. In contrast to the
compound 10p, the formation of alkenes 10q and 10r (55% and
52%, respectively) was not affected by the aforementioned
effects to a significant extent. The content of the corresponding
Z isomers did not exceed 15%, so that the stereochemical
outcome of the reaction was mainly controlled by repulsion
between the aldehyde side chain and the Bpin moiety of 1.
Further transformations of the (hetera)cycloalkylidenemethyl
boronates obtained by the boron-Wittig olefination included
deprotection of the amino group, as well as the double bond
reduction (Table 3). In particular, treatment of 3h–j with HCl
afforded amines 14h–j as hydrochlorides in 95–97% yield
Alternatively, when hydrogenation of the compounds 3g–j was
carried out prior to the deprotection step, boron pinacolates
16g–j were obtained in 68–86% overall yields. The double bond
reduction in 3d and 3e afforded the corresponding cycloalkylme-
Scheme 6. Structures of 11–13.
In the case of saturated acyclic ketones, the target alkenes 10o
and 10p were obtained in 63% and 78% yields, respectively. In
Table 3. Synthesis of 14h–j, 15g–j, and 16g–j.
Entry
1
3
14
Yield, %
15
Yield, %
90
16
Yield, %
75
–
-
3g
3h
15g
15h
16g
16h
2
3
4
97
97
95
85
91
90
91
93
95
14h
3i
3j
14i
14j
15i
15j
16i
16j
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based on the spectral data for its derivative 14i. The assignment of
configurations of the compounds 10m and 10r was done on the basis of
3JH-H coupling constants, and was consistent with the results obtained for
10k,l and 10q, respectively. 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)).
thylboronates 17d and 17e in 91% and 99% yields, respectively
(Scheme 7).
General procedure for the synthesis of the compounds 3a–j, 3l–p,
10a–f, 10i–m, and 10o–r. 2,2,6,6-Tetramethylpiperidine (85.0 g, 0.60
mol) was dissolved in THF (1 L) and cooled to –30 °C under Ar
atmosphere. n-BuLi (240 mL of 2.5 M solution in hexane) was added
dropwise, and the reaction mixture was stirred at the same temperature
for 30 min. Next, the reaction was cooled to –78 °C, and a solution of
bis[(pinacolato)boryl]methane (1) (134 g, 0.50 mol) in THF (1 L) was
added dropwise. After stirring for 30 min, a solution of the indicated
amount of the corresponding ketone in THF (2 mL per 1 mmol) was
added dropwise at –78 °C. The reaction mixture was allowed to slowly
warm up to rt, and stirred overnight. The obtained mixture was then
cooled to 0 °C, and aq. NH4Cl (250 mL) was added dropwise. After
additional stirring for 1 h, the resulting mixture was filtered and the
solvent was rotary evaporated. H2O (300 mL) was added to the obtained
residue, and the aqueous layer was extracted with EtOAc (3×400 mL).
The combined organic phase was washed with brine (250 mL), dried
over the anhydrous Na2SO4 and concentrated under vacuum. The
Scheme 7. Synthesis of the compounds 17.
Conclusions
The scope of boron-Wittig reaction of 1,1-bis[(pinacolato)-
boryl]alkanes with aldehydes and ketones was significantly
extended by a number of functionalized carbonyl compounds,
and efficiency of this method was studied on the multigram scale. obtained crude product was purified by column chromatography (gradient
hexane – t-BuOMe as eluent).
Although steric factors had major influence on stereochemical
outcome for non-symmetric substrates (resulting in the
predominant formation of the corresponding E isomers), in some
cases it was outweighed by other factors. In particular,
coordination of one of the boron atoms of the Bpin moieties to
2-(Cyclobutylidenemethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(3a). Yield: 73.0 g (84%) from 120 g of 1 and 94.1 g of cyclobutanone
(4a); colourless liquid. 1H NMR (500 MHz, CDCl3) δ 5.07 (quint, J = 2.2
Hz, 1H), 2.90 (t, J = 7.4 Hz, 2H), 2.76 (t, J = 7.8 Hz, 2H), 1.94 (quint, J =
the heteroatom-containing substituents was found to be signify-
7.9 Hz, 2H), 1.23 (s, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 170.0,
can not only for acyclic compounds, but also for conformationally
restricted cyclic ketones. In the case of functionalized aldehydes,
this effect provided only minor contribution and led to less than
15% of the expected Z-isomers. The proposed approach was
successfully applied for the preparation of sp3-enriched
(hetera)cycloalkylidenemethylboronates, as well as their fully
saturated derivatives, which can be considered as advanced
building blocks for organic synthesis and drug discovery, in
particular, for combinatorial chemistry based on the Suzuki–
Miyaura cross-couplings.
108.8, 82.5, 34.8, 34.3, 24.8, 16.6 ppm. MS (EI): m/z = 194 [M]+. Anal.
Calcd. for C11H19BO2: C 68.08; H 9.87. Found: C 67.70; H 10.05.
2-(Cyclopentylidenemethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(3b).[27,28] Yield: 76.4
g (82%) from 120 g of 1 and 113 g of
cyclopentanone (4b); yellow solid, mp 40–43 °C. 1H NMR (500 MHz,
CDCl3) δ 5.27 (s, 1H), 2.52 (t, J = 7.1 Hz, 2H), 2.36 (t, J = 7.1 Hz, 2H),
1.69 (quint, J = 6.9 Hz, 2H), 1.62 (quint, J = 6.9 Hz, 2H), 1.25 (s, 12H)
ppm. 13C NMR (126 MHz, CDCl3) δ 171.4, 107.5, 82.0, 36.5, 32.8, 26.3,
25.4, 24.4 ppm. MS (EI): m/z = 208 [M]+. Anal. Calcd. for C12H21BO2: C
69.26; H 10.17. Found: C 68.86; H 10.15.
2-(Cyclohexylidenemethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(3c).[27,28] Yield: 84.5
g (85%) from 120 g of 1 and 132 g of
Experimental Section
cyclohexanone (4c); colourless oil. 1H NMR (400 MHz, CDCl3) δ 5.00 (s,
1H), 2.50 (t, J = 5.6 Hz, 2H), 2.18 (t, J = 5.6 Hz, 2H), 1.62 – 1.49 (m, 6H),
1.24 (s, 12H) ppm. 13C NMR (101 MHz, CDCl3) δ 167.1, 110.0, 82.6,
40.2, 33.3, 28.8, 28.6, 26.5, 25.0 ppm. MS (EI): m/z = 222 [M]+. Anal.
Calcd. for C13H23BO2: C 70.29; H 10.44. Found: C 70.64; H 10.19.
General. The solvents were purified according to the standard
procedures.[33] Bis[(pinacolato)boryl]methane was prepared by the
method reported in the literature.[34] All other starting materials were
obtained from commercial sources. 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 downfield from TMS as an internal standard. The assignment of
configurations of the compounds 3e, 3l, 10a–f, 10i–l, 10n–q, 14i was
done by NOESY experiments. The configuration of 3i was assigned
Methyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-
cyclobutanecarboxylate (3d). Yield: 84.7 g (90%) from 100 g of 1 and
71.7 g of methyl 3-oxocyclobutanecarboxylate (4d); colourless liquid. H
1
NMR (500 MHz, CDCl3) δ 5.14 (s, 1H), 3.65 (s, 3H), 3.20 – 3.00 (m, 4H),
2.96 – 2.87 (m, 1H), 1.19 (s, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ
175.5, 162.8, 110.9, 82.6, 51.7, 37.9, 37.8, 33.0, 24.84, 24.78 ppm. 11B
NMR (160 MHz, CDCl3): δ 29.4 ppm. MS (EI): m/z = 252 [M]+. Anal.
Calcd. for C13H21BO4: C 61.93; H 8.40. Found: C 62.19; H 8.45.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900648
European Journal of Organic Chemistry
FULL PAPER
(Z)-Ethyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-
cyclopentanecarboxylate (3e). Yield: 65.9 g (63%) from 100 g of 1 and
87.4 g of ethyl 3-oxocyclopentanecarboxylate (4e); yellow liquid. 1H NMR
(500 MHz, CDCl3) δ 5.23 (s, 1H), 4.10 (q, J = 7.1 Hz, 2H), 2.92 (dd, J =
17.8, 8.0 Hz, 1H), 2.79 (quint, J = 8.4 Hz, 1H), 2.64 (dd, J = 17.9, 8.8 Hz,
1H), 2.56 – 2.46 (m, 1H), 2.41 – 2.29 (m, 1H), 2.01 – 1.90 (m, 1H), 1.85 –
1.74 (m, 1H), 1.27 – 1.21 (m, 3H), 1.20 (s, 12H) ppm. 13C NMR (126 MHz,
CDCl3): δ 175.5, 168.2, 109.6, 82.6, 60.3, 44.5, 36.6, 36.0, 29.4, 24.8,
14.2 ppm. 11B NMR (160 MHz, CDCl3): δ 29.7 ppm. MS (EI): m/z = 280
[M]+. Anal. Calcd. for C15H25BO4: C 64.31; H 8.99. Found: C 63.97; H
8.63.
45.7, 45.1, 38.8, 32.7, 28.6, 25.0 ppm. MS (EI): m/z = 323 [M]+. Anal.
Calcd. for C17H30BNO4: C 63.17; H 9.36; N 4.33. Found: C 62.78; H 9.06;
N 4.08.
2-((Dihydrofuran-3(2H)-ylidene)methyl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (3l). Yield: 46.4 g (74%) from 80.0 g of 1 and 51.4 g of
dihydrofuran-3(2H)-one (4l); colourless solid, mp 60–63 °C. The
compound was obtained as ca. 5:95 mixture of E/Z stereoisomers. The
assigned resonance signals of the major Z-isomer are given. 1H NMR
(500 MHz, CDCl3) δ 5.34 (quint, J = 2.1 Hz, 1H), 4.42 (s, 2H), 3.83 (t, J =
6.6 Hz, 2H), 2.60 (t, J = 6.6 Hz, 2H), 1.21 (s, 12H) ppm. 13C NMR (126
MHz, CDCl3) δ 165.5, 107.8, 83.1, 71.6, 67.7, 36.1, 24.9 ppm. MS (EI):
m/z = 210 [M]+. Anal. Calcd. for C11H19BO3: C 62.89; H 9.12. Found: C
62.59; H 8.75.
Ethyl
4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-
cyclohexanecarboxylate (3f). Yield: 30.7 g (35%) from 80.0 g of 1 and
152 g of ethyl 4-oxocyclohexanecarboxylate (4f); yellow liquid. 1H NMR
(400 MHz, CDCl3) δ 5.03 (s, 1H), 4.08 (q, J = 7.1 Hz, 2H), 3.13 – 3.02 (m,
1H), 2.44 (tt, J = 11.0, 3.7 Hz, 1H), 2.31 (dt, J = 13.4, 4.3 Hz, 1H), 2.15
(td, J = 12.8, 4.4 Hz, 1H), 2.08 – 1.93 (m, 3H), 1.59 (qd, J = 12.5, 4.9 Hz,
2H), 1.21 (s, 12H), 1.20 – 1.18 (m, 3H) ppm. 13C NMR (101 MHz, CDCl3)
δ 175.3, 164.0, 111.6, 82.6, 60.1, 42.6, 38.2, 31.3, 30.4, 30.2, 24.8, 24.7,
14.2 ppm. 11B NMR (160 MHz, CDCl3): δ 29.9 ppm. MS (APCI): m/z =
295 [M+H]+. Anal. Calcd. for C16H27BO4: C 65.32; H 9.25. Found: C
65.24; H 9.01.
2-((Dihydro-2H-pyran-4(3H)-ylidene)methyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (3m). Yield: 43.5 g (65%) from 80.0 g of 1 and 59.8
g of dihydro-2H-pyran-4(3H)-one (4m); colourless oil. 1H NMR (400 MHz,
CDCl3) δ 5.09 (s, 1H), 3.69 (q, J = 5.9 Hz, 4H), 2.66 (t, J = 5.6 Hz, 2H),
2.30 (t, J = 5.6 Hz, 2H), 1.24 (s, 12H) ppm. 13C NMR (101 MHz, CDCl3) δ
160.6, 111.8, 82.7, 69.4, 69.3, 39.8, 34.1, 24.8 ppm. MS (EI): m/z = 224
[M]+. Anal. Calcd. for C12H21BO3: C 64.31; H 9.45. Found: C 64.65; H
9.28.
tert-Butyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
4-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-
yl)methylene)azetidine-1-carboxylate (3g). Yield: 95.2 g (72%) from
120 g of 1 and 230 g of tert-butyl 3-oxoazetidine-1-carboxylate (4g);
colourless oil. H NMR (500 MHz, CDCl3) δ 5.24 (quint, J = 2.4 Hz, 1H),
4.55 – 4.52 (m, 2H), 4.44 – 4.41 (m, 2H), 1.37 (s, 9H), 1.16 (s, 12H) ppm.
13C NMR (126 MHz, CDCl3) δ 156.3, 154.8, 110.9, 83.1, 79.4, 60.6, 59.8,
28.3, 24.7 ppm. MS (APCI): m/z = 196 [M–C(O)OC(CH3)3+H]+. Anal.
Calcd. For C15H26BNO4: C 61.03; H 8.88; N 4.75. Found: C 61.38; H
8.66; N 4.56.
yl)methylene)tetrahydro-2H-thiopyran 1,1-dioxide (3n). Yield: 54.4 g
(67%) from 80.0 g of 1 and 66.3 g of dihydro-2H-thiopyran-4(3H)-one
1,1-dioxide (4n); colourless solid, mp 155–157 °C. 1H NMR (500 MHz,
CDCl3) δ 5.29 (s, 1H), 3.11 – 2.99 (m, 6H), 2.77 – 2.70 (m, 2H), 1.22 (s,
12H) ppm. 13C NMR (126 MHz, CDCl3) δ 155.1, 118.8, 83.3, 52.5, 52.3,
36.4, 29.2, 24.8 ppm. 11B NMR (160 MHz, CDCl3): δ 29.0 ppm. MS (EI):
m/z = 272 [M]+. Anal. Calcd. for C12H21BO4S: C 52.96; H 7.78; S 11.78.
Found: C 53.29; H 7.52; S 12.01.
1
tert-Butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-
pyrrolidine-1-carboxylate (3h). Yield: 66.5 g (48%) from 120 g of 1 and
124 g of tert-butyl 3-oxopyrrolidine-1-carboxylate (4h); yellow liquid. The
compound was obtained as ca. 1:1 mixture of E/Z isomers, and existed
2-(1,4-Dioxaspiro[4.5]decan-8-ylidenemethyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (3o). Yield: 66.1 g (79%) from 80.0 g of 1 and 69.9
g of 1,4-dioxaspiro[4.5]decan-8-one (4o); colourless oil. 1H NMR (500
MHz, CDCl3) δ 5.09 – 5.04 (m, 1H), 3.93 (s, 4H), 2.68 – 2.61 (m, 2H),
2.36 – 2.30 (m, 2H), 1.74 – 1.65 (m, 4H), 1.22 (s, 12H) ppm. 13C NMR
(126 MHz, CDCl3) δ 163.6, 112.0, 108.4, 82.6, 64.3, 36.6, 36.0, 35.7,
29.4, 24.8 ppm. 11B NMR (160 MHz, CDCl3): δ 29.7 ppm. MS (EI): m/z =
280 [M]+. Anal. Calcd. for C15H25BO4: C 64.31; H 8.99. Found: C 64.24; H
8.74.
1
as ca. 2:1 mixture of rotamers. H NMR (500 MHz, CDCl3) δ 5.34 – 5.30
(m, 0.5H), 5.30 – 5.26 (m, 0.5H), 4.24 – 4.08 (m, 1H), 4.04 – 3.93 (m,
1H), 3.55 – 3.39 (m, 2H), 2.82 (t, J = 7.5 Hz, 1H), 2.64 (t, J = 7.5 Hz, 1H),
1.46 (s, 4.5H), 1.44 (s, 4.5H), 1.26 – 1.19 (m, 12H) ppm. 13C NMR (126
MHz, CDCl3) δ 162.9 and 162.1, 154.6 and 154.6, 110.0, 83.2 and 83.1,
79.4 and 79.3, 52.9 and 50.6, 46.2 and 45.8 and 45.0 and 44.5, 35.4 and
34.7 and 32.0 and 31.4, 28.6, 24.98 and 24.96 ppm. MS (APCI): m/z =
209 [M–C(O)OC(CH3)3+H]+. Anal. Calcd. For C16H28BNO4: C 62.15; H
9.13; N 4.53. Found: C 62.13; H 9.35; N 4.93.
(1R,5S)-tert-Butyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)methylene)-8-azabicyclo[3.2.1]octane-8-carboxylate (3p). Yield:
74.0 g (71%) from 80.0 g of 1 and 101 g of (1R,5S)-tert-butyl 3-oxo-8-
azabicyclo[3.2.1]octane-8-carboxylate (4p); colourless oil. The compound
existed as ca. 1:1 mixture of rotamers. 1H NMR (500 MHz, CDCl3) δ 5.21
(s, 1H), 4.30 – 4.21 (m, 1H), 4.20 – 4.11 (m, 1H), 2.98 (d, J = 14.3 Hz,
1H), 2.70 – 2.48 (m, 0.5H), 2.40 – 2.23 (m, 0.5H), 2.06 (d, J = 14.0 Hz,
1H), 1.86 – 1.79 (m, 2H), 1.58 – 1.45 (m, 3H), 1.44 (s, 9H), 1.24 – 1.19
(m, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 159.1, 153.7, 117.5, 82.8,
79.3, 54.9 and 54.6, 54.3 and 54.0, 45.3 and 44.7, 39.5 and 38.7, 28.59,
28.58, 28.0, 25.0 and 24.7 ppm. 11B NMR (160 MHz, CDCl3): δ 29.4 ppm.
MS (EI): m/z = 249 [M–C(O)OC(CH3)3+H]+. Anal. Calcd. for C19H32BNO4:
C 65.34; H 9.23; N 4.01. Found: C 65.45; H 8.90; N 4.17.
(Z)-tert-Butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methy-
lene)piperidine-1-carboxylate (3i). Yield: 72.4 g (50%) from 120 g of 1
and 134 g of tert-butyl 3-oxopiperidine-1-carboxylate (4i); yellow oil. 1H
NMR (400 MHz, CDCl3) δ 5.10 (s, 1H), 4.26 (s, 2H), 3.40 (t, J = 5.6 Hz,
2H), 2.31 – 2.25 (m, 2H), 1.65 – 1.56 (m, 2H), 1.43 (s, 9H), 1.22 (s, 12H)
ppm. 13C NMR (101 MHz, CDCl3) δ 157.8, 154.9, 113.9, 83.0, 79.3, 48.1,
43.4, 36.7, 28.6, 25.9, 24.9 ppm. MS (EI): m/z = 323 [M]+, 266 [M–
C(CH3)3]+, 209 [M–CO2–(CH3)2CCH2]+. Anal. Calcd. For C17H30BNO4: C
63.17; H 9.36; N 4.33. Found: C 62.85; H 9.45; N 4.59.
tert-Butyl 4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-
piperidine-1-carboxylate (3j). Yield: 96.5 g (80%) from 100 g of 1 and
112 g of tert-butyl 4-oxopiperidine-1-carboxylate (4j); colourless solid, mp
110–112 °C. 1H NMR (400 MHz, CDCl3) δ 5.14 (s, 1H), 3.48 – 3.39 (m,
4H), 2.59 (t, J = 5.9 Hz, 2H), 2.24 (t, J = 6.1 Hz, 2H), 1.45 (s, 9H), 1.25 (s,
12H) ppm. 13C NMR (126 MHz, CDCl3) δ 161.5, 154.9, 113.2, 82.9, 79.6,
(E)-tert-Butyl 3-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyli-
dene)piperidine-1-carboxylate (8i). The obtained crude product was
purified by column chromatography (gradient hexane – EtOAc 20:1 to 9:1
as eluent). Yield: 3.39 g (48%) from 5.90 g of 7 and 5.00 g of tert-butyl 3-
oxopiperidine-1-carboxylate (4i); colourless oil. 1H NMR (500 MHz,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900648
European Journal of Organic Chemistry
FULL PAPER
CDCl3) δ 4.25 (s, 2H), 3.36 (t, J = 5.9 Hz, 2H), 2.26 (t, J = 6.4 Hz, 2H),
1.64 (s, 3H), 1.62 – 1.56 (m, 2H), 1.41 (s, 9H), 1.23 (s, 12H) ppm. 13C
NMR (126 MHz, CDCl3) δ 155.0, 148.0, 120.4, 83.1, 79.0, 47.8, 43.6,
28.6, 27.9, 24.8, 24.0, 15.8 ppm. 11B NMR (160 MHz, CDCl3) δ 30.8 ppm.
MS (EI): m/z = 337 [M]+. Anal. Calcd. for C18H32BNO4: C 64.10, H 9.56, N
4.15. Found: C 64.22, H 9.41, N 3.83.
[M]+. Anal. Calcd. for C15H20BNO4: C 62.31; H 6.97; N 4.84. Found: C
62.47; H 6.71; N 5.09.
2-(2-(4-Methoxyphenyl)prop-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (10e).[36,38,39] Yield: 40.9 g (50%) from 80.0 g of 1 and
67.2 g of 1-(4-methoxyphenyl)ethanone (9e); yellow oil. The compound
was obtained as ca. 25:75 mixture of E/Z isomers. 1H NMR (500 MHz,
CDCl3) δ 7.48 (d, J = 7.7 Hz, 0.5H) and 7.28 (d, J = 7.7 Hz, 1.5H), 6.85 (d,
J = 7.7 Hz, 0.5H) and 6.82 (d, J = 7.7 Hz, 1.5H), 5.72 (s, 0.25H) and 5.41
(s, 0.75H), 3.81 (s, 3H), 2.40 (s, 0.75H) and 2.20 (s, 2.25H), 1.31 (s, 3H)
and 1.18 (s, 9H) ppm. 13C NMR (126 MHz, CDCl3) δ 159.6 and 159.2,
157.1, 136.1 and 135.5, 128.9 and 127.0, 116.1, 113.5 and 112.9, 82.9
and 82.8, 55.2, 27.7 and 20.0, 24.9 and 24.7 ppm. 11B NMR (160 MHz,
CDCl3): δ 29.9 and 22.3 ppm. MS (APCI): m/z = 275 [M+H]+. Anal. Calcd.
for C16H23BO3: C 70.09; H 8.46. Found: C 70.24; H 8.25.
(E)-2-(1-(Dihydrofuran-3(2H)-ylidene)ethyl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (8l). Yield 6.03 g from 13.70 g of 7 and 5.00 g of
dihydrofuran-3(2H)-one (4l). The product was obtained as a mixture with
ca. 20% mol. of the starting 1,1-[bis[(pinacolato)boryl]ethane (7)
(according to 1H NMR); its purification by column chromatography was
unsuccessful. 1H NMR (400 MHz, CDCl3) δ 4.38 – 4.35 (m, 2H), 3.80 (t, J
= 6.9 Hz, 2H), 2.49 – 2.40 (m, 2H), 1.64 (s, 3H), 1.17 (s, 12H) ppm. 13C
NMR (101 MHz, CDCl3) δ 157.0, 116.1, 83.1, 71.8, 67.7, 32.1, 24.9, 17.4
ppm. 11B NMR (160 MHz, CDCl3) δ 29.9 ppm.
(E)-2-(2-(2-Chlorophenyl)prop-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (10f). Yield: 39.9 g (48%) from 80.0 g of 1 and 69.2 g of
1-(2-chlorophenyl)ethanone (9f); colourless solid, mp 35–38 °C. 1H NMR
(500 MHz, CDCl3) δ 7.34 – 7.28 (m, 1H), 7.21 – 7.15 (m, 2H), 7.14 – 7.09
(m, 1H), 5.61 (s, 1H), 2.15 (s, 3H), 1.03 (s, 12H) ppm. 13C NMR (126
MHz, CDCl3) δ 157.1, 143.0, 131.6, 129.6, 129.0, 127.9, 126.1, 119.9,
82.7, 27.8, 24.6 ppm. 11B NMR (160 MHz, CDCl3): δ 29.2 ppm. MS
(APCI): m/z = 279 [M+H]+. Anal. Calcd. for C15H20BClO2: C 64.67; H
7.24; Cl 12.73. Found: C 64.37; H 7.22; Cl 12.96.
4,4,5,5-Tetramethyl-2-(2-phenylprop-1-en-1-yl)-1,3,2-dioxaborolane
(10a).[35–38] Yield: 5.88 g (43%) from 15.0 g of 1 and 10.1 g of
acetophenone (9a); yellow liquid. The compound was obtained as ca.
50:50 mixture of E/Z isomers. 1H NMR (400 MHz, CDCl3) δ 7.51 – 7.46
(m, 1H), 7.33 – 7.23 (m, 4H), 5.75 (s, 0.5H), 5.46 (s, 0.5H), 2.40 (s, 1.5H),
2.20 (s, 1.5H), 1.30 (s, 6H), 1.13 (s, 6H) ppm. 13C NMR (126 MHz,
CDCl3) δ 157.9 and 157.8, 143.9 and 143.3, 128.3 and 127.7, 128.0,
127.5, 125.9, 83.1, 27.9 and 20.2, 25.0 and 24.7 ppm. 11B NMR (160
MHz, CDCl3): δ 29.9 ppm. MS (EI): m/z = 244 [M]+. Anal. Calcd. for
C15H21BO2: C 73.80; H 8.67. Found: C 73.72; H 8.31.
4-(1-(4-Methoxyphenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)vinyl)pyridine (10i). Yield: 8.49 g (45%) from 15.0 g of 1 and 15.5 g of
(4-methoxyphenyl)(pyridin-4-yl)methanone (9i); yellow solid, mp 104–
106 °C. The compound was obtained as ca. 52:48 mixture of E/Z isomers.
Although the pure analytical sample of the E-isomer was isolated by
chromatography, two isomers showed very poor separation. The
assigned resonance signals of the isolated E-isomer are given. 1H NMR
(400 MHz, DMSO-d6) δ 8.52 (d, J = 5.2 Hz, 2H), 7.20 (d, J = 5.2 Hz, 2H),
7.08 (d, J = 8.3 Hz, 2H), 6.92 (d, J = 8.3 Hz, 2H), 6.00 (s, 1H), 3.77 (s,
3H), 1.12 (s, 12H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 159.3, 155.6,
149.7, 149.0, 132.0, 130.7, 122.0, 120.8, 113.3, 83.0, 55.1, 24.4 ppm.
MS (EI): m/z = 337 [M]+. Anal. Calcd. for C20H24BNO3: C 71.23; H 7.17; N
4.15. Found: C 71.29; H 6.90; N 4.06.
1-Methyl-5-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-1-en-
2-yl)-1H-pyrazole (10b). Yield: 37.0 g (50%) from 80.0 g of 1 and 55.6 g
of 1-(1-methyl-1H-pyrazol-5-yl)ethanone (9b); colourless oil. The
compound was obtained as ca. 58:42 mixture of E/Z isomers. 1H NMR
(500 MHz, CDCl3) δ 7.35 (d, J = 2.0 Hz, 0.4H) and 7.33 (d, J = 1.9 Hz,
0.6H), 6.17 (d, J = 2.0 Hz, 0.4H) and 6.02 (d, J = 1.9 Hz, 0.6H), 5.70 (q, J
= 1.6 Hz, 0.6H) and 5.44 (s, 0.4H), 3.86 (s, 1.2H) and 3.71 (s, 1.8H), 2.27
(s, 1.2H) and 2.06 (d, J = 1.6 Hz, 1.8H), 1.27 (s, 4.8H) and 1.07 (s, 7.2H)
ppm. 13C NMR (126 MHz, CDCl3) δ 147.6 and 147.4, 146.1 and 144.1,
137.9 and 137.8, 123.5 and 119.5, 105.3 and 104.6, 83.3 and 83.1, 38.4
and 36.6, 28.1 and 21.8, 24.9 and 24.7 ppm. MS (APCI): m/z = 249
[M+H]+. Anal. Calcd. for C13H21BN2O2: C 62.93; H 8.53; N 11.29. Found:
C 63.26; H 8.49; N 11.39.
4,4,5,5-Tetramethyl-2-(3,3,3-trifluoro-2-phenylprop-1-en-1-yl)-1,3,2-
dioxaborolane (10j). Yield: 49.8 g (56%) from 80.0 g of 1 and 77.9 g of
2,2,2-trifluoro-1-phenylethanone (9j); yellow liquid. The compound was
obtained as ca. 40:60 mixture of E/Z isomers. 1H NMR (500 MHz, CDCl3)
δ 7.46 – 7.34 (m, 5H), 6.37 (s, 0.6H), 6.14 (s, 0.4H), 1.35 (s, 4.8H), 1.11
(s, 7.2H) ppm. 13C NMR (126 MHz, CDCl3) δ 146.1 (q, J = 30.4 Hz) and
143.7 (q, J = 30.5 Hz), 136.2 and 134.5, 129.3, 128.9, 128.5, 128.0,
127.5, 123.7 (q, J = 275.3 Hz) and 123.0 (q, J = 274.6 Hz), 110.1, 84.6
and 84.2, 24.8 and 24.6 ppm. 19F NMR (376 MHz, CDCl3) δ –61.7 (1.2 F)
and –67.6 (1.8 F) ppm. 11B NMR (160 MHz, CDCl3): δ 29.9 ppm. MS (EI):
m/z = 298 [M]+. Anal. Calcd. for C15H18BF3O2: C 60.44; H 6.09. Found: C
60.48; H 6.47.
(E)-4-(1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)prop-1-en-2-
yl)pyridine (10c). Yield: 44.6 g (61%) from 80.0 g of 1 and 54.2 g of 1-
(pyridin-4-yl)ethanone (9c); yellow liquid. The compound was obtained as
ca. 99:1 mixture of E/Z isomers. The assigned resonance signals of the
1
major E-isomer are given. H NMR (500 MHz, CDCl3) δ 8.50 (d, J = 5.8
Hz, 2H), 7.28 (d, J = 5.8 Hz, 2H), 5.84 (s, 1H), 2.32 (s, 3H), 1.25 (s, 12H)
ppm. 13C NMR (126 MHz, CDCl3) δ 154.6, 150.7, 149.9, 120.3, 118.9,
83.3, 24.9, 19.3 ppm. 11B NMR (160 MHz, CDCl3): δ 29.7 ppm. MS (EI):
m/z = 245 [M]+. Anal. Calcd. for C14H20BNO2: C 68.60; H 8.22; N 5.71.
Found: C 68.63; H 7.87; N 5.82.
4,4,5,5-Tetramethyl-2-(2-(4-nitrophenyl)prop-1-en-1-yl)-1,3,2-
(E)-2-(4-Methoxystyryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(10k).[40–42] Yield: 9.03 g (62%) from 15.0 g of 1 and 11.4 g of 4-
methoxybenzaldehyde (9k); yellow solid, mp 54–56 °C. 1H NMR (400
MHz, CDCl3) δ 7.43 (d, J = 8.6 Hz, 2H), 7.35 (d, J = 18.4 Hz, 1H), 6.86 (d,
J = 8.6 Hz, 2H), 6.01 (d, J = 18.4 Hz, 1H), 3.81 (s, 3H), 1.31 (s, 12H)
ppm. 13C NMR (126 MHz, CDCl3) δ 160.4, 149.2, 130.5, 128.6, 114.1,
113.7, 83.3, 55.4, 24.9 ppm. MS (EI): m/z = 260 [M]+. Anal. Calcd. for
C15H21BO3: C 69.26; H, 8.14. Found: C 68.91; H 8.48.
dioxaborolane (10d). Yield: 18.6 g (43%) from 40.0 g of 1 and 23.4 g of
1-(4-nitrophenyl)ethanone (9d); orange solid. The compound was
obtained as ca. 80:20 mixture of E/Z isomers. 1H NMR (500 MHz, CDCl3)
δ 8.20 – 8.10 (m, 2H), 7.59 (d, J = 8.2 Hz, 1.6H) and 7.42 (d, J = 8.2 Hz,
0.4H), 5.83 (s, 0.8H) and 5.60 (s, 0.2H), 2.40 (s, 2.4H) and 2.21 (d, J =
6.1 Hz, 0.6H), 1.31 (s, 9.6H) and 1.12 (s, 2.4H) ppm. 13C NMR (126 MHz,
CDCl3) δ 155.8 and 155.1, 150.2 and 150.0, 147.2 and 147.1, 128.5 and
126.6, 123.5 and 122.8, 119.7, 83.3 and 83.2, 27.7 and 20.0, 24.9 and
24.6 ppm. 11B NMR (160 MHz, CDCl3): δ 29.7 ppm. MS (EI): m/z = 289
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900648
European Journal of Organic Chemistry
FULL PAPER
(E)-2-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)pyridine
(10l).[43,44] Yield: 29.0 g (42%) from 80.0 g of 1 and 47.9 g of
picolinaldehyde (9l); beige oil. H NMR (400 MHz, CDCl3) δ 8.59 (d, J =
4.0 Hz, 1H), 7.64 (td, J = 7.7, 1.8 Hz, 1H), 7.45 (d, J = 18.3 Hz, 1H), 7.39
(d, J = 7.7 Hz, 1H), 7.18 – 7.14 (m, 1H), 6.62 (d, J = 18.3 Hz, 1H), 1.30 (s,
12H) ppm. 13C NMR (126 MHz, CDCl3) δ 155.5, 149.7, 148.8, 136.4,
123.0, 122.2, 120.8, 83.4, 24.8 ppm. MS (EI): m/z = 231 [M]+. Anal. Calcd.
for C13H18BNO2: C 67.57; H 7.85; N 6.06. Found: C 67.47; H 7.96; N 6.13.
NMR (126 MHz, CDCl3) δ 151.5, 151.1, 118.6, 93.2 and 93.1, 82.9, 79.1
and 78.8, 67.0 and 66.8, 60.2 and 59.7, 27.9, 27.1 and 25.9, 24.6, 24.5
and 23.5 ppm. MS (APCI): m/z = 254 [M–C(CH3)3–CO2+2H]+. Anal.
Calcd. for C18H32BNO5: C 61.20; H 9.13; N 3.96. Found: C 61.31; H 9.27;
N 4.24.
1
Potassium trifluoro(oxetan-3-ylidenemethyl)borate (3k). 2,2,6,6-
Tetramethylpiperidine (105 g, 0.739 mol) was dissolved in THF (1.2 L)
and cooled to –30 °C under Ar atmosphere. n-BuLi (296 mL of 2.5 M
solution in hexane) was added dropwise, and the reaction mixture was
stirred at the same temperature for 30 min. Next, the reaction was cooled
to –78 °C, and a solution of bis[(pinacolato)boryl]methane (1) (165 g,
0.616 mol) in THF (1.2 L) was added dropwise. After stirring for 30 min, a
solution of oxetan-3-one (4k) (160 g, 2.22 mol) in THF (3 L) was added
dropwise at –78 °C. The reaction mixture was allowed to slowly warm up
to rt, and stirred overnight. The obtained mixture was then cooled to 0 °C,
and aq. NH4Cl (250 mL) was added dropwise. After additional stirring for
1h, the resulting mixture was filtered and the solvent was rotary
evaporated. H2O (300 mL) was added to the obtained residue, and the
aqueous layer was extracted with EtOAc (3×400 mL). The combined
organic phase was washed with brine (250 mL), dried over the
anhydrous Na2SO4 and concentrated under vacuum. The obtained crude
product was dissolved in acetone (2.5 L) and cooled to 0 °C. A solution of
KHF2 (192 g, 2.46 mol) in H2O (2.5 L) was added dropwise, and the
resulting mixture was stirred for 4 h. The solvent was rotary evaporated
and the residue was dried under vacuum. The obtained solids were
dissolved in acetone (2 L) and the solution was refluxed overnight. Then,
the solids were filtered off and washed with hot acetone (0.5 L). The
solvent was evaporated; the precipitate was washed with ether (0.5 L)
and dried under vacuum. Yield: 24.9 g (23%); colourless solid, mp 227–
229 °C. 1H NMR (500 MHz, DMSO-d6) δ 5.06 – 5.02 (m, 2H), 4.99 – 4.96
(m, 2H), 4.92 (quint, J = 4.8, 2.5 Hz, 1H) ppm. 13C NMR (126 MHz,
DMSO-d6) δ 138.4 (q, J = 4.1 Hz), 125.8, 81.6, 80.5 ppm. 19F NMR (376
MHz, DMSO-d6) δ –135.9 – –136.7 (m) ppm. 11B NMR (160 MHz,
DMSO-d6): δ 2.3 (q, J = 54.3 Hz) ppm. MS (EI): m/z = 118 [M–KF]+. Anal.
Calcd. for C4H5BF3KO: C 27.30; H 2.86. Found: C 27.70; H 2.74.
(E)-5-Chloro-1,3-dimethyl-4-(2-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)vinyl)-1H-pyrazole (10m). Yield: 17.7 g (42%) from
40.0
g of 1 and 36.5 g of 5-chloro-1,3-dimethyl-1H-pyrazole-4-
carbaldehyde (9m); yellow solid, mp 77–79 °C. 1H NMR (500 MHz,
CDCl3) δ 7.13 (d, J = 18.8 Hz, 1H), 5.92 (d, J = 18.8 Hz, 1H), 3.71 (s, 3H),
2.29 (s, 3H), 1.26 (s, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 147.5,
138.3, 127.1, 115.4, 114.6, 83.3, 35.9, 24.9, 14.2 ppm. MS (EI): m/z =
282 [M]+. Anal. Calcd. for C13H20BClN2O2: C 55.26; H 7.13; N 9.91; Cl
12.55. Found: C 55.43; H 6.86; N 10.16; Cl 12.26.
(E)-2-(2-Cyclopropylprop-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (10o). Yield: 39.1 g (63%) from 80.0 g of 1 and 75.3 g of
1-cyclopropylethanone (9o); yellow liquid. The compound was obtained
as ca. 84:16 mixture of E/Z isomers. 1H NMR (500 MHz, CDCl3) δ 5.13 (s,
0.14H) and 5.06 (s, 0.86H), 1.86 (s, 2.6H) and 1.49 (s, 0.4H), 1.47 – 1.42
(m, 1H), 1.24 (s, 1.7H), 1.23 (s, 10.3H), 0.69 – 0.59 (m, 2H), 0.58 – 0.54
(m, 2H) ppm. 13C NMR (126 MHz, CDCl3) δ 163.9 and 162.9, 114.1 and
109.9, 82.6, 24.9, 21.1 and 20.2, 18.5 and 16.4, 6.8 and 5.8 ppm. MS
(EI): m/z = 208 [M]+. Anal. Calcd. for C12H21BO2: C 69.26; H 10.17.
Found: C 69.09; H 10.49.
(Z)-2-(4,4-Dimethoxy-2-methylbut-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (10p). Yield: 59.6 g (78%) from 80.0 g of 1 and 78.9 g of
4,4-dimethoxybutan-2-one (9p); yellow liquid. The compound was
obtained as ca. 4:96 mixture of E/Z isomers. The assigned resonance
signals of the major Z-isomer are given. 1H NMR (500 MHz, CDCl3) δ
5.21 (s, 1H), 4.45 (t, J = 6.0 Hz, 1H), 3.31 (s, 6H), 2.70 (d, J = 6.0 Hz,
2H), 1.89 (s, 3H), 1.21 (s, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 158.4,
116.9, 105.0, 82.8, 53.3, 39.3, 27.9, 24.9 ppm. MS (EI): m/z = 256 [M]+.
Anal. Calcd. for C13H25BO4: C 60.96; H 9.84. Found: C 61.34; H 10.18.
(E)-4-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)phenol
(10n). 2,2,6,6-Tetramethylpiperidine (25.5 g, 0.18 mol) was dissolved in
THF (300 mL) and cooled to –30 °C under Ar atmosphere. n-BuLi (72 mL
of 2.5 M solution in hexane) was added dropwise, and the reaction
mixture was stirred at the same temperature for 30 min. Next, the
(S)-2-(2-(2,2-Dimethyl-1,3-dioxolan-4-yl)vinyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (10q).[45] Yield: 20.9 g (55%) from 40.0 g of 1 and
58.3 g of (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (9q); colourless
liquid. The compound was obtained as ca. 85:15 mixture of E/Z isomers.
1H NMR (400 MHz, CDCl3) δ 6.54 (dd, J = 18.0, 6.4 Hz, 0.85H) and 6.41
(dd, J = 14.3, 8.3 Hz, 0.15H), 5.74 (dd, J = 18.0, 1.3 Hz, 0.85H) and 5.53
(d, J = 13.7 Hz, 0.15H), 5.17 (q, J = 6.8 Hz, 0.15H) and 4.54 (q, J = 6.8
Hz, 0.85H), 4.17 (dd, J = 8.2, 6.4 Hz, 0.15H) and 4.11 (dd, J = 8.2, 6.3
Hz, 0.85H), 3.64 (t, J = 7.8 Hz, 0.85H) and 3.55 (t, J = 7.8 Hz, 0.15H),
1.42 (s, 3H), 1.39 (s, 3H), 1.26 (s, 12H) ppm. 13C NMR (101 MHz, CDCl3)
δ 151.5 and 149.6, 109.8 and 109.5, 83.6 and 83.5, 78.2, 75.6, 69.6 and
69.2, 26.9 and 26.7, 26.1 and 26.0, 25.0 and 24.8 ppm. MS (EI): m/z =
254 [M]+. Anal. Calcd. for C13H23BO4: C 61.44; H 9.12. Found: C 61.17; H
9.43.
reaction
bis[(pinacolato)boryl]methane (1) (40.0 g, 0.15 mol) in THF (300 mL) was
added dropwise. After stirring for 30 min, solution of 4-
was
cooled
to
–78
°C,
and
a
solution
of
a
((trimethylsilyl)oxy)benzaldehyde (9n) (36.5 g, 0.188 mol) in THF (380
mL) was added dropwise at –78 °C. The reaction mixture was allowed to
slowly warm up to rt, and stirred overnight. The obtained mixture was
then cooled to 0 °C, and saturated aq. NH4Cl (225 mL) was added
dropwise. After additional stirring for 4 h, the resulting mixture was
filtered and the solvent was rotary evaporated. H2O (200 mL) was added
to the obtained residue, and the aqueous layer was extracted with EtOAc
(3×300 mL). The combined organic phase was washed with brine (75
mL), dried over the anhydrous Na2SO4 and concentrated under vacuum.
Yield: 13.6 g (37%); beige solid, mp 151–153 °C. The compound was
obtained as ca. 97:3 mixture of E/Z isomers. The assigned resonance
signals of the major E-isomer are given. 1H NMR (400 MHz, CDCl3) δ
7.37 – 7.27 (m, 3H), 6.78 (d, J = 8.2 Hz, 2H), 5.97 (d, J = 18.4 Hz, 1H),
5.83 (br s, 1H), 1.30 (s, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 156.6,
149.4, 130.3, 128.7, 115.6, 113.3, 83.5, 24.8 ppm. MS (APCI): m/z = 247
[M+H]+. Anal. Calcd. for C14H19BO3: C, 68.32; H, 7.78. Found: C, 68.67;
H, 7.59.
(S)-tert-Butyl
2,2-dimethyl-4-(2-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)vinyl)oxazolidine-3-carboxylate (10r). Yield: 27.4 g
(52%) from 40.0 g of 1 and 102.7 g of (R)-tert-butyl 4-formyl-2,2-
dimethyloxazolidine-3-carboxylate (9r); yellow liquid. The compound was
obtained as ca. 90:10 mixture of E/Z isomers. The compound existed as
a ca. 1:1 mixture of rotamers. 1H NMR (400 MHz, CDCl3) δ 6.60 – 6.34
(m, 1H), 5.63 – 5.37 (m, 1H), 4.47 (s, 0.5H), 4.29 (s, 0.5H), 4.04 (dd, J =
8.9, 6.5 Hz, 1H), 3.79 – 3.71 (m, 1H), 1.65 – 1.56 (m, 3H), 1.55 – 1.44 (m,
7H), 1.43 – 1.35 (m, 5H), 1.25 (s, 9H), 1.24 – 1.17 (m, 3H) ppm. 13C
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900648
European Journal of Organic Chemistry
FULL PAPER
General procedure for the synthesis of the compounds 14h–j. N-Boc
protected amine 3 (0.10 mol) was dissolved in dioxane (100 mL), and 4
M solution of HCl in dioxane (250 mL) was added. The reaction mixture
was stirred for 2 h, and the solvent was rotary evaporated. The residue
was triturated with Et2O (150 mL), the precipitate was filtered off and
dried under vacuum.
– 3.55 (m, 0.5H), 3.52 – 3.41 (m, 1H), 3.37 (t, J = 8.3 Hz, 0.5H), 3.28 –
3.14 (m, 1H), 2.78 (dt, J = 17.0, 9.8 Hz, 1H), 2.32 – 2.20 (m, 1H), 2.02 –
1.94 (m, 1H), 1.49 – 1.43 (m, 1H), 1.43 (s, 9H), 1.25 – 1.20 (m, 12H),
0.93 – 0.79 (m, 2H) ppm. 13C NMR (126 MHz, cdcl3) δ 154.6, 83.1, 78.7,
53.4 and 52.8, 45.8 and 45.5, 35.0 and 34.2, 34.1 and 33.2, 28.5, 24.8,
15.0 ppm. MS (APCI): m/z = 211 [M–C(O)OC(CH3)3+H]+. Anal. Calcd. for
C16H30BNO4: C 61.75; H 9.72; N 4.50. Found: C 62.12; H 10.11; N 4.58.
3-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-
yl)methylene)pyrrolidine hydrochloride (14h). Yield 17.2 g (97%) from
tert-Butyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-
22.3
g
of tert-butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
piperidine-1-carboxylate (15i). Yield: 39.6 g (91%) from 43.2 g of (Z)-
tert-butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)pipe-
ridine-1-carboxylate (3i); yellow oil. 1H NMR (400 MHz, CDCl3) δ 3.93 (d,
J = 12.1 Hz, 2H), 2.61 (t, J = 12.6 Hz, 1H), 2.34 (t, J = 11.7 Hz, 1H), 1.79
(d, J = 13.1 Hz, 1H), 1.65 – 1.51 (m, 2H), 1.41 (s, 9H), 1.38 – 1.33 (m,
1H), 1.21 (s, 12H), 1.09 – 0.95 (m, 1H), 0.74 – 0.58 (m, 2H) ppm. 13C
NMR (101 MHz, CDCl3) δ 154.9, 83.2, 79.1, 51.9, 43.8, 33.5, 32.5, 28.6,
25.4, 24.9, 16.5 ppm. MS (APCI): m/z = 225 [M–C(O)OC(CH3)3+H]+. Anal.
Calcd. for C17H32BNO4: C 62.78; H 9.92; N 4.31. Found: C 62.55; H 9.70;
N 4.03.
yl)methylene)pyrrolidine-1-carboxylate (3h); yellow solid, mp 155–157 °C.
The compound was obtained as ca. 1:1 mixture of E/Z isomers. H NMR
1
(400 MHz, CDCl3) δ 9.94 (br s, 2H), 5.46 (s, 1H), 5.40 (t, J = 2.3 Hz, 1H),
4.09 (s, 0.5H), 3.91 (s, 0.5H), 3.49 – 3.39 (m, 1H), 3.39 – 3.32 (m, 1H),
2.94 (t, J = 7.7 Hz, 1H), 2.76 (t, J = 7.5 Hz, 1H), 1.20 (s, 12H) ppm. 13C
NMR (126 MHz, CDCl3) δ 155.9 and 155.4, 113.6 and 113.2, 83.7 and
83.4, 50.3 and 48.7, 45.9 and 44.8, 33.4 and 30.4, 24.9 ppm. MS (EI):
m/z = 209 [M–HCl]+, 194 [M–HCl–CH3]+. Anal. Calcd. for C11H21BClNO2:
C 53.81; H 8.62; N 5.70; Cl 14.44. Found: C 54.01; H 8.47; N 5.93; Cl
14.08.
tert-Butyl
4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-
(Z)-3-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-
piperidine-1-carboxylate (15j).[47] Yield: 42.3 g (90%) from 46.7 g of
yl)methylene)piperidine hydrochloride (14i). Yield 19.9 g (97%) from
tert-butyl
4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-
1
25.6
g
of (Z)-tert-butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
piperidine-1-carboxylate (3j); colourless oil. H NMR (400 MHz, CDCl3) δ
4.01 (s, 2H), 2.67 (t, J = 12.1 Hz, 2H), 1.67 – 1.57 (m, 3H), 1.43 (s, 9H),
1.22 (s, 12H), 1.17 – 1.01 (m, 2H), 0.75 (d, J = 6.7 Hz, 2H) ppm. 13C
NMR (101 MHz, CDCl3) δ 155.0, 83.1, 79.2, 44.2, 34.6, 32.5, 28.6, 25.0,
19.4 ppm. MS (EI): m/z = 325 [M]+. Anal. Calcd. for C17H32BNO4: C
62.78; H 9.92; N 4.31. Found: C 62.86; H 10.14; N 4.29.
yl)methylene)piperidine-1-carboxylate (3i); colourless solid, mp 230–
232 °C. 1H NMR (400 MHz, DMSO-d6) δ 9.44 (br s, 2H), 5.30 (s, 1H),
3.87 (s, 2H), 3.11 – 3.02 (m, 2H), 2.36 (t, J = 6.4 Hz, 2H), 1.84 – 1.72 (m,
2H), 1.22 (s, 12H) ppm. 13C NMR (126 MHz, DMSO-d6) δ 153.1, 117.6,
83.1, 45.7, 42.5, 34.3, 24.6, 23.0 ppm. MS (EI): m/z = 223 [M–HCl]+, 208
[M–HCl–CH3]+. Anal. Calcd. for C12H23BClNO2: C 55.53; H 8.93; N 5.40;
Cl 13.66. Found: C 55.64; H 9.17; N 5.22; Cl 13.81.
Methyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)cyclo-
butanecarboxylate (17d). Yield: 37.8 g (91%) from 41.2 g of methyl 3-
((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)cyclobutane-
carboxylate (3d); colourless liquid. The compound was obtained as ca.
25:75 mixture of E/Z stereoisomers. 1H NMR (400 MHz, CDCl3) δ 3.65 (s,
0.75H) and 3.62 (s, 2.25H), 3.12 – 3.02 (m, 0.25H) and 2.89 (quint, J =
9.2 Hz, 0.75H), 2.61 – 2.52 (m, 0.25H) and 2.45 – 2.37 (m, 0.75H), 2.36
– 2.26 (m, 2H), 1.92 – 1.79 (m, 2H), 1.20 (s, 12H), 0.98 (d, J = 7.9 Hz,
0.5H) and 0.92 (d, J = 6.9 Hz, 1.5H) ppm. 13C NMR (126 MHz, CDCl3) δ
176.9 and 175.8, 83.1 and 82.9, 51.7 and 51.6, 34.7 and 34.5, 34.0 and
32.8, 28.6 and 28.3, 24.9, 19.4 ppm. MS (EI): m/z = 254 [M]+. Anal. Calcd.
for C13H23BO4: C 61.44; H 9.12. Found: C 61.78; H 8.85.
4-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)piperidine
hydrochloride (14j). Yield 23.8 g (97%) from 31.2 g of tert-butyl 4-
((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)piperidine-1-
carboxylate (3j); colourless solid, mp 180–182 °C. 1H NMR (400 MHz,
CDCl3) δ 9.66 (br s, 2H), 5.20 (s, 1H), 3.25 – 3.15 (m, 4H), 2.95 (t, J =
6.0 Hz, 2H), 2.58 (t, J = 5.9 Hz, 2H), 1.20 (s, 12H) ppm. 13C NMR (126
MHz, CDCl3) δ 154.8, 116.3, 83.2, 45.3, 45.2, 35.1, 28.9, 24.9 ppm. MS
(APCI): m/z = 224 [M–Cl]+. Anal. Calcd. for C12H23BClNO2: C 55.53; H
8.93; N 5.40; Cl 13.66. Found: C 55.13; H 9.05; N 5.76; Cl 13.70.
General procedure for the synthesis of the compounds 15g–j and
17d,e. Alkene 3 (0.10 mol) was dissolved in THF (100 mL), and 10% Pd–
C (1.5 g) was added. The flask was evacuated, backfilled with hydrogen
gas from a balloon and left to stir overnight at rt.The reaction mixture was
filtered, and the solvent was rotary evaporated.
Ethyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)cyclo-
pentanecarboxylate (17e). Yield: 25.4 g (99%) from 25.5 g of (Z)-ethyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)methylene)cyclopentanecarboxylate (3e); yellow liquid. The compound
was obtained as a mixture of diastereomers. 1H NMR (400 MHz, CDCl3)
δ 4.00 (q, J = 7.1 Hz, 2H), 3.67 – 3.57 (m, 1H), 2.75 – 2.57 (m, 1H), 2.09
– 1.97 (m, 1H), 1.96 – 1.86 (m, 1H), 1.86 – 1.60 (m, 4H), 1.13 (s, 15H),
0.81 – 0.70 (m, 2H) ppm. 13C NMR (101 MHz, CDCl3) δ 176.6, 82.9, 67.9
and 60.0, 43.8 and 43.0, 39.3 and 38.2, 36.7 and 35.4, 35.1 and 34.3,
29.7 and 28.9, 25.6 and 24.8, 17.2, 14.2 ppm. 11B NMR (160 MHz,
CDCl3): δ 33.6 ppm. MS (EI): m/z = 282 [M]+. Anal. Calcd. for C15H27BO4:
C 63.85; H 9.64. Found: C 64.20; H 9.50.
tert-Butyl
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-
azetidine-1-carboxylate (15g).[46] Yield: 40.4 g (90%) from 44.6 g of tert-
butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)azetidine-
1
1-carboxylate (3g); colourless oil. H NMR (400 MHz, CDCl3) δ 3.98 (t, J
= 8.3 Hz, 2H), 3.47 (dd, J = 8.5, 5.7 Hz, 2H), 2.70 – 2.57 (m, 1H), 1.38 (s,
9H), 1.18 (s, 12H), 1.05 (d, J = 7.9 Hz, 2H) ppm. 13C NMR (101 MHz,
CDCl3) δ 156.5, 83.3, 79.0, 56.6, 28.5, 25.3, 24.9, 17.0 ppm. MS (EI):
m/z = 297 [M]+. Anal. Calcd. for C15H28BNO4: C 60.62; H 9.50; N 4.71.
Found: C 60.96; H 9.81; N 4.96.
3-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)azetidine
2,2,2-trifluoroacetate (16g). tert-Butyl 3-((4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)methyl)azetidine-1-carboxylate (15g) (39.5 g, 0.133
mol) was dissolved in CH2Cl2 (40 mL), and CF3COOH (40 mL) was
added. The reaction mixture was stirred for 2 h and the solvent was
evaporated under reduced pressure. The residue was dissolved in H2O
(200 mL) and the aqueous phase was washed with CH2Cl2 (2×250 mL).
The aqueous phase was concentrated under reduced pressure and dried
tert-Butyl
pyrrolidine-1-carboxylate (15h). Yield: 25.3 g (85%) from 29.6 g of tert-
butyl 3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-
yl)methylene)pyrrolidine-1-carboxylate (3h); yellow oil. The compound
existed as ca. 1:1 mixture of rotamers.1H NMR (500 MHz, CDCl3) δ 3.62
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10.1002/ejoc.201900648
European Journal of Organic Chemistry
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1
under vacuum (0.09 mbar) at 60 °C. Yield: 31.0 g (75%); beige liquid. H
NMR (500 MHz, D2O) δ 4.06 (t, J = 9.7 Hz, 2H), 3.68 (t, J = 9.2 Hz, 2H),
3.06 – 2.94 (m, 1H), 1.10 (s, 12H), 1.07 (d, J = 8.0 Hz, 2H) ppm. 13C
NMR (126 MHz, D2O) δ 162.4 (q, J = 36.2 Hz), 116.0 (q, J = 290.9 Hz),
75.6, 53.4, 28.5, 23.7, 18.9 ppm. 19F NMR (470 MHz, D2O) δ –75.8 ppm.
MS (APCI): m/z = 198 [M–CF3COO]+. Anal. Calcd. for C12H21BF3NO4: C
46.33; H 6.80; N 4.50. Found: C 46.72; H 7.19; N 4.44.
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General procedure for the synthesis of the compounds 15h–j. N-Boc
protected amine 15 (0.10 mol) was dissolved in dioxane (100 mL), and 4
M solution of HCl in dioxane (250 mL) was added. The reaction mixture
was stirred for 2 h, and the solvent was rotary evaporated. The residue
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3-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)pyrrolidine
hydrochloride (16h). Yield: 16.1 g (91%) from 22.3 g of tert-butyl 3-
((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)pyrrolidine-1-
carboxylate (15h); yellow oil. 1H NMR (400 MHz, CDCl3) δ 9.58 (s, 2H),
3.49 (s, 1H), 3.40 (s, 1H), 3.23 (s, 1H), 2.81 – 2.67 (m, 2H), 2.45 – 2.35
(m, 1H), 2.21 – 2.16 (m, 1H), 1.54 (quint, J = 9.7 Hz, 1H), 1.20 (s, 12H),
0.93 (d, J = 7.3 Hz, 2H) ppm. 13C NMR (126 MHz, CDCl3) δ 83.6, 51.3,
44.9, 34.6, 32.7, 24.9, 14.2 ppm. MS (EI): m/z = 212 [M–Cl]+. Anal. Calcd.
for C11H23BClNO2: C 53.37; H 9.36; N 5.66; Cl 14.32. Found: C 53.43; H
9.41; N 6.01; Cl 14.52.
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hydrochloride (16i). Yield: 26.2 g (93%) from 35.0 g of tert-butyl 3-
((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)piperidine-1-carbo-
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xylate (15i); beige solid, mp 173–176 °C. H NMR (500 MHz, DMSO-d6)
δ 9.35 – 9.29 (m, 1H), 9.22 – 9.11 (m, 1H), 3.14 – 3.03 (m, 2H), 2.64 (q,
J = 11.7 Hz, 1H), 2.41 (q, J = 11.4 Hz, 1H), 1.86 (s, 1H), 1.75 – 1.58 (m,
3H), 1.17 (s, 12H), 1.10 – 1.00 (m, 1H), 0.69 (dd, J = 15.9, 5.9 Hz, 1H),
0.59 (dd, J = 15.9, 8.4 Hz, 1H) ppm. 13C NMR (126 MHz, DMSO-d6) δ
82.9, 49.3, 42.8, 30.4, 29.3, 24.6, 21.8, 15.8 ppm. MS (APCI): m/z = 226
[M–Cl]+. Anal. Calcd. for C12H25BClNO2: C 55.10; H 9.63; N 5.35; Cl
13.55. Found: C 55.42; H 9.95; N 5.57; Cl 13.46.
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4-((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)piperidine
hydrochloride (16j). Yield: 30.6 g (95%) from 40.0 g of tert-butyl 4-
((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)piperidine-1-
carboxylate (15j); colourless solid, mp 178–180 °C. 1H NMR (500 MHz,
DMSO-d6) δ 9.23 (s, 1H), 9.00 (s, 1H), 3.14 (d, J = 12.3 Hz, 2H), 2.77 (q,
J = 12.0 Hz, 2H), 1.71 (d, J = 13.8 Hz, 2H), 1.69 – 1.58 (m, 1H), 1.41 –
1.29 (m, 2H), 1.16 (s, 12H), 0.66 (d, J = 6.9 Hz, 2H) ppm. 13C NMR (126
MHz, DMSO-d6) δ 83.2, 43.5, 30.9, 30.2, 25.1, 19.0 ppm. MS (EI): m/z =
226 [M–Cl]+. Anal. Calcd. for C12H25BClNO2: C 55.10; H 9.63; N 5.35; Cl
13.55. Found: C 55.28; H 9.98; N 5.62; Cl 13.72.
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Keywords: organoboron compounds • boron-Wittig olefination •
alkenes • boronic esters
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FULL PAPER
Boron-Wittig reaction
Maksym Kovalenko, Dmytro V.
Yarmoliuk, Dmytro Serhiichuk, Daria
Chernenko, Vladyslav Smyrnov, Artur
Breslavskyi, Oleksandr V. Hryshchuk,
Ihor Kleban, Dr. Yuliya Rassukana, Dr.
Andriy V. Tymtsunik, Prof. Dr. Andrey A.
Tolmachev, Yuliya O. Kuchkovska and
Dr. Oleksandr O. Grygorenko*
The boron-Wittig olefination of aliphatic and aromatic ketones and aldehydes with
bis[(pinacolato)boryl]methane is described. The 2,2-disubstituted and 2-
monosubstituted alkenylboronic acid esters were obtained on a multigram scale
with 35–90% yield.
Page No. – Page No.
The boron-Wittig olefination of
aldehydes and ketones with
bis[(pinacolato)boryl]methane: an
extended reaction scope
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