Enantioselective β-boration of acyclic enones by a [2.2]paracyclophane-based N-heterocyclic carbene copper(I) catalyst

Article abstract of DOI:10.1021/jo302694d

A new planar and centrally chiral bicyclic 1,2,4-triazolium salt has been synthesized from [2.2]paracyclophane and phenylglycinol. The N-heterocyclic carbene (NHC) copper(I) complex generated in situ by the reaction of the triazolium salt and Cu₂

Full text of DOI:10.1021/jo302694d

Note
pubs.acs.org/joc
Enantioselective β‑Boration of Acyclic Enones by a
[2.2]Paracyclophane-Based N‑Heterocyclic Carbene Copper(I)
Catalyst
Lei Zhao, Yudao Ma,* Fuyan He, Wenzeng Duan, Jianqiang Chen, and Chun Song*
Department of Chemistry, Shandong University, Shanda South Road No. 27, Jinan 250100, P. R. China
S
* Supporting Information
ABSTRACT: A new planar and centrally chiral bicyclic 1,2,4-
triazolium salt has been synthesized from [2.2]paracyclophane
and phenylglycinol. The N-heterocyclic carbene (NHC)
copper(I) complex generated in situ by the reaction of the
triazolium salt and Cu2O was an efficient catalyst for the
asymmetric β-boration of acyclic enones, producing β-boryl ketones in high yields and enantioselectivities.
he preparation of chiral organoboron compounds remains
an active area of research in chemical synthesis because
mol % of Cu2O, 5 mol % of Cs2CO3, 1.1 equiv of B2Pin2, 1.0
equiv of 1a, and 2 equiv of MeOH in THF, the desired
boration reaction proceeded rapidly at 0 °C affording product
2a in 95% yield and 72% ee (Table 1, entry 1). However, the
chiral triazolium salt (S,Rp)-3 gave the boration product 2a in
90% yield but in only 34% ee (Table 1, entry 2). Disappointed
with these results, we screened similar chiral triazolium salts
4a−d derived from L-pyroglutamic acid which have been
successfully used in asymmetric organocatalytic reactions.9 It
was found that ligands 4a−c catalyzed the reaction of 1a and
B2Pin2 only in moderate enantioselectivities (Table 1, entries
3−5). Improved enantioselectivity was obtained with ligand 4d
(Table 1, entry 6), but the result was still not satisfactory. Then,
we tested amino-indanol derived triazolium salts 5a−c10 and
phenylglycinol derived triazolium salt 6a−b11 as the ligand. We
were pleased to find that the reaction afforded improved
enantioselectivity (83% ee) with ligand 6a (Table 1, entry 10).
As shown in previous reports, planar chiral [2.2]paracyclophane
has attracted considerable interest in asymmetric catalysis.12 We
were interested to see if introduction of a planar chiral
[2.2]paracyclophane at the N1 position could enhance the
enantioselectivity in the asymmetric conjugate boration
reaction. Then we synthesized triazolium salts (R,Rp)-7 and
(R,Sp)-7 and tested them in the β-boration of chalcone. To our
delight, the boration product 2a was obtained in 97% ee and
92% ee, respectively, with the same absolute configuration
(Table 1, entries 12−13). The results indicated that the
diastereomers (R,Sp)-7 showed similar catalytic capability
compared to (R,Rp)-7. Interestingly, the chiral triazolium salt
(R,Rp)/(R,Sp)-7 derived from racemic 4-formohydrazino[2.2]-
paracyclophane hydrochloride also afforded high enantioselec-
tivity (93% ee). A screening of ligand 7 showed that the
absolute configuration of product 2a was determined by the
central chirality of the triazolium salts 7 and the planar chirality
is immaterial. To obtain a better yield and enantioselectivity, we
T
the C−B bond can be converted into a wide variety of
functional groups without loss of enantiopurity.1 In the past few
years, various methods have been devised for the synthesis of
these compounds.2 The most common access to α-chiral
organoboron compounds is asymmetric conjugate addition of
diboron reagents to α,β-unsaturated compounds, and a variety
of catalytic systems have been developed.3 Nonetheless,
designing an efficient chiral ligand to meet the needs of the
conjugate boration reaction in good yield and enantioselectivity
is still a challenge.
Catalysis mediated by NHCs and their metal complexes has
emerged as a powerful tool for asymmetric synthesis because
these catalysts have several significant advantages over their
phosphine counterparts.4 The first attempt to catalyze the
asymmetric β-boration of α,β-unsaturated carbonyl compounds
by an NHC complex was made by Fernan
́
dez and co-workers.5
Since then, many groups have studied copper complexes of
NHCs in asymmetric conjugate boration reactions.6 Recently, a
very significant development from the group of Hoveyda used
NHCs in an enantioselective metal-free conjugate boration
reaction.7 Despite the fact that many exciting results have been
achieved, most of them were obtained with harsh conditions,
such as low reaction temperatures and long reaction times. Very
recently, our group identified a planar and centrally chiral
bicyclic triazolium ligand which induced exceptional enantio-
selectivities in the copper(I)-mediated β-boration of α,β-
unsaturated N-acyloxazolidinones.8 But the catalyst system
induced the β-boration of α,β-unsaturated acyclic enones in
only moderate enantioselectivity. In our quest to develop an
efficient catalyst for the asymmetric conjugate boration
reaction, we therefore report another bicyclic triazolium ligand
based on [2.2]paracyclophane and its applications in the
asymmetric copper(I)-catalyzed β-boration of α,β-unsaturated
acyclic enones.
To begin our study, chalcone 1a was used as a model
substrate. With 5 mol % of chiral triazolium salt (S,Sp)-3, 2.5
Received: December 11, 2012
Published: January 20, 2013
© 2013 American Chemical Society
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The Journal of Organic Chemistry
Note
a
Table 1. Screening of the Reaction Conditions
b
entry
ligand
(S,Sp)-3
solvent
time (min)
yield (%)
ee (%)
1
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
toluene
Et2O
CH2Cl2
dioxane
20
30
20
40
20
40
20
20
20
20
20
15
20
20
10
60
40
40
95
90
95
89
93
85
91
92
89
96
94
97
92
94
99
81
91
83
72(R)
34(R)
45(R)
12(S)
67(R)
76(R)
80(R)
37(R)
64(R)
83(R)
38(R)
97(R)
92(R)
93(R)
98(R)
95(R)
97(R)
95(R)
2
(S,Rp)-3
3
4a
4
4b
5
4c
6
4d
7
5a
8
5b
9
5c
10
11
12
13
14
15
16
17
18
6a
6b
(R,Rp)-7
(R,Sp)-7
(R,Rp)/(R,Sp)-7
(R,Rp)-7
(R,Rp)-7
(R,Rp)-7
(R,Rp)-7
a
The reaction was carried out with ligand (5 mol %), Cu2O (2.5 mol %), Cs2CO3 (5 mol %), B2Pin2 (0.11 mmol), 1a (0.1 mmol), and MeOH (0.2
b
mmol) in solvent (1 mL) at 0 °C. Determined by HPLC analysis using a chiral stationary phase (Chiralpak IA column).
then investigated the impact of solvent on the boration reaction
with triazolium salt (R,Rp)-7 as the optimal ligand. The solvent
effect study showed that toluene was the best among the
solvents tested (99% yield, 98% ee, Table 1, entry 15). Hence,
we chose the ligand (R,Rp)-7 and the solvent toluene as the
optimal conditions.
With the optimized reaction conditions in hand, a range of
α,β-unsaturated enones were screened for the reaction (Table
2). It appears that substituents on the aromatic rings of the
unsaturated enones have little effect on the reactivity and
enantioselectivity (Table 2, entries 1−12). Moreover, a
heteroaryl group was also tolerated and gave the corresponding
compound 2m in good yield (92%) and enantioselectivity (96%
ee). The scope was also extended to alkyl-substituted α,β-
unsaturated enones. When a methyl group was introduced at
the β-position of the α,β-unsaturated enone, the corresponding
product was obtained in good yield (88%) and enantioselec-
tivity (95% ee). However, the enone with a methyl group at the
carbonyl carbon gave the β-boryl ketone 2o in only moderate
enantioselectivity (47% ee). In order to test the hindrance
effect, a relatively hindered moiety, the t-Bu group, was
introduced at the carbonyl carbon which gave the β-boryl
ketone 2p in good yield (94%) and enantioselectivity (97% ee).
The different enantioselectivities of β-boryl ketone 2n−p
demonstrated that when an alkyl group is introduced at the
carbonyl carbon position of the α,β-unsaturated enone, the
steric hindrance of the alkyl group could affect the
enantioselectivity.
To further demonstrate the applicability of our catalytic
process, a gram-scale reaction was attempted with only 0.1 mol
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The Journal of Organic Chemistry
Note
a
capable of promoting the desired enantioselective β-boryl
ketones under mild conditions. Our designed triazolium salts
behaved as powerfully as the triazolium salts used in
organocatalytic processes.13 Another improvement over the
literature benchmark is that the reaction time was short, and
scale-up to a gram quantity using only 0.1 mol % catalyst at
room temperature could give the product in nearly quantitative
yield and excellent enantioselectivity (95% ee).
Table 2. Investigating the Substrate Scope of the Reaction
b
entry
R1
R2
yield (%)
ee (%)
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
99(2a)
97(2b)
93(2c)
98(2d)
95(2e)
96(2f)
95(2g)
98(2h)
97(2i)
99(2j)
97(2k)
96(2l)
92(2m)
88(2n)
93(2o)
94(2p)
98
97
95
97
99
95
97
97
98
97
95
97
96
95
47
97
2
2-ClC6H4
3-ClC6H4
4-ClC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
4-MeC6H4
1-Naphthyl
Ph
3
EXPERIMENTAL SECTION
■
Triazolium salt 6b was synthesized following a reported procedure.11b
4
Triazolium Salt 6b. White solid: Mp 118−120 °C, [α]D20 = −82.0
5
1
6
(c 0.5, CHCl3); H NMR (300 MHz, CDCl3) δ 10.82 (s, 1H), 7.56
(dd, J = 6.4, 2.9 Hz, 2H), 7.49−7.35 (m, 3H), 6.98 (s, 2H), 6.83 (s,
1H), 5.33 (d, J = 16.3 Hz, 1H), 5.12 (d, J = 16.3 Hz, 1H), 4.57 (dd, J =
12.7, 4.1 Hz, 1H), 4.35 (dd, J = 12.7, 2.4 Hz, 1H), 2.33 (s, 3H), 2.09
(s, 6H)); 13C NMR (75 MHz, CDCl3) δ 149.5, 144.9, 142.2, 136.6,
134.9, 131.0, 129.8, 129.7, 129.5, 127.4, 69.2, 62.0, 58.4, 21.2, 17.6;
HRMS (ESI-TOF) calcd for C20H22N3O (M − Cl)+, 320.1757; found:
320.1795.
General Procedure for the Synthesis of Triazolium Salt 7. To
a solution of iminoether11 (191 mg, 1.0 mmol) in MeOH (4 mL) was
added 4-formohydrazino[2.2]paracyclophane hydrochloride8 (303 mg,
1.0 mmol) at room temperature. The mixture was warmed to 50 °C
and stirred for 2 h. Then solvent was evaporated under reduced
pressure, and trimethyl orthoformate (4 mL) was added to the residue.
The reaction mixture was stirred for 5 h at 100 °C. After completion
(monitored 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 as a white solid.
7
8
9
10
11
12
13
14
15
16
4-FC6H4
4-MeOC6H4
4-MeC6H4
Ph
Ph
Ph
2-Furyl
Me
Ph
Ph
Me
Ph
tBu
a
The reaction was carried out with (R,Rp)-7 (5 mol %), Cu2O (2.5
mol %), Cs2CO3 (5 mol %), B2Pin2 (0.11 mmol), 1 (0.1 mmol), and
MeOH (0.2 mmol) in toluene (1 mL) at 0 °C. Determined by HPLC
b
analysis using a chiral stationary phase (Chiralpak IA column).
% of (R,Rp)-7 at room temperature. Under these conditions,
the reaction was completed in 2 h and gave the β-boryl ketone
2a in 98% yield and 95% enantioselectivity (Scheme 1), which
is the most effective catalysis ever reported in an asymmetric
boron conjugate addition reaction under mild conditions.6a
Triazolium Salt (R,Rp)-7. White solid: 413 mg, 93% yield, mp
20
1
218−220 °C; [α]D = −147.0 (c 0.5, CHCl3); H NMR (300 MHz,
CDCl3) δ 11.14 (s, 1H), 7.63 (d, J = 3.9 Hz, 2H), 7.51−7.37 (m, 3H),
6.92 (d, J = 6.9 Hz, 1H), 6.87−6.47 (m, 7H), 5.37 (d, J = 16.1 Hz,
1H), 5.20 (d, J = 16.2 Hz, 1H), 4.61 (d, J = 13.0 Hz, 1H), 4.35 (d, J =
11.8 Hz, 1H), 3.40−2.87 (m, 8H); 13C NMR (75 MHz, CDCl3) δ
149.6, 142.7, 142.2, 139.4, 139.3, 137.4, 136.9, 135.9, 134.0, 133.8,
133.5, 132.9, 132.6, 130.6, 129.5, 129.3, 127.5, 127.1, 68.9, 62.1, 58.3,
35.1, 34.7, 34.7, 32.5; HRMS (ESI-TOF) calcd for C27H26N3O (M −
Cl)+, 408.2076; found, 408.2066.
Scheme 1. Asymmetric β-Boration of 1a on a Gram Scale
Triazolium Salt (R,Sp)-7. White solid: 395 mg, 89% yield, mp
20
1
230−232 °C; [α]D = +75.0 (c 0.3, CHCl3); H NMR (300 MHz,
CDCl3) δ 11.14 (s, 1H), 7.73 (dd, J = 7.9, 1.5 Hz, 2H), 7.51−7.33 (m,
3H), 7.02 (d, J = 1.5 Hz, 1H), 6.86−6.46 (m, 6H), 6.26 (dd, J = 7.9,
1.8 Hz, 1H), 5.38 (d, J = 16.3 Hz, 1H), 5.17 (d, J = 16.3 Hz, 1H), 4.52
(dt, J = 29.0, 8.2 Hz, 2H), 3.85−3.64 (m, 1H), 3.30−2.91 (m, 6H),
2.7−2.62 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 149.5, 143.0, 142.9,
139.6, 139.0, 137.2, 136.5, 135.8, 134.2, 133.5, 133.3, 132.9, 132.5,
129.9, 129.6, 128.8, 127.6, 127.3, 68.9, 62.1, 58.3, 35.0, 34.8, 34.7, 32.5;
HRMS (ESI-TOF) calcd for C27H26N3O (M − Cl)+, 408.2076; found,
408.2079.
According to the X-ray structure of (R,Rp)-7 (see Supporting
Information) and the absolute configuration of the product, a
postulated model of the transition state is depicted in Figure 1.
General Procedure for the Copper-Catalyzed β-Boration of
α,β-Unsaturated Enones. Under an argon atmosphere, triazolium
salt 7 (2.22 mg, 5 × 10−3 mmol) and Cu2O (0.35 mg, 2.5 × 10−3
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
yellow solution of the Cu complex. Then the solvent was evaporated
under argon at 80 °C, and 1.0 mL of anhydrous toluene was added at
room temperature. Cs2CO3 (1.6 mg, 5 × 10−3 mmol) and
bis(pinacolato)diboron (27.9 mg, 0.11 mmol) were added consec-
utively. The mixture was stirred at room temperature for 5 min and
cooled to 0 °C. Then α,β-unsaturated enones (0.1 mmol) and MeOH
(8 μL, 0.2 mmol) were added simultaneously to the stirred mixture.
After the mixture was stirred for 10 min at 0 °C, the solvent was
removed in vacuum and the crude product was purified by flash
column chromatography to afford the corresponding product 2.
(R)-1,3-Diphenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propan-1-one (2a). Colorless oil: 33.3 mg, 99% yield, 98% ee;
Figure 1. Postulated model of transition states.
The exceptional enantioselectivity is rationalized by avoiding
the steric collision with the R2 group in the favored transition
state. The poor enantioselectivity of product 2o could also be
explained by the small hindered methyl group at the carbonyl
carbon.
In conclusion, although asymmetric conjugate boration
reactions have been well established, we found that [2.2]-
paracyclophane-based 1,2,4-triazolium copper complexes are
20
[α]D = −19.2 (c 0.2, CHCl3). The enantiomeric excess was
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The Journal of Organic Chemistry
Note
determined by HPLC with a Chiralpak IA column: λ = 254 nm;
eluent, hexane/i-PrOH (50:1); flow rate = 0.5 mL/min; tR = 9.0 min
(S, minor); tR = 10.0 min (R, major). Other spectra and properties
data matched those reported in the literature.6c
mL/min; tR = 11.7 min (minor); tR = 13.8 min (major). Other spectra
and properties data matched those reported in the literature.3f
(R)-1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-3-p-tolylpropan-1-one (2h). Colorless oil: 34.3 mg, 98% yield,
97% ee; [α]D20 = −25.0 (c 0.2, CHCl3). The enantiomeric excess was
determined by HPLC with a Chiralpak IA column: λ = 254 nm;
eluent, hexane/i-PrOH (50:1); flow rate = 0.5 mL/min; tR = 14.5 min
(minor); tR = 18.6 min (major). Other spectra and properties data
matched those reported in the literature.6c
(R)-3-(2-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2b). Colorless oil: 35.9
20
mg, 97% yield, 98% ee; [α]D = +17.5 (c 0.2, CHCl3). The
enantiomeric excess was determined by HPLC with a Chiralpak IA
column: λ = 254 nm; eluent, hexane/i-PrOH (200:1); flow rate = 0.5
1
mL/min; tR = 15.8 min (minor), tR = 16.9 min (major); H NMR
(R)-3-(Naphthalen-1-yl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2i). Colorless oil: 37.5
(300 MHz, CDCl3) δ 7.99−7.89 (m, 2H), 7.52 (ddd, J = 6.5, 3.8, 1.2
Hz, 1H), 7.42 (ddd, J = 7.1, 4.8, 2.7 Hz, 3H), 7.33 (dd, J = 7.8, 1.5 Hz,
1H), 7.17 (td, J = 7.5, 1.5 Hz, 1H), 7.09 (td, J = 7.6, 1.8 Hz, 1H),
3.51−3.41 (m, 2H), 3.34−3.24 (m, 1H), 1.28 (s, 6H), 1.22 (s, 6H);
13C NMR (75 MHz, CDCl3) δ 199.3, 140.1, 136.8, 134.3, 132.9, 130.6,
129.6, 128.5, 128.1, 127.1, 126.8, 83.6, 41.6, 24.7, 24.6, 24.5; HRMS
(ESI-TOF) calcd for C21H24BClO3 (M + H)+, 371.1585; found,
371.1582.
20
mg, 97% yield, 98% ee; [α]D = −45.0 (c 0.3, CHCl3). The
enantiomeric excess was determined by HPLC with a Chiralpak IA
column: λ = 254 nm; eluent, hexane/i-PrOH (200:1); flow rate = 0.5
mL/min; tR = 23.8 min (minor); tR = 27.8 min (major). Other spectra
and properties data matched those reported in the literature.6c
(R)-1-(4-Fluorophenyl)-3-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2j).3f Colorless oil: 35.1
20
mg, 99% yield, 97% ee; [α]D = −14.4 (c 0.2, CHCl3). The
(R)-3-(3-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
enantiomeric excess was determined by HPLC with a Chiralpak IA
1,3,2-dioxaborolan-2-yl)propan-1-one (2c). Colorless oil: 34.5
20
column: λ = 254 nm; eluent, hexane/i-PrOH (25:1); flow rate = 0.5
mg, 93% yield, 95% ee; [α]D = −75.5 (c 0.2, CHCl3). The
1
mL/min; tR = 12.1 min (minor), tR = 15.2 min (major); H NMR
enantiomeric excess was determined by HPLC with a Chiralpak IA
(300 MHz, CDCl3) δ 8.05−7.93 (m, 2H), 7.36−7.27 (m, 4H), 7.22−
7.03 (m, 3H), 3.52 (dd, J = 18.2, 10.7 Hz, 1H), 3.37 (dd, J = 18.2, 5.2
Hz, 1H), 2.79 (dd, J = 10.7, 5.1 Hz, 1H), 1.24 (s, 6H), 1.16 (s, 6H);
13C NMR (75 MHz, CDCl3) δ 198.1, 167.4 (d, J = 252.7 Hz), 141.8,
133.3 (d, J = 3.0 Hz), 130.7 (d, J = 9.2 Hz), 128.5, 128.4, 125.6, 115.7
(d, J = 21.7 Hz), 83.4, 43.1, 27.3, 24.6, 24.5; HRMS (ESI-TOF) calcd
for C21H24BFO3 (M + H)+, 355.1881; found, 355.1887.
column: λ = 254 nm; eluent, hexane/i-PrOH (50:1); flow rate = 0.5
mL/min; tR = 13.0 min (minor); tR = 17.3 min (major); H NMR
1
(300 MHz, CDCl3) δ 8.02−7.91 (m, 2H), 7.61−7.50 (m, 1H), 7.44 (t,
J = 7.5 Hz, 2H), 7.30 (s, 1H), 7.24−7.10 (m, 3H), 3.47 (qd, J = 18.3,
7.9 Hz, 2H), 2.78 (dd, J = 10.4, 5.3 Hz, 1H), 1.25 (s, 6H), 1.17 (s,
6H); 13C NMR (75 MHz, CDCl3) δ 199.3, 144.2, 136.6, 134.2, 133.1,
129.7, 128.5, 128.4, 128.1, 126.6, 125.8, 83.5, 42.9, 26.9, 24.6, 24.5;
HRMS (ESI-TOF) calcd for C21H24BClO3 (M + H)+, 371.1585;
found, 371.1574.
(R)-1-(4-Methoxyphenyl)-3-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2k).3f Colorless oil: 35.5
20
mg, 97% yield, 95% ee; [α]D = −58.3 (c 0.2, CHCl3). The
(R)-3-(4-Chlorophenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
enantiomeric excess was determined by HPLC with a Chiralpak IA
1,3,2-dioxaborolan-2-yl)propan-1-one (2d). Colorless oil: 36.3
20
column: λ = 254 nm; eluent, hexane/i-PrOH (50:1); flow rate = 0.5
mg, 98% yield, 97% ee; [α]D = −28.2 (c 0.2, CHCl3). The
1
mL/min; tR = 23.9 min (minor); tR = 35.9 min (major); H NMR
enantiomeric excess was determined by HPLC with a Chiralpak IA
column: λ = 254 nm; eluent, hexane/i-PrOH (10:1); flow rate = 0.5
mL/min; tR = 10.4 min (minor); tR = 12.4 min (major). Other spectra
and properties data matched those reported in the literature.3f
(R)-3-(2-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2e). Colorless oil: 34.8
(300 MHz, CDCl3) δ 8.00−7.88 (m, 2H), 7.34−7.26 (m, 4H), 7.21−
7.10 (m, 1H), 6.96−6.85 (m, 2H), 3.86 (s, 3H), 3.44 (qd, J = 18.1, 8.0
Hz, 2H), 2.77 (dd, J = 10.7, 5.3 Hz, 1H), 1.24 (s, 6H), 1.16 (s, 6H);
13C NMR (75 MHz, CDCl3) δ 198.1, 163.3, 142.1, 130.3, 129.9, 128.5,
128.4, 125.5, 113.6, 83.3, 55.4, 42.9, 27.4, 24.6, 24.5; HRMS (ESI-
TOF) calcd for C22H27BO4 (M + H)+, 367.2081; found, 367.2078.
(R)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-1-p-tolylpropan-1-one (2l). Colorless oil: 33.6 mg, 96% yield,
97% ee; [α]D20 = −42.5 (c 0.2, CHCl3). The enantiomeric excess was
determined by HPLC with a Chiralpak IA column: λ = 254 nm;
eluent, hexane/i-PrOH (50:1); flow rate = 0.5 mL/min; tR = 15.3 min
20
mg, 95% yield, 99% ee; [α]D = −92.5 (c 0.2, CHCl3). The
enantiomeric excess was determined by HPLC with a Chiralpak IA
column: λ = 254 nm; eluent, hexane/i-PrOH (200:1); flow rate = 0.5
1
mL/min; tR = 26.1 min (minor); tR = 27.1 min (major). H NMR
(300 MHz, CDCl3) δ 7.92 (dd, J = 5.3, 3.4 Hz, 2H), 7.55−7.45 (m,
1H), 7.44−7.35 (m, 2H), 7.28 (dd, J = 7.4, 1.7 Hz, 1H), 7.13 (td, J =
7.8, 1.7 Hz, 1H), 6.85 (ddd, J = 11.7, 9.1, 4.6 Hz, 2H), 3.79 (s, 3H),
3.48 (dd, J = 18.0, 8.6 Hz, 1H), 3.30 (dd, J = 18.0, 6.1 Hz, 1H), 3.12
(dd, J = 8.5, 6.1 Hz, 1H), 1.26 (s, 6H), 1.20 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 200.1, 157.1, 137.2, 132.6, 130.9, 130.4, 128.3, 128.05,
126.8, 120.6, 110.2, 83.3, 55.1, 41.5, 24.8, 24.6, 21.1; HRMS (ESI-
TOF) calcd for C22H27BO4 (M + H)+, 367.2081; found, 367.2082.
(R)-3-(3-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2f). Colorless oil: 35.2
1
(minor); tR = 24.7 min (major); H NMR (300 MHz, CDCl3) δ 7.86
(d, J = 8.2 Hz, 2H), 7.34−7.26 (m, 4H), 7.23 (d, J = 8.1 Hz, 2H),
7.19−7.11 (m, 1H), 3.53 (dd, J = 18.2, 10.8 Hz, 1H), 3.45−3.33 (m,
1H), 2.78 (dd, J = 10.7, 5.2 Hz, 1H), 2.40 (s, 3H), 1.24 (s, 6H), 1.16
(s, 6H); 13C NMR (75 MHz, CDCl3) δ 199.3, 143.6, 142.1, 134.3,
129.1, 128.5, 128.4, 128.3, 125.5, 83.3, 43.2, 27.2, 24.6, 24.5, 21.6;
HRMS (ESI-TOF) calcd for C22H27BO3 (M + H)+, 351.2132; found,
351.2137.
(R)-3-(Furan-2-yl)-1-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)propan-1-one (2m). Colorless oil: 30.0 mg, 92%
yield, 96% ee; [α]D20 = −7.5 (c 0.2, CHCl3). The enantiomeric excess
was determined by HPLC with a Chiralpak IA column: λ = 254 nm;
eluent, hexane/i-PrOH (50:1); flow rate = 0.5 mL/min; tR = 14.8 min
(minor); tR = 19.9 min (major). Other spectra and properties data
matched those reported in the literature.14
20
mg, 96% yield, 95% ee; [α]D = +22.5 (c 0.2, CHCl3). The
enantiomeric excess was determined by HPLC with a Chiralpak IA
column: λ = 254 nm; eluent, hexane/i-PrOH (50:1); flow rate = 0.5
1
mL/min; tR = 17.7 min (minor); tR = 24.2 min (major); H NMR
(300 MHz, CDCl3) δ 7.96 (dd, J = 5.2, 3.3 Hz, 2H), 7.60−7.49 (m,
1H), 7.49−7.38 (m, 2H), 7.20 (t, J = 7.9 Hz, 1H), 6.88 (dd, J = 8.0, 5.3
Hz, 2H), 6.76−6.68 (m, 1H), 3.79 (s, 3H), 3.62−3.36 (m, 2H), 2.78
(dd, J = 10.8, 5.1 Hz, 1H), 1.25 (s, 6H), 1.17 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 199.7, 159.6, 143.6, 136.8, 132.9, 129.4, 128.5, 128.1,
120.8, 113.9, 111.2, 83.4, 55.1, 43.3, 27.3, 24.6. HRMS (ESI-TOF)
calcd for C22H27BO4 (M + H)+, 367.2081; found, 367.2082.
(S)-1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)butan-1-one (2n). Colorless oil: 24.1 mg, 88% yield, 95% ee;
20
[α]D = +12.5 (c 0.2, CHCl3). The enantiomeric excess was
determined by HPLC with a Chiralpak IA column: λ = 254 nm;
eluent, hexane/i-PrOH (50:1); flow rate = 0.5 mL/min; tR = 11.1 min
(R, minor); tR = 15.3 min (S, major). Other spectra and properties
data matched those reported in the literature.6c
(R)-4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)butan-2-one. (2o). Colorless oil: 25.5 mg, 93% yield, 47% ee;
(R)-3-(4-Methoxyphenyl)-1-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one (2g). Colorless oil: 34.8
20
mg, 95% yield, 97% ee; [α]D = −16.5 (c 0.2, CHCl3). The
enantiomeric excess was determined by HPLC with a Chiralpak IA
column: λ = 254 nm; eluent, hexane/i-PrOH (10:1); flow rate = 0.5
1680
dx.doi.org/10.1021/jo302694d | J. Org. Chem. 2013, 78, 1677−1681

The Journal of Organic Chemistry
Note
7
20
20
[α]D = −15.1 (c 0.2, CHCl3) (lit. [α]D = −34.2 (c 1.06, CHCl3)
92% ee (R)). The enantiomeric excess was determined by HPLC with
a Chiralpak IA column: λ = 254 nm; eluent, hexane/i-PrOH (100:1);
flow rate = 0.5 mL/min; tR = 14.7 min (S, minor); tR = 18.0 min (R,
major). Other spectra and properties data matched those reported in
the literature.6c
(6) (a) Park, J. K.; Lackey, H. H.; Rexford, M. D.; Kovnir, K.;
Shatruk, M.; McQuade, D. T. Org. Lett. 2010, 12, 5008. (b) H.-Weil,
D.; Abboud, K. A.; Hong, S. Chem. Commun. 2010, 46, 7525.
(c) Hong, B.; Ma, Y.; Zhao, L.; Duan, W.; He, F.; Song, C.
Tetrahedron: Asymmetry 2011, 22, 1055.
(7) Wu, H.; Radomkit, S.; O’Brien, J. M.; Hoveyda, A. H. J. Am.
(R)-4,4-Dimethyl-1-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-diox-
aborolan-2-yl)pentan-3-one (2p). Colorless oil: 29.7 mg, 94%
yield, 97% ee; [α]D20 = −41.5 (c 0.2, CHCl3). The enantiomeric excess
was determined by HPLC with a Chiralpak IA column: λ = 254 nm;
eluent, hexane/i-PrOH (200:1); flow rate = 0.5 mL/min; tR = 13.2
min (minor); tR = 13.9 min (major). The specific rotation of the
Chem. Soc. 2012, 134, 8277.
(8) Zhao, L.; Ma, Y.; Duan, W.; He, F.; Chen, J.; Song, C. Org. Lett.
2012, 14, 5780.
(9) (a) He, L.; Zhang, Y. R.; Huang, X. L.; Ye, S. Synthesis 2008, 17,
2825. (b) Enders, D.; Han, J. Tetrahedron: Asymmetry 2008, 19, 1367.
(c) Shao, P. L.; Chen, X. Y.; Ye, S. Angew. Chem., Int. Ed. 2010, 122,
8590. (d) Sun, L. H.; Shen, L. T.; Ye, S. Chem. Commun. 2011, 47,
10136.
(10) (a) Kerr, M. S.; Read de Alaniz, J.; Rovis, T. J. Org. Chem. 2005,
70, 5725. (b) Takikawa, H.; Suzuki, K. Org. Lett. 2007, 9, 2713.
(c) Allen, S. E.; Mahatthananchai, J.; Bode, J. W.; Kozlowski, M. C. J.
Am. Chem. Soc. 2012, 134, 12098.
(11) (a) Ma, Y.; Wei, S.; Wu, J.; Yang, F.; Liu, B.; Lan, J.; Yang, S.;
You, J. Adv. Synth. Catal. 2008, 350, 2645. (b) Struble, J. R.; Bode, J.
W. Org. Synth. 2010, 87, 362.
(12) (a) Pye, P. J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante,
R. P.; Reider, P. J. J. Am. Chem. Soc. 1997, 119, 6207. (b) Hermanns,
20
corresponding hydroxyl ketone was [α]D = +58.5 (c 0.2, CHCl3).
The absolute configuration was determined by comparing this value
with the reported literature15 (lit. [α]D24 = −32.9 (c 2.27, CHCl3) 52%
ee (S)). Other spectra and properties data matched those reported in
the literature.14
ASSOCIATED CONTENT
* Supporting Information
■
S
X-ray crystallographic data (CIF file of 7a) and detailed spectral
data for products. This material is available free of charge via
the Internet at http://pubs.acs.org.
N.; Dahmen, S.; Bolm, C.; Brase, S. Angew. Chem., Int. Ed. 2002, 41,
̈
3692. (c) Dahmen, S.; Brase, S. J. Am. Chem. Soc. 2002, 124, 5940.
̈
AUTHOR INFORMATION
Corresponding Author
*E-mail: ydma@sdu.edu.cn; chunsong@sdu.edu.cn.
■
(d) Gibson, S. E.; Knight, J. D. Org. Biomol. Chem. 2003, 1, 1256.
(e) Bolm, C.; Focken, T.; Raabe, G. Tetrahedron: Asymmetry 2003, 14,
1733. (f) Wu, X.-W.; Zhang, T.-Z.; Hou, X.-L. Tetrahedron: Asymmetry
2004, 15, 2357. (g) Whelligan, D. K.; Bolm, C. J. Org. Chem. 2006, 71,
Notes
4609. (h) Furstner, A.; Alcarazo, M.; Krause, H.; Lehmann, C. W. J.
̈
The authors declare no competing financial interest.
Am. Chem. Soc. 2007, 129, 12676. (i) Jiang, B.; Lei, Y.; Zhao, X. L. J.
Org. Chem. 2008, 73, 7833. (j) Aly, A. A.; Brown, A. B. Tetrahedron
ACKNOWLEDGMENTS
■
2009, 65, 8055. (k) Schneider, J. F.; Falk, F. C.; Frohlich, R.; Paradies,
̈
We are grateful for the financial support from the National
Natural Science Foundation of China (Grant No. 20671059)
and Shandong Provincial Natural Science Foundation
(ZR2011BM013).
J. Eur. J. Org. Chem. 2010, 2265. (l) Gleiter, R.; Hopf, H. Modern
Cyclophane Chemistry; Wiley-VCH: Weinheim, 2004.
(13) Francos, J.; Grande-Carmona, F.; Faustino, H.; Iglesias-
Siguenaz, J.; Díez, E.; Alonso, I.; Fernad
́
ez, R.; Lassaletta, J. M.;
̈
Lop
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ez, F.; Mascarenas, J. L. J. Am. Chem. Soc. 2012, 134, 14322.
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