Synthesis of 3-mono-substituted binaphthyl-based secondary amine catalysts via monobromination of an axially chiral dicarboxylic acid derivative

Article abstract of DOI:10.1021/jo500637q

A facile synthetic route to a 3-bromo binaphthyl-based secondary amine through the monobromination of an axially chiral dicarboxylic acid derivative has been developed. The combination of this new procedure with coupling reactions established an efficient synthetic approach to a series of binaphthyl-based secondary amine catalysts containing various functional groups in an efficient way.

Full text of DOI:10.1021/jo500637q

Note
pubs.acs.org/joc
Synthesis of 3‑Mono-Substituted Binaphthyl-Based Secondary
Amine Catalysts via Monobromination of an Axially Chiral
Dicarboxylic Acid Derivative
Taichi Kano, Momotaro Takeda, Ryu Sakamoto, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
S
* Supporting Information
ABSTRACT: A facile synthetic route to a 3-bromo binaphthyl-based
secondary amine through the monobromination of an axially chiral
dicarboxylic acid derivative has been developed. The combination of this
new procedure with coupling reactions established an efficient synthetic
approach to a series of binaphthyl-based secondary amine catalysts
containing various functional groups in an efficient way.
n asymmetric catalysis, the design of a novel chiral motif is
highly important for the development of new chiral ligands
the neopentyl ester (S)-8 with magnesium bis(2,2,6,6-tetra-
I
methylpiperamide) [Mg(tmp)2] prepared in THF, and
subsequent bromination with bromine (Scheme 1a).3 In this
method, both mono- and dibrominated products, which are
inseparable, were obtained simultaneously. To circumvent this
synthetic issue, we examined the monolithiation and sub-
sequent bromination of (S,R)-9, which could be easily obtained
by the fractional recrystallization of the diastereomeric mixture
of 9 prepared from racemic 1,1′-binaphthyl-2,2′-dicarboxylic
acid (7) and (R)-1-phenylethylamine,7 utilizing the amide
group as an effective directing group for ortho-metalation
(Scheme 1b).8
We first performed the bromination of (S,R)-9 by using Br2
as a brominating agent after the lithiation with t-butyllithium
and N,N,N′,N′-tetramethylethylenediamine (TMEDA)
(Scheme 2). However, the desired product (S,R)-10 was
obtained in only 24% yield along with substantial amounts of
recovered starting material in 76% yield. Use of N-
bromosuccinimide resulted in a slightly increased yield, giving
(S,R)-10 in 46% yield with the recovery of 47% of (S,R)-9.
Fortunately, when 1,2-dibromotetrafluoroethane was used as a
brominating agent, the starting material was completely
consumed and (S,R)-10 was obtained in 92% yield.9 It is
worth mentioning that, in the case of diastereomeric amide
(R,R)-9, the desired brominated product was not obtained at all
under the same reaction conditions, which implied that
stereochemical combination of the amide and the binaphthyl
moiety significantly affected the ortho-lithiation step (Scheme
3).
or catalysts providing unprecedented reactivity and selectivity.
Among them, C2-symmetric structures have been widely
applied to various chiral ligands or catalysts, such as BINAP,
BINOL, bisoxazoline (BOX), and salen complexes.1 On the
other hand, C1-symmetric structures, such as 3-mono-
substituted binaphthyl-based ligands or catalysts, frequently
show unique reactivities and/or selectivities;2 however, the
utilizations of them in asymmetric reactions are relatively scarce
to date.
We have previously designed C1-symmetric binaphthyl-based
secondary amine catalysts (S)-1 and (S)-2 containing an acid
functional group at the 3-position for enamine catalysis.3,4
These catalysts have been successfully utilized in several
asymmetric reactions and have shown unique reactivity and
selectivity in comparison with commonly used proline and its
derivatives. 3-Mono-substituted binaphthyl-based secondary
amine structures were also found in amine organocatalysts
(S)-3 and (S)-4 as well as a phase-transfer catalyst (S)-5
(Figure 1).5,6 Despite their utility, however, the applications of
3-mono-substituted binaphthyl-based amines in asymmetric
reactions are still rare due to their synthetic inefficiency. In the
course of our research, we set out to investigate a novel
procedure to effectively access the binaphthyl-based secondary
amine (S)-6 as a key intermediate for a series of binaphthyl-
based secondary amine catalysts. Herein, we wish to report our
result on this subject.
We then examined the transformation of (S,R)-10 to the
cyclic secondary amine (S)-6 (Scheme 4). Refluxing in thionyl
chloride transformed the amide to a nitrile through an imidoyl
chloride (von Braun amide degradation),10 and subsequent
reduction with BH3-THF gave the amino alcohol (S)-11. The
obtained (S)-11 was successfully cyclized with BBr3 to the
In our previous procedures for (S)-1 and (S)-2, the deficit
step was the monobromination by the ortho-magnesiation of
Received: March 18, 2014
Published: April 7, 2014
© 2014 American Chemical Society
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Note
Figure 1. Binaphthyl-based organocatalysts.
Scheme 1. Synthetic Approaches to 3-Bromo-binaphthyl Structures
Scheme 2. Monobromination of (S,R)-9
Scheme 4. Synthesis of Secondary Amine (S)-6
Scheme 3. Monobromination of (R,R)-9
yield. Subsequent hydrogenation of (S)-14 gave the amino
trifluoromethanesulfonamide (S)-2.
secondary amine (S)-6 without either protection of the amino
group or sulfonylation of the hydroxyl group.
Finally, amino alcohol (S)-16 as a new type of amine
organocatalyst was successfully synthesized. The palladium-
catalyzed borylation of (S)-12 with bis(pinacolato)diboron
(B2(pin)2) gave the boronic pinacol ester (S)-15 in 90% yield.
Following introduction of a hydroxyl group at the 3-position of
(S)-15 by oxidation with mCPBA,12 deprotection of the Z
group successfully afforded (S)-16. The obtained (S)-16 was
found to effectively catalyze the anti-selective Mannich reaction
between 3-phenylpropanal and an α-imino ester to give the
corresponding anti-Mannich adduct with excellent enantiose-
lectivity (Scheme 6).4a
With the key intermediate (S)-6 in hand, various substituents
could be introduced at the 3-position of the binaphthyl moiety
by coupling reactions after the protection of the amino group
by the benzyloxycarbonyl (Z) group (Scheme 5). For instance,
benzyloxy carbonylation of (S)-12 with CO in benzyl alcohol
afforded the benzyl ester (S)-13 in 87% yield. Then,
hydrogenation of (S)-13 gave the amino acid (S)-1, which
could be easily isolated by the recrystallization instead of the
purification by using an ion-exchange resin.3 On the other
hand, the palladium-catalyzed amination of (S)-12 with
benzophenone imine,11 hydrolysis, and subsequent treatment
with Tf2O afforded trifluoromethanesulfonamide (S)-14 in 88%
In summary, we have developed a new synthetic route to the
3-bromo binaphthyl-based secondary amine structure through
the monobromination. This new procedure enabled us to
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a
Scheme 5. Synthesis of a Series of Binaphthyl-Based Secondary Amine Catalysts
a
Reagents and conditions: (a) benzyl chloroformate (Z-Cl), Et3N, THF, rt (88%); (b) CO, Pd(OAc)2, dppp, EtNiPr2, DMSO/BnOH (87%); (c)
H2, Pd/C, MeOH, 40 °C (80%); (d) (i) benzophenone imine, Pd2(dba)3, BINAP, NaOtBu, toluene, reflux, then 1 N HCl, THF, reflux; (ii) Tf2O,
N,N-dimethylaniline, CH2Cl2, rt (88% for three steps); (e) H2, Pd/C, MeOH, 40 °C (93%); (f) B2(pin)2, Pd(OAc)2, KOAc, DMF, 85 °C (90%);
(g) (i) mCPBA, H2O/EtOH, 0 °C; (ii) H2, Pd/C, MeOH, 40 °C (45% for two steps).
at room temperature. The reaction mixture was quenched with 1 N
HCl and extracted with ethyl acetate. The combined organic layers
were washed with brine, dried over Na2SO4, and concentrated. The
residue was purified by flash column chromatography on silica gel
(hexane/ethyl acetate = 3/1 as eluent) to afford (S,R)-10 (1.90 g, 3.68
mmol, 92% yield). Pale yellow solid. mp 149−150 °C. [α]2D4 = −175.3
Scheme 6. anti-Selective Mannich Reaction Catalyzed by
(S)-16
1
(c 1.05, CHCl3). H NMR (400 MHz, CDCl3) δ 8.25 (1H, s), 8.02
(1H, d, J = 8.5 Hz), 7.96 (1H, d, J = 8.2 Hz), 7.82 (2H, app t, J = 8.1
Hz), 7.55−7.50 (2H, m), 7.30 (1H, t, J = 7.7 Hz), 7.22 (1H, t, J = 7.7
Hz), 7.10−6.94 (5H, m), 6.45−6.43 (2H, br), 6.24 (1H, br), 4.93−
4.86 (1H, m), 1.37 (3H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3)
δ 170.1, 168.6, 140.7, 135.5, 134.5, 134.2, 133.9, 132.4, 131.9, 131.3,
129.4, 128.3, 128.0, 127.6, 127.5, 127.2, 127.1, 126.5, 126.3, 125.5,
125.0, 115.2, 49.2, 20.2 (The several signals for aromatic carbons were
not identified due to the overlap of peaks.); IR (neat) 2972, 1700,
1617, 1556, 1243, 908, 731 cm−1; HRMS (ESI-TOF) Calcd for
C30H22BrNNaO3: 546.0675 ([M + Na]+), Found: 546.0679 ([M +
Na]+).
synthesize various types of amine organocatalysts containing
acidic functionalities in an efficient way.
EXPERIMENTAL SECTION
■
General Information. Infrared (IR) spectra were recorded on an
FT-IR spectrometer. 1H NMR spectra were measured on 400 and 500
MHz spectrometers. Chemical shifts were reported in parts per million
(ppm) from tetramethylsilane as an internal standard. Data were
reported as follows: chemical shift, integration, multiplicity (s = singlet,
d = doublet, t = triplet, q = quintet, m = multiplet, br = broad, and app
= apparent), coupling constants (Hz), and assignment. 13C NMR
spectra were recorded on 100 and 125 MHz spectrometers with
complete proton decoupling. Chemical shifts were reported in ppm
from the residual solvent as an internal standard. The high-resolution
mass spectra (HRMS) were performed on an ESI-TOF mass
spectrometer. Optical rotations were measured on a digital polar-
imeter.
Bromo Amine (S)-6. A mixture of (S,R)-10 (1.05 g, 2 mmol),
thionyl chloride (10 mL), and one drop of DMF was refluxed for 3 h,
and excess thionyl chloride was removed under reduced pressure. To a
solution of the residue in THF (10 mL) was added a 0.95 M solution
of BH3-THF (9.6 mL) at 0 °C. After stirring for 1 h at 0 °C, the
mixture was refluxed overnight. The resulting mixture was quenched
with NaHCO3 aq. at 0 °C and then extracted with ethyl acetate. The
organic layer was washed with brine, dried over Na2SO4, and
concentrated. The residue was roughly purified by flash column
chromatography on silica gel (hexane/ethyl acetate 1:1 to ethyl acetate
only as eluent) to give (S)-11. To a solution of (S)-11 in CH2Cl2 (25
mL) was added BBr3 (500 μL, 5.3 mmol) at 0 °C. The reaction
mixture was stirred at 0 °C for 3 h. The mixture was then quenched
with saturated NaHCO3 and extracted with CH2Cl2. The combined
organic layers were washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by flash column chromatog-
raphy on silica gel (ethyl acetate as eluent) to afford (S)-6 (397 mg,
In experiments requiring dry solvents, the dehydrated tetrahy-
drofuran (THF) and dichloromethane (CH2Cl2) were purchased and
used. N,N,N′,N′-Tetramethylethylenediamine (TMEDA) was distilled
from CaH2 and was stored over 4 Å molecular sieves. The following
products are all known: (S)-1,3 (S)-2,4 and (S,R)-9.7
Bromo Amide (S,R)-10. To a stirred solution of TMEDA (3 mL,
20 mmol) in THF (16 mL) was added a 1.67 M pentane solution of t-
BuLi (12 mL, 20 mmol) at −78 °C. After stirring for 30 min at −78
°C, (S,R)-9 (1.96 g, 4 mmol) in THF (24 mL) was added to the
mixture at the same temperature. The reaction mixture was stirred for
30 min at −78 °C and then stirred for 1 h at 0 °C. To the mixture was
added 1,2-dibromotetrafluoroethane (2.4 mL, 20 mmol) at −78 °C.
The mixture was stirred for 30 min at −78 °C and then stirred for 2 h
1.06 mmol, 53% yield). Pale yellow solid. mp 118−119 °C. [α]D24
=
1
485.0 (c 1.19, CHCl3). H NMR (400 MHz, CDCl3) δ 8.26 (1H, s),
7.99 (1H, d, J = 8.2 Hz), 7.95 (1H, d, J = 8.2 Hz), 7.84 (1H, d, J = 8.5
Hz), 7.59 (1H, d, J = 8.2 Hz), 7.46 (2H, app t, J = 7.5 Hz), 7.37 (1H,
d, J = 14.2 Hz), 7.35 (1H, d, J = 14.2 Hz), 7.29−7.23 (2H, m), 4.46
(1H, d, J = 13.1 Hz), 3.88 (1H, d, J = 11.8 Hz), 3.42 (1H, d, J = 11.8
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Note
Hz), 3.34 (1H, d, J = 13.1 Hz), 2.11 (1H, br); 13C NMR (125 MHz,
CDCl3) δ 137.0, 134.9, 134.6, 134.0, 133.6, 133.0, 131.8, 131.1, 130.4,
129.4, 128.3, 127.6, 127.2, 127.1 (two peaks are overlapped), 126.4,
126.1, 125.9, 125.5, 121.9, 48.5, 47.4; IR (neat) 3053, 1554, 979, 909,
729 cm−1; HRMS (ESI-TOF) Calcd for C22H17BrN: 374.0539 ([M +
H]+), Found: 374.0554 ([M + H]+).
silica gel (hexane/ethyl acetate 3:1 as eluent) to give the
corresponding aminated product. To a stirred solution of the produxt
(ca. 1.53 mmol) in CH2Cl2 (95 mL) were added N,N-dimethylaniline
(190 μL, 1.53 mmol) and Tf2O (258 μL, 1.53 mmol) at 0 °C. The
reaction mixture was stirred at room temperature overnight. The
mixture was then quenched with saturated NaHCO3 and extracted
with CH2Cl2. The combined organic layers were washed with brine,
and dried over Na2SO4, and concentrated. The residue was purified by
flash column chromatography on silica gel (hexane/ethyl acetate = 5/
1) to afford (S)-14 (828 mg, 1.43 mmol, 88% yield for 2 steps). White
solid. mp 115−117 °C. [α]D21 = 12.41 (c 0.98, CHCl3). 1H NMR (400
MHz, CDCl3) δ 8.18 (1H, s), 8.00 (1H, d, J = 8.5 Hz), 7.96 (2H, app
d, J = 8.2 Hz), 7.56 (1H, d, J = 8.5 Hz), 7.51 (2H, app t, J = 7.1 Hz),
7.42−7.24 (9H, m), 5.24 (2H, m), 5.10 (1H, d, J = 12.3 Hz), 4.73
(1H, d, J = 12.8 Hz), 3.78 (1H, d, J = 12.6 Hz), 3.67 (1H, d, J = 14.7
Hz); 13C NMR (125 MHz, CDCl3) δ 158.6, 135.7, 135.7, 135.3, 133.5,
133.3, 132.3, 131.6, 130.1, 129.7, 129.5, 128.7, 128.6, 128.4, 128.3,
128.1, 128.1, 127.8, 127.4, 127.4, 127.0, 126.7, 126.5, 126.4, 125.6,
120.1 (C−F, d, J = 323.1 Hz, CF3), 68.4, 49.7, 41.8; IR (neat) 3064,
1668, 1420, 1218, 1194, 732 cm−1; HRMS (ESI-TOF) Calcd for
C31H23F3N2NaO4S: 599.1223 ([M + Na]+), Found: 599.1206 ([M +
Na]+).
N-Z Protected Amine (S)-12. To a solution of (S)-6 (200 mg,
0.53 mmol) were added TEA (800 μL, 2.65 mmol) and benzyl
chloroformate (Z-Cl) (350 μL, 2.65 mmol) at 0 °C. After stirring at
room temperature overnight, the mixture was quenched with
NaHCO3 aq. at 0 °C and then extracted with ethyl acetate. The
organic layer was washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by flash column chromatog-
raphy on silica gel (hexane/ethyl acetate 7:1 as eluent) to give (S)-12
(239 mg, 0.47 mmol, 88% yield). White solid. mp 98−100 °C. [α]D26
=
1
−28.2 (c 1.23, CHCl3). H NMR (500 MHz, 50 °C, CDCl3) δ 8.26
(1H, s), 7.98 (1H, d, J = 8.2 Hz), 7.94 (1H, d, J = 8.2 Hz), 7.83 (1H, d,
J = 7.9 Hz), 7.59 (1H, br), 7.47 (2H, app t, J = 7.5 Hz), 7.43−7.41
(2H, m), 7.37−7.23 (7H, m), 5.75 (1H, br), 5.26 (1H, d, J = 12.5 Hz),
5.18 (1H, d, J = 12.2 Hz), 5.07 (1H, br), 3.66 (1H, d, J = 13.0 Hz),
3.57 (1H, d, J = 13.3 Hz); 13C NMR (125 MHz, 50 °C, CDCl3) δ
154.6, 137.6, 136.8, 134.7, 134.0, 133.3, 132.8, 132.2, 132.0, 131.3,
130.6, 129.8, 128.4, 128.4, 128.4, 128.0, 127.9, 127.7, 127.3, 127.2,
127.0, 126.4, 126.3, 126.0, 122.0, 67.4, 48.0, 46.5; IR (neat) 1696,
1414, 1244, 1203, 1100, 750, 736 cm−1; HRMS (ESI-TOF) Calcd for
C30H22BrNNaO2: 530.0726 ([M + Na]+), Found: 530.0720 ([M +
Na]+).
Amino Trifluoromethanesulfonamide (S)-2. To a stirred
solution of (S)-14 (160 mg, 0.278 mmol) in MeOH (32 mL) was
added 10% palladium on carbon (80 mg) at room temperature. The
mixture was then hydrogenated under H2 (balloon) at 40 °C overnight
and filtered through Celite. After removal of the solvent under reduced
pressure, the residue was purified by flash column chromatography
(CH2Cl2/MeOH = 20:1 as eluent) to afford (S)-2 (114 mg, 0.26
Benzyl Ester (S)-13. Compound (S)-12 (166 mg, 0.325 mmol),
Pd(OAc)2 (13.5 mg, 0.06 mmol), bis(diphenylphosphino)propane
(dppp) (24.5 mg, 0.06 mmol), and iPr2NEt (300 μL, 1.76 mmol) in
DMSO (1 mL) and BnOH (1 mL) were charged into an autoclave
under an argon atmosphere. After pressurized with CO (10 atm), the
mixture was heated to 100 °C with stirring for 24 h. After cooling to
room temperature, the reaction mixture was poured into water and
extracted with AcOEt. The organic layer was washed with brine, dried
over Na2SO4, and then concentrated. The residue was purified by flash
column chromatography on silica gel (CH2Cl2 as eluent) to give (S)-
13 (160 mg, 0.284 mmol, 87% yield). Pale yellow solid. mp 70−72 °C.
1
mmol, 93% yield). Pale yellowish solid. H NMR, 13C NMR, IR, and
HRMS data were consistent with previously reported values.4
Boronic Pinacol Ester (S)-15. A mixture of (S)-12 (102 mg, 0.20
mmol), bis(pinacolato)diboron (55 mg, 0.22 mmol), Pd(OAc)2 (1.5
mg, 0.006 mmol), and KOAc (59 mg, 0.60 mmol) in DMF (1 mL)
was heated at 85 °C and stirred for 5 h under an argon atmosphere.
After cooling to room temperature, the mixture was then quenched
with H2O and extracted with AcOEt. The combined organic layers
were washed with brine, dried over Na2SO4, and concentrated. The
residue was purified by flash column chromatography on silica gel
(hexane/ethyl acetate = 5/1 as eluent) to afford (S)-15 (100 mg, 0.18
mmol, 90% yield). White solid. mp 102−104 °C. [α]1D5 = −18.1 (c
[α]2D5 = −1.9 (c 2.1, CHCl3). H NMR (400 MHz, 50 °C, CDCl3) δ
1
8.41 (1H, s), 7.85 (2H, app d, J = 8.2 Hz), 7.81 (1H, d, J = 8.2 Hz),
7.46−7.12 (17H, m), 5.98 (1H, d, J = 13.5 Hz), 5.22 (2H, br), 5.05
(2H, br), 4.95 (1H, br), 3.61 (1H, d, J = 13.1 Hz), 3.44 (1H, d, J =
13.5 Hz); 13C NMR (100 MHz, 50 °C, CDCl3) δ 167.6, 154.9, 137.5,
137.0, 136.1, 134.7, 133.4, 133.0, 132.9, 132.1, 131.5, 131.2, 129.6,
129.2, 128.6, 128.41, 128.37, 128.2, 128.0, 127.9, 127.8, 127.5, 127.2,
127.2, 126.7, 126.2, 125.9, 67.3, 67.2, 48.2, 43.3 (The several signals
for aromatic carbons were not identified due to the overlap of peaks.);
IR (neat) 2926, 1695, 1416, 1236, 733 cm−1; HRMS (ESI-TOF)
Calcd for C38H30NO4: 564.2169 ([M + H]+), Found: 564.2154 ([M +
H]+).
1
0.48, CHCl3). H NMR (500 MHz, 60 °C, CDCl3) δ 8.50 (1H, s),
7.96−7.90 (3H, m), 7.57 (1H, br), 7.43 (2H, app t, J = 7.5 Hz), 7.38−
7.20 (9H, m), 5.96 (1H, d, J = 13.0 Hz), 5.24−5.12 (3H, m), 3.68
(1H, d, J = 13.3 Hz), 3.59 (1H, d, J = 13.0 Hz), 1.39−1.25 (12H, m);
13C NMR (125 MHz, 60 °C, CDCl3) δ 154.9, 138.3, 137.3, 136.6,
135.8, 135.2, 133.3, 132.9, 132.8, 132.4, 131.7, 129.1, 128.8, 128.4,
128.4, 128.3, 127.7, 127.7, 127.5, 127.4, 127.1, 127.0, 126.0, 125.8,
125.7, 84.2, 83.4, 67.1, 48.0, 45.6, 25.0, 24.9, 24.8, 24.7; IR (neat)
2978, 1695, 1415, 1345, 1243, 732 cm−1; HRMS (ESI-TOF) Calcd for
C36H34BNNaO4: 578.2479 ([M + Na]+), Found: 578.2491 ([M +
Na]+).
Amino Acid (S)-1. To a stirred solution of (S)-13 (102 mg, 0.18
mmol) in MeOH (15 mL) was added 10 mol % palladium on carbon
(51 mg) at room temperature. The mixture was then hydrogenated
under H2 (balloon) at 40 °C for 12 h and filtered through Celite. After
the removal of the solvent, (S)-1 was recrystallized from MeOH and
Amino Alcohol (S)-16. To a stirred solution of (S)-16 (100 mg,
0.18 mmol) in H2O (270 μL) and EtOH (1.2 mL) was added mCPBA
(ca. 70%, 45 mg, 0.18 mmol) at 0 °C. The reaction mixture was stirred
at 0 °C for 1 h. The mixture was then quenched with saturated
Na2CO3 and extracted with AcOEt. The combined organic layers were
washed with brine, dried over Na2SO4, and concentrated. The residue
was roughly purified by flash column chromatography on silica gel
(hexane/ethyl acetate = 4/1) to afford the 3-hydroxy N-Z protected
secondary amine, which was used for the next step without further
purification. To a stirred solution of the product in MeOH (12 mL)
was added 10 mol % palladium on carbon (13 mg) at room
temperature. The mixture was then hydrogenated under H2 (balloon)
at 40 °C for 1 h and filtered through Celite. After removal of the
solvent under reduced pressure, the residue was purified by flash
column chromatography (CH2Cl2/MeOH = 9:1 as eluent) to afford
(S)-16 (25 mg, 0.081 mmol, 45% yield for 2 steps). Pale brownish
1
Et2O (49.2 mg, 0.145 mmol, 80% yield). White solid. H NMR, 13C
NMR, IR, and HRMS data were consistent with previously reported
values.3
Trifluoromethanesulfonamide (S)-14. A mixture of (S)-12 (829
mg, 1.63 mmol), benzophenone imine (354 mg, 1.96 mmol), BINAP
(161 mg, 0.26 mmol), Pd2(dba)3 (74.3 mg, 0.08 mmol), and NaOBut
(218 mg, 2.27 mmol) in toluene (29 mL) was heated at 110 °C and
stirred for 16 h under an argon atmosphere. After cooling to room
temperature, the reaction mixture was filtered through a Celite pad,
and the filter cake was washed with ethyl acetate. The filtrate was
concentrated in vacuo. The residue was dissolved in 1 N HCl (5 mL)
and THF (45 mL). After refluxing for 1 h, the mixture was then
quenched with NaHCO3 and extracted with ethyl acetate. The organic
layer was washed with brine, dried over Na2SO4, and concentrated.
The residue was roughly purified by flash column chromatography on
solid. mp 193−195 °C. [α]D23 = 442.4 (c 1.1, MeOH). H NMR (400
1
MHz, CD3OD) δ 8.03 (1H, d, J = 8.0 Hz), 7.95 (1H, d, J = 8.2 Hz),
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7.73 (1H, d, J = 8.2 Hz), 7.63 (1H, d, J = 8.5 Hz), 7.47 (1H, t, J = 6.9
Hz), 7.37−7.34 (3H, m), 7.27 (1H, t, J = 7.6 Hz), 7.15 (1H, d, J = 8.0
Hz), 7.02 (1H, t, J = 6.5 Hz), 4.56 (1H, d, J = 12.6 Hz), 3.92 (1H, d, J
= 12.3 Hz), 3.48 (1H, d, J = 12.1 Hz), 3.04 (1H, d, J = 12.8 Hz); 13C
NMR (125 MHz, CD3OD) δ 153.9, 138.7, 136.9, 136.9, 135.5, 132.6,
130.9, 129.8, 129.6, 128.4, 128.2, 128.2, 128.2, 127.9 (two peaks are
overlapped), 127.7, 127.4, 124.6, 121.5, 111.5, 47.3, 39.6; IR (neat)
1597, 1342, 1150, 1109, 822, 748 cm−1; HRMS (ESI-TOF) Calcd for
C22H18NO: 312.1383 ([M + H]+), Found: 312.1370 ([M + H]+).
The Mannich Reaction between 3-Phenylpropanal and N-
PMP-Protected α-Imino Ester Catalyzed by (S)-16. To a solution
of (S)-16 (1.6 mg, 0.005 mmol) and 3-phenylpropanal (40 μL, 0.30
mmol) in CHCl3 (200 μL) was added N-PMP-protected α-imino ester
(21 mg, 0.10 mmol) at 0 °C. After 4 h of stirring at 0 °C, the reaction
mixture was quenched with H2O and extracted with ethyl acetate. The
combined organic layer was washed with water, dried over Na2SO4,
and concentrated. The residue was purified by flash column
chromatography on silica gel to afford a Mannich adduct (22.5 mg,
0.066 mmol, 66% yield, anti/syn = 7/1, 98% ee (anti)), which was then
reduced with LiAlH4 for determining the enantiomeric excess. 1H
NMR, 13C NMR, IR, HRMS, HPLC, and [α] data were consistent
with previously reported values.4a,13
(6) (a) Kano, T.; Lan, Q.; Wang, X.; Maruoka, K. Adv. Synth. Catal.
2007, 349, 556. (b) Shirakawa, S.; Wu, X.; Maruoka, K. Angew. Chem.,
Int. Ed. 2013, 52, 14200.
(7) Oi, S.; Matsuzaka, Y.; Yamashita, J.; Miyano, S. Bull. Chem. Soc.
Jpn. 1989, 62, 956.
̂
(8) Snieckus, V. Chem. Rev. 1990, 90, 879.
(9) The use of 1,2-dibromotetrachloroethane instead of 1,2-
dibromotetrafluoroethane gave the desired product in 67% yield
with the 3-chloro product in 18% yield.
(10) Vaughan, W. R.; Carlson, R. D. J. Am. Chem. Soc. 1962, 84, 769.
(11) Wolfe, J. P.; Åhman, J.; Sadighi, J. P.; Singer, R. A.; Buchwald, S.
L. Tetrahedron Lett. 1997, 38, 6367.
(12) Chen, D.-S.; Huang, J.-M. Synlett 2013, 24, 499.
́
(13) Franzen, J.; Marigo, M.; Fielenbach, D.; Wabnitz, T. C.;
Kjærsgaard, A.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 18296.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of NMR spectra of all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: maruoka@kuchem.kyoto-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research from MEXT, Japan. R.S. thanks the Japan Society for
the Promotion of Science for Young Scientists for Research
Fellowships.
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