Multigram Synthesis of Heterabicyclo[n.1.0]alkan-1-yl Trifluoroborates

Article abstract of DOI:10.1002/ejoc.202000977

An approach to the synthesis of oxa- and azabicyclo[n.1.0]alkan-1-yl trifluoroborates on a multigram scale was developed. Two synthetic strategies were evaluated: the first based on the lithiation–borylation of the corresponding 2-bromoallyl derivatives, and the other relying on regioselective hydroboration of the appropriate hetera-substituted enynes. The second method appeared to be more efficient in terms of scalability and substrate scope. Further steps included ring closing-metathesis, mild palladium-catalyzed cyclopropanation with diazomethane, and reaction with KHF₂ and furnished the title compounds in up to 50 g scale in a single run (10–41 % overall yield, 4–5 steps).

Full text of DOI:10.1002/ejoc.202000977

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Multigram synthesis of heterabicyclo[n.1.0]alkan-1-yl
trifluoroborates
Authors: Ihor Kleban, Yevhen Krokhmaliuk, Sofiia Reut, Serhii
Shuvakin, Vyacheslav V. Pendyukh, Oleksandr I. Khyzhan,
Dmytro S. Yarmoliuk, Andriy Tymtsunik, Yuliya V. Rassukana,
and Oleksandr Grygorenko
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000977
Link to VoR: https://doi.org/10.1002/ejoc.202000977
0
1/2020

European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
Multigram synthesis of heterabicyclo[n.1.0]alkan-1-
yl trifluoroborates
[
a,b]
[a,c]
Sofiia Reut,[a,c] Serhii Shuvakin,[a,c] Vyacheslav V. Pendyukh,[a]
Ihor Kleban,
Yevhen Krokhmaliuk,
Oleksandr I. Khyzhan,[a] Dmytro S. Yarmoliuk,[a] Dr. Andriy V. Tymtsunik,*[a,d] Dr. Yuliya V. Rassukana,[b,d]
Dr. Oleksandr O. Grygorenko[a,c]
Abstract: An approach to the synthesis of oxa- and
azabicyclo[n.1.0]alkan-1-yl trifluoroborates on a multigram scale was
developed. Two synthetic schemes were evaluated: the first one
based on the lithiation – borylation of the corresponding 2-bromoallyl
derivatives, and another one relying on regioselective hydroboration
of the appropriate hetera-substituted enynes. The second method
appeared to be more efficient in terms of scalability and substrate
scope. Further steps included ring closing-metathesis, mild
palladium-catalyzed cyclopropanation with diazomethane, and
couplings involves partially unsaturated reagents of general
structure 2, which are highly effective in e.g. Suzuki – Miyaura
reaction and are hence widely used for that reason.[
Nevertheless, introducing the double bond alters significantly
chemical properties of the products obtained, as well as results
in increasing sp2 carbon atom fraction and “flattening” of their
molecules, which is not compatible with the spirit of “thinking in
3D”-type concepts of medicinal chemistry mentioned above.
22–28]
reaction with KHF
2
and furnished the title compounds on up to ca.
50 g scale in a single run (10–41% overall yield, 4–5 steps).
Introduction
Saturated heterocycles have always been considered as
attractive structural motifs for early drug discovery;[1–3] interest to
these compounds has even increased in recent years when
concepts like “escape from flatland”[4,5] and “lead-likeness”[6–8]
have been established in medicinal chemistry. While synthetic
methodologies allowing for the construction of the saturated
Figure 1. Heteroaliphatic organoboron derivatives – potential reagents for the
C–C coupling reactions
A possible idea to solve this issue includes the use of a
heterocyclic rings are of immense value to synthetic chemistry,
alternative approach relying on the use of building blocks[9]
cyclopropane ring as an isostere of the double bond.[
29,30]
It
should be noted that cyclopropylboronic acids and their
derivatives have attracted increasing attention in recent
years.[31,32,41,42,33–40] Having partially unsaturated nature,
cyclopropyl boronates possess sufficient reactivity towards the
Suzuki – Miyaura reaction conditions, while keeping some
important structural features of the parent saturated analogues
already including heteroaliphatic moieties is also worth attention.
In most cases, common reactions of such compounds include
C–N bond formation.[10,11] Building blocks providing new C–C
bonds are relatively rarer; typically, they are organoboron
derivatives which have gained momentum with recent advances
2
3
[12–15]
in sp -sp couplings.
Molander’s photoredox and related
(
e.g. chirality). Application of this design concept to
methodologies are excellent examples of introducing building
blocks of type 1 (X = BF -
K ) into such transformations (Figure
+
heteroaliphatic organoboron derivatives leads to hetera-
substituted bicyclo[n.1.0]alkan-1-yl boronates 3, which are the
key compounds in this study.
1
3
);[16–21] however, building blocks 1 have low reactivity under
1
other commonly used C–C coupling conditions. An alternative
It should be noted that in 2017, Harris and co-workers published
a communication describing synthesis and coupling reactions of
trifluoroborates 4a–c (Figure 2).[43] The published approach to
the preparation of these compounds relied on the Simmons –
Smith reaction of the corresponding cyclic vinyl boronates as the
key step; it had moderate yield (46–51%) and was performed at
up to 3 g scale of the final product. Meanwhile, the utility of the
building blocks of type 4 for medicinal chemistry has been
approved by successful C–C couplings since 1-aryl-3-azabicyc-
lo[3.1.0]hexane motif and similar bicyclic cores are widespread
among biologically active compounds, clinical candidates
bicifadine (for pain treatment), centanafadine (for attention deficit
hyperactivity disorder), and amitifadine (for the treatment of
addiction) being among the most prominent examples.[ The
ultimate goal of our current work was the development of the
approach that steps back to classical palladium-catalyzed
[
[
a]
b]
Enamine Ltd. (www.enamine.net)
Chervonotkatska 78, Kyiv 02094, Ukraine
E-mail: tsunik@ukr.net
Institute of Organic Chemistry, National Academy of Sciences of
Ukraine
Murmanska Street 5, Kyiv 02094, Ukraine
Taras Shevchenko National University of Kyiv
Volodymyrska Street 60, Kyiv 01601, Ukraine
National Technical University of Ukraine "Igor Sikorsky Kyiv
Polytechnic Institute"
[
c]
d]
[
Prospect Peremogy 37, Kyiv 03056, Ukraine
Supporting information for this article is given via a link at the end of
the document.
43]
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
general and efficient method for the preparation of aza-, oxa-
and thia-substituted bicyclo[n.1.0]alkan-1-yl boronates of type 3,
which could be used at the multigram scale. Specifically, we
were interested in the synthesis of trifluoroborates 4a–j (Figure
corresponding triflates 7b and 7g with bis(pinacolato)diboron
(Scheme 1). This approach has been reported in the literature
for both O- and N-derived compounds 5b[ and 5g.
44]
[27]
3
).
Figure 3. Target molecules of this study
Figure 2. Some useful azabicyclo[n.1.0]alkanes reported in the literature
Results and Discussion
Our strategy for the preparation of the building blocks 4a–j was
quite straightforward and relied on cyclopropanation of the
appropriate cyclic vinyl boronates 5a–j. The most accessible
substrates in these series were pinacol esters 5b and 5g since
they could be prepared from the corresponding symmetric
ketones 6b and 6g via the palladium-catalyzed reaction of the
Scheme 1. Known synthesis of heteroaliphatic vinyl boronates 5b and 5g
Table 1. Synthesis of boronates 5a, 5c, 5d, and 5i–k using the modified method of Renaud and Ouellet
#
1
2
3
4
5
6
X
n
1
2
1
2
3
3
Vinyl bromide 9 (yield, %)
Acyclic boronate 8 (yield, %)
Cyclic boronate 5 (yield, %)
Overall yield of 5
7.6 g, 16%
NBoc
NBoc
O
9a (44)
9c (48)
9d (76)
9h (60)
9i (52)
9j (80)
8a (45)
8c (52)
8d (65)
8h (75)
8i (58)
8j (55)
5a (84)
5c (72)
5d (85)
5h (81)
5i (70)[a]
5j (60)[a]
7.2 g, 18%
16.3 g, 42%
17.6 g, 36%
7.7 g, 21%
O
NBoc
O
14.9 g, 26%
[
a]
The reaction was performed in toluene at reflux.
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European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
Table 2. Synthesis of boronates 5a–k using an alternative method developed in this work
#
1
2
3
4
5
6
7
8
X
n
1
2
1
1
2
2
3
3
Enyne 10 (yield, %)
10a (87)
10c (92)
10d[a]
Acyclic boronate 8 (yield, %)
Cyclic boronate 5 (yield, %)
5a (85)
Overall yield of 5
74.8 g, 60%
61.3 g, 57%
82.2 g, 40%
9.66 g, 40%
32.0 g, 57%
188 g, 44%
11.3 g, 52%
32.0 g, 29%
NBoc
NBoc
O
8a (82)
8c (86)
8d (48)[b]
8e (46)[b]
8f (71)
5c (72)
5d (85)
S
10e[a]
5e (86)[c]
SO
2
10f (91)[c]
10h (74)
10i (94)
5f (88)
O
8h (73)
8i (77)
5h (81)
NBoc
O
5i (72)[d]
10j (80)
8j (60)
5j (60)[d]
[
a]
Used in the next step without isolation or purification [b] Yield for two steps [c] 2nd generation Hoveyda – Grubbs catalyst (5% mol) was used. [d] The reaction was
performed in toluene at reflux. [c] Compound 10f was obtained by oxidation of 10e with MCPBA (2 eq, CH
2
Cl , rt)
2
The method was not effective for other substrates of type 5 due
to the regioselectivity problem at the first step of the reaction
sequence. Therefore, synthesis of N- and O-substituted cyclic
vinyl boronates 5a, 5c, 5d, and 5h–j relied on an alternative
method by Renaud and Ouellet[23] including ring-closing meta-
thesis as the key transformation (Table 1), which was used by
the previous authors for the preparation of 5a, 5d, and 5h on ca.
occurred upon attempted preparation of 8h from 80 g of 9h in a
single run using the procedures developed. Moreover, the
method did not work for the preparation of sulfur-containing
boronates 5e and 5f since the corresponding synthetic interme-
diates 8e or 8f could not be obtained according to the proposed
scheme.
Therefore, an alternative approach was considered which relied
on copper-catalyzed hydroboration of enynes 10, in turn,
obtained by alkylation of the corresponding O-, N-, or S-
nucleophiles with propargyl bromide (Table 2). Using the
conditions similar to those reported for other propargylic deriva-
1
00 mg scale. We have found that intermediate 8d could be
obtained using the reported procedure in 65% overall yield on up
to 22.4 g scale. For the ring-closing metathesis of 8d, the
original protocol was modified to ensure its scalability. In
particular, the benzene solvent was replaced with less toxic
tives (bis(pinacolato)diboron, CuCl, t-Bu
3
4
PHBF , t-BuONa,
CH
used, and the concentration of the substrate was increased from
.004–0.05 M to 0.33 M to minimize the solvent consumption.
As a result, the target product 5d was obtained in 85% yield
16.3 g scale).
2
Cl
2
, the more stable 2nd generation Grubbs catalyst was
MeOH in toluene),[45] the target product 8h was obtained from
10h in 73% yield with good regioselectivity: less than 3% of the
corresponding terminal boronate was observed in the crude
0
1
product by H NMR. The method worked well for all the
(
substrates 10 and appeared to be very efficient upon scale up
so that up to 236 g of the target products 8 (for the case of 8h)
could be obtained. Ring-closing metathesis of these dienes
using the optimized protocol described above also showed good
scalability (up to 188 g for the case of 5h).
For the preparation of the remaining cyclic vinyl boronate 5f,
chemoselective oxidation of 5e with MCPBA was envisaged
initially. Unfortunately, the target product could not be obtained
in all attempts. Therefore, oxidation of 10e was performed
Using these optimized conditions, the substrates 5a, 5c, and 5i
were obtained in 72–84% yield on a 7.2–17.6 g scale (Table 1).
In the case of 5i and 5j, the metathesis step was performed at
elevated temperature (toluene, reflux; 70% and 60% yield,
respectively).
Unfortunately, the synthesis was not amendable to further scale-
up. The lithiation – borylation step appeared to be the bottleneck
of the method. Thus, a considerable drop of the yield (to 16%)
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European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
instead (MCPBA (2 eq), CH
1
5
2
Cl
0f (91% yield) was transformed into target sulfolene derivative
f using the common reaction sequence described above (62%
2
, rt), and the resulting product
Pd(OAc)
2
(5% mol) proceeded with high efficiency already at
0 C and gave target cyclopropane derivative 11b in 73% yield
(58.9 g scale) (Table 3). The method was also efficient for the
preparation of other bicyclic boronates 11a, 11c, 11d, and 11g–j
yield over 2 steps).
(
but not 11e and 11f); the products were obtained in 38–64%
Table 3. Synthesis of trifluoroborates 4a–k
yield on 6.87–39.5 g scale. In the case of 5d, a repetition of the
procedure with the crude product obtained after the first run (i.e.
using larger excess of the diazomethane) was required.
It should be noted that high reactivity of vinyl boronates 5
bearing a trisubstituted double bond towards diazomethane is
not usual since, in our experience, trisubstituted alkenes
typically do not react under such conditions.[35,49,50] A more
detailed study of this phenomenon will be reported in another
publication. A possible explanation of the fact that 5e and 5f did
not react with the carbenoid under the aforementioned
conditions might include catalyst poisoning and electron-
withdrawing effects of the sulfone moiety, respectively. The latter
statement is also partially confirmed by the fact that compound
5d also demonstrated lowered reactivity.
#
1
2
3
4
X
n
1
1
2
1
m
1
2
1
1
Starting
material 5
Product 11
(yield, %)
Product
(yield, %)
4
Overall
yield of 4[
a]
NBoc
NBoc
NBoc
O
5a
5b
5c
5d
11a (64)
11b (73)
11c (63)
11d (51)[b]
4a (94)
4b (99)
4c (92)
4d (98)
11.2 g,
36%
Finally, the synthesized boronates 11a–j were transformed into
53.5 g
1%
the corresponding trifluoroborates 4a–j (which are more suitable
4
substrates for the C–C and C–N coupling reactions[
41,43]
using
51]
the standard protocol (94–98% yield, up to ca. 50 g scale).[
35.1 g,
3%
3
12.3 g,
Conclusions
2
–
–
0%
5
6
7
S
1
1
1
1
1
2
5e
5f
11e (0)
11f (0)
–
Two approaches to the synthesis of heterabicyclo[n.1.0]alkan-1-
yl trifluoroborates 4 were evaluated for the multigram prepa-
ration of the title compounds. One synthetic scheme was based
on the lithiation – borylation of the corresponding 2-bromoallyl
derivatives 9; it could be used to obtain up to ca. 10–15 g of the
target products but was not amendable to further scale-up.
Moreover, it could not be applied to the sulfur-containing
derivatives. An alternative approach that relied on copper-
catalyzed chemo- and regioselective hydroboration of enynes 10
was more convenient and worked well on up to 236 g scale of
acyclic boronates 8. Further ring-closing metathesis of 8 was
also optimized for a hundred-gram scale; special conditions
were required for the sulfur (II)-containing diene (i.e. the use of
SO
2
–
O
5g
11g (58)
4g (96)
20.5 g,
1%
3
6
7
8
O
2
3
3
1
1
1
5h
5i
11h (50)
4h (95)
26.4 g
1%
2
NBoc
O
11i (40)
4i (94)
6.81 g,
0%
2
11j (38)[a]
4j (95)[a]
5j
5.48 g
0%
1
[
a]
Including synthesis of 5 according to Scheme 1 or Table 2 [b] After the two
nd
Hoveyda – Grubbs 2 generation catalyst), as well as for the
reactions leading to the formation of seven-membered rings
consecutive runs with the same sample
(
elevated temperatures). To construct the bicyclic system of the
The final part of this study was related to the cyclopropanation of
the substrates 5a–j. Initially, the reported method (i.e. the
Simmons – Smith reaction)[43] was checked for scalability with
substrate 5b; unfortunately, the yield of the target product 11b
was not satisfactory. Therefore, we have switched our efforts to
the elaboration of an alternative cyclopropanation procedure. A
recent publication by AbbVie chemists attracted our attention;
they described flow reactor-based cyclopropanation of various
styrylboronic esters with diazomethane on up to 2.4 mmol
scale.[35] Although we had some concerns about using this
dangerous reagent, recent procedures for safe generation and
handling of diazoalkane solutions[46–48] prompted us to consider
this approach for the cyclopropanation of 5. It was found that a
title compounds, palladium-catalyzed cyclopropanation of
resulting heterocyclic alkenyl boronates 5 with diazomethane
appeared to be very efficient. The reaction proceeded very
smoothly already at 0 C, which is not common for the
trisubstituted alkenes. Therefore, despite the use of the
potentially dangerous reagent, a safe protocol for the key
cyclopropanation step could be developed. The method worked
well for oxa- and aza-, but not for sulfa-substituted derivatives.
Finally, pinacolates 11 were transformed into target oxa- and
azabicyclo[n.1.0]alkan-1-yl trifluoroborates 4 on up to ca. 50 g
scale in a single run (10–41% yield over 4–5 steps).
reaction of 5b with CH
2
N
2
in t-BuOMe in the presence of Experimental Section
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European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
General. The solvents were purified according to the standard
methods.[52] Compounds 5b[44] and 5g[27] were obtained using the
reported procedures. All other starting materials were purchased 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
(CAUTION! Vigorous gas evolution and reaction mixture thickening was
observed). After the addition was complete, the reaction mixture was
heated at 30 C for 1 h, and 2,3-dibromopropene (124.7 g, 0.624 mol)
was added dropwise at rt. The reaction mixture was refluxed overnight
(monitored by 1H NMR spectra), then cooled, and H
added carefully dropwise. The organic phase was separated, dried over
Na SO , and evaporated in vacuo.
2
O (400 mL) was
2
4
3
-(Allyloxy)-2-bromoprop-1-ene (9d). Yield 35.3 g (76%) from allyl
1
alcohol (15.2 g, 0.262 mol). Brownish liquid. H NMR (500 MHz, CDCl
3
):
100.7 MHz for Carbon-13). Chemical shifts are reported in ppm downfield
δ = 5.99–5.86 (m, 2H), 5.63 (s, 1H), 5.32 (dt, J = 17.2, 1.9 Hz, 1H), 5.23
dt, J = 10.9, 1.9 Hz, 1H), 4.11 (d, J = 1.9 Hz, 2H), 4.05 (dt, J = 5.5, 1.9
from TMS as an internal standard. 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)). High-resolution mass spectra
(
Hz, 2H) ppm. Other spectral and physical data were in accordance with
the literature.[53]
(
HRMS) were recorded on Agilent Infinity 1260 UHPLC system coupled
4
1
5
5
-((2-Bromoallyl)oxy)but-1-ene (9h). Yield 79.5 g (60%) from but-3-en-
to 6224 Accurate Mass TOF LC/MS system.
1
-ol (50.0 g, 0.624 mol). Brownish liquid; H NMR (500 MHz, CDCl
3
): δ =
.92 (s, 1H), 5.90–5.78 (m, 1H), 5.61 (s, 1H), 5.12 (d, J = 17.3 Hz, 1H),
.07 (d, J = 10.3 Hz, 1H), 4.11 (s, 2H), 3.54 (t, J = 6.7 Hz, 2H), 2.38 (q,
General procedure for the synthesis of 9a, 9c, and 9i. To a solution of
the corresponding amine (0.350 mol) in THF (700 mL), 2,3-dibromo-
propene (63.0 g, 0.315 mol) was added dropwise, and the resulting
13
1
J = 6.7 Hz, 2H) ppm; C{ H} NMR (126 MHz, CDCl
3
): δ = 134.9, 129.6,
117.3, 116.6, 74.9, 69.8, 34.1 ppm; HRMS (ESI) m/z calcd. for
mixture was stirred for 2 h at rt. Then Et
75.5 g, 0.345 mol) were added, and the reaction mixture was left
overnight at rt. The solvent was removed in vacuo, the residue was
dissolved in EtOAc (700 mL), washed with 1 M aq KH PO (500 mL),
O (500 mL), and brine (500 mL). The organic phase was dried over
Na SO and evaporated in vacuo.
3
N (88 mL, 0.630 mol) and Boc
2
O
+
C
7
H11BrONa [M+Na] 212.9891; found: 212.9894.
(
5
-((2-Bromoallyl)oxy)pent-1-ene (9j). Yield 75.8 g (80%) from pent-4-
en-1-ol (39.7 g, 0.462 mol). Brownish liquid; 1H NMR (500 MHz, CDCl
):
δ = 5.90 (q, J = 1.7 Hz, 1H), 5.87–5.75 (m, 1H), 5.60 (d, J = 1.7 Hz, 1H),
2
4
3
H
2
2
4
5
2
.03 (dq, J = 17.1, 1.7 Hz, 1H), 4.97 (dd, J = 10.4, 1.7 Hz, 1H), 4.07 (s,
H), 3.48 (t, J = 6.7 Hz, 2H), 2.15 (q, J = 6.7 Hz, 2H), 1.70 (quint, J = 6.7
tert-Butyl allyl(2-bromoallyl)carbamate (9a). Yield 42.5 g (44%) from
13
1
Hz, 2H) ppm; C{ H} NMR (126 MHz, CDCl
3
): δ = 138.1, 129.9, 117.2,
allyl amine (20.0 g, 0.350 mol). Colorless liquid; the compound existed as
1
C
14.9, 74.9, 69.8, 30.2, 28.8 ppm; HRMS (ESI) m/z calcd. for
8
H13BrONa [M+Na] 227.0047; found: 227.0041.
1
a mixture of rotamers; H NMR (400 MHz, CDCl
3
): δ = 5.84–5.61 (m, 2H),
+
5
3
.56 (s, 1H), 5.22–5.02 (m, 2H), 4.07 (s, 1H), 4.01 (s, 1H), 3.89 (s, 1H),
.82 (s, 1H), 1.53 (s, 2H) and 1.46 (s, 7H) ppm; MS (EI): m/z = 220/222
]+; HRMS (ESI) m/z calcd. for Na [M+Na]+
18BrNO
General procedure for the synthesis of 10a, 10c, and 10i. To a
suspension of NaH (54.0 g, 60% in mineral oil, 1.35 mol) in DMF (1.3 L),
a solution of the corresponding N-Boc-amine (0.900 mol) in DMF (200
mL) was added dropwise at –10 C. The reaction mixture was stirred at
[M–C
4
H
8
C
11
H
2
2
98.0418; found: 298.0414. Other spectral and physical data were in
accordance with the literature.[53]
0
C for 30 min, and propargyl bromide (215 g, 1.80 mol) was added
tert-Butyl (2-bromoallyl)(but-3-en-1-yl)carbamate (9c). Yield 18.2 g
dropwise at 0 C. The reaction mixture was left at rt overnight (monitored
(
48%) from homoallylamine (9.28 g, 0.131 mol). Reddish liquid; the
compound existed as a mixture of rotamers; 1H NMR (500 MHz, CDCl
):
δ = 5.86–5.74 (m, 1H), 5.71 (d, J = 11.0 Hz, 1H), 5.56 (s, 1H), 5.08 (d, J
1
by H NMR spectra). H
2
O (200 mL) was added carefully dropwise to the
O (2.5 L). The
resulting mixture was extracted with t-BuOMe (3700 mL). The combined
3
reaction mixture, followed by an additional amount of H
2
=
3
18.2 Hz, 1H), 5.04 (d, J = 11.0Hz, 1H), 4.09 and 4.02 (s, 2H), 3.32 and
.27 (t, J = 7.8Hz, 2H), 2.30 (t, J = 7.8Hz, 2H), 1.48 and 1.46 (s, 9H)
organic phases were washed with brine (1 L), dried over Na
evaporated in vacuo.
2 4
SO , and
13
1
3
ppm; C{ H} NMR (126 MHz, CDCl ): δ = 155.3 and 155.0, 135.2, 129.9
and 129.7, 117.0 and 116.7, 116.3, 80.1, 55.0 and 54.5, 46.5 and 46.4,
tert-Butyl allyl(prop-2-yn-1-yl)carbamate (10a). Yield 153 g (87%) from
+
3
3.0 and 32.5, 28.3 ppm; MS (CI): m/z = 234/236 [M–C
4
H
8
+H] ; HRMS
tert-butyl allylcarbamate (141 g, 0.900 mol). Physical state; the
+
(
ESI) m/z calcd. for C12
H
20BrNO
2
Na [M+Na] 312.0575; found: 312.0570.
1
compound existed as a mixture of rotamers; H NMR (600 MHz, CDCl
3
):
δ = 5.75 (ddq, J = 16.6, 11.3, 5.9 Hz, 1H), 5.22–5.09 (m, 2H), 4.15–3.93
tert-Butyl (2-bromoallyl)(pent-4-en-1-yl)carbamate (9i). The product
was purified by flash chromatography (hexanes – EtOAc (12:1) as
eluent). Yield 21.3 g (52%) from pent-4-en-1-amine (11.4 g, 0.135 mol).
(
m, 2H), 3.91 (s, 2H), 2.16 (s, 1H), 1.44 (s, 9H) ppm. Other spectral and
[54]
physical data were in accordance with the literature.
1
Yellowish liquid; the compound existed as a mixture of rotamers; H NMR
tert-Butyl but-3-en-1-yl(prop-2-yn-1-yl)carbamate (10c). Yield 65.0 g
(400 MHz, CDCl
3
): δ = 5.77 (ddt, J = 17.2, 10.3, 6.6 Hz, 1H), 5.70–5.60
(
92%) from tert-butyl but-3-en-1-ylcarbamate (53.2 g, 0.311 mol).
(m, 1H), 5.52 (s, 1H), 5.00 (d, J = 17.2 Hz, 2H), 4.95 (d, J = 10.6 Hz, 1H),
1
Brownish liquid; H NMR (500 MHz, CDCl
3
): δ = 6.04–5.88 (m, 1H), 5.58
4
2
.05 and 3.98 (s, 2H), 3.21 (dd, J = 17.2, 7.5 Hz, 2H), 2.02 (q, J = 7.5 Hz,
H), 1.60 (quint, J = 7.5 Hz, 2H), 1.43 (s, 9H) ppm; 13C{ H} NMR (101
(d, J = 7.6 Hz, 1H), 5.56 (d, J = 2.8 Hz, 1H), 3.93 (dd, J = 7.6, 2.8Hz, 2H),
1
3
.84 (d, J = 3.3Hz, 2H), 2.54 (d, J = 3.3 Hz, 1H) ppm. Other spectral and
MHz, CDCl
3
): δ = 155.4 and 155.0, 137.8, 129.9, 116.9 and 116.3, 115.0,
physical data were in accordance with the literature.[
55]
8
0.0, 54.8 and 54.3, 46.4, 31.0, 28.3, 27.4 and 27.2 ppm; HRMS (ESI)
+
2
m/z calcd. for C13H22BrNO Na [M+Na] 326.0732; found: 326.0729.
tert-Butyl pent-4-en-1-yl(prop-2-yn-1-yl)carbamate (10i). The product
was purified by flash chromatography (hexanes – EtOAc (15:1) as
eluent). Yield 59.6 g (94%) from tert-butyl pent-4-en-1-ylcarbamate (52.6
g, 0.284 mol). Brownish liquid; the compound existed as a mixture of
General procedure for the synthesis of 9d, 9h, and 9j. NaH (27.7 g,
0% in mineral oil, 0.692 mol) was washed with hexanes (3250 mL)
under an argon flow. Et O (700 mL) was added, followed by dropwise
addition of the corresponding alkenol (0.694 mol) upon stirring
6
2
rotamers; 1H NMR (400 MHz, CDCl
3
): δ = 5.91–5.67 (m, 1H), 5.08–4.87
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
(
m, 2H), 4.14–3.85 (m, 2H), 3.29 (q, J = 7.0 Hz, 2H), 2.17 and 2.15 (t, J =
mL, 1.7 M in pentane, 0.177 mol) was added dropwise at –78 C. The
reaction mixture was stirred at –78 C for 1 h, and then 2-isopropoxy-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (31.2 g, 0.167 mol) was added
dropwise at the same temperature. The reaction mixture was allowed to
warm to rt and then stirred for an additional 1.5 h. 4 M aq HCl was added
2
.6 Hz, 1H), 2.03 (quint, J = 7.0 Hz, 2H), 1.64 (sept, J = 7.0Hz, 2H), 1.45
and 1.43 (s, 9H) ppm; 13C{ H} NMR (126 MHz, CDCl
1
3
): δ = 155.1, 137.9,
1
14.9, 80.1 and 79.9, 76.0, 71.2, 46.1, 36.5 and 36.0, 30.9, 28.4, 27.2
+
2
ppm; HRMS (ESI) m/z calcd. for C13H21NO Na [M+Na] 246.1470; found:
246.1462.
dropwise to pH = 6–7, followed by H
2
O (300 mL) was. A precipitate that
formed was filtered and washed with Et
2
O (100 mL). An organic phase
was separated from the filtrate, dried over Na
vacuo.
2 4
SO , and evaporated in
General procedure for the preparation of 10d, 10h, and 10j. NaH
80.0 g, 60% in mineral oil, 1.99 mol) was washed with hexanes (3500
mL) under an argon flow. Et O (1.5 L) was added, followed by dropwise
(
2
addition of the corresponding alkenol (1.66 mol) (CAUTION! Vigorous
gas evolution and reaction mixture thickening was observed). After the
addition was complete, the reaction mixture was heated at 30 C for 1 h,
and propargyl bromide (237 g, 1.99 mol) was added dropwise at rt. The
reaction mixture was refluxed overnight (monitored by 1H NMR spectra),
General procedure for the synthesis of boronates 8 from enynes 10.
To a solution of compound 10 (1.36 mol) in toluene (4 L), CuCl (13.5 g,
0.136 mol), B
2
Pin
2
(380 g, 1.50 mol), (t-Bu)
3 4
PHBF (47.4 g, 0.163 mol),
NaOt-Bu (39.2 g, 0.408 mol) were added at rt under argon atmosphere.
Then MeOH (110 mL, 2.69 mol) was added in portions at rt (CAUTION!
Vigorous reaction: in several minutes, the internal temperature increased
to ca. 80 C). The resulting mixture was stirred at ambient temperature
2
then cooled, and H O (700 mL) was added carefully dropwise. The
organic phase was separated, dried over Na
vacuo.
2 4
SO , and evaporated in
1
for 2 h (monitored by H NMR). Then the mixture was filtered through
SiO
2
(500 g), the pad was washed with EtOAc (1 L), and the combined
extracts were evaporated in vacuo.
3-(Prop-2-yn-1-yloxy)prop-1-ene (10d), from allyl alcohol (42.1 g, 0.726
mol). The compound was not isolated in pure form but used in the next
step as an Et
literature.[56]
2
O solution. The spectral data were in accordance with the
tert-Butyl
carbamate (8a).
allyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)-
[23]
The product was purified by flash chromatography
(
hexanes – EtOAc (20:1) as eluent). Yield 103 g (82%) from compound
1
0a (74.4 g, 0.381 mol). Yellowish liquid; the compound existed as a
): δ = 5.87 (s, 1H), 5.77
br. s, 1H), 5.63 (s, 1H), 5.09 (d, J = 12.7 Hz, 2H), 3.96 and 3.95 (s, 2H),
4
1
5
4
2
1
-(Prop-2-yn-1-yloxy)but-1-ene (10h). Yield 136 g (74%) from but-3-en-
-ol (120 g, 1.67 mol). Brownish liquid; 1H NMR (400 MHz, CDCl
): δ =
mixture of rotamers; 1H NMR (400 MHz, CDCl
3
3
(
3
.90–5.70 (m, 1H), 5.09 (d, J = 17.2 Hz, 1H), 5.04 (d, J = 10.2 Hz, 1H),
.14 (d, J = 2.5Hz, 2H), 3.57 (t, J = 6.6Hz, 2H), 2.40 (t, J = 2.5Hz, 1H),
.84 and 3.75 (s, 2H), 1.44 (s, 9H), 1.26 (s, 12H) ppm; 13C{ H} NMR (126
): δ = 155.7 and 155.4, 148.5, 134.1 and 133.8, 128.7 and
28.4, 116.2 and 115.7, 83.5 and 83.2, 79.6 and 79.2, 49.5 and 48.8,
1
.35 (q, J = 6.6 Hz, 2H) ppm; 1 C{ H} NMR (101 MHz, CDCl
3
1
MHz, CDCl
3
1
3
): δ = 134.9,
16.5, 79.8, 74.2, 69.3, 58.1, 33.9 ppm. Other spectral and physical data
were in accordance with the literature.[56]
28.3, 24.7, 24.6 (br. s) ppm; HRMS (ESI) m/z calcd. for C
17
H
31BNO
4
+
[M+H] 324.2346; found: 324.2347.
5
-(Prop-2-yn-1-yloxy)pent-1-ene (10j). Yield 87.7 g (80%) from pent-4-
1
tert-Butyl but-3-en-1-yl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)allyl)carbamate (8c). The product was purified by flash
chromatography (hexanes – EtOAc (18:1) as eluent). Yield 54.3 g (86%)
en-1-ol (76.0 g, 0.884 mol). Colorless liquid; H NMR (500 MHz, CDCl
δ = 5.90–5.75 (m, 1H), 5.12–4.90 (m, 2H), 4.14 (dd, J = 7.1, 2.5 Hz, 2H),
3
):
3
1
1
.53 (q, J = 7.1 Hz, 2H), 2.46–2.39 (m, 1H), 2.14 (quint, J = 7.1 Hz, 2H),
.78–1.62 (m, 2H) ppm; 1 C{ H} NMR (126 MHz, CDCl
3
1
from compound 10c (39.1 g, 0.187 mol). Yellowish liquid; the compound
3
): δ = 138.1,
1
existed as a mixture of rotamers; H NMR (400 MHz, CDCl
3
): δ = 5.87 (d,
14.9, 80.0, 74.1, 69.5, 58.0, 30.2, 28.7 ppm. Other spectral and physical
data were in accordance with the literature.[57]
J = 2.8 Hz, 1H), 5.83–5.66 (m, 1H), 5.61 (s, 1H), 5.05(d, J = 18.0Hz, 1H),
.00 (d, J = 10.7 Hz, 1H), 3.96 and 3.90 (s, 2H), 3.26 and 3.19 (t, J = 7.4
5
Hz, 2H), 2.26 (q, J = 7.4Hz, 2H), 1.46 and 1.44 and 1.41 (m, 9H), 1.26 (s,
Allyl(prop-2-yn-1-yl)sulfane (10e). To a solution of allyl mercaptan
2H) ppm; 13C{ H} NMR (126 MHz, CDCl
1
): δ = 155.7 and 155.5, 135.7,
28.5 and 128.3, 116.3, 83.5, 79.1, 50.4 and 50.1, 46.6 and 46.5, 33.2
1
1
3
(50.0 g, 0.674 mol) in acetone (750 mL), K
2 3
CO (186 g, 1.35 mol) was
added, followed by dropwise addition of propargyl bromide (57.0 mL,
and 32.6, 28.4, 24.8, 24.6 (br. s) ppm; MS (EI): m/z = 237 [M–C
CO
]+; HRMS (ESI) m/z calcd. for C18 [M+H]+ 338.2503; found:
38.2506.
4 8
H –
0
.741 mol) at rt. The reaction mixture was refluxed overnight (monitored
by 1H NMR spectra), then filtered. The precipitate was washed with
2
H33BNO
4
3
acetone (500 mL), and the solvent was distilled off from the combined
filtrates at atmospheric pressure to ca. 40% of its volume. The residue
2
-(3-(Allyloxy)prop-1-en-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
was diluted with H
The combined organic extracts were dried over Na
2
O (500 mL) and extracted with pentane (3300 mL).
SO and evaporated
(8d). Yield 78.1 g (48%, over two steps) from allyl alcohol (42.1 g, 0.726
2
4
1
mol). Yellowish liquid; H NMR (400 MHz, CDCl
3
): δ = 6.00–5.82 (m, 3H),
at atmospheric pressure. Yield 46.9 g. Brownish liquid; used in the next
step without additional purification. The spectral and physical data were
in accordance with the literature.[58]
5.28 (d, J = 17.3 Hz, 1H), 5.15 (d, J = 10.3 Hz, 1H), 4.09 (s, 2H), 4.00 (d,
J = 5.6 Hz, 2H), 1.25 (s, 12H) ppm. Other spectral and physical data
were in accordance with the literature.[23]
4
-(Prop-2-yn-1-ylsulfonyl)but-1-ene (10f).[59] To a solution of 10e (45.4
g, 0.405 mol) in CH Cl (800 mL), MCPBA (140 g, 0.810 mol) was added
in portions at 0 C. The resulting mixture was left stirring at rt overnight.
Then 10% aq K CO (500 mL) was added, the organic phase was
separated, washed with (500 mL), dried over Na SO and
2
-(3-(Allylthio)prop-1-en-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborola-
2
2
ne (8e). The product was purified by flash chromatography (hexanes –
EtOAc (40:1) as eluent). Yield 74.4 g (46%, over two steps) from allyl
mercaptan (50.0 g, 0.674 mol). Purified by column chromatography
2
3
H
2
O
2
4
,
(
hexanes – EtOAc (40:1) as eluent). Colorless liquid; %); 1H NMR (500
MHz, CDCl ): δ = 5.84 (d, J = 2.7 Hz, 1H), 5.82–5.72 (m, 1H), 5.63 (d, J
2.7Hz, 1H), 5.10 (d, J = 3.7 Hz, 1H), 5.08 (s, 1H), 3.20 (s, 2H), 3.06 (d,
evaporated in vacuo. Yield 53.0 g (91%). Brownish liquid. The spectral
and physical data were in accordance with the literature.[
59,60]
3
=
13
1
J = 7.2 Hz, 2H), 1.29 (s, 12H) ppm; C{ H} NMR (126 MHz, CDCl
3
): δ =
General procedure for the synthesis of boronates 8 from dienes 9.
To a solution of 9 (82.0 mmol) in Et O (200 mL), a solution of t-BuLi (104
134.6, 130.1, 116.9, 83.7, 34.7, 33.5, 24.7, 24.5 (br. s) ppm; HRMS (ESI)
2
+
2
m/z calcd. for C12H22BO S [M+H] 241.1434; found: 241.1434.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
2
-(3-(Allylsulfonyl)prop-1-en-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxabo-
tert-Butyl but-3-en-1-yl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)allyl)carbamate (5c). The product was purified by flash
chromatography (hexanes – EtOAc (5:1) as eluent). Yield 61.3 g (72%)
from compound 8c (92.8 g, 0.276 mol). Colorless crystals, m.p. 104–
106C; the compound existed as a mixture of rotamers; 1H NMR (400
rolane (8f). The product was purified by flash chromatography (hexanes
–
0
2
1
2
1
EtOAc (4:1) as eluent). Yield 75.2 g (71%) from compound 10f (61.5 g,
1
.389 mol). Brownish liquid; H NMR (400 MHz, CDCl
.5 Hz, 1H), 6.00 (s, 1H), 5.92 (dq, J = 17.3, 7.5 Hz, 1H), 5.47 (d, J =
0.2 Hz, 1H), 5.42 (d, J = 17.3 Hz, 1H), 3.79 (s, 2H), 3.67 (d, J = 7.5 Hz,
H), 1.26 (s, 12H) ppm; 13C{ H} NMR (126 MHz, CDCl
25.0, 124.6, 84.4, 56.7, 56.2, 24.7, 24.4 (br. s) ppm; HRMS (ESI) m/z
S [M+NH
]+ 290.1597; found: 290.1598.
3
): δ = 6.21 (d, J =
MHz, CDCl
(s, 2H), 1.45 (s, 9H), 1.23 (s, 12H) ppm; C{ H} NMR (101 MHz, CDCl
δ = 154.9, 140.5 and 139.8, 127.8 and 127.1, 83.3, 79.3, 44.5, 40.1 and
3
): δ = 6.61 (s, 1H), 3.96 (s, 2H), 3.44 (t, J = 5.8 Hz, 2H), 2.17
1
13
1
3
): δ = 138.5,
3
):
calcd. for C12
H
25BNO
4
4
39.0, 28.5, 26.4, 24.7 ppm; MS (EI): m/z = 252 [M–C
4
H
8
]+; HRMS (ESI)
+
m/z calcd. for C16
H
28BNO
4
Na [M+H] 332.2009; found: 332.2005.
2-(3-(But-3-en-1-yloxy)prop-1-en-2-yl)-4,4,5,5-tetramethyl-1,3,2-di-
oxaborolane (8h). Yield 236 g (73%) from compound 10h (149 g, 1.36
2-(2,5-Dihydrofuran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(5d).[23] The product was purified by flash chromatography (hexanes –
1
mol). Yellowish liquid; H NMR (400 MHz, CDCl
3
): δ = 5.97–5.73 (m, 3H),
5
3
.06 (d, J = 17.2 Hz, 1H), 4.99 (d, J = 10.2 Hz, 1H), 4.09–4.04 (m, 2H),
.46 (q, J = 6.7 Hz, 2H), 2.33 (q, J = 6.7 Hz, 2H), 1.24 (s, 12H) ppm.
EtOAc (10:1) as eluent). Yield 82.2 g (85%) from compound 8d (110 g,
1
0.493 mol). Yellowish oil; H NMR (400 MHz, CDCl
3
): δ = 6.52 (t, J = 2.6
Other spectral and physical data were in accordance with the
literature.[23]
Hz, 1H), 4.77–4.69 (m, 2H), 4.69–4.61 (m, 2H), 1.25 (s, 12H) ppm;
C{ H} NMR (126 MHz, CDCl ): δ = 141.1, 83.5, 78.0, 76.4, 24.7, 24.5
3
13
1
+
(
C
br. s) ppm; MS (EI): m/z = 196 [M] ; HRMS (ESI) m/z calcd. for
+
10
H
18BO
3
[M+H] 197.1349; found: 197.1343.
tert-Butyl pent-4-en-1-yl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)allyl)carbamate (8i). The product was purified by flash
chromatography (hexanes – EtOAc (6:1) as eluent). Yield 57.6 g (77%)
from compound 10i (47.5 g, 0.213 mol). Yellowish liquid; %); the
2-(2,5-Dihydrothiophen-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(5e). Yield 9.66 g (86%) from compound 8e (12.7 g, 53.0 mmol);
compound existed as a mixture of rotamers; 1H NMR (500 MHz, CDCl
δ = 5.87 (d, J = 3.0 Hz, 1H), 5.81 (dq, J = 16.9, 7.4 Hz, 1H), 5.61 (s, 1H),
Hoveyda – Grubbs 2 generation catalyst (1.33 g, 2.12 mmol) was used
nd
3
):
nd
instead of Grubbs 2 generation catalyst. Beige powder, m.p. 78–80C;
1
5.02 (d, J = 16.9 Hz, 1H), 4.95 (d, J = 10.2 Hz, 1H), 3.96 and 3.90 (s, 2H),
H NMR (400 MHz, CDCl
3
): δ = 6.60–6.42 (m, 1H), 3.92–3.73 (m, 4H),
1.25 (s, 12H) ppm; 13C{ H} NMR (126 MHz, CDCl
41.5, 24.8. 22.2 (br. s) ppm; MS (EI): m/z = 212 [M] ; HRMS (ESI) m/z
calcd. for C10
1
): δ = 143.5, 83.7, 41.6,
3
.20 and 3.13 (t, 7.4 Hz, 2H), 2.03 (q, J = 7.4 Hz, 2H), 1.61 (quint, J = 7.4
3
Hz, 2H), 1.47 and 1.42 (s, 9H), 1.27 (s, 12H) ppm; 13C{ H} NMR (126
1
+
+
MHz, CDCl
and 49.9, 46.5, 31.1, 28.4, 27.7 and 27.3, 24.8, 24.0 (br. s) ppm; HRMS
ESI) m/z calcd. for C19
[M+H]+ 352.2659; found: 352.2669; m/z
calcd. for C19 34BNO Na [M+Na] 374.2478; found: 374.2482.
3
): δ = 155.8, 138.2, 128.4 and 128.2, 114.6, 83.5, 79.0, 50.2
H
18BO
2
S [M+H] 213.1120; found: 213.1119.
(
H35BNO
4
3
1
-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5-dihydrothiophene
,1-dioxide (5f). The product was purified by flash chromatography
+
H
4
(
hexanes – EtOAc (2:1) as eluent). Yield 32.0 g (88%) from compound 8f
(40.5 g, 0.149 mol). Brownish crystals, m.p. 115–117C; 1H NMR (500
MHz, CDCl ): δ = 6.77–6.65 (m, 1H), 3.87–3.82 (m, 2H), 3.82–3.78 (m,
2H), 1.28 (s, 12H) ppm; C{ H} NMR (126 MHz, CDCl
4,4,5,5-Tetramethyl-2-(3-(pent-4-en-1-yloxy)prop-1-en-2-yl)-1,3,2-
dioxaborolane (8j). The product was purified by flash chromatography
3
13
1
(
1
hexanes – EtOAc (10:1) as eluent). Yield 63.7 g (60%) from compound
3
): δ = 137.2, 84.5,
]+; HRMS (ESI)
1
0j (52.2 g, 0.421 mol). Yellowish liquid; H NMR (400 MHz, CDCl
3
): δ =
57.4, 56.9, 24.7, 24.6 ppm; MS (EI): m/z = 180 [M–SO
m/z calcd. for C10
2
+
5.88 (s, 2H), 5.80 (ddt, J = 17.0, 10.2, 6.9 Hz, 1H), 4.99 (dt, J = 17.0, 2.1
H
17BO
4
SNa [M+Na] 267.0838; found: 267.0847.
Hz, 1H), 4.92 (dd, J = 10.2, 2.1 Hz, 1H), 4.04 (s, 2H), 3.43 (t, J = 6.9 Hz,
H), 2.11 (q, J = 6.9 Hz, 2H), 1.66 (quint, J = 6.9 Hz, 2H), 1.24 (s, 12H)
2
2
-(5,6-Dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborola-
13
1
ppm; C{ H} NMR (126 MHz, CDCl
3
): δ = 138.5, 129.1, 114.5, 83.5, 72.3,
[23]
ne (5h). The product was purified by flash chromatography (hexanes –
EtOAc (8:1) as eluent). Yield 188 g (81%) from compound 8h (263 g,
6
C
9.8, 30.4, 29.0, 24.8, 24.3 (br. s) ppm; HRMS (ESI) m/z calcd. for
H26BO [M+H] 253.1975; found: 253.1975.
14 3
+
.10 mol). Brownish crystals; m.p. 115–117C; 1H NMR (500 MHz,
1
CDCl
3
): δ = 6.77–6.65 (m, 1H), 3.87–3.82 (m, 2H), 3.82–3.78 (m, 2H),
13
1
General procedure for the large-scale synthesis of boronates 5a–h.
1.28 (s, 12H) ppm; C{ H} NMR (126 MHz, CDCl
56.9, 24.7, 24.6 ppm; MS (EI): m/z = 180 [M–SO
calcd. for C11
3
): δ = 137.2, 84.5, 57.4,
]+; HRMS (ESI) m/z
[M+H] 211.1506; found: 211.1500.
A solution of compound 8 (1.00 mol) in CH
argon flow for 1 h, then cooled to rt, and Grubbs 2 generation catalyst
2
Cl
2
(3 L) was refluxed under
2
nd
+
H
20BO
3
(
41.1 g, 0.05 mol) was added carefully. The reaction mixture was stirred
at rt overnight (monitored by 1H NMR spectra). After the reaction was
complete, the mixture was filtered through SiO (500 g), the pad was
General procedure for the large-scale synthesis of boronates 5i and
2
5
j. A solution of compound 8 (0.238 mol) in toluene (715 mL) was
washed with EtOAc (1 L), and the combined filtrates were evaporated in
vacuo.
nd
refluxed under argon flow for 1 h, then cooled to rt, and Grubbs 2
generation catalyst (9.78 g, 11.9 mmol) was added carefully. The
reaction mixture was refluxed overnight (monitored by 1H NMR spectra).
tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5-dihydro-
1
chromatography (hexanes – EtOAc (5:1) as eluent). Yield 74.8 g (85%)
from compound 8a (96.4 g, 0.298 mol). Yellowish oil; the compound
After the reaction was complete, the mixture was filtered through SiO
2
(200 g), the pad was washed with EtOAc (250 L), and the combined
filtrates were evaporated in vacuo.
H-pyrrole-1-carboxylate (5a).[23] The product was purified by flash
existed as a mixture of rotamers; 1H NMR (500 MHz, CDCl
): δ = 6.46
and 6.41 (s, 1H), 4.31–4.02 (m, 4H), 1.45 (s, 9H), 1.26 (s, 12H) ppm;
3
tert-Butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,7-tet-
rahydro-1H-azepine-1-carboxylate (5i The product was purified by
13
1
C{ H} NMR (126 MHz, CDCl
3
): δ = 153.6, 141.6 and 141.1, 130.0 and
flash chromatography (hexanes – EtOAc (4:1) as eluent). Yield 11.3 g
1
23.3, 83.9, 79.6 and 78.9, 55.6 and 55.3, 54.9 and 54.8, 28.6, 25.0
1
(
72%) from compound 8i (17.0 g, 48.6 mmol). Brownish oil; H NMR (400
ppm; MS (EI): m/z = 239 [M–C
C
4
H
8
]+; HRMS (ESI) m/z calcd. for
MHz, CDCl
Hz, 2H), 1.78 (q, J = 6.0 Hz, 2H), 1.40 (s, 9H), 1.23 (s, 12H) ppm; C{ H}
NMR (101 MHz, CDCl ): δ = 155.7, 147.6, 83.3, 78.9, 47.6, 45.7, 28.9,
3
): δ = 6.60 (s, 1H), 3.95 (s, 2H), 3.51 (s, 2H), 2.27 (q, J = 6.0
+
15
H
26BNO
4
Na [M+Na] 318.1852; found: 318.1848.
13
1
3
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
2
8.4, 25.8, 24.8, 24.7 ppm; MS (EI): m/z = 267 [M–C
4
H
8
]+; HRMS (ESI)
tert-Butyl 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-azabicyc-
lo[4.1.0]heptane-3-carboxylate (11c).[43] The product was purified by
flash chromatography (gradient hexanes to hexanes – t-BuOMe (9:1) as
+
m/z calcd. for C17
for C17 30BNO
H
31BNO
4
[M+H] 324.2346; found: 324.2347; m/z calcd.
+
H
4
Na [M+Na] 346.2166; found: 346.2167.
eluent). Yield 39.5 g (63%) from compound 5c (60.0 g, 0.194 mol). White
1
powder, m.p. 78–81 C; H NMR (400 MHz, CDCl
3
): δ = 3.73 (d, J = 13.6
4,4,5,5-Tetramethyl-2-(2,5,6,7-tetrahydrooxepin-3-yl)-1,3,2-dioxabo-
Hz, 1H), 3.55 (d, J = 13.6 Hz, 1H), 3.37 (dt, J = 12.4, 5.7 Hz, 1H), 2.91
ddd, J = 13.6, 8.8, 5.7 Hz, 1H), 1.91 (dq, J = 12.4, 5.7 Hz, 1H), 1.82–
rolane (5j). The product was purified by flash chromatography (hexanes
(
–
0
EtOAc (11:1) as eluent). Yield 32.0 g (60%) from compound 8j (60.0 g,
.238 mol). Colorless liquid; 1H NMR (500 MHz, CDCl
): δ = 6.80–6.68
1.69 (m, 2H), 1.43 (s, 9H), 1.20 (s, 12H), 0.84 (dd, J = 8.8, 4.2 Hz, 1H),
3
1
0
.40 (t, J = 4.2 Hz, 1H) ppm; 13C{ H} NMR (126 MHz, CDCl
3
): δ = 155.2,
(
1
m, 1H), 4.27 (s, 2H), 3.83 (td, J = 5.7, 2.4Hz, 2H), 2.46–2.33 (m, 2H),
.80 (td, J = 5.7, 2.4 Hz, 2H), 1.22 (s, 12H) ppm; 1 C{ H} NMR (126 MHz,
3
1
83.1, 79.0, 43.6, 40.3, 39.7, 28.5, 24.7, 22.1, 14.8, 4.0 (br. s) ppm; MS
(
EI): m/z = 267 [M–C
4
H
8
]+; HRMS (ESI) m/z calcd. for C17
H
31BNO
4
3
CDCl ): δ = 148.2, 83.3, 72.6, 69.4, 29.0, 28.6, 24.7, 24.5 ppm; MS (EI):
[M+H]+ 324.2346; found: 324.2344; m/z calcd. for
C
30BNO Na
+
[M+H]+ 225.1662;
17
H
4
m/z = 224 [M] ; HRMS (ESI) m/z calcd. for C12H22BO
3
+
[M+Na] 346.2166; found: 346.2165.
found: 225.1662.
2
-(3-Oxabicyclo[3.1.0]hexan-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxabo-
General procedure for the synthesis of cyclopropanes 11. A solution
of boronate 5 (0.250 mol) in t-BuOMe (500 mL) was cooled to –10 C,
and Pd(OAc) (2.81 g, 12.5 mmol) was added. Then a freshly prepared
2
solution of diazomethane in t-BuOMe (0.8 mol/L, 600 mL, 0.75 mol) was
added slowly upon stirring so that the temperature remained below 0 C.
rolane (11d). The general procedure was repeated with the crude
product obtained after the first run (so that two repetitive runs were
required to complete the transformation). The product was purified by
flash chromatography (gradient hexanes to hexanes – t-BuOMe (4:1) as
eluent). Yield 15.9 g (51%) from compound 5d (29.1 g, 0.148 mol).
Brownish solid, m.p. 57–58C; H NMR (500 MHz, CDCl
(
CAUTION! Diazomethane solutions are potentially explosive and should
1
3
): δ = 3.83 (d, J
be handled with great care. The glassware used should contain no
smallest defects, and direct contact of the solution or its vapors with
ground-glass joints should be avoided, e.g. by applying a polytetrafluoro-
ethylene (fum) tape. It is also not recommended to further increase the
scale of this procedure in common (non-flow) reactors; several runs
should be performed to obtain larger quantities of the product). After the
addition was complete, the reaction mixture was stirred at the same
=
8.3 Hz, 1H), 3.78 (d, J = 8.3 Hz, 1H), 3.72 (d, J = 8.3 Hz, 1H), 3.62 (dd,
J = 8.3, 3.4 Hz, 1H), 1.71 (dt, J = 7.0, 3.4 Hz, 1H), 1.22 (s, 12H), 0.80 (dd,
J = 7.0, 3.4 Hz, 1H), 0.56 (t, J = 3.4 Hz, 1H) ppm; 13C{ H} NMR (126 MHz,
CDCl
1
3
): δ = 83.2, 71.1, 69.0, 25.0, 24.7, 24.6, 12.2 ppm; HRMS (ESI) m/z
+
calcd. for C11
H
20BO
3
[M+H] 211.1506; found: 211.1505.
temperature for an additional 1 h, then filtered through SiO
evaporated in vacuo.
2
(20 g) and
2-(3-Oxabicyclo[4.1.0]heptan-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxabo-
rolane (11g). The product was purified by flash chromatography
(
gradient hexanes to hexanes – t-BuOMe (4:1) as eluent). Yield 22.7 g
Preparation of the diazomethane solution:[61] 50% aq KOH (330 mL) and
(58%) from compound 5g (36.7 g, 0.174 mol). White powder, m.p. 81–
1
83C; H NMR (500 MHz, CDCl
3
): δ = 3.99 (d, J = 11.3 Hz, 1H), 3.82 (dd,
t-BuOMe (700 mL) were placed into a 3-L round-bottomed reactor. The
mixture was cooled to 5 °C, and 113 g (1.10 mol) of nitrosomethylurea
was added portionwise upon stirring. The aqueous phase was separated;
the organic phase was dried over solid NaOH and decanted. The
resulting solution contained 0.8 M of diazomethane (determined as
described in the literature[61]) and was used immediately in the next step.
J = 11.3, 3.1 Hz, 1H), 3.58 (ddd, J = 11.3, 5.8, 3.1 Hz, 1H), 3.14 (td, J =
1
1
8
1.3, 5.8 Hz, 1H), 2.01 (ddd, J = 14.3, 5.8, 3.1 Hz, 1H), 1.64 (ddd, J =
4.3, 11.3, 5.8 Hz, 1H), 1.21 (s, 12H), 1.11–1.02 (m, 1H), 0.93 (dd, J =
.3, 3.1 Hz, 1H), 0.63 (dd, J = 5.8, 3.1 Hz, 1H) ppm; 13C{ H} NMR (126
1
MHz, CDCl
3
): δ = 83.1, 65.5, 64.7, 24.7, 24.5, 17.1, 16.1, 1.6 (br. s) ppm;
+
[M+H]+
MS (EI): m/z = 224 [M] ; HRMS (ESI) m/z calcd. for C12
H
22BO
3
2
25.1662; found: 225.1661.
tert-Butyl 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-azabicyc-
lo[3.1.0]hexane-3-carboxylate (11a).[43] The product was purified by
flash chromatography (gradient hexanes to hexanes – t-BuOMe (9:1) as
eluent). Yield 14.2 g (64%) from compound 5a (21.2 g, 71.8 mmol).
2-(3-Oxabicyclo[4.1.0]heptan-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxabo-
rolane (11h). The product was purified by flash chromatography
gradient hexanes to hexanes – t-BuOMe (4:1) as eluent). Yield 28.0 g
(50%) from compound 5h (52.5 g, 0.250 mol). Yellowish oil; 1H NMR
500 MHz, CDCl ): δ = 4.00 (d, J = 11.4 Hz, 1H), 3.81 (d, J = 11.4 Hz,
H), 3.46 (ddd, J = 11.4, 5.6, 3.8 Hz, 1H), 3.23 (ddd, J = 11.4, 9.2, 5.6 Hz,
(
Yellowish crystals, m.p. 66–69 C; the compound existed as a mixture of
1
rotamers; H NMR (400 MHz, CDCl
3
): δ = 3.58 (d, J = 10.8 Hz, 1H), 3.44
(
1
3
(d, J = 10.8 Hz, 1H), 3.38 (d, J = 10.8 Hz, 1H), 3.31 (dd, J = 10.8, 4.2 Hz,
1
=
H), 1.60 (dt, J = 7.8, 4.2 Hz, 1H), 1.40 (s, 9H), 1.20 (s, 12H), 0.93 (dd, J
7.8, 4.2 Hz, 1H), 0.39 (t, J = 4.2 Hz, 1H) ppm; 1 C{ H} NMR (126 MHz,
3
1
1H), 1.94–1.77 (m, 1H), 1.25–1.22 (m, 1H), 1.20 (s, 12H), 0.94–0.82 (m,
H), 0.64 (dd, J = 5.6, 3.8 Hz, 1H) ppm; 13C{ H} NMR (126 MHz, CDCl
1
2
3
):
CDCl
3
): δ = 155.2 and 155.1, 83.4, 79.0 and 78.9, 49.5 and 49.3, 48.1
δ = 83.1, 67.6, 63.5, 24.6, 22.8, 16.5, 14.2, 11.2 (br. s) ppm; HRMS (ESI)
and 47.8, 28.5, 24.6, 23.7 and 23.1, 15.2 and 15.1, 11.2 (br. s) ppm; MS
+
+
1
6
m/z calcd. for C12
H
22BO
3
[M+H] 225.1662; found: 225.1661.
(
EI): m/z = 253 [M–C
4
H
8
]
;
H
R
M
S
(
E
S
I
)
m
/
z
c
a
l
c
d
.
f
o
r
C
H28BNO Na
4
+
[M+Na] 332.2009; found: 332.2007.
tert-Butyl 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-azabicyc-
lo[5.1.0]octane-3-carboxylate (11i). The product was purified by flash
chromatography (gradient hexanes to hexanes – t-BuOMe (4:1) as
eluent). Yield 8.57 g (40%) from compound 5i (20.5 g, 63.6 mmol). White
tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-
pyridine-1(2H)-carboxylate (11b).[43] The product was purified by flash
chromatography (gradient hexanes to hexanes – t-BuOMe (9:1) as
powder, m.p. 85–87C; the compound existed as a mixture of rotamers;
H NMR (400 MHz, CDCl ): δ = 3.79 (d, J = 14.5 Hz, 1H), 3.75–3.72 (m,
3
eluent). Yield 58.9 g (73%) from compound 5b (77.2 g, 0.250 mol). White
1
1
powder, m.p. 72–74 C; H NMR (400 MHz, CDCl
3
): δ = 3.83 (d, J = 14.1
1
1
H), 3.41 (d, J = 14.5 Hz, 1H), 2.80–2.56 (m, 1H), 2.04–1.89 (m, 1H),
.89–1.74 (m, 1H), 1.67–1.49 (m, 3H), 1.46 (s, 9H), 1.22 (s, 12H), 0.72
Hz, 1H), 3.58–3.25 (m, 3H), 2.84 (s, 1H), 2.13–1.98 (m, 1H), 1.62–1.52
m, 1H), 1.43 (s, 9H), 1.20 (s, 12H), 0.88 (s, 1H), 0.41 (t, J = 4.8 Hz, 1H)
(
13
1
13
1
(dd, J = 8.9, 4.0 Hz, 1H), 0.41 (t, J = 5.1 Hz, 1H) ppm; C{ H} NMR (151
MHz, CDCl ): δ = 155.4 and 155.0, 83.0, 78.8, 49.1, 48.4 and 48.0, 28.4,
27.5 and 26.7, 27.1 and 26.4, 24.7 and 24.4, 20.7 and 20.6, 13.1 and
ppm; C{ H} NMR (126 MHz, CDCl
3
): δ = 155.2, 83.2, 79.1, 42.1, 41.3,
+
3
4
0.3, 28.4, 24.7, 23.9, 16.6, 15.9 ppm; MS (EI): m/z = 267 [M–C
HRMS (ESI) m/z calcd. for C17
46.2165.
4
H
8
] ;
Na [M+Na]+ 346.2166; found:
30BNO
4
H
12.6, 8.8 (br. s) ppm; MS (EI): m/z = 281 [M–C
4
H
8
]+; HRMS (ESI) m/z
3
+
calcd. for C18
H
33BNO
4
[M+H] 338.2503; found: 338.2496.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.202000977
FULL PAPER
2-(3-Oxabicyclo[5.1.0]octan-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxabo-
m.p. >200 C; 1H NMR (400 MHz, [D
6
]DMSO): δ = 3.73 (d, J = 10.7Hz,
rolane (11j). The product was purified by flash chromatography (gradient
hexanes to hexanes – t-BuOMe (4:1) as eluent). Yield 6.87 g (38%) from
compound 5j (18.2 g, 76.0 mmol). Colorless oil; 1H NMR (500 MHz,
1H), 3.65 (dd, J = 10.7, 4.5Hz, 1H), 3.33–3.27 (m, 1H), 2.97 (td, J = 10.7,
4.5Hz, 1H), 1.69 (dt, J = 14.2, 4.5Hz, 1H), 1.30 (ddd, J = 14.2, 10.0, 5.8
Hz, 1H), 0.48 (dt, J = 8.7, 4.5Hz, 1H), 0.31–0.22 (m, 1H), –0.10– –0.18
(m, 1H) ppm; 13C{ H} NMR (151 MHz, [D
1
]DMSO): δ = 66.8, 64.5, 26.7,
]DMSO): δ =
O [M–K]– 165.0698;
CDCl
3
): δ = 4.19 (d, J = 12.2 Hz, 1H), 3.75–3.59 (m, 1H), 3.48 (t, J = 12.2
6
14.5, 13.0, 8.1 (br. s) ppm; 19F{ H} NMR (376 MHz, [D
–147.6 ppm; HRMS (ESI) m/z calcd. for C H BF
6 9 3
1
Hz, 1H), 3.31 (d, J = 12.2 Hz, 1H), 2.26–2.09 (m, 1H), 1.72–1.65 (m, 1H),
6
1
3
.63–1.48 (m, 2H), 1.36–1.27 (m, 1H), 1.22 (s, 12H), 0.85 (dd, J = 8.1,
.7 Hz, 1H), 0.72 (dd, J = 5.7, 3.7 Hz, 1H) ppm; 13C{ H} NMR (126 MHz,
1
found: 165.0705.
CDCl
3
): δ = 83.0, 75.1, 74.0, 30.8, 29.4, 24.6, 22.4, 17.5, 12.4 (br. s)
+
ppm; MS (EI): m/z = 238 [M] ; HRMS (ESI) m/z calcd. for C13
H
24BO
3
Potassium (3-oxabicyclo[4.1.0]heptan-1-yl)trifluoroborate (4h). Yield
6.4 g (95%) from compound 11h (30.5 g, 0.136 mol). White powder,
m.p. >200 C; 1H NMR (500 MHz, [D
]DMSO): δ = 3.65–3.56 (m, 2H),
+
[M+H] 239.1818; found: 239.1817.
2
6
General procedure for the preparation of trifluoroborates 4. To a
solution of compound 11 (0.232 mol) in MeOH (930 mL) and MeCN (930
3.36 (s, 1H), 2.94 (td, J = 10.6, 5.4 Hz, 1H), 1.68–1.51 (m, 2H), 0.67–
0.59 (m, 1H), 0.28 (dd, J = 7.8, 1.9 Hz, 1H), –0.12 (d, J = 4.3 Hz, 1H)
ppm; 13C{ H} NMR (126 MHz, [D
1
]DMSO): δ = 69.9, 64.0, 24.5, 14.4,
]DMSO): δ = –144.9
O [M–K]– 165.0698; found:
mL), a solution of KF (53.9 g, 0.928 mol) in H
2
O (93 mL), followed by a
6
10.9 (br. s), 10.5 ppm; 19F{ H} NMR (470 MHz, [D
ppm; HRMS (ESI) m/z calcd. for C H BF
6 9 3
1
suspension of tartaric acid (66.3 g, 0.475 mol) in THF (350 mL). The
reaction mixture was stirred at rt for 2 h; the precipitate was filtered and
washed with MeCN (300 mL). The combined filtrates were evaporated in
6
165.0710.
2
vacuo to dryness, and the residue was triturated with t-BuOMe or Et O.
Potassium (tert-butyl 3-azabicyclo[5.1.0]octane-3-carboxylate-1-yl)-
trifluoroborate (4i). Yield 6.81 g (94%) from compound 11i (7.68 g, 22.8
Potassium (tert-butyl 3-azabicyclo[3.1.0]hexane-3-carboxylate-1-yl)-
trifluoroborate (4a).[43] Yield 11.2 g (94%) from compound 11a (12.7 g,
mmol). White powder, m.p. >200 C; the compound existed as a mixture
1
4
1.2 mmol). White powder, m.p. >200 C; the compound existed as a
of rotamers; H NMR (600 MHz, [D
6
]DMSO): δ = 3.67–3.46 (m, 2H), 3.17
1
mixture of rotamers; H NMR (400 MHz, [D
6
]DMSO): δ = 3.31 (s, 1H),
and 3.07 (d, J = 13.5 Hz, 1H), 2.81–2.63 (m, 1H), 1.76 (td, J = 9.5, 4.5 Hz,
1H), 1.56–1.45 (m, 1H), 1.45–1.29 (m, 2H), 1.36 (s, 9H), 0.68–0.58 (m,
1H), 0.12–0.04 (m, 1H), –0.35 (s, 1H) ppm; 13C{ H} NMR (126 MHz,
3
1
.20–3.02 (m, 3H), 1.35 (s, 9H), 0.94 (s, 1H), 0.34 (dd, J = 7.2, 2.9 Hz,
H), –0.41 (s, 1H) ppm; 13C{ H} NMR (126 MHz, [D
1
1
6
]DMSO): δ = 155.1
and 154.9, 78.1 and 78.1, 52.3 and 51.9, 49.7 and 49.4, 28.6, 19.6, 18.8,
6
[D ]DMSO): δ = 155.5 and 154.8, 77.8, 51.0 and 50.7, 47.5 and 46.5,
28.7, 27.8 and 27.6, 27.4 and 27.0, 25.3, 17.2 and 16.9, 10.9 and 10.6
3.0 ppm; 19F{ H} NMR (376 MHz, [D
1
]DMSO): δ = –142.9 ppm; HRMS
1
6
–
ppm; 19F{ H} NMR (376 MHz, [D
1
(
ESI) m/z calcd. for C10
H
16BF
3
NO
2
[M–K] 250.1226; found: 250.1239.
6
]DMSO): δ = –145.8 ppm; HRMS (ESI)
–
m/z calcd. for C12
H
20BF
3
NO
2
[M–K] 278.1539; found: 278.1553.
Potassium (tert-butyl 3-azabicyclo[4.1.0]heptane-3-carboxylate-6-yl)-
trifluoroborate (4b).[43] Yield 53.5 g (99%) from compound 11b (57.5 g,
Potassium (3-oxabicyclo[5.1.0]octan-1-yl)trifluoroborate (4j). Yield
5.48 g (95%) from compound 11j (6.31 g, 26.5 mmol). White powder, m.p.
0
.178 mol). White powder, m.p. 241–243 C; the compound existed as a
1
>200 C; 1H NMR (600 MHz, [D
mixture of rotamers; H NMR (500 MHz, [D
6
]DMSO): δ = 3.56–3.36 (m,
6
]DMSO): δ = 3.66 (d, J = 13.0 Hz, 1H),
3
H), 3.07 (dt, J = 12.0, 5.7 Hz, 1H), 2.87 (s, 1H), 1.74 (s, 1H), 1.36 (s,
3.59–3.48 (m, 2H), 2.92 (t, J = 10.8 Hz, 1H), 1.83–1.69 (m, 2H), 1.43 (dd,
J = 13.0, 5.5 Hz, 1H), 1.36–1.25 (m, 0H), 0.71 (dd, J = 8.0, 4.4 Hz, 1H),
0.13–0.03 (m, 1H), –0.03 (d, J = 8.0 Hz, 1H) ppm; 13C{ H} NMR (126
9
H), 1.31–1.17 (m, 1H), 0.58 (s, 1H), 0.22 (dd, J = 7.6, 2.8 Hz, 1H), –0.28
s, 1H) ppm; 13C{ H} NMR (126 MHz, [D
1
1
(
6
]DMSO): δ = 154.7, 78.1, 43.3
and 42.6, 41.7, 28.6, 26.1 and 25.6, 25.4, 13.2 and 13.0, 8.7 ppm;
MHz, [D
6
]DMSO): δ = 75.5, 73.9, 30.4, 29.1, 25.3, 18.4, 10.7 ppm;
19
1
19
1
F{ H} NMR (376 MHz, [D
calcd. for C11 KNO
6
]DMSO): δ = –147.2 ppm; HRMS (ESI) m/z
[M–K] 264.1383; found: 264.1397.
F{ H} NMR (376 MHz, [D ]DMSO): δ = –144.7 ppm; HRMS (ESI) m/z
calcd. for C H11BF O [M–K] 179.08550; found: 179.0866.
7 3
6
–
–
H
18BF
3
2
Potassium (tert-butyl 3-azabicyclo[4.1.0]heptane-3-carboxylate-1-yl)-
trifluoroborate (4c).[43] Yield 35.1 g (92%) from compound 11c (40.7 g,
Acknowledgements
0
.126 mol). White powder, m.p. >200 C; the compound existed as a
1
mixture of rotamers; H NMR (500 MHz, [D
6
]DMSO): δ = 3.58 (s, 1H),
The work was funded by Enamine Ltd. O.O.G. also received
funding from Ministry of Education and Science of Ukraine (grant
No. 19BF037-03). The authors thank Prof. Andrey A. Tolmachev
for his encouragement and support, Dr. Alexey V. Dobrydnev for
his help with manuscript preparation, Dr. Andriy Kozytskyi and
Mr. Artur Breslavskyi for NMR experiments, and Mr. Denys
Bylina for HRMS measurements.
3
0
.28–3.03 (m, 2H), 2.70 (s, 1H), 1.68 (s, 1H), 1.58 (s, 1H), 1.35 (s, 9H),
.60 (s, 1H), 0.20 (d, J = 7.8 Hz, 1H), –0.34 (s, 1H) ppm; 13C{ H} NMR
1
(
2
–
126 MHz, [D
6
]DMSO): δ = 155.1 and 154.7, 77.9, 45.7, 44.9, 41.5, 28.7,
3.4 and 23.1, 12.1, 11.1 ppm; 19F{ H} NMR (376 MHz, [D
1
]DMSO): δ =
[M–K] 264.1383;
6
–
146.2 ppm; HRMS (ESI) m/z calcd. for C11 NO
H
18BF
3
2
found: 263.1382.
Potassium (3-oxabicyclo[3.1.0]hexan-1-yl) trifluoroborate (4d). Yield
2.3 g (98%) from compound 11d (13.9 g, 66.0 mmol). White powder,
m.p. >200 C; 1H NMR (500 MHz, [D
]DMSO): δ = 3.57 (d, J = 7.6Hz,
H), 3.45 (qd, J = 7.6, 2.0 Hz, 2H), 3.40 (dd, J = 7.6, 2.9 Hz, 1H), 1.02
dd, J = 6.8, 2.9 Hz, 1H), 0.20 (dd, J = 6.8, 2.0 Hz, 1H), –0.23 (s, 1H)
1
Keywords: Organoboron compounds • Cyclopropanes •
Heteroaliphatic compounds • Bicyclic compounds • Suzuki–
Miyaura reaction
6
1
(
13
1
ppm; C{ H} NMR (101 MHz, [D
s), 10.4 ppm; F{ H} NMR (470 MHz, [D ]DMSO): δ = –140.5 ppm;
HRMS (ESI) m/z calcd. for C H BF O [M–K] 151.0542; found: 151.0551.
5 7 3
6
]DMSO): δ = 73.5, 69.8, 21.1, 18.4 (br.
19
1
6
–
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European Journal of Organic Chemistry
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Entry for the Table of Contents
FULL PAPER
Heteroaliphatic trifluoroborates
Ihor Kleban, Yevhen Krokhmaliuk, Sofiia
Reut, Serhii Shuvakin, Vyacheslav V.
Pendyukh, Oleksandr I. Khyzhan,
Dmytro S. Yarmoliuk, Dr. Andriy V.
Tymtsunik,* Dr. Yuliya V. Rassukana,
Dr. Oleksandr O. Grygorenko
Multigram synthesis of oxa- and azabicyclo[n.1.0]alkan-1-yl trifluoroborates relying
on efficient 4–5-step reaction sequences is described.
Page No. – Page No.
Multigram synthesis of
heterabicyclo[n.1.0]alkan-1-yl
trifluoroborates
Twitter accounts: @EnamineLtd @KyivUniversity @DrGregor2
This article is protected by copyright. All rights reserved.