Synthesis of fluorine-substituted [2.2]paracyclophane-based carbene precursors for copper-catalyzed enantioselective boration of α,β-unsaturated ketones

Article abstract of DOI:10.1016/j.tetasy.2016.12.005

Fluorine-substituted [2.2]paracyclophane-based carbene precursors have been successfully synthesized and applied to copper-catalyzed asymmetric β-boration of α,β-unsaturated ketones. Fluorination of the planar chiral carbenes has a beneficial impact on th

Full text of DOI:10.1016/j.tetasy.2016.12.005

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of fluorine-substituted [2.2]paracyclophane-based
carbene precursors for copper-catalyzed enantioselective
boration of
a,b-unsaturated ketones
y
y
⇑
⇑
Linyong Wang , Meng Ye , Lei Wang, Wenzeng Duan, Chun Song , Yudao Ma
Department of Chemistry, Shandong University, Shanda South Road No. 27, Jinan 250100, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Fluorine-substituted [2.2]paracyclophane-based carbene precursors have been successfully synthesized
and applied to copper-catalyzed asymmetric b-boration of ,b-unsaturated ketones. Fluorination of the
planar chiral carbenes has a beneficial impact on the catalytic performance of the relevant complexes.
A variety of chiral b-boryl ketones were obtained in excellent yields (up to 99%) and with high enantios-
electivities (up to 99% ee).
Received 23 August 2016
Revised 18 November 2016
Accepted 22 November 2016
Available online xxxx
a
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
with p-conjugated skeletons. In addition to the special electronic
properties, the [2.2]paracyclophane backbone as a planar chiral
source has inspired great interest from researchers in asymmetric
catalysis.8 Over the past few years, we have exploited the use of
planar chiral NHC precursors derived from [2.2]paracyclophane
as ligands for transition metal-catalyzed asymmetric transforma-
tions, including copper-catalyzed enantioselective boration.9 We
synthesized a series of planar chiral pseudo-ortho-substituted
[2.2]paracyclophane-based NHC precursors and evaluated their
transannular electronic effects and chiral discrimination ability
Chiral organoboron compounds play a critical role in the field of
synthetic chemistry because the carbon–boron bond can be chan-
ged into a wide range of functional groups without a loss of enan-
tiopurity.1 Recently,
a large number of methods have been
developed for the synthesis of these compounds.2 The most
straightforward approach to access chiral organoboron compounds
is catalytic enantioselective conjugate addition of diboron reagents
to
the copper-catalyzed asymmetric b-boration of
a
,b-unsaturated carbonyl compounds.3 Yun et al. first reported
a,b-unsaturated
based on the Cu-catalyzed asymmetric b-boration of a,b-unsatu-
carbonyl compounds.4 Subsequently, Fernández et al. disclosed
the first successful example of the carbene-copper catalyzed enan-
tioselective boration reaction.5 Since then, catalysis mediated by
N-heterocyclic carbenes (NHCs) as well as their metal complexes,
has been developed as a powerful tool for the synthesis of chiral
organoboron compounds.6 Nevertheless, designing more efficient
NHCs as well as their metal complexes that are more reactive
and stereoselective in the established reactivity remains a major
focus.
rated esters.9i Our efforts led to the development of a planar
chiral carbene-copper catalyst derived from the fluorinated
[2.2]paracyclophane, which exhibited an exceptionally high
reactivity and enantioselectivity in the asymmetric b-boration of
a
,b-unsaturated esters by virtue of transannular electronic
effects.9i To probe the effect of backbone fluorination on the
catalytic activity, we have focused our attention on the
preparation of new fluorine-substituted [2.2]paracyclophane-
based carbene precursors. Herein, we report the modifications of
this type of ligand on the [2.2]paracyclophane skeleton and their
Cyclophanes are a class of aromatic compounds, which consist
of two phenyl rings locked face-to-face by aliphatic chains.7 The
[2.2]paracyclophane core holds the two phenyl rings together with
a well-defined orientation and facilitates strong through-space
electronic interactions between the upper and lower rings in
addition to the through-bond interactions normally associated
application in the copper-catalyzed asymmetric b-boration of
b-unsaturated ketones.
a,
2. Results and discussion
We designed three new planar chiral NHC precursors based
on the [2.2]paracyclophane skeleton (Fig. 1). The synthetic
route to the fluorine-substituted [2.2]paracyclophane based
imidazolium bromide is shown in Scheme 1. Our work started from
⇑
Corresponding author. Tel.: +86 531 88361869; fax: +86 531 88364464.
E-mail addresses: chunsong@sdu.edu.cn (C. Song), ydma@sdu.edu.cn (Y. Ma).
These authors contributed equally to this work.
y
http://dx.doi.org/10.1016/j.tetasy.2016.12.005
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
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2
L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
enantiomerically pure (RP)-2b (Scheme 2). The N-formylation
N
N
product 4b was obtained in good yield by treating 3b with a
mixture of acetic anhydride and formic acid at 50 °C for 24 h.
Next, 4b under acidic conditions underwent hydrolysis to give
formohydrazine hydrochloride 5b, which was used for next step
directly without further purification. Finally, (R, RP)-L3 was
obtained in high yield by reacting 5b with iminoether at 50 °C
for 3 h, followed by ring-closing with triethyl orthoformate
110 °C for 5 h (Scheme 2).
Br
Br
N
N
F
F
F
F
L2
(Sp)-
L1
(Sp)-
O
O
N
N
N
N
N
N
With the optimal routes to enantiomerically pure NHC precur-
sors, we set out to explore the catalytic activity of these fluorine-
substituted [2.2]paracyclophane-based NHC precursors. We
focused on the copper-catalyzed asymmetric boration of chalcones
as this transformation with high levels of enantioselectivity was
achieved by a NHC-copper catalyst prepared from unsubstituted
[2.2]paracyclophane-based bicyclic 1,2,4-triazolium salt (R,RP)-
L4.9f We tested to determine if the introduction a fluorine atom
at the pseudo-ortho position of [2.2]paracyclophane backbone
could enhance the enantioselectivity in the asymmetric
conjugate boration reaction. Therefore, we used the NHC-copper
complex as the catalyst generated in THF by the reaction of the
triazolium salt (R,RP)-L3 and Cu2O for the asymmetric b-boration
Ph
Ph
Cl
Cl
F
L3
(R,Rp)-
L4
(R,Rp)-
Figure 1. Structures of [2.2]paracyclophane-based NHC precursors.
enantiomerically pure (RP)-4-amino-13-bromo[2.2]paracyclo-
phane 1a or (RP)-4-amino-12-bromo[2.2]paracyclophane 1b.10
The (RP)-4-bromo-12-fluoro [2.2]paracyclophane 2b was easily
obtained in enantiopure form from enantiomerically pure (RP)-1b
by the Balz-Schiemann reaction at 60 °C. However, it was con-
firmed that the thermal decomposition of diazonium fluoroborate
derived from (RP)-1a was accompanied by partial racemization,
affording the product 4-bromo-13-fluoro[2.2]paracyclophane 2a
with an er value of 74:26 by chiral HPLC analysis.11 Enantiomeri-
cally pure (RP)-2a was achieved by recrystallization (three times
from hexane).
Next, (SP)-4-amino-13-fluoro[2.2]paracyclophane 4a was pre-
pared in high yields from (RP)-2a via Pd-catalyzed amination, fol-
lowed by imine 3a hydrolysis under acidic conditions.10b
Compound (SP)-4a was reacted with aqueous glyoxal in THF to
furnish the desired diimine 5a in quantitative yield.
Subsequently, the diimine was treated with a solution of silver
trifluoromethanesulfonate and chloromethyl pivalate in dark
conditions at 40 °C to form imidazolium triflate. Finally, the
of
a,b-unsaturated ketone 6a. Unfortunately, our initial attempt
to promote this transformation using THF as solvent was not
successful, affording product 7a in 91% yield and 88% ee (Table 1,
entry 1). The reaction parameters were investigated with
a
particular emphasis on solvent effects. Among the solvents
screened (Table 1, entries 1–7), toluene gave the best result in
terms of both enantioselectivity (97% ee) and yield (98%); hence
it was chosen as the optimal solvent. Inspired by this result,
several alcohol additives were next examined using (R,RP)-L3 as
the ligand and toluene as the solvent. Increasing the size of the
alkyl moiety of the alcohol to ethyl, iso-propyl as well as tert-
butyl led to a decrease in the yield and enantiomeric excess
accordingly (Table 1, entries 8–10). The reasonable outcomes
that were comparable to those obtained with alkyl alcohols were
also achieved when fluorine-substituted alcohols, such as 2,2,2-
trifluoroethanol (TFE) or 3,3,3,30,30,30-hexafluoro-2-propanol
(HFIP), were used as additives (Table 1, entries 11–12).
pseudo-gem
imidazolium bromide (SP)-L2 was obtained from its triflate
analogue by anion exchange with saturated KBr aqueous
fluorine-substituted
[2.2]paracyclophane-based
a
solution. In addition, (SP)-L1 was also synthesized from (RP)-2b
using the same procedure as described above (Scheme 1).
On the basis of our previous report,9e (RP)-pseudo-ortho
To further our understanding of this new class of NHC precur-
sors, we turned our attention to the planar chiral fluorine-substi-
tuted [2.2]paracyclophane-based imidazolium salts (SP)-L1 and
(SP)-L2 (Table 2). We first applied the above optimized reaction
fluorine-substituted
[2.2]paracyclophanyl
benzophenone
hydrazone 3b was easily prepared in high yields from
conditions for
a,b-unsaturated ketone 6a to the model substrate
(Ph)2C=NH
1. HBF4, isoamyl nitrite
R
Pd-dppf, t-BuONa
toluene 110 oC
Br
2. toluene, 60
&
Br
F
NH2
3. recrystallization
1a
3a
2a
28% yield
1. HCl/ THF
O
O
2. NaOH
N=C(Ph)2
NH2
4a 74% yield
THF
F
F
1. AgOTf
ClCH2OOPiv
Br
2. KBr / CH2Cl2
N
N
N
N
F
F
F
F
5a
L2
(SP)-
Scheme 1. Synthesis of imidazolium bromide.
43% yield
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L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
CHO
NN
Ph
Ph
Ph
Br
NHN
(Ph)2C=NNH2
Ph
HCOOH / Ac2O
pd-dppf / t-BuONa
F
F
F
toluene, 110 oC
3b 83% yield
2b
4b 84% yield
O
CHO
O
N
N
N
N
NH2HCl
N
C2H5OH / HCl
Ph
OMe
C
Ph
Cl
1. MeOH, 50 o
F
F
2. HC(OEt)3,110 oC
L3
(R,RP)-
90% yield
5b
80% yield
Scheme 2
Scheme 2. Synthesis of triazolium chloride.
Table 1
Optimization of the reaction conditionsa
Bpin
O
Cu2O (2.5 mol%)
(RP,RP)-L3 (5.0 mol%)
O
Cl
Cl
B2(Pin)2
Cs2CO3 (5.0 mol%)
ROH (2.0 equiv)
solvent, 0 oC
7a
6a
Entry
Solvent
ROH (2 equiv)
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
THF
DCM
Dioxane
DME
Ether
CH3CN
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
i-PrOH
t-BuOH
CF3CH2OH
(CF3)2CHOH
91
94
96
95
95
88
98
96
94
91
95
82
88 (R)
90 (R)
94 (R)
90 (R)
90 (R)
65 (R)
97 (R)
94 (R)
93 (R)
92 (R)
93 (R)
90 (R)
9
10
11
12
a
The reaction was carried out with(R,RP)-L3 (5.0 mol %), Cu2O (2.5 mol %), Cs2CO3 (5.0 mol %), B2(Pin)2 (0.11 mmol), 6a (0.1 mmol), and ROH (0.2 mmol) in solvent (1.0 mL)
at 0 °C for 8 min.
b
Isolated yield.
c
Determined by chiral HPLC (CHIRALPAK IA Columns) analysis.
Table 2
Examination of chiral NHC precursors and temperature
Bpin
O
O
Cu2O (2.5 mol%)
L
(5.0 mol%)
B2(Pin)2
Cs2CO3 (5.0 mol%)
MeOH (2.0 equiv)
toluene, temperature
6b
7b
Entry
Ligand
T (°C)
Time
Yield (%)
ee%
1
2
3
4
5
6
(SP)-L1
(SP)-L2
(R,RP)-L3
(R,RP)-L3
(R,RP)-L3
(R,RP)-L4
0
0
0
ꢀ20
ꢀ40
ꢀ20
3 h
3 h
8 min
30 min
60 min
30 min
86
93
99
99
67
85
85 (S)
82 (S)
98 (R)
99 (R)
99 (R)
97 (R)
chalcone 6b. As expected, the asymmetric conjugate boration reac-
tion also proceeded using planar chiral imidazolium salts (SP)-L1
and (SP)-L2 as ligands, providing the desired product 7b with mod-
erate enantioselectivities (Table 2, entries 1 and 2). Using 1,2,4-tri-
azolium salt (R,RP)-L3 as the ligand, the desired boration reaction
was completed within 8 minutes at 0 °C, affording product 7b with
99% yield and 98% ee (Table 2, entry 3). The results indicated that
the planar and centrally chiral 1,2,4-triazolium salt (R,RP)-L3
showed a much better catalytic performance compared to the pla-
nar chiral imidazolium salts (SP)-L1 and (SP)-L2. At this stage, the
impact of temperature on the boration reaction was examined.
The enantioselectivity could be increased from 98% to 99% ee by
Please cite this article in press as: Wang, L.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.12.005

4
L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
decreasing the reaction temperature from 0 to ꢀ20 °C while
extending the reaction time from 8 to 30 min (Table 2, entry 4).
The boration reaction still proceeded smoothly with excellent
enantiomeric excess at ꢀ40 °C, albeit the yield of the reaction
decreased (Table 2, entry 5). It was found that fluorination of the
planar chiral carbene had a beneficial impact on the catalytic per-
formance of the relevant NHC-copper complex. Thus, the NHC–
copper catalyst generated from unsubstituted [2.2]paracyclo-
phane-based 1,2,4-triazolium salt (R,RP)-L4 displayed lower cat-
alytic activity at ꢀ20 °C (Table 2, entry 6).
were taken on a polarimeter with a wavelength of 589 nm. The
concentration ‘c’ has units of g/100 ml (or 10 mg/ml) unless other-
wise noted.
4.2. (RP)-4-Bromo-13-fluoro[2.2]paracyclophane 2a
Enantiomerically pure (RP)-4-amino-13-bromo[2.2]paracyclo-
phane 1a10a (180 mg, 0.60 mmol) was added slowly to a stirred
solution of 40% HBF4 (0.30 mL, 1.80 mmol) in ethanol (0.50 mL)
at 0 °C until a clear solution was achieved. The solution was
cooled to ꢀ5 °C, and then iso-amyl nitrite (0.30 mL, 2.2 mmol)
was added dropwise. The temperature was kept at ꢀ5 °C and
stirring was continued for another 1 h. Diethyl ether (0.70 mL)
was added to the reaction mixture and then the resulting
precipitate was filtered, washed with diethyl ether (2.0 mL), and
finally dried under vacuum to give the diazonium fluoroborate
which was used directly without further purification (204 mg,
85% yield). A mixture of diazonium fluoroborate (204 mg) in
toluene (50.0 mL) was stirred and heated to 80–90 °C until
nitrogen no longer evolved. The solvent was evaporated at
reduced pressure and the residue was purified by
chromatography on silica gel (hexanes as the eluent) affording
product 2a (110 mg, 70% yield) with an er value of 74:26 by
chiral HPLC analysis.12 After recrystallization three times from hex-
ane, enantiomerically pure (RP)-2a was obtained as a white solid.
The optimized reaction conditions were used for further evalu-
ation of the substrate scope (Table 3). The boration reactions of
chalcones bearing various substituents at the benzene rings in
the presence of the NHC-copper catalyst derived from (R,RP)-L3
proceeded rapidly to give the corresponding products in high
yields and with excellent enantioselectivities (Table 3, entries
1–8 and 10–12). These results revealed that the substituents at
the benzene rings of chalcones had little effect on the reactivity
or enantioselectivity, no matter whether it is electron-donating
or electron-withdrawing. An extended aromatic ring such as
naphthalene was also tolerated and provided the desired product
with excellent enantioselectivity (Table 3, entry 8). Moreover, a
heteroaromatic thiophene-substituted substrate was compatible
with the reaction conditions and afforded the corresponding
product in 96% yield and with 98% ee (Table 3, entries 13). Further-
more, the scope was extended to alkyl-substituted
a,b-unsaturated
Yield: 31 mg (28%, 99.7% ee); mp: 168–170 °C; [
a]
20 = ꢀ145.8
D
enones. Unfortunately, the enone with a methyl group at the car-
bonyl carbon gave the b-boryl ketone with poor enantioselectivity
(48% ee). However, when the substrate bearing a t-butyl group
substituted at the carbonyl carbon was subjected to the boration
reaction, the excellent enantioselectivity (98% ee) was obtained
again. It is worth noting that the steric hindrance of the alkyl group
at the carbonyl carbon can significantly affect the enantioselectiv-
ity (Table 3, entries 14–15). In contrast, when a methyl group was
(c 0.39, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt):
d 6.77 (d,
J = 1.8 Hz, 1H), 6.39–6.53 (m, 4H), 6.14 (dd, J = 11.4 Hz, 1.5 Hz,
1H), 3.54–3.70 (m, 2H), 2.88–3.13 (m, 5H), 2.74–2.82 (m, 1H);
13C NMR (75 MHz, CDCl3): d 166.2 (d, J = 246.8 Hz), 141.7 (d,
J = 6.8 Hz), 140.4, 135.8, 134.8 (d, J = 7.5 Hz), 134.7, 131.6, 124.7
(d, J = 17.3 Hz), 123.4, 120.4, 120.1, 34.4, 34.3, 34.2, 27.4; HRMS
(ESI): Calcd for (M+H)+ C16H15BrF: 305.0341, found: cannot be ion-
ized by ESI.
introduced at the b-position of the
a,b-unsaturated enone, the
corresponding product was obtained with high enantiomeric
excess (Table 3, entry 16). trans-4-Hexen-3-one was also readily
borated to give the adduct in 99% yield and with 96% ee (Table 3,
entry 17).
4.3. (SP)-4-Amino-13-fluoro[2.2]paracyclophane 4a
In a glove box, an oven-dried Schlenk tube were charged with
Pd-DPPF (7.32 mg, 0.01 mmol), 4,12-bis(benzhydrylideneamino)
[2,2]paracyclophane (5.67 mg, 0.01 mmol), enantiomerically pure
(RP)-2a (304 mg, 1.0 mmol), benzhydrylideneamine (271 mg,
1.5 mmol), sodium t-butoxide (144 mg, 1.5 mmol) and anhydrous
toluene (3.0 mL). The mixture was stirred at 110 °C under nitrogen
for 12 h. After the reaction mixture was cooled to room tempera-
ture, and diluted with CH2Cl2 (10.0 mL), HOAc was added to the
mixture until the stirred solution tested acidic (pH 6), and then
washed with water (3 ꢁ 10.0 mL). The solvent was removed under
reduced pressure to give a residue, which was purified by silica gel
column chromatography using hexanes:ethyl acetate (10:0–10:2)
as eluent to give the crude product (SP)-3a as a yellow solid. To
the solution of (RP)-3a (1.0 mmol) in THF (6.0 mL) was added con-
centrated HCl (12.0 M, 0.25 mL, 3.0 mmol), and stirred at 30 °C for
4 h. After the yellow mixture fading, the solvent was removed
under vacuum. The residue was dissolved in ethanol (10.0 mL)
and stirred, after which saturated NaOH (10.0 M, 0.15 mL,
1.5 mmol) was added dropwise until the stirred mixture tested
basic (pH 9). The solvent was removed under reduced pressure,
and the residue was purified by chromatography on silica gel (pet-
roleum ether/ethyl acetate = 10:1) to furnish the desired product
(SP)-4-amino-13-fluoro[2.2]paracyclophane 4a. Yield: 179 mg
3. Conclusion
In conclusion, the fluorine-substituted [2.2]paracyclophane-
based carbene precursors have been successfully synthesized and
applied to copper-catalyzed asymmetric b-borations of a,b-unsat-
urated ketones. It was found that fluorination of the planar chiral
carbenes has a beneficial impact on the catalytic activity of rele-
vant complexes. The planar and centrally chiral 1,2,4-triazolium
salt (R,RP)-L3 exhibited a significantly better catalytic performance
compared to the planar chiral imidazolium salts (SP)-L1 and (SP)-
L2. The boration reactions of a,b-unsaturated ketones in the pres-
ence of the NHC-copper catalyst derived from (R,RP)-L3 proceeded
rapidly to give the corresponding chiral b-boryl ketones in excel-
lent yields (up to 99%) and enantioselectivities (up to 99% ee).
4. Experimental
4.1. General
(74%, white solid); mp: 182–184 °C, [
a
]
20 = ꢀ82.5 (c 0.29, CH2Cl2);
Commercially available reagents were used without further
purification unless otherwise noted. Solvents were reagent grade
and purified by standard techniques. Melting points were recorded
on a melting point apparatus and are uncorrected. 1H and 13C spec-
tra were recorded on 300 MHz spectrometers. Mass spectra were
recorded on an Accurate-Mass LC-ESI-Q-TOF-MS. Optical rotations
D
1HNMR (300 MHz, CDCl3): d 6.50–6.34 (m, 2H), 6.30 (d, J = 7.7 Hz,
1H), 6.24 (dd, J = 11.8, 1.4 Hz, 1H), 6.09 (dd, J = 7.7, 1.4 Hz, 1H),
5.76 (s, 1H), 3.66–3.53 (m, 1H), 3.37–3.24 (m, 1H), 3.07–2.94 (m,
3H), 2.93–2.87 (m, 1H), 2.86–2.72 (m, 2H); 13C NMR (75 MHz,
CDCl3): d 162.4 (d, J = 242.0 Hz) 145.1, 141.5 (d, J = 7.5 Hz), 140.1,
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L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
Table 3
Investigating the substrate scope of the reactiona
L3
(R,RP)-
(5.0 mol%)
O
Bpin O
Cu2O (2.5 mol%)
B2(Pin)2
R1
R2
R1
R2
Cs2CO3 (5.0 mol%)
MeOH (2.0 equiv)
toluene, -20 oC
6
7
Entry
R1
R2
Yield (%)b
ee (%)c,d
1
2
3
4
5
6
7
8
3-ClC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
98 7a
99 7b
97 7c
98 7d
99 7e
96 7f
95 7g
99 7h
97 7i
99 7j
97 (R)
99 (R)
99 (R)
98 (R)
98 (R)
96 (R)
99 (R)
98 (R)
99 (R)
97 (R)
98 (R)
97 (R)
98 (R)
48 (R)
98 (R)
92 (R)
96 (ꢀ)
2-ClC6H4
4-ClC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
4-MeC6H4
1-Naphthyl
Ph
Ph
Ph
2-Thienyl
Ph
Ph
9
10
11
12
13
14
15
16
17
4-FC6H4–
4-MeOC6H4
4-MeC6H4
Ph
Me
t-Bu
Ph
97 7k
99 7l
96 7m
91 7n
99 7o
99 7p
99 7q
Me
Me
Et
a
The reaction was carried out with (R,RP)-L3 (5.0 mol %), Cu2O (2.5 mol %), Cs2CO3 (5.0 mol %), B2(Pin)2 (0.11 mmol), 6 (0.1 mmol), and MeOH (0.2 mmol) in toluene
(1.0 mL) at ꢀ20 °C for 30 min.
b
Isolated yield.
Determined by chiral HPLC (CHIRALPAK IA) analysis.
The absolute configuration was established by comparison of the specific rotation with the literature value.
c
d
134.9, 134.7 (d, J = 5.3 Hz), 128.8 (d, J = 2.3 Hz), 124.3 (d,
J = 17.3 Hz), 123.4 (d, J = 13.5 Hz), 121.4, 119.8, 119.5, 34.6, 34.5,
30.8, 26.1; HRMS (ESI): Calcd for (M+H)+ C16H17NF: 242.1345,
Found: 242.1345.
143.2, 141.8, 136.4, 135.9, 134.5 (d, J = 10.5 Hz), 133.7, 132.7,
128.9, 125.3 (d, J = 12.8 Hz), 125.2, 123.8, 123.2, 117.1 (d,
J = 21.8 Hz), 34.1, 33.0, 31.0, 28.4; HRMS (ESI): Calcd for (MꢀBr)+
C35H31N2F2: 517.2455, Found: 517.2452.
4.4. General procedure for the synthesis of imidazolium
4.4.2. Imidazolium bromide (SP)-L2
bromide (SP)-L1 and (SP)-L2
(SP)-L2 was prepared as described above. Yield: 65 mg (43.2%,
white solid); mp: 238–240 °C; [
a
]
D
20 = ꢀ68.0 (c 0.30, CH2Cl2); 1H
40% Glyoxal (0.12 mL, 1.0 mmol) was added to a stirring solu-
tion of (Sp)-4a or (Sp)-4b (121 mg, 0.5 mmol) in THF (1.5 ml) and
the mixture was stirred at room temperature for 4–8 h before a
yellow precipitate separated out. After the reaction was complete
as indicated by TLC, the yellow precipitate diimine 5a or 5b was fil-
tered, dried and prepared for the next step directly without further
purification.
To a stirring solution of AgOTf (77 mg, 0.3 mmol) in THF
(1.0 mL) was added chloromethyl pivalate (0.04 mL, 0.27 mmol)
and the resulting suspension was sealed and stirred for 20 min in
the dark. After the above diimine in CH2Cl2 (2.0 mL) was added
to the suspension, the mixture continued to be stirred in dark at
40 °C for 24 h. After the reaction was complete as indicated by
TLC, the suspension was filtered and solvent was removed under
vacuum. The residue was purified by chromatographed on silica
gel (CH2Cl2/ethanol = 30/1) to give the desired imidazolium triflate
as a white solid. The corresponding imidazolium bromide (SP)-L1
or (SP)-L2 was obtained by anion exchange of its imidazolium tri-
flate analogue with a saturated aqueous KBr.9b
NMR (300 MHz, DMSO) d 10.14 (s, 1H), 8.51 (s, 2H), 7.13 (d,
J = 1.3 Hz, 2H), 6.85–6.76 (m, 6H), 6.70 (d, J = 1.5 Hz, 2H), 6.66 (d,
J = 10.2 HZ, 2H), 3.32–3.04 (m, 14H), 2.94–2.80 (m, 2H); 13C NMR
(75 MHz, CDCl3) d 161.9 (d, J = 242.3 Hz), 143.1 (d, J = 7.5 Hz),
141.3, 137.2, 136.7, 135.4 (d, J = 6.0 Hz), 135.1, 133.7, 132.4,
128.4, 125.5, 124.8 (d, J = 18.0 Hz), 123.7, 121.0 (d, J = 21.7 Hz),
33.9, 33.7, 30.1, 29.1; HRMS (ESI): Calcd for (MꢀBr)+ C35H31N2F2:
517.2455, Found: 517.2451.
4.5. (RP)-N-(4-Fluoro[2.2]paracyclophan-12-yl)benzophenone
hydrazone 3b
An oven-dried Schlenk tube was charged with (Rp)-4-bromo-
12-fluoro[2.2]paracyclophane 2b (700 mg, 2.3 mmol), benzophe-
none hydrazone (677 mg, 3.45 mmol), Pd-DPPF (16.8 mg,
0.023 mmol), NaOtBu (340 mg, 3.45 mmol) and toluene (5.0 mL).
The mixture was stirred at 120 °C under nitrogen for 2 h. After
the reaction was complete as indicated by TLC, the reaction mix-
ture was cooled to room temperature and diluted with CH2Cl2
(20 mL), after which acetic acid was added to the mixture until
the stirred solution tested acidic (pH 6–7). The organic phase
was washed with water (2 ꢁ 10 mL) and the solvent was removed
under reduced pressure to give a residue, which was purified by
flash column chromatography (petroleum ether/ ethyl acet-
ate = 6/1) to afford the product (RP)-3b. Yield: 801 mg (83%, yellow
4.4.1. Imidazolium bromide (SP)-L1
(SP)-L1 was prepared as described above. Yield: 40 mg (26.9%,
white solid); mp >250 °C (dec); [
a
]
20 = ꢀ212.3 (c 0.15, CH2Cl2) 1H
D
NMR (300 MHz, CDCl3) d 9.70 (s, 1H), 7.99 (s, 2H), 7.17 (s, 2H),
6.81 (d, J = 8.0 Hz, 2H), 6.70 (d, J = 7.8 Hz, 2H), 6.62 (dd, J = 11.7,
8.3 Hz, 4H), 6.25 (d, J = 9.8 Hz, 2H), 3.46 (ddd, J = 13.6, 10.0,
4.0 Hz, 2H), 3.40–3.05 (m, 10H), 2.95–2,75 (m, 4H). 13C NMR
(75 MHz, CDCl3) d 160.1 (d, J = 241.5 Hz), 143.3 (d, J = 3.0 Hz),
solid); mp: 154–156 °C; [
(300 MHz, CDCl3) d 7.72–7.54 (m, 5H), 7.47–7.27 (m, 6H), 6.92 (s,
a
]
20 = ꢀ540 (c 0.3, CHCl3); 1H NMR
D
1H), 6.50 (t, J = 7.8 Hz, 1H), 6.35 (dd, J = 12.6, 1.2 Hz, 1H), 6.31 (d,
Please cite this article in press as: Wang, L.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.12.005

6
L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
J = 7.8 Hz, 1H), 6.22 (d, J = 7.8 Hz, 1H), 6.14 (dd, J = 7.5, 1.5 Hz, 1H),
3.51–3.36 (m, 1H), 3.20–2.89 (m, 3H), 2.78–2.47 (m, 4H). 13C NMR
(75 MHz, CDCl3) d 161.3 (d, J = 244.5 Hz), 144.8, 143.5, 142.3 (d,
J = 7.5 Hz), 142.2, 138.3, 135.5, 135.4, 133.2, 129.8, 129.4, 129.1,
128.3, 128.0, 127.9, 126.5, 126.4, 125.2 (d, J = 18.0 Hz), 124.2,
124.0, 122.6, 122.4,117.4 (d, J = 22.5 Hz), 115.8, 34.1, 32.8, 32.3,
30.1; HRMS (ESI): Calcd for [M+H]+ (C29H26FN2): 421.2080, found:
421.2154.
143.5 (d, J = 7.5 Hz), 142.3, 142.2, 137.0, 136.9, 136.5, 134.8 (d,
J = 5.3 Hz), 133.9 (d, J = 10.5 Hz), 132.0, 131.3, 129.9, 129.7, 128.4,
127.6, 125.7 (d, J = 18.0 Hz), 124.3, 123.6, 119.6 (d, J = 21.8 Hz),
69.3, 62.3, 58.9, 34.0, 33.2, 31.6, 29.6; HRMS (ESI): Calcd for (Mꢀ
Cl)+ C27H25N3FO: 426.1982, Found: 426.1973.
4.8. General procedure for the optimization of the reaction
conditions (Table 1)
Under
a nitrogen atmosphere, triazolium salt (R,RP)-L3
4.6. (RP)-N-Formyl-N-(4-fluoro[2.2]paracyclophan-12-yl)benzo-
(2.22 mg, 5.0 ꢁ 10ꢀ3 mmol) and Cu2O (0.35 mg, 2.5 ꢁ 10ꢀ3 mmol)
were added to 1.0 mL of anhydrous THF in an oven-dried Schlenk
flask. The mixture was stirred at 60 °C overnight to give a colorless
solution of the carbene–Cu complex. After the solvent was evapo-
rated under nitrogen at 80 °C, 1.0 mL of anhydrous solvent, Cs2CO3
(1.6 mg, 5.0 ꢁ 10ꢀ3 mmol) and bis(pinacolato)diboron (27.9 mg,
0.11 mmol) were added consecutively at room temperature. The
mixture was stirred at room temperature for 5 min and cooled to
0 °C. The chalcone derivative 6a (24.2 mg, 0.1 mmol) and alcohol
(0.2 mmol) were added simultaneously to the stirred mixture.
After the mixture was stirred for 8 min, the solvent was removed
in a vacuum and the crude product was purified by flash column
chromatography (ethyl acetate/hexanes = 1: 20) to afford the
desired product 7a.
phenone hydrazone 4b
An oven-dried Schlenk tube was charged with Ac2O (10.5 mL,
111 mmol) and HCOOH (2.8 mL, 139 mmol), the resulting solution
was stirred at 60 °C under nitrogen for 1.5 h. After the solution was
cooled to 0 °C, (RP)-3b (776 mg, 1.84 mmol) was slowly added to
the stirring solution. The mixture was stirred at 0 °C for 30 minutes
then warmed to 50 °C and stirred for another 36 h. After the reac-
tion was complete as indicated by TLC, the solvent was removed
under reduced pressure and a saturated solution of NaHCO3
(15 mL) was added to the residue. The mixture was extracted with
CH2Cl2 (3 ꢁ 15 mL) and the combined CH2Cl2 extract was dried
over anhydrous Na2SO4. After being concentrated under reduced
pressure, the crude product was purified by flash column chro-
matography (petroleum ether/ethyl acetate = 5/1) to afford the
product (RP)-4b. Yield: 694 mg (84%, yellow solid); mp: 143–
4.9. General procedure for the evaluation of ligand and
temperature effects (Table 2)
145 °C; [
a]
D
20 = ꢀ528 (c 0.2, CHCl3); 1H NMR (300 MHz, CDCl3) d
8.13 (s, 1H), 7.75 (s, 1H), 7.72 (d, J = 1.5 Hz, 1H), 7.47 (t,
J = 7.2 Hz, 1H), 7.40–7.33 (m, 2H), 7.30–7.27 (m, 1H), 7.23–7.21
(m, 2H), 7.05 (d, J = 7.2 Hz, 2H), 6.59–6.54 (m, 1H), 6.50–6.45 (m,
2H), 6.36–6.26 (m, 3H), 3.58–3.49 (m, 1H), 3.32 (t, J = 11.1 Hz,
1H), 3.15–3.04 (m, 1H), 3.00–2.83 (m, 4H), 2.69–2.59 (m, 1H);
13C NMR (75 MHz, CDCl3) d 175.0, 160.9 (d, J = 243.6 Hz), 157.5,
143.2 (d, J = 6.8 Hz), 140.6, 139.7, 136.7, 135.9, 135.3, 134.9 (d,
J = 6.0 Hz), 133.4, 133.1, 131.4, 130.1, 129.6, 129.5, 129.2, 128.3,
128.2, 127.7 (d, 11.3 Hz), 125.7 (d, J = 17.3 Hz), 123.4, 118.7 (d,
J = 21.8 Hz), 34.3, 33.3, 32.9, 29.6; HRMS (ESI): Calcd for [M+H]+
(C30H26FN2O): 449.2029, found: 449.1960.
Under a nitrogen atmosphere, imidazolium bromide (5 ꢁ 10ꢀ3
-
mmol), and Cu2O (0.35 mg, 2.5 ꢁ 10ꢀ3 mmol) were added to
1.0 mL anhydrous CH2Cl2 in an oven dried Schlenk flask. The mix-
ture was stirred at 40 °C for 72 h to give a colorless solution of the
carbene–Cu complex. After the solvent was evaporated under
nitrogen at 60 °C, 1.0 mL of anhydrous toluene, Cs2CO3 (1.6 mg,
5 ꢁ 10ꢀ3 mmol) and bis(pinacolato)diboron (27.9 mg, 0.11 mmol)
were added consecutively at room temperature. The mixture was
stirred at room temperature for 5 min and then cooled to the tem-
perature indicated in Table 2. Chalcone 6b (20.7 mg, 0.1 mmol) and
MeOH (8.0 lL, 0.2 mmol) were added simultaneously to the stirred
mixture. After the mixture was stirred for a given time period, the
solvent was removed in a vacuum and the crude product was puri-
fied by flash column chromatography (ethyl acetate/hexanes = 1:
20) to afford the desired product 7b.
4.7. Triazolium chloride (R,RP)-L3
(RP)-4b (674 mg, 1.5 mmol) was dissolved in a solution of
6.0 mL of EtOH, 54 lL of H2O and 3.0 mL of EtOH/HCl (8.0 M,
24 mmol). The resulting red solution was stirred at 25 °C for 3 h.
After the reaction was finished as indicated by TLC, the solvent
was removed in vacuo and the residue was washed with Et2O
(3 ꢁ 4 mL) to afford the desired (Rp)-4-fluoro-12-formohydrazino
[2.2]paracyclophane hydrochloride 5b (384 mg, 80% yield) as a
white solid, which was used for next step directly without further
purification.
(Rp)-5b (320 mg, 1.0 mmol) was added to a solution of imi-
noether12 (191 mg, 1.0 mmol) in MeOH (3 mL) at room tempera-
ture. The mixture was warmed to 50 °C and stirred for 2 h. After
the solvent was evaporated under reduced pressure, trimethyl
orthoformate (3.0 mL) was added to the residue. The reaction mix-
ture was then stirred for 2 h at 110 °C. After the reaction was com-
plete as indicated by TLC, the solvent was removed in vacuo and
the residue was purified by flash column chromatography (CH2Cl2/
MeOH = 20/1) to afford the product triazolium salt (R,RP)-L3. Yield:
4.10. General procedure for the evaluation of the substrate
scope (Table 3)
Under
a nitrogen atmosphere, triazolium salt (R,RP)-L3
(2.22 mg, 5 ꢁ 10ꢀ3 mmol) and Cu2O (0.35 mg, 2.5 ꢁ 10ꢀ3 mmol)
were added to 1.0 mL of anhydrous THF in an oven-dried Schlenk
flask. The mixture was stirred at 60 °C overnight to give a colorless
solution of the carbene–Cu complex. After the solvent was evapo-
rated under nitrogen at 80 °C, 1.0 mL of anhydrous toluene, Cs2CO3
(1.6 mg, 5 ꢁ 10ꢀ3 mmol) and bis(pinacolato)diboron (27.9 mg,
0.11 mmol) were added consecutively at room temperature. The
mixture was stirred at room temperature for 5 min and cooled to
ꢀ20 °C. Chalcone derivative 6 (0.1 mmol) and MeOH (8.0
lL,
0.2 mmol) were added simultaneously to the stirred mixture. After
the mixture was stirred for 30 min, the solvent was removed in a
vacuum and the crude product was purified by flash column chro-
matography (ethyl acetate/hexanes = 1: 20) to afford the corre-
sponding product 7.
415 mg (90%, white solid); mp: 212–214 °C; [
a
]
20 = ꢀ40.5 (c 0.1,
D
CHCl3); 1H NMR (300 MHz, CDCl3) d 10.20 (s, 1H), 7.61 (d,
J = 3.3 Hz, 2H), 7.48–7.47 (m, 3H), 7.03 (s, 1H), 6.80–6.58 (m, 5H),
6.50 (d, J = 7.1 Hz, 1H), 5.42–5.34 (m, 1H), 5.21 (d, J = 16.5 Hz,
1H), 4.63 (d, J = 12.0 Hz, 1H), 4.40 (d, J = 12.0 Hz, 1H), 3.55–3.37
(m, 1H), 3.32 –3.02 (m, 4H), 2.91–2.74 (m, 2H), 2.72–2.69 (m,
1H); 13C NMR (75 MHz, CDCl3) d 161.0 (d, J = 246.8 Hz), 150.0,
4.10.1. (R)-3-(3-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 7a
Colorless oil: 36.3 mg, 98% yield, 97% ee; [
CHCl3); the enantiomeric excess was determined by HPLC with a
a]
25 = ꢀ81.0 (c 0.1,
D
Please cite this article in press as: Wang, L.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.12.005

L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
7
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 12.9 min (S, minor), tR = 17.1 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
(R, major); Other spectra and properties data matched those
reported in the literature.6e
4.10.9. (R)-3-(Naphthalen-1-yl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 7i
4.10.2. (R)-1,3-Diphenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
Colorless oil; 37.4 mg, 97% yield, 99% ee; [
a]
25 = ꢀ59.4 (c 0.2,
D
lan-2-yl)propan-1-one 7b
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 15.1 min (S, minor), tR = 16.4 min
(R, minor); Other spectra and properties data matched those
reported in the literature.6e
Colorless oil: 33.2 mg, 99% yield, 99% ee; [
a]
25 = ꢀ20.1 (c 0.15,
D
CHCl3); The enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (600:1),
flow rate = 0.5 mL minꢀ1; tR = 31.2 min (S, minor), tR = 38.8 min
(R, major); Other spectra and properties data matched those
reported in the literature.6e
4.10.10. (R)-1-(4-Fluorophenyl)-3-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 7j
4.10.3. (R)-3-(2-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
Colorless oil; 35 mg, 99% yield, 97% ee; [
a]
D
25 = ꢀ39.1 (c 0.2,
1,3,2-dioxaborolan-2-yl)propan-1-one 7c
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 13.8 min (S, minor), tR = 19.5 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
Colorless oil: 36 mg, 97% yield, 99% ee; [a]
25 = + 25.0 (c 0.2,
D
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (200:1),
flow rate = 0.5 mL minꢀ1; tR = 17.6 min (S, minor), tR = 19.1 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
4.10.11. (R)-1-(4-Methoxyphenyl)-3-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 7k
4.10.4. (R)-3-(4-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
Colorless oil; 35.4 mg, 97% yield, 98% ee; [
a
]
D
25 = ꢀ40.0 (c 0.1,
1,3,2-dioxaborolan-2-yl)propan-1-one 7d
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 26.7 min (S, minor), tR = 39.9 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
Colorless oil: 36.4 mg, 98% yield, 98% ee; [
a
]
D
25 = ꢀ33.3 (c 0.2,
CHCl3); The enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 15.6 min (S, minor), tR = 22.9 min
(R, major); Other spectra and properties data matched those
reported in the literature.6e
4.10.12. (R)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)-1-p-tolylpropan-1-one 7l
4.10.5. (R)-3-(2-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
Colorless oil; 34.6 mg, 99% yield, 97% ee; [
a]
25 = ꢀ43.0 (c 0.1,
D
1,3,2-dioxaborolan-2-yl)propan-1-one 7e
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 16.1 min (S, minor), tR = 26.8 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
Colorless oil: 36.2 mg, 99% yield, 98% ee; [
a]
25 = ꢀ122.5 (c 0.1,
D
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (200:1),
flow rate = 0.5 mL minꢀ1; tR = 28.7 min (S, minor), tR = 29.9 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
4.10.13. (R)-3-(Thienyl-2-yl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-di-oxaborolan-2-yl)propan-1-one 7m
4.10.6. (R)-3-(3-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
Colorless oil; 31.3 mg, 96% yield, 98% ee; [
a]
25 = ꢀ27.0 (c 0.1,
D
1,3,2-dioxaborolan-2-yl)propan-1-one 7f
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50: 1),
flow rate = 0.5 mL minꢀ1; tR = 14.0 min (S, minor), tR = 18.6 min
(R, major); Other spectra and properties data matched those
reported in the literature.9h
Colorless oil: 35.1 mg, 96% yield, 96% ee; [
a
]
D
25 = ꢀ56.3 (c 0.2,
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50:1),
flow rate = 0.5 mL minꢀ1; tR = 18.2 min (S, minor), tR = 24.6 min
(R, major); Other spectra and properties data matched those
reported in the literature.9f
4.10.14. (R)-4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)-butan-2-one 7n
4.10.7. (R)-3-(4-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
Colorless oil: 24.9 mg, 91% yield, 48% ee; [
a]
25 = ꢀ15.5 (c 0.2,
D
1,3,2-dioxaborolan-2-yl)propan-1-one 7g
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm; eluent: hexane/i-PrOH (100:1);
flow rate = 0.5 mL minꢀ1; tR = 12.9 min (S, minor); tR = 15.2 min
(R, major). Other spectra and properties data matched those
reported in the literature.6d
Colorless oil: 34.8 mg, 95% yield, 99% ee; [
a
]
D
25 = ꢀ16.8 (c 0.2,
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50:1),
flow rate = 0.5 mL minꢀ1; tR = 19.3 min (S, minor), tR = 26.8 min
(R, major); Other spectra and properties data matched those
reported in the literature.6e
4.10.15. (R)-4,4-Dimethyl-1-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)pentan-3-one 7o
4.10.8. (R)-1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
Colorless oil: 31.3 mg, 99% yield, 98% ee; [
a]
25 = ꢀ38.8 (c 0.2,
D
2-yl)-3-p-tolylpropan-1-one 7h
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm; eluent: hexane/i-PrOH (50:1);
flow rate = 0.5 mL minꢀ1; tR = 9.2 min (S, minor); tR = 9.6 min (R,
major). Other spectra and properties data matched those reported
in the literature.6f
Colorless oil; 34.7 mg, 99% yield, 98% ee; [
a
]
D
25 = ꢀ29.3 (c 0.2,
CHCl3); the enantiomeric excess was determined by HPLC with a
Chiralpak IA column: k = 254 nm, eluent: hexane/i-PrOH (50:1),
flow rate = 0.5 mL minꢀ1; tR = 12.9 min (S, minor), tR = 17.9 min
Please cite this article in press as: Wang, L.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.12.005

8
L. Wang et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
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4.10.16. (R)-1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)butan-1-one 7p
Colorless oil: 27.2 mg, 99% yield, 92% ee; [
a]
20 = ꢀ13.8 (c 0.4,
D
CH2Cl2); The enantiomeric excess was determined by HPLC with
a Chiralpak IA column, k = 254 nm, eluent: hexane/i-PrOH (50:1),
flow rate = 0.5 mL/min; tR = 10.1 min (S, minor), tR = 12.0 min (R,
major); Other spectra and properties data matched those reported
in the literature.6e
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4.10.17. (ꢀ)-5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)
hexan-3-one 7q
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Colorless oil: 22.4 mg, 99% yield, 96% ee; [
a]
20 = ꢀ0.2 (c 0.17,
D
CH2Cl2); The enantiomeric excess was determined by HPLC with
a Chiralpak IA column after the product was converted into the
corresponding benzoylate derivative, k = 220 nm, eluent: hexane/
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those reported in the literature.3j
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Acknowledgments
Financial support from the National Natural Science Foundation
of China (Grant Nos. 21372144, 81473085) and Department of
Science and Technology of Shandong Province is gratefully
acknowledged.
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Please cite this article in press as: Wang, L.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.12.005