Synthesis of planar chiral imidazo[1,5-a]pyridinium salts based on [2.2]paracyclophane for asymmetric β-borylation of enones

Article abstract of DOI:10.1016/j.tetasy.2011.06.023

Novel planar chiral pseudo-geminal and pseudo-ortho-oxazoline substituted [2.2]paracyclophanyl imidazo[1,5-a]pyridinium triflates were synthesized. During the synthesis of a pseudo-ortho imidazo[1,5-a]pyridinium triflate based on [2.2]paracyclophane, the

Full text of DOI:10.1016/j.tetasy.2011.06.023

Tetrahedron: Asymmetry 22 (2011) 1055–1062
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of planar chiral imidazo[1,5-a]pyridinium salts
based on [2.2]paracyclophane for asymmetric b-borylation of enones
⇑
Bing Hong, Yudao Ma , Lei Zhao, Wenzeng Duan, Fuyan He, Chun Song
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:
Novel planar chiral pseudo-geminal and pseudo-ortho-oxazoline substituted [2.2]paracyclophanyl imi-
dazo[1,5-a]pyridinium triflates were synthesized. During the synthesis of a pseudo-ortho imidazo[1,5-
a]pyridinium triflate based on [2.2]paracyclophane, the diastereoisomers of 4-amino-12-oxazoli-
nyl[2.2]paracyclophane were separated. The imidazo[1,5-a]pyridinium triflates were used as carbene
precursors in Cu-catalyzed enantioselective conjugate b-borylation of enones. In preliminary tests of a
series of ligands and substrates, we obtained up to 84% enantioselectivity.
Received 14 April 2011
Accepted 16 June 2011
Available online 27 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
enantioselective b-borylation of enones, which is a useful meth-
od in enantioselective synthesis.13 In recent years, several publi-
Since the first isolation of free N-heterocyclic carbenes (NHCs)
by Arduengo in 1991,1 they have been widely applied in organo-
metallic catalysis2 and organocatalysis.3 Since most of the NHC
complexes of the late transition metals are kinetically robust,4
cations have focused on this transformation, but most of them
used josiphos-type ligands.14 The NHC complexes used in this
work have rarely been reported.15 Herein, we report using 1–2
and 14 to prepare Cu(NHC) complexes in situ16 and the applica-
tion of them in the catalytic b-borylation of enones.
the
r-donor capacity and the molecular shape of their ligands
are readily modified by varying the substituents at the N-atoms
or on the cyclic backbone. Initial successful results in using chiral
NHC ligands in organometallic catalysis were reported a decade
ago.5 Since then, chemists have designed and synthesized many
chiral carbene ligands and applied them in asymmetric catalysis.6
Planar chiral molecules, such as ferrocene derivatives7 and
substituted [2.2]paracyclophanes8 play an important role in asym-
metric catalysis. Planar chiral substituted [2.2]paracyclophanes
were first reported used as ligands in asymmetric catalysis in
1997.9 Since then, many types of asymmetric substituted
[2.2]paracyclophanes have been synthesized and applied in several
asymmetric transformations such as chiral ligands.8 In most of
these ligands, the chelating groups contain N, O,8a,d,10 N, P, or
biphosphine.9,11 Planar chiral carbene ligands derived from
[2.2]paracyclophane have been rarely reported6b,12 and oxazoline
substituted planar chiral imidazo[1,5-a]pyridinium salts have not
been synthesized to date.
N
Ph
O
N
N
Ph
OTf
OTf
N
O
N
N
1a
1b
N
Ph
OTf
O
Herein, we report the synthesis of pseudo-geminal and pseudo-
ortho oxazoline substituted [2.2]paracyclophanyl imidazo
[1,5-a]pyridinium triflates 1–2 (Fig. 1) from 4-bromo-13-oxazoli-
nyl[2.2]paracyclophane and 4-bromo-12-oxazolinyl[2.2]paracy-
clophane. Then we preliminarily tested their application in the
N
N
OTf
N
N
O
N
Ph
2b
2a
⇑
Corresponding author. Tel.: +86 531 88361869; fax: +86 531 88565211.
E-mail address: ydma@sdu.edu.cn (Y. Ma).
Figure 1. Regio- and diastereoisomers of pseudo-geminal and pseudo-ortho-oxaz-
olinyl[2.2]paracyclophanyl pyridinium salts.
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.06.023

1056
B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
geminal diastereoisomers, we obtained the target products 2a
2. Results and discussion
and 2b (Scheme 2).
The absolute configurations of 1a and 2a were determined by
comparing the specific rotation of 10 and 11 with the reported lit-
erature values.21 Compounds 10 and 11 were obtained by hydroly-
sis of 5a and 9a (Scheme 3).
Based on the directing effects of substituted [2.2]paracyclo-
phane, we were able to synthesize both diastereoisomers of
pseudo-geminal and pseudo-ortho oxazoline substituted [2.2]para-
cyclophanyl imidazo[1,5-a]pyridinium triflates 1–2. The phenyl
group was chosen as the substituent on the oxazoline ring because
(R)-phenylglycinol is inexpensive and the size of the phenyl group
is large enough for resolution, but not so bulky as to inhibit
reaction.
2.3. Catalytic asymmetric reaction
With these imidazo[1,5-a]pyridinium triflates in hand, we
briefly examined their application in the asymmetric b-borylation
of enones. The combination of the planar chirality of [2.2]paracy-
clophane with the central chirality of oxazoline gives rise to inter-
esting interactions between the two chiral elements (Table 1).
The Cu(NHC) complexes were prepared in situ by incubating a
mixture of Cu2O, KI, and imidazo[1,5-a]pyridinium triflate in sol-
vent at 60 °C under an Ar atmosphere.16 Next, Cs2CO3, bis(pinaco-
lato)diboron, chalcone, and MeOH were added consecutively. In
the presence of catalytic imidazo[1,5-a]pyridinium triflate
(5 mol %), the reaction proceeded smoothly to afford the addition
products.
2.1. Synthesis of pseudo-geminal diastereoisomers
Following the literature,8e,17 we synthesized a mixture of dias-
teroisomers of 4-bromo-13-oxazolinyl[2.2]paracyclophane 3a and
3b, which could be easily separated by column chromatography
on silica gel. Compounds 3a and 3b were converted into 4a and
4b by treatment with n-BuLi in THF at ꢀ78 °C followed by trapping
with CO2 and acidifying with HCl. Then by using a modified Curtius
process with DPPA (diphenylphosphoryl azide), we obtained the
4-amino-13-oxazolinyl[2.2]paracyclophane 5a and 5b.18
When we tested the effects of different imidazo[1,5-a]pyridini-
um triflates in the b-borylation of chalcone, the best result was
obtained by using pseudo-ortho ligand 2a (entry 3), in which the
planar chirality and central chirality have a cooperative effect.
However, the lowest ee was given by its diastereoisomer 2b with
a mismatched pair of chiralites (entry 4). Since the substituted
functional groups were the same in these four imidazo[1,5-a]pyrid-
inium triflates, the different results show that the substituted posi-
tions on the [2.2]paracyclophane scaffold play an important role in
the asymmetric catalysis. We ascribe the poor ee obtained from the
pseudo-geminal ligands to their structures, in which the coordinat-
ing atoms point in opposite directions and cannot chelate the metal
well (Fig. 2). Among the solvents tested, THF gave the best yields
and enantiomeric excess. Although the reaction rates were much
faster in isopropanol and t-butanol, the enantioselectivity was not
good.
The reaction of 5a and 5b with 2-pyridine aldehyde in refluxing
toluene resulted in the formation of imines in good yield as yellow
oils. Since they were not stable, we used them directly for the for-
mation of imidazoles 1a and 1b according to the method of Glorius
using AgOTf and chloromethyl pivalate12b,19 (Scheme 1).
2.2. Synthesis of pseudo-ortho diastereoisomers
We started the synthesis of 2a and 2b from 4-bromo-12-oxaz-
olinyl[2.2]paracyclophane 7a and 7b, which can be prepared from
racemic 4,12-dibromo[2.2]paracyclophane 6 according to the liter-
ature.8e,12a Compounds 7a and 7b were inseparable at this step.
Next, 4-bromo-12-oxazolinyl[2.2]paracyclophane was reacted
with benzhydrylideneamine under Pd-catalyzed amination,20
which afforded the corresponding imines 8a and 8b. Fortunately,
we could separate 8a and 8b by column chromatography on silica
gel. Compound 8a was obtained as a yellow solid, however, 8b was
a yellow oil and not stable enough for further purification. The
substituted [2.2]paracyclophane imines 8a and 8b were easily con-
verted into their amino analogues 9a and 9b by acid hydrolysis
with aqueous HCl. Using the same procedure as for the pseudo-
In an attempt to improve the catalytic enantioselectivity, we
modified ligand 2a by synthesis of the tert-butyl analogue 14 from
(S,Sp)-4-bromo-12-(4-t-butyloxazolin-2-yl)[2.2]paracyclophane
(Scheme 4).12,20 By using imidazo[1,5-a]pyridinium triflate 14, the
enantioselectivity when using chalcone as substance was
1. n-BuLi then CO2
1. DPPA, toluene, r.t.
2. H+
N
N
2. 10% KOHaq, reflux
Ph
Ph
O
O
Br
COOH
3a
4a
N
Ph
1. 2-pyridine aldehyde
N
O
toluene, reflux
Ph
2. AgOTf, chloromethyl pivalate
O
OTf
N
NH2
N
5a
1a
Scheme 1. Synthesis of pseudo-geminal diastereoisomers.

B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
1057
NH
Ph
Pd-DPPF/co-catalyst
tBuONa/toluene
N
Br
Ph
Ph
O
Br
Br
7a and 7b
6
inseparable
N
Ph
O
Ph
Ph
HCl aq
THF
N
+
N
N
O
Ph
Ph
8a
8b
Ph
N
1. 2-pyridine aldehyde
toluene, reflux
Ph
O
NH2
2. AgOTf, chloromethyl
pivalate
+
N
O
NH2
Ph
9a
9b
N
Ph
OTf
O
N
N
+
OTf
N
N
O
N
Ph
2a
2b
Scheme 2. Synthesis of pseudo-ortho diastereoisomers.
enhanced from 64% to 76% ee. Finally, several other enones were
tested in order to evaluate the effect of different substrates. The
best result was obtained when using p-chlorochalcone.
3. Conclusion
HCl aq
N
COOH
NH2
Ph
In conclusion, a series of planar chiral bidentate NHC precursors
based on [2.2]paracyclophane were designed and synthesized.
They were successfully applied to a copper-catalyzed asymmetric
b-borylation, which was convenient and effective, revealing mod-
erate to good enantioselectivity for this reaction.
O
NH2
10
5a
N
Ph
4. Experimental section
4.1. General methods
COOH
O
HCl aq
NH2
Enones were prepared by the standard method reported in the
literature.22 The commercially available reagents were used as re-
ceived without further purification. The solvents were purified by
standard methods. Reactions were magnetically stirred under an
Ar atmosphere and monitored by thin layer chromatography
NH2
9a
11
Scheme 3. Synthesis of enantiopure pseudo-geminal and pseudo-ortho amino acids
based on [2.2]paracyclophane.

1058
B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
Table 1
Asymmetric b-borylation of chalcones by Cu(NHC) complexesa
O
Cu(NHC) complex
solvent
O
O
O
B
*
R1
Cs2CO3/B2(pin)2
MeOH
R2
R1
R2
15a-g
L
R1
R2
Solvent
Product
Yieldb (%)
ee (%) (Config.)c
1
2
3
4
5
6
1a
1b
2a
2b
2a
2a
2a
2a
14
14
14
14
14
14
14
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
THF
THF
THF
THF
1,4-dioxane
DME
Isopropanol
t-BuOH
THF
THF
THF
THF
THF
THF
THF
15a
15a
15a
15a
15a
15a
15a
15a
15a
15b
15c
15d
15e
15f
88
93
97
87
91
44
96
78
93
90
87
96
73
92
91
16 (R)
6
(R)
64 (R)
(S)
4
42 (R)
46 (R)
60 (R)
46 (R)
76 (S)
84 (–)
80 (–)
78 (+)
78 (–)
72 (R)
62 (S)
7d
8d
9
Ph
9
p-ClC6H4
p-MeOC6H4
p-MeC6H4
1-Naph
Me
10
11
12
13
14
Ph
15g
a
The complex was formed in solvent with L (5 mol %), Cu2O (2.3 mol %), and KI (6 mol %) at 60 °C. The reaction was carried out at room temperature using Cs2CO3 (5 mol %),
40 mg chalcone, 54 mg B2(pin)2 (1.1 equiv) and MeOH (2 equiv) after preparing the Cu complex.
b
Isolated yield.
c
Enantiomeric excesses were determined by chiral HPLC analysis (Chiralpak IA column). The absolute configuration of 15 was determined by comparison of the specific
rotation with the literature value.14c
d
Without adding MeOH.
Figure 2. ORTEP diagram of the molecular structure of 1b. Ellipsoids are drawn at the 50% probability level. The solvent molecules have been omitted. Hydrogen atoms have
been removed for clarity.

B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
1059
NH
10.58 mmol) and DPPA (1.41 mL, 10.58 mmol) were added. The
solution was stirred at room temperature for 30 min and then re-
fluxed for 2 h. Next, KOH aq (10%, 50 mL) was added and the mix-
ture was refluxed for another 3 h. Finally, the solution was cooled
to room temperature, the organic phase was separated, and the
aqueous phase was extracted with CH2Cl2 (3 ꢁ 30 mL). The organic
phase was combined and concentrated. The crude product was
purified by column chromatography on silica gel (hexane/
EtAc = 1:2), giving 1.61 g (83%) of 5a as a white solid. Mp 187–
Ph
Ph
1. Pd-DPPF/co-catalyst
tBuONa/toluene
Br
NH2
2. HCl aq
N
N
O
O
12
13
188 °C; ½a 2D0
ꢂ
¼ þ41:0 (c 0.3, CH2Cl2); 1H NMR (300 MHz, CDCl3,
rt) d 2.69–2.80 (m, 1H), 2.88–2.95 (m, 2H), 2.97–3.24 (m, 4H),
3.50 (br s, 2H), 4.22 (t, J = 8.4 Hz, 1H), 4.31–4.41 (m, 1H), 4.74
(dd, J = 10.2, 8.4 Hz, 1H), 5.29–5.40 (m, 1H), 5.51 (d, J = 1.8 Hz,
1H), 6.18 (dd, J = 7.8, 1.8 Hz, 1H), 6.37 (d, J = 7.8 Hz, 1H), 6.44 (d,
J = 7.8 Hz, 1H), 6.64 (dd, J = 7.8, 1.8 Hz, 1H), 7.23–7.26 (m, 1H),
7.27–7.38 (m, 5H); 13C NMR (75 MHz, CDCl3, rt) d 31.2, 32.2,
34.7, 34.8, 70.6, 74.0, 121.3, 122.5, 124.4, 125.0, 126.9, 127.6,
128.8, 132.4, 134.6, 134.9, 136.0, 138.5, 140.5, 140.6, 142.4,
146.3, 166.1; HRMS(ESI): calcd for C25H25N2O (M+H)+ 369.1967,
found 369.1963.
OTf
1. 2-pyridine aldehyde
toluene, reflux
N
N
2. AgOTf, chloromethyl
pivalate
N
O
14
Scheme 4. Synthesis of (S,Sp)-3-{12-(4-t-butyloxazolin-2-yl)[2.2]paracyclophane-
4-yl}imidazo[1,5-a]pyridinium triflate.
4.2.3. (R,4Rp,13Sp)-3-{13-(4-Phenyloxazolin-2-
yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflate
1a
(TLC). Purification of reaction products was carried out by column
chromatography on silica gel. Melting points were recorded on a
melting point apparatus and are uncorrected. Optical rotations
were measured on a polarimeter and are reported in degrees (c
g/100 mL, solvent). 1H and 13C NMR spectra were recorded on a
Bruker AVANCE-300 at 298 K. Chemical shifts are reported in parts
per million (ppm) downfield from tetramethylsilane (TMS) with
reference to the internal standard for 1H NMR and 13C NMR spec-
tra. HRMS spectra were recorded on an Agilent 100 ABI-API4000
spectrometer. Enantiomeric excess was determined using HPLC
on a Chiralpak IA chiral column.
At first, (R,4Rp,13Sp)-4-amino-13-(4-phenyloxazolin-2-yl)[2.2]
paracyclophane 5a (0.50 g, 1.36 mmol) was dissolved in toluene,
then 2-pyridine aldehyde (0.130 mL, 1.36 mmol) was added. The
solution was stirred and refluxed overnight. After cooling to room
temperature, the solution was subjected to column chromatogra-
phy on silica gel (CH2Cl2/EtAc/NEt3 = 10:1:0.01) and the corre-
sponding imine was obtained as a yellow oil, which was not
stable enough for further purification and so was used to prepare
1a directly. To a suspension of AgOTf (0.56 g, 2.18 mmol) in CH2Cl2
(3.0 mL) was added chloromethyl pivalate (0.32 mL, 2.18 mmol)
and the resulting suspension was sealed and stirred for 30 min in
the dark. Then the above imine in CH2Cl2 (2.0 mL) was added
and the solution was stirred in a sealed tube in the dark at 40 °C
for 12 h. After the solution was cooled to room temperature, EtOH
(2.0 mL) was added and filtered. The solvent was removed from the
filtrate in vacuo and 1a was obtained as a white solid by chroma-
tographing the crude product on a silica gel column (CH2Cl2/
4.2. Synthesis of pseudo-geminal and pseudo-ortho ligands
4.2.1. (R,4Rp,13Sp)-4-Carboxy-13-(4-phenyloxazolin-2-
yl)[2.2]paracyclophane 4a
At
first,
(R,4Sp,13Rp)-4-bromo-13-(4-phenyloxazolin-2-
yl)[2.2]paracyclophane 3a (5.00 g, 11.56 mmol) was placed in a
Schlenk flask under an argon atmosphere and dissolved in anhy-
drous THF (80 mL). After cooling to ꢀ78 °C, a solution of n-BuLi
in pentane (9.40 mL, 15.04 mmol) was added slowly. The solution
was stirred at ꢀ78 °C for another 1 h and was bubbled with CO2 for
30 min. The solution was allowed to warm to room temperature
while continuing the bubbling of CO2, then acidified with 2 M
HCl to pH 5–6, and extracted with dichloromethane (3 ꢁ 100
mL). The organic phase was dried with Na2SO4 and concentrated
to give crude product, which was purified with column chromatog-
raphy on silica gel (EtAc/petroleum = 2:8 to 5:5) yielding 3.73 g
MeOH = 30:1) (yield: 0.59 g, 70.0%). Mp 107–108 °C;
½
a 2D0
ꢂ
¼
þ43:9 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 2.82–2.93
(m, 1H), 2.97–3.03 (m, 1H), 3.22–3.40 (m, 4H), 3.47–3.56 (m,
1H), 3.83 (t, J = 8.7 Hz, 1H), 4.05–4.13 (m, 1H), 4.34 (t, J = 9.6 Hz,
1H), 4.61–4.68 (m, 1H), 6.71–6.89 (m, 4H), 6.95–6.98 (m, 2H),
7.05–7.13 (m, 2H), 7.18–7.29 (m, 4H), 7.50–7.53 (m, 2H), 7.68 (s,
1H), 8.96 (s, 1H), 10.32 (s, 1H); 13C NMR (75 MHz, CDCl3, rt) d
30.1, 34.5, 34.7, 36.6, 70.5, 73.5, 113.4, 117.8, 118.2, 120.8 (q,
J = 318 Hz), 124.5, 125.3, 125.4, 125.5, 125.6, 126.2, 127.6, 128.7,
129.6, 132.6, 133.5, 134.5, 135.2, 136.1, 136.3, 137.4, 140.5,
140.6, 142.05, 143.3, 163.8; HRMS(ESI): calcd for C32H28N3O
(MꢀOTf)+ 470.2232, found 470.2435.
(81.1%) of 4a as a white solid. Mp 182–184 °C; ½a D20
¼ ꢀ22:8 (c
ꢂ
0.3, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 3.05–3.21 (m, 6H),
3.95–4.01 (m, 1H), 4.30–4.40 (m, 1H), 4.44–4.54 (m, 1H), 4.64
(dd, J = 10.2, 8.4 Hz, 1H), 5.34 (t, J = 9.6 Hz, 1H), 6.66–6.77 (m,
4H), 7.11–7.14 (m, 3H), 7.16–7.26 (m, 3H), 7.35–7.38 (m, 1H);
13C NMR (75 MHz, CDCl3, rt) d 34.5, 34.7, 34.8, 34.9, 70.8, 73.6,
126.8, 127.3, 128.2, 128.5, 128.8, 133.2, 134.8, 135.0, 135.7,
136.4, 137.5, 139.2, 139.7, 141.7, 142.4, 144.1, 163.9, 172.9;
HRMS(ESI): calcd for C26H24NO3 (M+H)+ 398.1756, found 398.1760.
4.2.4. (R,4Sp,13Rp)-3-{13-(4-Phenyloxazolin-2-
yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflate
1b
Compound 1b was obtained by the same procedure as for 1a as
white crystals (76.1%). Mp 198–200 °C;
½
a 2D0
ꢂ
¼ þ16:7 (c 0.3,
CH2Cl2); 1H NMR (300 MHz, DMSO, rt) d 2.95–3.29 (m, 5H), 3.37–
3.48 (m, 2H), 3.71 (dd, J = 9.9, 8.4 Hz, 1H), 4.17–4.25 (m, 1H),
4.61 (dd, J = 10.5, 8.4 Hz, 1H), 5.14 (t, J = 10.2 Hz, 1H), 6.73–6.77
(m, 2H), 6.88–6.70 (m, 3H), 7.04–7.14 (m, 7H), 7.36 (d, J = 1.8 Hz,
1H), 7.74 (d, J = 8.4 Hz, 1H), 8.40–8.43 (m, 2H), 9.97 (d, J = 1.2 Hz,
1H); 13C NMR (75 MHz, DMSO, rt) d 30.4, 34.5, 34.6, 36.6, 69.4,
72.9, 113.7, 118.4, 118.9, 120.8 (q, J = 318 Hz), 124.2, 125.5,
4.2.2. (R,4Rp,13Sp)-4-Amino-13-(4-phenyloxazolin-2-
yl)[2.2]paracyclophane 5a
At
first,
(R,4Sp,13Rp)-4-carboxy-13-(4-phenyloxazolin-
2-yl)[2.2]paracyclophane 4a (2.10 g, 5.29 mmol) was dissolved in
toluene (120 mL) at room temperature. Then NEt3 (1.53 mL,

1060
B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
125.7, 126.0, 126.7, 127.2, 128.9, 130.0, 132.7, 133.3, 135.0, 135.8,
136.4, 137.1, 137.7, 140.2, 141.4, 142.4, 142.7, 162.6; HRMS(ESI):
calcd for C32H28N3O (MꢀOTf)+ 470.2232, found 470.2415.
75.5, 113.6, 117.9, 118.2, 120.8 (q, J = 318 Hz), 124.6, 124.9,
126.3, 126.8, 127.2, 127.9, 128.2, 129.0, 130.2, 130.5, 132.8,
134.0, 135.4, 135.6, 136.0, 137.4, 139.4, 140.7, 142.4, 142.7,
166.7; HRMS(ESI): calcd for C32H28N3O (MꢀOTf) + 470.2232, found
470.2227.
4.2.5. (R,Rp)-4-Benzhydrylideneamino-12-(4-phenyl oxazolin-2-
yl)[2.2]paracyclophane 8a
In a glovebox, a diastereomeric mixture of 4-bromo-12-(4-phe-
nyloxazolin-2-yl)[2.2]paracyclophane (1.05 g, 2.43 mmol), 4,12-
bis(benzhydry lideneamino)[2.2]paracyclophane (30.8 mg, 0.073
mmol), Pd–DPPF (59.5 mg, 0.073 mmol), benzhydrylideneamine
(0.66 g, 3.64 mmol), and sodium tert-butoxide (0.35 g, 3.64 mmol)
were placed in an oven-dried Schlenk flask, then toluene (2.0 mL)
was added. The mixture was stirred at 110 °C under Ar for 12 h.
Then the mixture was allowed to cool to room temperature and
water (10 mL) was added. The solution was extracted with CH2Cl2
(3 ꢁ 10 mL). The organic phase was combined and distilled in va-
cuo. A yellow oil was obtained and subjected to column chroma-
tography on silica gel (CH2Cl2/NEt3 = 99.8:0.2). Compound 8a was
separated from the diastereomeric mixture as a yellow semisolid
and could be further purified by recrystallization from EtOH to af-
4.2.8. (R,Sp)-4-Amino-12-(4-phenyloxazolin-2-yl)[2.2]
paracyclophane 9b
Compound 9b was synthesized by the same method as for 9a
from
4-bromo-12-(4-phenyloxazolin-2-yl)[2.2]paracyclophane
(1.05 g, 2.43 mmol) as a white solid (0.40 g, 44.8%). Mp 122–
123 °C; ½a 2D0
ꢂ
¼ þ64:0 (c 0.3, CH2Cl2); 1H NMR (300 MHz, CDCl3,
rt) d 2.66–2.72 (m, 1H), 2.75–3.05 (m, 3H), 3.09–3.23 (m, 3H),
3.92–4.01 (m, 1H), 4.22–4.35 (m, 3H), 4.85 (dd, J = 10.2, 8.4 Hz,
1H), 5.45 (dd, J = 10.2, 8.7 Hz, 1H), 5.63 (s, 1H), 6.17–6.20 (m,
1H), 6.33 (d, J = 7.8 Hz, 1H), 6.53–6.56 (m, 1H), 6.66 (d, J = 7.8 Hz,
1H), 7.29–7.44 (m, 5H), 7.84 (s, 1H); 13C NMR (75 MHz, CDCl3, rt)
d 32.1, 32.3, 34.5, 35.2, 70.2, 74.5, 120.3, 122.6, 124.3, 126.8,
127.6, 127.7, 128.6, 128.9, 135.0, 135.1, 135.8, 139.1, 140.2,
141.4, 142.5, 145.5, 166.0; HRMS(ESI): calcd for
C25H25N2O
ford a yellow solid (0.61 g, 47%). Mp 187–188 °C; ½a D20
¼ þ188:7 (c
ꢂ
(M+H)+ 369.1967, found 369.1962.
0.3, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 2.55–2.63 (m, 1H),
2.74–2.84 (m, 3H), 3.05–3.13 (m, 1H), 3.37–3.48 (m, 2H), 4.11 (t,
J = 8.4 Hz, 1H), 4.18–4.22 (m, 1H), 4.64–4.70 (m, 1H), 5.33–5.40
(m, 2H), 6.27–6.30 (m, 1H), 6.68 (d, J = 7.8 Hz, 1H), 6.61 (s, 2H),
6.92–6.96 (m, 2H), 7.11–7.20 (m, 3H), 7.25–7.34 (m, 5H), 7.40–
7.47 (m, 3H), 7.89 (dd, J = 8.4, 1.8 Hz, 2H), 8.05 (s, 1H); 13C NMR
(75 MHz, CDCl3, rt) d 32.9, 33.2, 33.8, 35.2, 70.8, 73.4, 124.4,
126.8, 127.2, 127.4, 127.7, 128.0, 128.1, 128.3, 128.7, 129.4,
129.5, 130.2, 131.2, 134.0, 135.1, 135.7, 136.8, 140.1, 140.4,
140.6, 140.7, 143.0, 148.5, 164.6, 164.7; HRMS(ESI): calcd for
4.2.9. (R,Sp)-3-{12-(4-Phenyloxazolin-2-yl)[2.2]paracyclo phane-
4-yl}imidazo[1,5-a]pyridinium triflate 2b
Compound 2b was prepared by the same procedure as 1a from
(R,Sp)-4-amino-12-(4-phenyloxazolin-2-yl)[2.2]paracyclophane 9b
as a white solid (76.3%). Mp 202–203 °C; ½a D20
¼ ꢀ122:4 (c 0.2,
ꢂ
CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 2.43–2.53 (m, 1H), 2.86–
2.96 (m, 1H), 2.99–3.12 (m, 3H), 3.33–3.44 (m, 2H), 4.09–4.17
(m, 1H), 4.58 (t, J = 9.0 Hz, 1H), 4.97 (dd, J = 9.9, 9.0 Hz, 1H), 5.49
(t, J = 9.6 Hz, 1H), 6.64 (s, 1H), 6.81–6.84 (m, 4H), 7.02–7.06 (m,
1H), 7.12–7.17 (m, 1H), 7.23 (s, 1H), 7.31–7.36 (m, 1H), 7.38–
7.41 (m, 1H), 7.42–7.48 (m, 2H), 7.54–7.57 (m, 2H), 8.57 (d,
J = 6.6 Hz, 1H), 9.00 (s, 1H), 10.28 (s, 1H); 13C NMR (75 MHz, CDCl3,
rt) d 32.1, 33.7, 34.3, 35.6, 69.8, 74.8, 113.9, 118.3, 120.8 (q,
J = 318 Hz), 124.5, 125.1, 126.1, 126.2, 127.0, 127.7, 128.4, 129.3,
130.5, 130.9, 133.2, 133.7, 135.6, 135.8, 136.3, 137.9, 139.6,
C
38H33N2O (M+H)+ 533.2593, found 533.2583.
4.2.6. (R,Rp)-4-Amino-12-(4-phenyloxazolin-2-
yl)[2.2]paracyclophane 9a
To a solution of (R,Rp)-4-benzhydry lideneamino-12-(4-phenyl-
oxazolin-2-yl)[2.2]paracyclophane 8a (0.50 g, 0.94 mmol) in THF
(5 mL) was added 2 M HCl aq (1.41 mL, 2.82 mmol). The solution
was stirred at room temperature for 2 h. After the yellow color
had faded, 1 M NaOH aq was added dropwise into the solution un-
til the pH reached 9, and the product was extracted with CH2Cl2
(3 ꢁ 5 mL). The organic phase was combined and dried with
MgSO4, then concentrated in vacuo, and subjected to column chro-
matography on silica gel to give 9a (0.34 g, 98.1%) as a white solid.
140.8, 141.7, 142.4, 166.0; HRMS(ESI): calcd for
C32H28N3O
+
(MꢀOTf) 470.2232, found 470.2239.
4.2.10. (4Rp,13Sp)-4-Amino-13-carboxy[2.2]paracyclo phane 10
At first, (R,4Rp,13Sp)-4-amino-13-(4-phenyloxazolin-2-
yl)[2.2]paracyclophane 5a (0.60 g, 1.63 mmol) was placed in a
flask, then 6 M HCl aq (30.0 mL) was added and the solution was
refluxed for 24 h. After cooling to room temperature, 6 M NaOH
aq was added dropwise into the solution until pH 5–6. The white
solid precipitated from the water and was extracted with CH2Cl2
(3 ꢁ 30 mL). The organic phase was combined, concentrated, and
then subjected to column chromatography on silica gel to afford
compound 10 0.36 g (82.7%) as a white solid. Mp >224 °C (dec);
Mp 176–177 °C; ½a D20
ꢂ
¼ þ34:9 (c 0.3, CH2Cl2); 1H NMR (300 MHz,
CDCl3, rt) d 2.62–2.70 (m, 1H), 2.75–3.01 (m, 3H), 3.05–3.21 (m,
3H), 3.89 (br s, 2H), 3.98–4.07 (m, 1H), 4.32 (t, J = 7.8 Hz, 1H),
4.77–4.83 (m, 1H), 5.45 (dd, J = 10.5, 7.5 Hz, 1H), 5.61 (d,
J = 1.5 Hz, 1H), 6.16–6.19 (m, 1H), 6.32 (d, J = 7.8 Hz, 1H), 6.51–
6.54 (m, 1H), 6.66 (d, J = 7.8 Hz, 1H), 7.29–7.44 (m, 5H), 7.82 (d,
J = 1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3, rt) d 32.1, 32.3, 34.4,
35.1, 70.1, 74.2, 120.4, 122.6, 124.3, 126.7, 127.6, 127.7, 128.6,
128.8, 135.1, 135.8, 139.0, 140.3, 141.4, 142.9, 145.6, 165.6;
HRMS(ESI): calcd for C25H25N2O (M+H)+ 369.1967, found 369.1961.
½
a 2D0
ꢂ
¼ þ84:0 (c 0.1, CH3OH); 1H NMR (300 MHz, DMSO, rt) d
2.46–2.56 (m, 1H), 2.69–3.00 (m, 5H), 3.19–3.26 (m, 1H), 4.27
(ddd, J = 13.2, 9.6, 6.0 Hz, 1H), 5.25 (d, J = 1.5 Hz, 1H), 5.97 (dd,
J = 7.5, 1.5 Hz, 1H), 6.25 (d, 7.8 Hz, 1H), 6.34 (d, J = 7.8 Hz, 1H),
6.64 (dd, J = 7.5, 1.8 Hz, 1H), 7.11 (d, J = 1.8 Hz, 1H); 13C NMR
(75 MHz, DMSO, rt) d 30.7, 32.1, 34.7, 120.4, 120.5, 123.7, 128.4,
133.5, 134.6, 134.8, 136.2, 138.1, 139.9, 142.3, 147.9, 169.5;
HRMS(ESI): calcd for C17H18NO2 (M+H)+ 268.1338, found 268.1336.
4.2.7. (R,Rp)-3-{12-(4-Phenyloxazolin-2-yl)[2.2]paracyclo
phane-4-yl}imidazo[1,5-a]pyridinium triflate 2a
Compound 2a was prepared by the same procedure as for 1a
from
(R,Rp)-4-amino-12-(4-phenyloxazolin-2-yl)[2.2]paracyclo-
phane 9a as a white solid (74.5%). Mp 215–216 °C; ½a D20
ꢂ
¼ þ187:5
4.2.11. (Rp)-4-Amino-12-carboxy[2.2]paracyclophane 11
Compound 11 was prepared by the same procedure as for 10 as
(c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 2.39–2.44 (m, 1H),
2.83–3.08 (m, 4H), 3.22–3.40 (m, 2H), 3.93–4.00 (m, 1H), 4.41 (t,
J = 7.8 Hz, 1H), 5.00 (t, J = 9.6 Hz, 1H), 5.81 (dd, J = 9.9, 7.8 Hz,
1H), 6.79 (m, 4H), 6.95–7.00 (m, 2H), 7.04–7.11 (m, 1H), 7.16 (s,
1H), 7.34–7.50 (m, 6H), 8.34 (d, J = 7.2 Hz, 1H), 8.81 (s, 1H), 10.78
(s, 1H); 13C NMR (75 MHz, CDCl3, rt) d 32.3, 33.6, 34.2, 35.3, 68.7,
a white solid (86.7%). Mp >212 °C (dec); ½a D20
¼ ꢀ31:3 (c 0.2,
ꢂ
CH3OH); 1H NMR (300 MHz, DMSO, rt) d 2.41–2.49 (m, 1H),
2.62–2.76 (m, 2H), 2.82–2.98 (m, 2H), 3.05–3.24 (m, 2H), 3.85–
3.93 (m, 1H), 5.24 (d, J = 1.5 Hz, 1H), 5.94 (dd, J = 7.5, 1.5 Hz, 1H),
6.15 (d, J = 7.5 Hz, 1H), 6.53 (dd, J = 7.8, 1.5 Hz, 1H), 6.60 (d,

B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
1061
J = 7.8 Hz, 1H), 7.70 (d, J = 1.8 Hz, 1H); 13C NMR (75 MHz, DMSO, rt)
d 31.9, 32.4, 34.5, 35.8, 120.1, 123.2, 129.6, 130.8, 135.2, 135.3,
137.0, 139.6, 140.8, 141.3, 147.2; HRMS(ESI): calcd for C17H18NO2
(M+H)+ 268.1338, found 268.1314.
this value with the reported literature14c {½a D20
ꢂ
¼ ꢀ107:3(c 0.2,
CHCl3), 95% ee (S)}.
4.3.2. (ꢀ)-3-(4-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 15b
4.2.12. (S,Sp)-4-Amino-12-(4-t-butyloxazolin-2-yl)[2.2]
paracyclophane 13
Compound 15b was prepared according to the general proce-
dure using 14 as the ligand to afford a waxy white solid (90%).
The ee (84% ee) was obtained by chiral HPLC analysis of 15b using
Compound 12 was prepared by the same procedure as for 9a
from
(S,Sp)-4-bromo-12-(4-t-butyloxazolin-2-yl)[2.2]paracyclo-
a
Chiralpak IA chiral column (i-PrOH/hexane = 1:10, flow
phane as colorless crystals (83.1%). Mp = 175–176 °C;
½
a 2D0
ꢂ
¼
0.5 mL minꢀ1
ꢂ
,
20 °C),
tmajor = 10.55 min;
tminor = 13.85 min;
þ17:5 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 1.05 (s, 9H),
2.62–2.72 (m, 1H), 2.79–2.97 (m, 3H), 3.08–3.22 (m, 5H), 3.97–
4.07 (m, 1H), 4.13 (dd, J = 10.2, 7.5 Hz, 1H), 4.26–4.31 (m, 1H),
4.36–4.43 (m, 1H), 5.52 (d, J = 1.8 Hz, 1H), 6.16 (dd, J = 7.8,
1.8 Hz, 1H), 6.31 (d, J = 7.8 Hz, 1H), 6.49 (dd, J = 7.8, 1.8 Hz, 1H),
6.63 (d, J = 7.8 Hz, 1H), 7.73 (s, 1H); 13C NMR (75 MHz, CDCl3, rt)
d 26.2, 32.1, 32.3, 34.3, 34.4, 34.6, 68.3, 76.0, 120.6, 122.7, 124.4,
127.7, 128.2, 134.9, 135.7, 138.9, 140.1, 141.4, 145.6, 164.3;
HRMS(ESI): calcd for C23H29N2O (M+H)+ 349.2280, found 349.2276.
½
a 2D0
¼ ꢀ62:3 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 1.17
(s, 6H), 1.24 (s, 6H), 2.77 (dd, J = 10.2, 5.7 Hz, 1H), 3.40 (dd,
J = 18.3, 5.4 Hz, 1H), 3.51 (dd, J = 18.3, 10.2 Hz, 1H), 7.24–7.26 (m,
4H), 7.41–7.46 (m, 2H), 7.52–7.58 (m, 1H), 7.94–7.97 (m, 2H);
13C NMR (75 MHz, CDCl3, rt) d 24.5, 24.6, 43.0, 83.5, 128.0, 128.5,
128.6, 129.7, 131.3, 133.0, 136.6, 140.5, 199.4.
4.3.3. (ꢀ)-3-(4-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-one 15c
Compound 15c was prepared according to the general proce-
dure using 14 as the ligand to afford a white semisolid (87%).
The ee (80% ee) was obtained by chiral HPLC analysis of 15c using
4.2.13. (S,Sp)-3-{12-(4-t-Butyloxazolin-2-
yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflate
14
Compound 14 was prepared by the same procedure as for 1a
from 13 as
a
Chiralpak IA chiral column (i-PrOH/hexane = 1:10, flow
0.5 mL minꢀ1, 20 °C), tmajor = 11.96 min; tminor = 15.21 min; ½a 2D0
¼
ꢂ
a
white solid (41.2%). Mp = 196–198 °C;
½
a 2D0
ꢂ
¼
ꢀ37:3 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 1.17 (s, 6H),
1.24 (s, 6H), 2.74 (dd, J = 10.5, 5.4 Hz, 1H), 3.50 (dd, J = 18.3,
10.5 Hz, 1H), 3.78 (s, 3H), 6.80–6.85 (m, 2H), 7.19–7.26 (m, 2H),
7.41–7.46 (m, 2H), 7.51–7.56 (m, 1H), 7.94–7.97 (m, 2H); 13C
NMR (75 MHz, CDCl3, rt) d 24.5, 24.6, 43.5, 55.2, 83.3, 114.0,
128.0, 128.5, 129.3, 132.9, 133.9, 136.8, 157.6, 199.8.
ꢀ235:7 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 1.07 (s,
9H), 2.36–2.39 (m, 1H), 2.76–2.80 (m, 1H), 2.86–2.93 (m, 1H),
2.96–3.09 (m, 2H), 3.27 (m, 1H), 3.39–3.47 (m, 1H), 3.99 (dd,
J = 13.2, 9.6 Hz, 1H), 4.35–4.38 (m, 2H), 4.52 (m, 1H), 6.77–6.84
(m, 5H), 7.07–7.15 (m, 2H), 7.20–7.26 (m, 1H), 7.68 (d, J = 9.3 Hz,
1H), 8.79 (d, J = 7.2 Hz, 1H), 9.47 (s, 1H), 10.32 (s, 1H); 13C NMR
(75 MHz, CDCl3, rt) d 25.9, 32.5, 33.6, 34.1, 34.4, 35.5, 69.4, 75.2,
113.8, 118.0, 118.1, 120.8 (q, J = 318 Hz), 125.1, 125.2, 126.0,
127.0, 127.1, 128.5, 130.5, 133.1, 133.8, 135.2, 135.4, 136.1,
137.6, 139.4, 140.7, 142.5, 165.5; HRMS(ESI): calcd for C30H32N3O
(Mꢀf)+ 450.2545, found 450.2543.
4.3.4. (+)-3-(4-Methylphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 15d
Compound 15d was prepared according to the general proce-
dure using 14 as the ligand to afford a white solid (96%). The ee
(78% ee) was obtained by chiral HPLC analysis of 15c using a Chir-
alpak IA chiral column (i-PrOH/hexane = 1:50, flow 0.5 mL minꢀ1
,
4.3. General experimental procedure for the enantioselective b-
borylation of chalcones
20 °C), tmajor = 12.81 min; tminor = 16.49 min; ½a D20
¼ þ88:2 (c 0.1,
ꢂ
CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 1.17 (s, 6H), 1.24 (s, 6H),
2.31 (s, 3H), 2.76 (dd, J = 10.8, 5.1 Hz, 1H), 3.38 (dd, J = 18.3,
5.1 Hz, 1H), 3.53 (dd, J = 18.3, 10.8 Hz, 1H), 7.07–7.10 (m, 2H),
7.18–7.20 (m, 2H), 7.40–7.45 (m, 2H), 7.50–7.56 (m, 1H), 7.93–
7.97 (m, 2H); 13C NMR (75 MHz, CDCl3, rt) d 21.0, 24.5, 24.6,
43.5, 83.3, 128.0, 128.3, 128.4, 129.2, 132.8, 135.0, 136.9, 138.8,
199.7.
The imidazo[1,5-a]pyridinium triflate (5.8 mg, 9.7 ꢁ 10ꢀ3
mmol), Cu2O (0.6 mg, 4.2 ꢁ 10ꢀ3 mmol), and KI (2.4 mg, 14.4 ꢁ
10ꢀ3 mmol) were added to 1.0 mL anhydrous THF in a Schlenk
flask under an atmosphere of Ar. The suspension was stirred at
60 °C overnight to give a yellow solution of the Cu complex. The
solution was cooled to room temperature. Next, Cs2CO3 (3.5 mg,
10.7 ꢁ 10ꢀ3 mmol) and bis(pinacolato)diboron (54.1 mg, 0.21
mmol) were added consecutively. The solution was stirred for
5 min after which chalcone (40.3 mg, 0.19 mmol) and then MeOH
4.3.5. (ꢀ)-3-(Naphthalen-1-yl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 15e
Compound 15d was prepared according to the general proce-
dure using 14 as the ligand to afford a colorless oil (73%). The ee
(78% ee) was obtained by chiral HPLC analysis of 15d using a Chir-
(7.8 ll, 0.38 mmol) were added. The reaction mixture was stirred
until no chalcone was detected by TLC. The solvent was removed
in vacuo and the product was purified by column chromatography
on silica gel. The enantiomeric excess was determined using HPLC
on a Chiralpak IA chiral column, with UV detection at 254 nm.
alpak IA chiral column (i-PrOH/hexane = 1:200, flow 1.0 mL min-1
,
20 °C), tmajor = 14.93 min; tminor = 19.18 min; ½a D20
¼ ꢀ31:3 (c 0.1,
ꢂ
CH2Cl2); 1H NMR (300 MHz, CDCl3, rt) d 1.17 (s, 6H), 1.27 (s, 6H),
3.48 (dd, J = 15.6, 2.4 Hz, 1H), 3.60–3.74 (m, 2H), 7.38–7.55 (m,
7H), 7.69 (d, 8.1 Hz, 1H), 7.82–7.85 (m, 1H), 7.94–7.96 (m, 2H),
8.21–8.24 (m, 1H); 13C NMR (75 MHz, CDCl3, rt) d 24.6, 24.7,
43.1, 83.6, 124.1, 125.4, 125.6, 125.7, 125.8, 126.4, 128.1, 128.5,
128.8, 132.1, 132.9, 134.2, 136.8, 138.7, 199.8.
4.3.1. (S)-1,3-Diphenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxa
borolan-2-yl)propan-1-one 15a
Using the general procedure, compound 15a was obtained as a
colorless oil (93%) with 14 as the ligand. The 1H NMR (300 MHz,
CDCl3, rt) results are in good agreement with those reported in
the literature.14c The ee (76% ee) was obtained by chiral HPLC anal-
ysis of 15a using a Chiralpak IA chiral column (i-PrOH/hex-
4.3.6. (R)-1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)butan-1-one 15f
Compound 15f was prepared according to the general proce-
dure using 14 as the ligand to afford a colorless oil. The 1H NMR
(300 MHz, CDCl3, rt) results are in good agreement with those re-
ported in the literature.14c The ee (72% ee) was obtained by chiral
ane = 1:10, flow 0.5 mL minꢀ1, 20 °C), tmajor = 9.53 min; tminor
=
12.15 min; ½a 2D0
ꢂ
¼ ꢀ69:4 (c 0.2, CH2Cl2); The specific rotation of
the corresponding hydroxyl ketone was
½ ꢂ
a 2D0
¼ ꢀ74:3 (c 0.2,
CH2Cl2). The absolute configuration was determined by comparing

1062
B. Hong et al. / Tetrahedron: Asymmetry 22 (2011) 1055–1062
2001, 3, 3225–3228; (c) van-Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.;
Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954–4955.
HPLC analysis of 15f using a Chiralpak IA chiral column (i-PrOH/
hexane = 1:50, flow 0.5 mL minꢀ1, 20 °C), tmajor = 9.58 min; tmi-
6. (a) Perry, M. C.; Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951–961; (b) Ma,
Y. D.; Song, C.; Ma, C.; Sun, Z.; Chai, Q.; Andrus, M. B. Angew. Chem., Int. Ed.
2003, 42, 5871–5874; (c) Larsen, A. O.; Leu, W.; Oberhuber, C. N.; Campbell, J.
E.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130–11131; (d) Martin, D.;
Kehrli, S.; d’Augustin, M.; Clavier, H.; Mauduit, M.; Alexakis, A. J. Am. Chem. Soc.
2006, 128, 8416–8417; (e) Douthwaite, R. E. Coord. Chem. Rev. 2007, 251, 702–
717; (f) Selim, K. B.; Matsumoto, Y.; Yamada, K.; Tomioka, K. Angew. Chem., Int.
Ed. 2009, 48, 8733–8735; (g) Enders, D.; Grossmann, A.; Fronert, J.; Raabe, G.
Chem. Commun. 2010, 46, 6282–6284; (h) Vora, H.; Rovis, T. J. Am. Chem. Soc.
2010, 132, 2860–2861; (i) Duguet, N.; Donaldson, A.; Leckie, S. M.; Kallström, E.
A.; Campbell, C. D.; Shapland, P.; Brown, T. B.; Slawin, A.; Smith, A. D.
Tetrahedron: Asymmetry 2010, 21, 601–616.
7. (a) Richards, C. J.; Locke, A. J. Tetrahedron: Asymmetry 1998, 9, 2377–2407; (b)
Dai, L.; Tu, T.; You, S.; Deng, W.; Hou, X. Acc. Chem. Res. 2003, 36, 659–667; (c)
Blaser, H. U.; Chen, W.; Camponovo, F.; Togni, A. Ferrocenes: Ligands, Materials
and Biomolecules; John Wiley & Sons, Ltd: Chichester, UK, 2008. pp 205–235;
(d) Diab, L.; Gouygou, M.; Manoury, E.; Kalck, P.; Urrutigoïty, M. Tetrahedron
Lett. 2008, 49, 5186–5189; (e) Duan, Z. C.; Hu, X. P.; Zhang, C.; Wang, D. Y.; Yu,
S. B.; Zheng, Z. J. Org. Chem. 2009, 74, 9191–9194.
8. (a) Dahmen, S.; Bräse, S. J. Am. Chem. Soc. 2002, 124, 5940–5941; (b) Gibson, S.
E.; Knight, J. D. Org. Biomol. Chem. 2003, 1, 1256–1269; (c) Wu, X. W.; Zhang, T.
Z.; Yuan, K.; Hou, X. L. Tetrahedron: Asymmetry 2004, 15, 2357–2365; (d) Bräse,
S.; Höfener, S. Angew. Chem., Int. Ed. 2005, 44, 7879–7881; (e) Whelligan, D. K.;
Bolm, C. J. Org. Chem. 2006, 71, 4609–4618; (f) Rozenberg, V.; Sergeeva, E.;
Hopf, H. In Modern Cyclophane Chemistry; Gleiter, R., Hopf, H., Eds.; Wiley-VCH:
Weinheim, Germany, 2004; p 435; (g) Aly, A. A.; Brown, A. B. Tetrahedron 2009,
65, 8055–8089.
nor = 11.33 min; ½a D20
¼ ꢀ29:8 (c 0.1, CH2Cl2); The absolute configu-
ꢂ
ration was determined by comparing this value with the reported
literature value14c {½a D20
¼ ꢀ58:1 (c 1.0, CHCl3), 97% ee (R)}.
ꢂ
4.3.7. (S)-4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)butan-2-one 15g
Compound 15g was prepared according to the general proce-
dure using 14 as the ligand to afford a colorless oil. The 1H NMR
(300 MHz, CDCl3, rt) results are in good agreement with those re-
ported in the literature.14c The ee (62% ee) was obtained by chiral
HPLC analysis of 15g using a Chiralpak IA chiral column (i-PrOH/
hexane = 1:50, flow 0.5 mL minꢀ1, 20 °C), tmajor = 10.49 min; tmi-
nor = 11.89 min; ½a D20
¼ ꢀ35:4 (c 0.1, CH2Cl2); The absolute configu-
ꢂ
ration was determined by comparing this value with the reported
literature14c {[½a D20
¼ ꢀ49:0 (c 1.0, CHCl3), 79% ee (S)}.
ꢂ
4.4. Crystallographic analysis of 1b
Colorless, needle-like crystals were grown from ethanol,
C
33H30F3N3O4.75S, M = 633.66, a = 16.9887(2) Å, b = 16.9887(2) Å,
c = 21.0226(4) Å,
= 6067.43(16) Å3, T = 291(2) K, Z = 8, 1.387 Mg/
m3. Final R indices [I > 2
(I)], R1 = 0.0931, wR2 = 0.2739; R indices
9. Pye, P. J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J. J. Am.
Chem. Soc. 1997, 119, 6207–6208.
v
r
10. (a) Rozenberg, V.; Danilova, T.; Sergeeva, E. V.; Shouklov, I. A.; Starikova, Z. A.;
Hopf, H.; Kühlein, K. Eur. J. Org. Chem. 2003, 3, 432–440; (b) Kreis, M.; Nieger,
M.; Bräse, S. J. Organomet. Chem. 2006, 691, 2171–2181; (c) Bolm, C.;
Whelligana, D. K. Adv. Synth. Catal. 2006, 348, 2093–2100; (d) Xin, D.; Ma, Y.;
He, F. Tetrahedron: Asymmetry 2010, 21, 333–338; (e) Vorontsova, N. V.;
Bystrova, G. S.; Antonov, D. Y.; Vologzhanina, A. V.; Godovikov, I. a.; Il’in, M. M.
Tetrahedron: Asymmetry 2010, 21, 731–738.
11. (a) Wu, X. W.; Yuan, K.; Sun, W.; Zhang, M. J.; Hou, X. L. Tetrahedron: Asymmetry
2003, 14, 107–112; (b) Whelligan, D. J.; Bolm, C. J. Org. Chem. 2006, 71, 4609–
4618; (c) Zhang, T. Z.; Dai, L. X.; Hou, X. L. Tetrahedron: Asymmetry 2007, 18,
1990–1994; (d) Jiang, B.; Lei, Y.; Zhao, X. J. Org. Chem. 2008, 73, 7833–7836.
12. (a) Bolm, C.; Focken, T.; Raabe, G. Tetrahedron: Asymmetry 2003, 14, 1733–
1746; (b) Ma, Q.; Ma, Y.; Liu, X.; Duan, W.; Qu, B.; Song, C. Tetrahedron:
Asymmetry 2010, 21, 292–298.
(all data), R1 = 0.1067, wR2 = 0.2985.
Crystallographic data (excluding structure factors) for 1b have
been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication number CCDC 821397. Copies of
the data can be obtained, free of charge, on application to CCDC,
12Union Road, Cambridge, CB2 1EZ, UK [fax: +44 (0) 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk].
Acknowledgments
Financial support from the National Natural Science Foundation
of China (20671059) and Department of Science and Technology of
Shandong Province is gratefully acknowledged. The authors thank
Dr. Pamela Holt for correcting the English.
13. Matteson, D. S. Stereodirected Synthesis with Organoboranes; Springer: Berlin,
1995. p 48–92.
14. (a) Lee, J. E.; Yun, J. Angew. Chem., Int. Ed. 2008, 47, 145–147; (b) Lee, J. E.; Yun, J.
Angew. Chem., Int. Ed. 2008, 120, 151–153; (c) Sim, H. S.; Feng, X.; Yun, J. Chem.
Eur. J. 2009, 15, 1939–1943; (d) Chea, H.; Sim, H. S.; Yun, J. Adv. Synth. Catal.
2009, 351, 855–858.
15. (a) Lillo, V.; Prieto, A.; Bonet, A.; Requejo, M. M.; Ramírez, J.; Pérez, P. J.;
Fernández, E. Organometallics 2009, 28, 659–662; (b) Park, J. K.; Lackey, H. H.;
Rexford, M. D.; Kovnir, K.; Shatruk, M.; McQuade, D. T. Org. Lett. 2010, 12,
5008–5011; (c) O’Brien, J. M.; Lee, K.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
10630–10633; (d) Weil, D. H.; Abboud, K. A.; Hong, S. Chem. Commun. 2010, 46,
7525–7527.
16. Chun, J.; Lee, H. S.; Jung, G.; Lee, S. W.; Kim, H. J.; Son, S. U. Organometallics
2010, 29, 1518–1521.
17. (a) Marchand, A.; Maxwell, A.; Mootoo, B.; Peltera, A.; Reid, A. Tetrahedron
2000, 56, 7331–7338; (b) Wu, X. W.; Hou, X. L.; Dai, L. X.; Tao, J.; Cao, B. X.; Sun,
J. Tetrahedron: Asymmetry 2001, 12, 529–532.
18. (a) Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94, 6203–6205;
(b) Hitchcock, P. B.; Hodgson, A.; Rowlands, G. J. Synlett 2006, 2625–2628.
19. (a) Glorius, F.; Altenhoff, G.; Goddard, R.; Lehmann, C. W. Chem. Commun. 2002,
2704–2705; (b) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. Angew.
Chem., Int. Ed. 2003, 42, 3690–3693; (c) Altenhoff, G.; Goddard, R.; Lehmann, C.
W.; Glorius, F. J. Am. Chem. Soc. 2004, 126, 15195–15201.
20. Qu, B.; Ma, Y.; Ma, Q.; Liu, X.; He, F.; Song, C. J. Org. Chem. 2009, 74, 6867–6869.
21. Pelter, A.; Crump, R.; Kidwell, H. Tetrahedron: Asymmetry 1997, 8, 3873–3880.
22. Kohler, E. P.; Chadwell, H. M. Org. Synth. Coll. 1932, 1, 78–81.
References
1. Arduengo, A. J.; Harlow, R. L.; Kilne, M. J. Am. Chem. Soc. 1991, 113, 361–363.
2. (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29; (b) Jafarpour, L.;
Nolan, S. P. J. Organomet. Chem. 2001, 617–618. 17–27; (c) Hillier, A. C.; Grasa,
G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.; Nolan, S. P. J. Organomet. Chem. 2002, 653,
69–82; (d) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290–1309; (e)
González, S. D.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612–3676; (f)
Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746–1787.
3. (a) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534–541; (b) Enders, D.;
Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606–5655; (c) Marion, N.;
González, S. D.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988–3000; (d) Li,
Y.; Feng, Z.; You, S. L. Chem. Commun. 2008, 19, 2263–2265; (e) Kayaki, Y.;
Yamamoto, M.; Ikariya, T. Angew. Chem., Int. Ed. 2009, 121, 4258–4261; (f) Lee,
K.; Zhugralin, A.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7253–7255; (g)
Shao, P. L.; Chen, X. Y.; Sun, L. H.; Ye, S. Tetrahedron Lett. 2010, 51, 2316–2318.
4. (a) Öfele, K.; Herrmann, W. A.; Mihalios, D.; Elison, M.; Herdtweck, E.; Scherer,
W.; Mink, J. J. Organomet. Chem. 1993, 459, 177–184; (b) Peris, E.; Loch, J. A.;
Mata, J.; Crabtree, R. H. Chem. Commun. 2001, 2, 201–202.
5. (a) Powell, M. T.; Hou, D. R.; Perry, M. C.; Cui, X.; Burgess, K. J. Am. Chem. Soc.
2001, 123, 8878–8879; (b) Seiders, T. J.; Ward, D. W.; Grubbs, R. H. Org. Lett.