Iridium-Catalyzed Enantioconvergent Allylation of a Boron-Stabilized Organozinc Reagent

Article abstract of DOI:10.1021/acs.joc.1c01076

An iridium-catalyzed enantioconvergent coupling of the versatile boron-stabilized organozinc reagent BpinCH2ZnI with a racemic branched allylic carbonate has been developed here, which differs from our previous work by using 1,1-bisborylmethane through the kinetic resolution process. The reaction has a broad substrate scope, and various chiral homoallylic organoboronic esters could be obtained in good yields with excellent enantioselectivities. The synthetic practicability of the products was demonstrated by their conversion to other useful families of compounds.

Full text of DOI:10.1021/acs.joc.1c01076

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Iridium-Catalyzed Enantioconvergent Allylation of a Boron-
Stabilized Organozinc Reagent
Panchi Guo and Miao Zhan*
Cite This: J. Org. Chem. 2021, 86, 9905−9913
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ABSTRACT: An iridium-catalyzed enantioconvergent coupling of
the versatile boron-stabilized organozinc reagent BpinCH2ZnI with
a racemic branched allylic carbonate has been developed here,
which differs from our previous work by using 1,1-bisborylmethane
through the kinetic resolution process. The reaction has a broad
substrate scope, and various chiral homoallylic organoboronic
esters could be obtained in good yields with excellent
enantioselectivities. The synthetic practicability of the products
was demonstrated by their conversion to other useful families of compounds.
Scheme 1. Enantioselective Allylic Alkylation of a Boron-
Stabilized Organometallic Reagent with Branched Racemic
Carbonates
INTRODUCTION
■
Organoboronic acid derivatives are important and versatile
compounds in chemistry.1 The boronyl groups serve as
platforms to access other functional groups in a stereospecific
manner.2 In addition, the organoboron compounds possess
important biological activities3 and have found great value in
drug molecules, such as bortezomib, ixazomib, crisaborole, and
vaborbactam. Therefore, general and selective methods for the
preparation of organoboron compounds, especially the chiral
variants, are desirable and have been extensively studied.
Traditionally, chiral organoboron compounds were obtained
by introducing one or more boryl group [B(OR)2] to the
substrates.4−8
In recent years, bis[(pinacolato)boryl]methane (1,1-bisbor-
ylmethane) has emerged and been actively pursued by the
synthetic community, which could introduce an α-boromethyl
group (CH2Bpin) to the substrate.9 Some asymmetric
transformations have been reported, such as the deborylative
addition of 1,1-bisborylalkanes to aldehydes,10 α-ketoesters,11
imines,12 α-imino esters,12 and α,β-unsaturated carbonyls.13
1,1-Bisborylalkanes were also applied to asymmetric allylic
substitution,14 arylation,15 and alkenylation16 reactions.
Our previous work showed that the silver-assisted and
iridium-catalyzed allylation of 1,1-bisborylmethane occurred
through a kinetic resolution process when branched allylic
carbonates were used as the electrophiles (Scheme 1a),
allowing the preparation of chiral β-substituted homoallylic
organoboronates.14b It is worth mentioning that an almost-
racemic product was obtained when a 1.5:1 ratio of 1 and 2
was used. The mechanism is proposed in Scheme 1b. For the
kinetic resolution process, the rate constants for the
nucleophilic attack (k4 and k5) on allyliridium complexes A
and B are greater than the rate of isomerization (k3, complex A
to B), which means that allyliridium complex A or B, once
formed, would be captured by the nucleophile AgCH2Bpin. It
Received: May 8, 2021
Published: June 29, 2021
https://doi.org/10.1021/acs.joc.1c01076
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 9905−9913
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Note
is possible to realize the enantioconvergent process if the rate
constant k3 is greater than k4 and k5 when another nucleophile,
i.e., MCH2Bpin, is used.
Table 2. Substrate Scope of the Iridium-Catalyzed Allylation
of BpinCH2ZnI
Here, we proposed an unique and versatile alternative
boron-stabilized organozinc reagent BpinCH2ZnI, which was
developed by the Knochel group (Scheme 1a).17 It is believed
that the stabilizing effect of BpinCH2ZnI comes from the
three-coordinate boron atom adjacent to the anionic center,18
and the compound can be stored at 4 °C under nitrogen for at
least one month without noticeable decomposition or a
decrease in concentration. Unlike the common organozinc
reagents used before,19 BpinCH2ZnI containing both the
versatile boron and zinc groups should has an immense
application potential and deserves high attention. Thus far,
BpinCH2ZnI has not been used in asymmetric catalysis.20
Herein, we hope to achieve the iridium-catalyzed enantio-
convergent allylation of this boron-stabilized organozinc
reagent by the well-established method21 and explore the
properties of this organozinc reagent (5 + 2 to 6, Scheme 1c).
RESULTS AND DISCUSSION
■
We commenced our study by investigating the model reaction
between BpinCH2ZnI 5 and the branched allylic carbonate 7,
adopting the previously established conditions.14d,22 By
employing the simple reaction conditions of 2 mol %
[Ir(cod)Cl]2 and 4 mol % Carreira’s phosphoramidite olefin
ligand (R)-L in THF, the desired product 8 was obtained in a
90% yield with 97% ee (Table 1, entry 1). The yield and
Table 1. Optimization of Conditions for the Iridium-
Catalyzed Allylation of BpinCH2ZnI
b
c
entry [Ir]:L equiv of 5 in THF
solvent
THF
THF
toluene
DME
1,4-dioxane
1,4-dioxane
1,4-dioxane
yield (%)
ee (%)
1
2
3
4
5
6
7
1:1
1:2
1:2
1:2
1:2
1:2
1:2
1.5 (0.71 M)
1.5 (0.71 M)
1.5 (0.71 M)
1.5 (0.71 M)
1.5 (0.71 M)
1.3 (0.71 M)
1.3 (0.35 M)
90
93
89
93
91
92
90
97
98
>99
99
>99
>99
>99
a
Reaction conditions are as follows: 7 (0.25 mmol), [Ir(cod)Cl]2 (2
mol %), and (R)-L (4 or 8 mol %) in 0.6 mL of solvent at room
b
temperature for 16 h. Determined by 1H NMR analysis of the crude
reaction mixture with 1,3,5-trimethoxybenzene as an internal
c
standard. Enantiomeric excess (ee) values were determined by chiral
HPLC analysis. DME, 1,2-dimethoxyethane.
enantioselectivity of the reaction could be slightly improved
when a higher amount of ligand (8 mol %, [Ir]/L = 1:2) was
used (Table 1, entry 2). With 1,4-dioxane as the optimal
solvent, product 8 was obtained in a 91% yield with greater
than 99% ee (Table 1, entry 5). Decreasing the amount of
BpinCH2ZnI had little effect on the yield and the
enantioselectivity (Table 1, entry 6). Although 5 was prepared
as a 0.71 M solution in THF, we found that decreasing the
concentration of 5 did not diminish the reaction outcome
(Table 1, entry 7).
a
Reaction conditions are as follows: unless otherwise noted, the
reactions were performed on a 0.25 mmol scale with 1.3 equiv of
BpinCH2ZnI, [lr(COD)Cl]2 (2 mol %), and (R)-L (8 mol %).
Isolated yields shown. Enantiomeric excess (ee) values were
determined by chiral HPLC analysis. [lr(COD)Cl]2 (1 mol %)
and (R)-L (4 mol %) were used.
b
With the above reaction conditions established, we explored
the scope of this methodology, as depicted in Table 2. We
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Note
resolution process, this reaction was an enantioconvergent
process when the branched allylic carbonates were used. The
reaction demonstrates an excellent enantioselectivity and a
broad substrate scope, including substrates with ortho-
substitutions, heterocycles, and alkynes. The synthetic utility
of this methodology was demonstrated by the preparation of
several useful synthetic intermediates. Importantly, we noticed
in this study that BpinCH2ZnI showed a different behavior
from that of 1,1-bisborylmethane and has an enormous
application potential. The exploration of other applications
of this boron-stabilized organozinc reagent are ongoing in our
lab.
found that the allylative substitution reaction could be
successfully performed on a 4.0 mmol with little effect on
the yield and enantioselectivity when only 1 mol %
[Ir(cod)Cl]2 was used. Besides, a variety of branched allylic
carbonates participated in these transformations in good yields
with excellent enantioselectivities. For example, halide
substituents on the aryl ring were well tolerated, providing
the corresponding products in 79−85% yields with greater
than 99% ee (6a−6f). Substrates with electron-withdrawing
substituents, such as trifluoromethoxy (6g), trifluoromethyl
(6h), nitro (6i), phenyl (6j), and ester (6k) groups, were
found to be compatible in this reaction. The aromatic ring
containing an electron-donating thiophenyl (6m) or methoxy
(6n and 6o) group proved to be a competent reaction partner.
It is noteworthy that substrates with sterically demanding
groups also furnished the products with high enantioselectiv-
ities (6o−6q). Gratifyingly, when 1,4-enyne was employed as
the electrophile, product 6r was obtained in an 85% yield with
greater than 99% ee. Furthermore, the reactions with
heteroaryl allylic carbonates containing dioxolane, thiophene,
pyridine, and indole groups yielded enantioenriched homo-
allylic organoboronic esters (6s−6w) with high efficiencies and
enantioselectivities.
EXPERIMENTAL SECTION
■
General Information. Flash column chromatography was
performed using silica gel from Yantai Huanghai. Anhydrous solvents
(tetrahydrofuran (THF) and 1,4-dioxane) were purchased from
Energy Chemicals and used as received. ICH2Bpin was purchased
from Innochem and Leyan. Zinc dust was purchased from Acros and
used as received. [Ir(cod)Cl]2 was purchased from Adamas and used
as received. The chiral ligands26 and allylic carbonates27 used in this
work were prepared according to literature procedures. All air-
sensitive manipulations were carried out under a nitrogen atmosphere
in a glovebox or by standard Schlenk techniques. Glassware was dried
at 110 °C for at least 1 h prior to use. NMR yields were determined
using 1,3,5-trimethoxybenzene as an internal standard. All reported
yields of the Ir-catalyzed allylation reactions are isolated yields after
chromatography.
To further demonstrate the synthetic practicability of this
methodology, the obtained chiral organoboron product 8 was
converted to other important classes of compounds using
established methods (Scheme 2). For example, homoallylic
General Analytical Information. NMR spectra were recorded
using Bruker Avance 400 MHz spectrometers and were referenced to
1
CHCl3 (7.27 and 77.16 ppm for H and 13C, respectively). High-
resolution mass spectra (HRMS) were obtained on a WATERS I-
Class VION IMS QTof spectrometer. Optical rotations were obtained
on an Anton-paar polarimeter. Enantiomeric excesses (ees) were
determined by chiral HPLC analysis using Waters 2695 Series
chromatographs with a mixture of HPLC-grade hexane and
isopropanol as the eluent.
Scheme 2. Representative Transformations of the
Homoallyl Boronates
General Procedure for the Ir-Catalyzed Allylation of
BpinCH2ZnI. In a nitrogen-filled glovebox, [Ir(cod)Cl]2 (3.4 mg,
0.0050 mmol, 2.0 mol %) and (R)-L (P-olefin ligand, 10.2 mg, 0.02
mmol, 8 mol %) were added to a screw-capped vial equipped with a
stir bar. To the vial was added anhydrous 1,4-dioxane (0.60 mL). The
mixture was stirred for 30 min at room temperature before the
addition of branched allylic tert-butyl carbonate 2 (0.25 mmol, 1.0
equiv). Then, BpinCH2ZnI in THF (0.46 mL, 0.325 mmol, 1.3 equiv,
0.71 M) was added to the mixture. The vial was then sealed with a
screw cap and removed from the glovebox. The reaction was stirred at
25 °C for 12 h. EtOAc (10 mL) was then added to the mixture. The
resulting mixture was washed with saturated NH4Cl (5 mL) and brine
(5 mL). The organic layer was then dried (Na2SO4), filtered, and
concentrated in vacuo. The pure product was obtained after column
chromatography.
((4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)zinc-
(II) Iodide. According to Knochel’s procedure,28,20c zinc powder
(5.17 g, 79.1 mmol, 2.0 equiv) was suspended in anhydrous THF (30
mL), and anhydrous 1,2-dibromoethane (744 mg, 3.96 mmol, 0.1
equiv) was added under vigorous stirring. The solution was brought
to reflux in a heating block for a minute and then allowed to cool to
room temperature. TMSCl (86.0 mg, 0.80 mmol, 0.02 equiv) was
added, and the mixture was again refluxed in a heating block for a
minute and then cooled to room temperature. After 15 min, a solution
of ICH2Bpin (10.6 g, 39.6 mmol, 1.0 equiv) in anhydrous THF (10
mL) was added to the mixture over 30 min. The stirring was stopped
after an additional 2 h, and the solids were allowed to settle over 48 h
at 4 °C. The clear and colorless supernatant that contained
IZnCH2Bpin was titrated against I2 (1.0 equiv) in THF to determine
its concentration (0.71 M). The reagent solution with the settled
alcohol 9 could be accessed easily by the oxidation of 8 with
NaBO3·4H2O. Moreover, the hydroxymethylated product 10
could be obtained by a reaction with LiCH2Cl and subsequent
oxidation without eroding the enantiomeric excess.23 Fur-
thermore, by using the method developed by the Aggarwal
group,24 the arylated products 11 and 12 were obtained with a
complete retention of the stereochemistry. These 1,2-diaryl
scaffolds are found in many drugs and naturally occurring
compounds and their preparation is challenging through
traditional protocols.25
CONCLUSION
■
In summary, we have successfully applied the boron-stabilized
organozinc reagent BpinCH2ZnI in the iridium-catalyzed
asymmetric allylation reaction. Unlike our previous method
for the allylation of 1,1-bisborylmethane through the kinetic
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Note
excess zinc was stored at 4 °C under nitrogen for one month without
noticeable decomposition or a decrease in concentration.
(400 MHz, CDCl3) δ 7.24 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz,
2H), 5.96 (ddd, J = 17.0, 10.2, 6.8 Hz, 1H), 5.05−4.96 (m, 2H), 3.58
(ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 1.28 (dd, J = 15.3, 8.0 Hz, 1H), 1.20
(dd, J = 15.4, 7.9 Hz, 1H), 1.15 (s, 12H); 13C{1H} NMR (101 MHz,
CDCl3) δ 144.2, 143.3, 131.8, 129.01, 128.5, 113.3, 83.3, 44.5, 24.9,
24.8; 11B{1H} NMR (128 MHz, CDCl3) δ 33.1; HRMS (ESI) m/z
(R)-4,4,5,5-Tetramethyl-2-(2-phenylbut-3-en-1-yl)-1,3,2-dioxa-
borolane (8). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
1
8 (940 mg, 91%, >99% ee) as a colorless oil. H NMR (400 MHz,
+
calcd for C16H22BClNaO2 (M + Na)+ 315.1294, found 315.1299.
CDCl3) δ 7.29−7.21 (m, 4H), 7.18−7.13 (m, 1H), 6.01 (ddd, J =
17.1, 10.2, 6.9 Hz, 1H), 5.04 (dd, J = 17.1, 1.0 Hz, 1H), 4.97 (dd, J =
10.2, 0.9 Hz, 1H), 3.61 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 1.34−1.21 (m,
2H), 1.14 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3) δ 145.8,
143.8, 128.4, 127.6, 126.2, 112.9, 83.2, 45.1, 24.9, 24.8; 11B{1H} NMR
(128 MHz, CDCl3) δ 33.2; HRMS (ESI) m/z calcd for
The enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AS-
H, hexanes/iPrOH 95:5, flow rate of 1 mL/min, λ = 210 nm), tR = 8.1
min (major), tR = 7.6 min (minor); [α]2D0 = +32.4 (c = 1, CHCl3).
(R)-2-(2-(3-Chlorophenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6e). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
+
C16H23BNaO2 (M + Na)+ 281.1683, found 281.1691. The
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 99.6:0.4, flow rate of 1 mL/min, λ = 210 nm), tR =
53.9 min (major), tR = 45.3 min (minor); [α]2D0 = +8.0 (c = 1,
CHCl3).
1
compound 6e (61 mg, 83%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.23−7.18 (m, 2H), 7.16−7.13 (m, 1H), 7.12−
7.09 (m, 1H), 5.97 (ddd, J = 17.1, 10.2, 6.8 Hz, 1H), 5.05 (dt, J =
17.4, 1.5 Hz, 1H), 5.01 (dt, J = 10.2, 1.3 Hz, 1H), 3.58 (ddd, J = 7.8,
7.8, 7.8 Hz, 1H), 1.29 (dd, J = 15.4, 8.0 Hz, 1H), 1.21 (dd, J = 15.4,
8.0 Hz, 1H), 1.15 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3) δ
147.9, 143.0, 134.1, 129.7, 127.9, 126.3, 125.8, 113.6, 83.4, 44.8, 24.9,
24.8; 11B{1H} NMR (128 MHz, CDCl3) δ 33.2; HRMS (ESI) m/z
(R)-2-(2-(4-Fluorophenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6a). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6a (57 mg, 83%, >99% ee) as a colorless oil. H NMR
+
calcd for C16H22BClNaO2 (M + Na)+ 315.1294, found 315.1298.
(400 MHz, CDCl3) δ 7.22−7.14 (m, 2H), 6.99−6.91 (m, 2H), 5.97
(ddd, J = 17.0, 10.2, 6.7 Hz, 1H), 5.04−4.95 (m, 2H), 3.59 (ddd, J =
7.8, 7.8, 7.8 Hz, 1H), 1.28 (dd, J = 15.3, 7.9 Hz, 1H), 1.21 (dd, J =
15.3, 8.1 Hz, 1H), 1.14 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3)
δ 161.5 (d, J = 243.5 Hz), 143.8, 141.4 (d, J = 3.1 Hz), 129.0 (d, J =
7.8 Hz), 115.1 (d, J = 21.1 Hz), 113.0, 83.3, 44.3, 24.9, 24.9; 19F
NMR (376 MHz, CDCl3) δ: −117.6; 11B{1H} NMR (128 MHz,
The enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 99.6:0.4, flow rate of 1 mL/min, λ = 210 nm), tR =
82.4 min (major), tR = 63.1 min (minor); [α]2D0 = +32.6 (c = 1,
CHCl3).
(R)-2-(2-(3,4-Dichlorophenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6f). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
+
CDCl3) δ 33.2; HRMS (ESI) m/z calcd for C16H23BFO2 (M + H)+
277.1770, found 277.1797. The enantiomeric excess of the product
was determined after being oxidized to the corresponding alcohol by
NaBO3·4H2O. HPLC (AD-H, hexanes/iPrOH 99:1, flow rate of 1
mL/min, λ = 210 nm), tR = 26.5 min (major), tR = 29.3 min (minor);
[α]2D0 = +23.6 (c = 1, CHCl3).
1
6f (65 mg, 80%, >99% ee) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 7.34−7.31 (m, 2H), 7.06 (dd, J = 8.3, 2.1 Hz, 1H), 5.94
(ddd, J = 17.0, 10.2, 6.8 Hz, 1H), 5.05 (dt, J = 12.7, 1.3 Hz, 1H), 5.02
(dt, J = 5.8, 1.4 Hz, 1H), 3.57 (ddd, J = 7.7, 7.7, 7.7 Hz, 1H), 1.31−
1.18 (m, 2H), 1.16 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3) δ
146.1, 142.6, 132.2, 130.3, 129.9, 129.8, 127.1, 114.0, 83.5, 44.2, 24.9;
11B{1H} NMR (128 MHz, CDCl3) δ 33.1; HRMS (ESI) m/z calcd
(R)-2-(2-(4-Bromophenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6b). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
+
for C16H21BCl2NaO2 (M + Na)+ 349.0904, found 349.0914. The
compound 6b (68 mg, 81%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.43−7.34 (m, 2H), 7.15−7.05 (m, 2H), 5.95
(ddd, J = 17.0, 10.2, 6.8 Hz, 1H), 5.05−4.96 (m, 2H), 3.57 (ddd, J =
7.8, 7.8, 7.8 Hz, 1H), 1.28 (dd, J = 15.3, 8.1 Hz, 1H), 1.20 (dd, J =
15.4, 7.9 Hz, 1H), 1.15 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3)
δ 144.8, 143.2, 131.4, 129.4, 119.9, 113.4, 83.3, 44.5, 24.9, 24.8;
11B{1H} NMR (128 MHz, CDCl3) δ 33.1; HRMS (ESI) m/z calcd
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 99:1, flow rate of 1 mL/min, λ = 210 nm), tR =
36.1 min (major), tR = 39.6 min (minor); [α]2D0 = +34.6 (c = 1,
CHCl3).
(R)-4,4,5,5-Tetramethyl-2-(2-(3-(trifluoromethoxy)phenyl)but-3-
en-1-yl)-1,3,2-dioxaborolane (6g). The crude product was purified
by silica gel chromatography (50:1, petroleum ether/EtOAc) to give
+
for C16H22BBrNaO2 (M + Na)+ 359.0788, found 359.0791. The
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 95:5, flow rate of 1 mL/min, λ = 210 nm), tR = 9.6
min (major), tR = 10.9 min (minor); [α]2D0 = +52.0 (c = 1, CHCl3).
(R)-2-(2-(3-Bromophenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6c). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6g (69 mg, 81%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.29 (t, J = 7.9 Hz, 1H), 7.16 (d, J = 7.8 Hz,
1H), 7.09 (s, 1H), 7.03 (d, J = 8.1 Hz, 1H), 5.97 (ddd, J = 17.1, 10.2,
6.8 Hz, 1H), 5.03 (t, J = 13.6 Hz, 2H), 3.62 (q, J = 7.6 Hz, 1H), 1.30
(dd, J = 15.4, 8.0 Hz, 1H), 1.24 (dd, J = 15.5, 8.1 Hz, 1H), 1.14 (s,
12H); 13C{1H} NMR (101 MHz, CDCl3) δ 149.4, 148.2, 143.0,
129.6, 126.0, 120.6 (q, J = 256.7 Hz), 120.3, 118.6, 113.7, 83.4, 44.8,
24.8, 24.8; 11B{1H} NMR (128 MHz, CDCl3) δ 33.1; HRMS (ESI)
1
compound 6c (66 mg, 79%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.38 (s, 1H), 7.32−7.27 (m, 1H), 7.18−7.11
(m, 2H), 5.97 (ddd, J = 17.1, 10.2, 6.8 Hz, 1H), 5.09−4.98 (m, 2H),
3.58 (ddd, J = 7.3, 7.3, 7.3 Hz, 1H), 1.28 (dd, J = 15.1, 7.8 Hz, 1H),
1.20 (dd, J = 15.6, 8.2 Hz, 1H), 1.15 (s, 12H); 13C{1H} NMR (101
MHz, CDCl3) δ 148.2, 142.9, 130.9, 130.0, 129.2, 126.3, 122.4, 113.6,
83.4, 44.8, 24.9, 24.9; 11B{1H} NMR (128 MHz, CDCl3) δ 33.2;
+
m/z calcd for C17H22BF3NaO3 (M + Na)+ 365.1506, found
365.1511. The enantiomeric excess of the product was determined
after being oxidized to the corresponding alcohol by NaBO3·4H2O.
HPLC (AD-H, hexanes/iPrOH 99:1, flow rate of 1 mL/min, λ = 210
nm), tR = 18.1 min (major), tR = 19.5 min (minor); [α]2D0 = +20.6 (c
= 1, CHCl3).
+
HRMS (ESI) m/z calcd for C16H22BBrNaO2 (M + Na)+ 359.0788,
found 359.0791. The enantiomeric excess of the product was
determined after being oxidized to the corresponding alcohol by
NaBO3·4H2O. HPLC (OD-H, hexanes/iPrOH 98.3:1.7, flow rate of 1
mL/min, λ = 210 nm), tR = 18.5 min (major), tR = 19.6 min (minor);
[α]2D0 = +34.8 (c = 1, CHCl3).
(R)-4,4,5,5-Tetramethyl-2-(2-(4-(trifluoromethyl)phenyl)but-3-
en-1-yl)-1,3,2-dioxaborolane (6h). The crude product was purified
by silica gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6h (64 mg, 79%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.53 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.0 Hz,
2H), 5.98 (ddd, J = 17.1, 10.2, 6.8 Hz, 1H), 5.08−4.99 (m, 2H), 3.67
(ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 1.32 (dd, J = 15.4, 8.1 Hz, 1H), 1.24
(dd, J = 15.4, 7.8 Hz, 1H), 1.14 (s, 12H); 13C{1H} NMR (101 MHz,
CDCl3) δ 149.9, 142.8, 128.5 (q, J = 32.3 Hz), 128.0, 125.3 (q, J = 3.8
(R)-2-(2-(4-Chlorophenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6d). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6d (62 mg, 85%, >99% ee) as a colorless oil. H NMR
9908
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The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Hz), 124.5 (q, J = 271.8 Hz), 83.4, 44.9, 24.9, 24.8; 11B{1H} NMR
(128 MHz, CDCl3) δ 33.1; HRMS (ESI) m/z calcd for
H, hexanes/iPrOH 99:1, flow rate of 1 mL/min, λ = 210 nm), tR =
50.0 min (major), tR = 60.4 min (minor); [α]2D0 = +40.2 (c = 1,
CHCl3).
+
C17H22BF3NaO2 (M + Na)+ 349.1557, found 349.1561. The
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 99:1, flow rate of 1 mL/min, λ = 210 nm), tR =
22.9 min (major), tR = 26.2 min (minor); [α]2D0 = +25.6 (c = 1,
CHCl3).
(R)-4,4,5,5-Tetramethyl-2-(2-(4-(phenylthio)phenyl)but-3-en-1-
yl)-1,3,2-dioxaborolane (6m). The crude product was purified by
silica gel chromatography (30:1, petroleum ether/EtOAc) to give
1
compound 6m (76 mg, 83%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.36−7.31 (m, 2H), 7.30−7.27 (m, 4H), 7.25−
7.19 (m, 3H), 6.01 (ddd, J = 17.1, 10.2, 6.8 Hz, 1H), 5.07 (dt, J =
17.1, 1.4 Hz, 1H), 5.01 (dt, J = 10.2, 1.2 Hz, 1H), 3.63 (ddd, J = 7.8,
7.8, 7.8 Hz, 1H), 1.32 (dd, J = 15.3, 8.0 Hz, 1H), 1.26 (dd, J = 15.3,
8.0 Hz, 1H), 1.18 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3) δ
145.4, 143.4, 137.0, 132.2, 130.1, 129.1, 128.6, 126.6, 113.3, 83.3,
44.7, 24.9, 24.8; 11B{1H} NMR (128 MHz, CDCl3) δ 33.1; HRMS
(ESI) m/z calcd for C22H27BNaO2S+ (M + Na)+ 389.1717, found
389.1721. The enantiomeric excess of the product was determined
after being oxidized to the corresponding alcohol by NaBO3·4H2O.
HPLC (AD-H, hexanes/iPrOH 95:5, flow rate of 1 mL/min, λ = 210
nm), tR = 14.4 min (major), tR = 16.8 min (minor); [α]2D0 = +41.4 (c
= 1, CHCl3).
(R)-4,4,5,5-Tetramethyl-2-(2-(3-nitrophenyl)but-3-en-1-yl)-1,3,2-
dioxaborolane (6i). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
1
6i (58 mg, 77%, >99% ee) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 8.12−8.11 (m, 1H), 8.04 (ddd, J = 8.1, 2.1, 0.9 Hz, 1H),
7.57 (d, J = 7.7 Hz, 1H), 7.46−7.42 (m, 1H), 6.00 (ddd, J = 17.0,
10.2, 6.8 Hz, 1H), 5.14−5.02 (m, 2H), 3.73 (ddd, J = 7.6, 7.6, 7.6 Hz,
1H), 1.35 (dd, J = 15.5, 7.8 Hz, 1H), 1.25 (dd, J = 15.5, 7.9 Hz, 1H),
1.15 (s, 6H), 1.15 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ
148.4, 148.0, 142.2, 134.0, 129.2, 122.8, 121.4, 114.4, 83.5, 44.7, 24.9;
11B{1H} NMR (128 MHz, CDCl3) δ 33.0; HRMS (ESI) m/z calcd
+
for C16H22BNNaO4 (M + Na)+ 326.1534, found 326.1548. The
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 99:1, flow rate of 1 mL/min, λ = 210 nm), tR =
121.5 min (major), tR = 114.6 min (minor); [α]2D0 = +25.4 (c = 1,
CHCl3).
(R)-2-(2-(3-Methoxyphenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6n). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6n (58 mg, 81%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.21 (t, J = 7.9 Hz, 1H), 6.89−6.77 (m, 2H),
6.77−6.68 (m, 1H), 6.02 (ddd, J = 17.1, 10.2, 6.9 Hz, 1H), 5.08 (dt, J
= 17.1, 1.4 Hz, 1H), 5.02−4.98 (m, 1H), 3.81 (s, 3H), 3.61 (ddd, J =
7.6, 7.6, 7.6 Hz, 1H), 1.34−1.22 (m, 2H), 1.18 (s, 12H); 13C{1H}
NMR (101 MHz, CDCl3) δ 159.7, 147.5, 143.6, 129.4, 119.9, 113.2,
113.1, 111.5, 83.2, 55.2, 45.2, 24.9, 24.8; 11B{1H} NMR (128 MHz,
(R)-2-(2-([1,1′-Biphenyl]-4-yl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6j). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
1
6j (73 mg, 88%, >99% ee) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 7.57 (d, J = 7.5 Hz, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.44−
7.39 (m, 2H), 7.34−7.28 (m, 3H), 6.04 (ddd, J = 17.1, 10.2, 6.9 Hz,
1H), 5.13−4.97 (m, 2H), 3.66 (ddd, J = 7.7, 7.7, 7.7 Hz, 1H), 1.38−
1.24 (m, 2H), 1.15 (s, 12H); 13C{1H} NMR (101 MHz, CDCl3) δ
144.9, 143.7, 141.3, 139.1, 128.8, 128.0, 127.2, 127.1, 127.1, 113.1,
83.3, 44.8, 24.9, 24.8; 11B{1H} NMR (128 MHz, CDCl3) δ 33.2;
+
CDCl3) δ 33.2; HRMS (ESI) m/z calcd for C17H25BNaO3 (M +
Na)+ 311.1789, found 311.1795. The enantiomeric excess of the
product was determined after being oxidized to the corresponding
alcohol by NaBO3·4H2O. HPLC (AS-H, hexanes/iPrOH 95:5, flow
rate of 1 mL/min, λ = 210 nm), tR = 12.4 min (major), tR = 11.5 min
(minor); [α]2D0 = +30.4 (c = 1, CHCl3).
+
HRMS (ESI) m/z calcd for C22H27BNaO2 (M + Na)+ 357.1996,
found 357.2001. The enantiomeric excess of the product was
determined after being oxidized to the corresponding alcohol by
NaBO3·4H2O. HPLC (AS-H, hexanes/iPrOH 98:2, flow rate of 1
mL/min, λ = 254 nm), tR = 18.3 min (major), tR = 16.8 min (minor);
[α]2D0 = +36.6 (c = 1, CHCl3).
(R)-2-(2-(2-Methoxyphenyl)but-3-en-1-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (6o). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6o (61 mg, 85%, 98% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.22−7.14 (m, 2H), 6.94−6.82 (m, 2H), 6.07
(ddd, J = 17.0, 10.2, 6.7 Hz, 1H), 5.02 (dt, J = 17.2, 1.6 Hz, 1H), 4.96
(dt, J = 10.2, 1.5 Hz, 1H), 4.07 (ddd, J = 7.5, 7.5, 7.5 Hz, 1H), 3.84 (s,
3H), 1.34−1.26 (m, 2H), 1.17 (s, 6H), 1.15 (s, 6H); 13C{1H} NMR
(101 MHz, CDCl3) δ 156.9, 143.3, 134.1, 127.9, 127.1, 120.6, 112.7,
110.7, 83.1, 55.6, 37.9, 24.9, 24.8; 11B{1H} NMR (128 MHz, CDCl3)
Methyl (R)-4-(1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
but-3-en-2-yl)benzoate (6k). The crude product was purified by
silica gel chromatography (10:1, petroleum ether/EtOAc) to give
1
compound 6k (63 mg, 80%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 7.95 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz,
2H), 5.98 (ddd, J = 17.1, 10.2, 6.8 Hz, 1H), 5.08−4.98 (m, 2H), 3.89
(s, 3H), 3.67 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 1.32 (dd, J = 15.4, 8.0
Hz, 1H), 1.25 (dd, J = 15.4, 8.0 Hz, 1H), 1.14 (s, 6H), 1.13 (s, 6H);
13C{1H} NMR (101 MHz, CDCl3) δ 167.3, 151.2, 142.9, 129.8,
+
δ 33.3; HRMS (ESI) m/z calcd for C17H25BNaO3 (M + Na)+
311.1789, found 311.1785. The enantiomeric excess of the product
was determined after being oxidized to the corresponding alcohol by
NaBO3·4H2O. HPLC (AS-H, hexanes/iPrOH 95:5, flow rate of 1
mL/min, λ = 210 nm), tR = 12.2 min (major), tR = 10.1 min (minor);
[α]2D0 = +33.6 (c = 1, CHCl3).
128.1, 127.7, 113.7, 83.3, 52.1, 45.1, 24.8, 24.8; 11B{1H} NMR (128
MHz, CDCl3) δ 33.0; HRMS (ESI) m/z calcd for C18H25BNaO4+ (M
+ Na)+ 339.1738, found 339.1733. The enantiomeric excess of the
product was determined after being oxidized to the corresponding
alcohol by NaBO3·4H2O. HPLC (AS-H, hexanes/iPrOH 95:5, flow
rate of 1 mL/min, λ = 210 nm), tR = 24.7 min (major), tR = 28.6 min
(minor); [α]2D0 = +43.0 (c = 1, CHCl3).
(R)-4,4,5,5-Tetramethyl-2-(2-(naphthalen-1-yl)but-3-en-1-yl)-
1,3,2-dioxaborolane (6p). The crude product was purified by silica
gel chromatography (50:1, petroleum ether/EtOAc) to give
1
compound 6p (62 mg, 81%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 1H), 7.85−7.80 (m, 1H),
7.72−7.65 (m, 1H), 7.53−7.38 (m, 4H), 6.13 (ddd, J = 16.9, 10.3, 6.4
Hz, 1H), 5.08 (dt, J = 17.2, 1.5 Hz, 1H), 5.03 (dt, J = 10.3, 1.3 Hz,
1H), 4.47 (ddd, J = 7.7, 7.7, 7.7 Hz, 1H), 1.47−1.41 (m, 2H), 1.11 (s,
6H), 1.07 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ 143.3, 141.6,
133.9, 131.5, 128.7, 126.7, 125.6, 125.5, 125.3, 124.0, 123.9, 113.4,
83.1, 39.6, 24.7, 24.6; 11B{1H} NMR (128 MHz, CDCl3) δ 33.3;
(R)-4,4,5,5-Tetramethyl-2-(2-(naphthalen-2-yl)but-3-en-1-yl)-
1,3,2-dioxaborolane (6l). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
1
6l (66 mg, 86%, >99% ee) as a white solid. H NMR (400 MHz,
CDCl3) δ 7.81−7.73 (m, 3H), 7.67 (s, 1H), 7.47−7.36 (m, 3H), 6.08
(ddd, J = 17.1, 10.2, 6.8 Hz, 1H), 5.14−4.99 (m, 2H), 3.79 (ddd, J =
7.5, 7.5, 7.5 Hz, 1H), 1.44−1.31 (m, 2H), 1.12 (s, 12H); 13C{1H}
NMR (101 MHz, CDCl3) δ 143.6, 143.2, 133.7, 132.3, 128.0, 127.8,
127.7, 126.6, 125.9, 125.6, 125.3, 113.3, 83.3, 45.2, 24.9, 24.8;
11B{1H} NMR (128 MHz, CDCl3) δ 33.3; HRMS (ESI) m/z calcd
+
HRMS (ESI) m/z calcd for C20H25BNaO2 (M + Na)+ 331.1840,
found 331.1841. The enantiomeric excess of the product was
determined after being oxidized to the corresponding alcohol by
NaBO3·4H2O. HPLC (AD-H, hexanes/iPrOH 95:5, flow rate of 1
mL/min, λ = 210 nm), tR = 13.5 min (major), tR = 14.3 min (minor);
[α]2D0 = −40.0 (c = 1, CHCl3).
+
for C20H25BNaO2 (M + Na)+ 331.1840, found 331.1833. The
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
9909
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Note
(R)-4,4,5,5-Tetramethyl-2-(2-(o-tolyl)but-3-en-1-yl)-1,3,2-dioxa-
borolane (6q). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
15.5, 8.0 Hz, 1H), 1.24 (dd, J = 15.1, 8.4 Hz, 1H), 1.15 (s, 12H);
13C{1H} NMR (101 MHz, CDCl3) δ 149.7, 147.7, 142.7, 140.9,
135.0, 123.4, 114.0, 83.4, 42.5, 24.9; 11B{1H} NMR (128 MHz,
CDCl3) δ 33.1; HRMS (ESI) m/z calcd for C15H23BNO2+ (M + H)+
260.1816, found 260.1817. The enantiomeric excess of the product
was determined after being oxidized to the corresponding alcohol by
NaBO3·4H2O. HPLC (AS-H, hexanes/iPrOH 90:10, flow rate of 1
mL/min, λ = 254 nm), tR = 14.4 min (major), tR = 9.2 min (minor);
[α]2D0 = +11.0 (c = 1, CHCl3).
1
6q (55 mg, 81%, 99% ee) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 7.23−7.01 (m, 4H), 5.94 (ddd, J = 17.0, 10.4, 6.6 Hz, 1H),
5.02−4.89 (m, 2H), 3.84 (ddd, J = 7.5, 7.5, 7.5 Hz, 1H), 2.37 (s, 3H),
1.33−1.22 (m, 2H), 1.11 (s, 6H), 1.09 (s, 6H); 13C{1H} NMR (101
MHz, CDCl3) δ 143.47, 143.43, 135.90, 130.22, 126.61, 126.19,
125.94, 112.77, 83.17, 40.41, 24.80, 24.74, 19.76; 11B{1H} NMR (128
MHz, CDCl3) δ 33.2; HRMS (ESI) m/z calcd for C17H25BNaO2+ (M
+ Na)+ 295.1840, found 295.1843. The enantiomeric excess of the
product was determined after being oxidized to the corresponding
alcohol by NaBO3·4H2O. HPLC (AD-H, hexanes/iPrOH 99.6:0.4,
flow rate of 0.3 mL/min, λ = 210 nm), tR = 129.7 min (major), tR =
113.3 min (minor); [α]2D0 = +6.6 (c = 1, CHCl3).
(R)-2-Methoxy-5-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)but-3-en-2-yl)pyridine (6v). The crude product was purified by
silica gel chromatography (4:1, petroleum ether/EtOAc) to give
1
compound 6v (58 mg, 81%, >99% ee) as a colorless oil. H NMR
(400 MHz, CDCl3) δ 8.02 (d, J = 2.4 Hz, 1H), 7.43 (dd, J = 8.5, 2.5
Hz, 1H), 6.67 (d, J = 8.5 Hz, 1H), 5.96 (ddd, J = 17.0, 10.2, 6.6 Hz,
1H), 5.06−4.96 (m, 2H), 3.91 (s, 3H), 3.57 (ddd, J = 7.8, 7.8, 7.8 Hz,
1H), 1.33−1.18 (m, 2H), 1.16 (s, 12H); 13C{1H} NMR (101 MHz,
CDCl3) δ 162.9, 145.7, 143.3, 138.1, 133.6, 113.4, 110.5, 83.4, 53.4,
41.6, 24.9; 11B{1H} NMR (128 MHz, CDCl3) δ 33.0; HRMS (ESI)
(R)-4,4,5,5-Tetramethyl-2-(2-(phenylethynyl)but-3-en-1-yl)-1,3,2-
dioxaborolane (6r). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
1
6r (60 mg, 85%, >99% ee) as a colorless oil. H NMR (400 MHz,
+
m/z calcd for C16H25BNO3 (M + H)+ 290.1922, found 290.1924.
CDCl3) δ 7.44−7.36 (m, 2H), 7.29−7.25 (m, 3H), 5.93 (ddd, J =
17.0, 10.2, 6.7 Hz, 1H), 5.33 (br d, J = 16.9 Hz, 1H), 5.06 (br d, J =
10.0 Hz, 1H), 3.51 (ddd, J = 7.1, 7.1, 7.1 Hz, 1H), 1.26 (s, 12H),
1.24−1.15 (m, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 139.8,
131.7, 128.2, 127.7, 124.1, 114.1, 91.9, 83.5, 82.7, 31.8, 25.0, 24.9;
11B{1H} NMR (128 MHz, CDCl3) δ 33.1; HRMS (ESI) m/z calcd
The enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AS-
H, hexanes/iPrOH 90:10, flow rate of 1 mL/min, λ = 220 nm), tR =
13.0 min (major), tR = 7.7 min (minor); [α]2D0 = +39.2 (c = 1,
CHCl3).
+
for C18H23BNaO2 (M + Na)+ 305.1683, found 305.1680. The
(R)-3-(1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-
2-yl)-1-tosyl-1H-indole (6w). The crude product was purified by silica
gel chromatography (10:1, petroleum ether/EtOAc) to give
enantiomeric excess of the product was determined after being
oxidized to the corresponding alcohol by NaBO3·4H2O. HPLC (AD-
H, hexanes/iPrOH 95:5, flow rate of 1 mL/min, λ = 210 nm), tR = 8.4
min (major), tR = 9.3 min (minor); [α]2D0 = −39.6 (c = 1, CHCl3).
(R)-2-(2-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)but-3-en-1-yl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6s). The crude product
was purified by silica gel chromatography (40:1, petroleum ether/
EtOAc) to give compound 6s (64 mg, 76%, >99% ee) as a colorless
oil. 1H NMR (400 MHz, CDCl3) δ 7.03−6.87 (m, 3H), 5.95 (ddd, J
= 17.0, 10.2, 6.7 Hz, 1H), 5.07−4.98 (m, 2H), 3.60 (ddd, J = 7.5, 7.5,
7.5 Hz, 1H), 1.32−1.17 (m, 2H), 1.16 (s, 12H); 13C{1H} NMR (101
MHz, CDCl3) δ 143.9, 143.1, 142.2, 142.1, 131.8 (t, J = 254.2 Hz),
122.5, 113.6, 109.1, 109.0, 83.4, 44.8, 24.9, 24.8; 19F NMR (376 MHz,
CDCl3) δ −50.12; 11B{1H} NMR (128 MHz, CDCl3) δ 33.0; HRMS
1
compound 6w (98 mg, 87%, 98% ee) as a white solid. H NMR
(400 MHz, CDCl3) δ 7.95 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 8.3 Hz,
2H), 7.54 (d, J = 7.8 Hz, 1H), 7.36 (s, 1H), 7.30−7.25 (m, 1H),
7.21−7.16 (m, 3H), 5.94 (ddd, J = 17.2, 10.1, 7.2 Hz, 1H), 5.05 (br d,
J = 17.1 Hz, 1H), 4.99 (br d, J = 10.1 Hz, 1H), 3.79 (ddd, J = 7.5, 7.5,
7.5 Hz, 1H), 2.32 (s, 3H), 1.36−1.31 (m, 2H), 1.17 (s, 6H), 1.15 (s,
6H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.8, 142.0, 135.6, 135.5,
130.5, 129.9, 127.1, 126.9, 124.6, 122.9, 122.5, 120.6, 114.1, 113.7,
83.4, 36.3, 24.9, 24.8, 21.7; 11B{1H} NMR (128 MHz, CDCl3) δ 33.1;
HRMS (ESI) m/z calcd for C25H30BNNaO4S+ (M + Na)+ 474.1881,
found 474.1899; HPLC (AD-H, hexanes/iPrOH 95:5, flow rate of 1
mL/min, λ = 210 nm), tR = 10.6 min (major), tR = 7.9 min (minor);
[α]2D0 = −34.6 (c = 1, CHCl3).
+
(ESI) m/z calcd for C17H21BF2NaO4 (M + Na)+ 361.1393, found
(R)-2-Phenylbut-3-en-1-ol (9). To NaBO3·4H2O (0.23 g, 1.5
mmol, 6.0 equiv) was added solution of (R)-4,4,5,5-tetramethyl-2-(2-
phenylbut-3-en-1-yl)-1,3,2-dioxaborolane (65 mg, 0.25 mmol) in
THF (2.0 mL) and H2O (2.0 mL) at room temperature. The reaction
mixture was stirred overnight and extracted with ethyl acetate. The
combined organic phases were washed with water and brine, dried
(Na2SO4), and concentrated under reduced pressure to give a crude
product. Purification by silica gel chromatography (6:1, petroleum
ether/ethyl acetate) afforded the product (R)-2-phenylbut-3-en-1-ol
(31 mg, 85%, >99% ee) as a colorless oil. 1H NMR (400 MHz,
CDCl3) δ 7.40−7.34 (m, 2H), 7.30−7.25 (m, 3H), 6.04 (ddd, J =
17.2, 10.4, 7.8 Hz, 1H), 5.28−5.18 (m, 2H), 3.91−3.78 (m, 2H), 3.56
(ddd, J = 7.3, 7.3, 7.3 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ
140.7, 138.3, 128.9, 128.1, 127.1, 117.3, 66.2, 52.7; HPLC (AD-H,
hexanes/iPrOH 99.6:0.4, flow rate of 1 mL/min, λ = 210 nm), tR =
53.9 min (major), tR = 45.3 min (minor); [α]2D0 = −59.8 (c = 1,
CHCl3). The analytical data are consistent with the literature.14b
(R)-3-Phenylpent-4-en-1-ol (10). A solution of (R)-4,4,5,5-
tetramethyl-2-(2-phenylbut-3-en-1-yl)-1,3,2-dioxaborolane (65 mg,
0.25 mmol) and bromochloromethane (0.275 mmol, 32.5 μL) in
THF (3 mL) was cooled to −78 °C and then treated with n-BuLi
(110 μL, 2.5 M in hexane) dropwise over 1 min. The reaction mixture
was allowed to slowly warm to room temperature and then stirred for
2 h. Then, the reaction mixture was quenched with a saturated aq.
NH4Cl solution (1.0 mL), extracted with ethyl acetate, washed with
water and brine, dried (Na2SO4), and concentrated under reduced
pressure. The crude product was dissolved in THF/H2O (1.5 mL/1.5
mL), and NaBO3·4H2O (1.5 mmol, 0.23 g) was added to the mixture.
The reaction mixture was stirred at room temperature overnight and
361.1398. The enantiomeric excess of the product was determined
after being oxidized to the corresponding alcohol by NaBO3·4H2O.
HPLC (AD-H, hexanes/iPrOH 99:1, flow rate of 1 mL/min, λ = 210
nm), tR = 28.1 min (major), tR = 34.1 min (minor); [α]2D0 = +40.2 (c
= 1, CHCl3).
(R)-4,4,5,5-Tetramethyl-2-(2-(thiophen-3-yl)but-3-en-1-yl)-1,3,2-
dioxaborolane (6t). The crude product was purified by silica gel
chromatography (50:1, petroleum ether/EtOAc) to give compound
1
6t (52 mg, 79%, >99% ee) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 7.24 (dd, J = 4.9, 3.0 Hz, 1H), 7.02−6.97 (m, 2H), 6.00
(ddd, J = 17.2, 10.1, 7.2 Hz, 1H), 5.05 (dt, J = 17.1, 1.5 Hz, 1H),
5.02−4.96 (m, 1H), 3.73 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 1.31 (dd, J =
12.9, 5.6 Hz, 1H), 1.27 (dd, J = 13.0, 5.7 Hz, 1H), 1.19 (s, 6H), 1.19
(s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ 146.6, 143.4, 127.6,
125.3, 119.7, 113.1, 83.3, 40.7, 24.9, 24.8; 11B{1H} NMR (128 MHz,
CDCl3) δ 33.5; HRMS (ESI) m/z calcd for C14H21BNaO2S+ (M +
Na)+ 287.1248, found 287.1242. The enantiomeric excess of the
product was determined after being oxidized to the corresponding
alcohol by NaBO3·4H2O. HPLC (AS-H, hexanes/iPrOH 95:5, flow
rate of 1 mL/min, λ = 210 nm), tR = 9.3 min (major), tR = 8.8 min
(minor); [α]2D0 = +6.6 (c = 1, CHCl3).
(R)-3-(1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-
2-yl)pyridine (6u). The crude product was purified by silica gel
chromatography (4:1, petroleum ether/EtOAc) to give compound 6u
(51 mg, 79%, >99% ee) as a colorless oil. 1H NMR (400 MHz,
CDCl3) δ 8.50 (d, J = 2.1 Hz, 1H), 8.43 (dd, J = 4.8, 1.6 Hz, 1H),
7.55−7.51 (m, 1H), 7.21 (ddd, J = 7.9, 4.8, 0.5 Hz, 1H), 5.99 (ddd, J
= 17.0, 10.3, 6.7 Hz, 1H), 5.06 (dt, J = 10.5, 1.4 Hz, 1H), 5.03 (dt, J =
3.7, 1.4 Hz, 1H), 3.64 (ddd, J = 7.9, 7.9, 7.9 Hz, 1H), 1.33 (dd, J =
9910
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J. Org. Chem. 2021, 86, 9905−9913

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Note
quenched with saturated aq. Na2S2O3 (5.0 mL). The mixture was
extracted with ethyl acetate. The organic phases were washed with
water and brine, dried (Na2SO4), and concentrated under reduced
pressure. Purification of the crude product by silica gel chromatog-
raphy (6:1, petroleum ether/ethyl acetate) gave product 10 as a
1H), 7.32−7.26 (m, 2H), 7.24−7.13 (m, 3H), 6.94 (t, J = 5.6 Hz,
1H), 6.01 (ddd, J = 17.4, 10.2, 7.5 Hz, 1H), 5.05 (br d, J = 10.2 Hz,
1H), 4.99 (br d, J = 17.4 Hz, 1H), 3.62 (ddd, J = 7.7, 7.7, 7.7 Hz, 1H),
3.13 (dd, J = 13.5, 7.9 Hz, 1H), 3.02 (dd, J = 13.5, 7.7 Hz, 1H);
13C{1H} NMR (101 MHz, CDCl3) δ 158.6 (d, J = 254.2 Hz), 145.4
(d, J = 5.0 Hz), 142.6, 140.2, 137.8 (d, J = 25.0 Hz), 135.9 (d, J = 13.3
Hz), 128.7, 127.7, 126.9, 125.9, 115.6, 49.7, 34.7; HRMS (ESI) m/z
calcd for C15H15FN+ (M + H)+ 228.1183, found 228.1192; HPLC
(AD-H, hexanes/iPrOH 99:1, flow rate of 0.7 mL/min, λ = 254 nm),
tR = 13.6 min (major), tR = 14.3 min (minor); [α]2D0 = +30.0 (c = 1,
CHCl3).
1
colorless oil (31 mg, 75% yield, >99% ee). H NMR (400 MHz,
CDCl3) δ 7.37−7.31 (m, 2H), 7.26−7.21 (m, 3H), 6.01 (ddd, J =
13.6, 8.0, 6.0 Hz, 1H), 5.14−5.07 (m, 2H), 3.70−3.60 (m, 2H), 3.50
(ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 2.09−1.94 (m, 2H); 13C{1H} NMR
(101 MHz, CDCl3) δ 143.8, 142.0, 128.7, 127.7, 126.5, 114.6, 61.1,
46.4, 38.1; HPLC (AD-H, hexanes/iPrOH 99.6:0.4, flow rate of 1
mL/min, λ = 210 nm), tR = 61.2 min (major), tR = 66.2 min (minor);
[α]2D0 = −69.8 (c = 1.5, CHCl3). The analytical data are consistent
with the literature.29
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01076.
■
sı
(S)-3-Phenyl-4-(thiophen-2-yl)butan-1-ol (11). Under a nitrogen
atmosphere, n-BuLi (120 μL, 2.5 M in hexane) was added dropwise to
a solution of thiophene (0.30 mmol, 24.0 μL) in THF (1.0 mL) at 0
°C, and the mixture was stirred for 30 min. Then, the mixture was
cooled to −78 °C, and a solution of (R)-4,4,5,5-tetramethyl-2-(2-
phenylbut-3-en-1-yl)-1,3,2-dioxaborolane (65 mg, 0.25 mmol) in
THF (1.0 mL) was added dropwise. The mixture was then stirred for
1 h. Next, a solution of NBS (0.30 mmol, 53.4 mg) in THF (1.0 mL)
was added dropwise. After 1 h, saturated aq. Na2S2O3 (2.0 mL) was
added to the mixture. Then, the reaction mixture was allowed to
warm to room temperature. Subsequently, water and brine were
added, and the mixture was extracted with ethyl acetate. The organic
layer was dried (Na2SO4), filtered, and concentrated under vacuum.
The crude product was used in the next step without further
purification. To the product obtained was added THF (0.50 mL) and
9-BBN (0.50 M, 0.90 mL). The mixture was stirred at room
temperature for 4 h. Then, a NaOH aqueous solution (0.5 mL, 3 M)
and 30% H2O2 (0.5 mL) were added, and the reaction mixture was
stirred at room temperature overnight. After extractive workup and
column chromatography, the title compound was isolated by silica gel
chromatography (6:1, petroleum ether/ethyl acetate) as a colorless oil
1H NMR spectra, 13C NMR spectra, and chiral HPLC
analysis data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Miao Zhan − Institute of Medical Research, Northwestern
Polytechnical University, Xi’an, Shaanxi 710072, P.
R.China; orcid.org/0000-0002-6492-5104;
Email: mzhan@nwpu.edu.cn
Author
Panchi Guo − Institute of Medical Research, Northwestern
Polytechnical University, Xi’an, Shaanxi 710072, P. R.China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01076
1
(40 mg, 69%, >99% ee). H NMR (400 MHz, CDCl3) δ 7.32−7.27
Notes
(m, 2H), 7.23−7.14 (m, 3H), 7.06 (d, J = 5.1 Hz, 1H), 6.87−6.80 (m,
1H), 6.65 (d, J = 3.2 Hz, 1H), 3.60−3.49 (m, 1H), 3.48−3.40 (m,
1H), 3.18−3.09 (m, 2H), 3.07−2.99 (m, 1H), 2.10−1.95 (m, 1H),
1.95−1.78 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.0,
142.9, 128.7, 127.8, 126.7, 126.7, 125.5, 123.5, 61.1, 44.9, 38.5, 37.7;
HRMS (ESI) m/z calcd for C14H16NaOS+ (M + Na)+ 255.0814,
found 255.0816; HPLC (AS-H, hexanes/iPrOH 98:2, flow rate of 1
mL/min, λ = 210 nm), tR = 33.0 min (major), tR = 25.6 min (minor);
[α]2D0 = +88.4 (c = 1.5, CHCl3).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was provided by the National Natural
Science Foundation of China (no. 22001210) and the
Fundamental Research Funds for the Central Universities
(no. 31020200QD016). We thank Professor Dawen Niu
(Sichuan University) for assistance in the preparation of this
manuscript.
(R)-3-Fluoro-4-(2-phenylbut-3-en-1-yl)pyridine (12). To an oven-
dried tube were added diisopropylamine (112 μL, 0.80 mmol, 2.0
equiv) and anhydrous THF (1.0 mL) under a nitrogen atmosphere.
Then, the reaction tube was cooled to −60 °C. n-BuLi (110 μL, 2.5 M
in hexanes) was added dropwise over 1 min, and the mixture was
stirred for 30 min. Next, 3-fluoropyridine (25 mg, 0.26 mmol) in
anhydrous THF (0.5 mL) was added, and the mixture was stirred for
30 min at −60 °C. Subsequently, the reaction mixture was cooled to
−78 °C. (R)-4,4,5,5-Tetramethyl-2-(2-phenylbut-3-en-1-yl)-1,3,2-di-
oxaborolane (52 mg, 0.2 mmol) in anhydrous THF (1.0 mL) was
added, and the mixture was stirred for 2 h at −78 °C. Next, 2,2,2-
trichlorethoxycarbonyl chloride (110 mg, 0.52 mmol) was added, and
the reaction mixture was stirred at −78 °C overnight. Then, the
reaction mixture was warmed to room temperature and stirred for 8 h.
Subsequently, water and saturated aqueous NaHCO3 were added, and
the mixture was extracted with ethyl acetate. The organic layers were
dried over anhydrous Na2SO4 and concentrated. Then, THF (1.0
mL) was added to the residue, and the solution was cooled to 0 °C.
Then, NaOH (2 M in H2O, 0.8 mL) and H2O2 (30% in H2O, 0.8
mL) were added, and the reaction mixture was stirred at room
temperature overnight. The mixture was extracted with ethyl acetate.
The organic phase was dried (Na2SO4) and concentrated in vacuo.
The crude product was purified by silica gel chromatography (3:1,
petroleum ether/ethyl acetate) as a colorless oil (34 mg, 75%, >99%
ee). 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 8.21 (d, J = 4.8 Hz,
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