A dual-catalysis approach to the kinetic resolution of 1,2-diaryl-1,2- diaminoethanes

Article abstract of DOI:10.1039/c2cc36361e

The kinetic resolution of racemic C₂-symmetric 1,2-diaryl-1,2-diaminoethanes was accomplished for the first time through application of a dual-catalysis approach.

Full text of DOI:10.1039/c2cc36361e

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A Dual-Catalysis Approach to the Kinetic Resolution of 1,2-diaryl-1,2-
diaminoethanes
Chang Min, Nisha Mittal, Chandra Kanta De, and Daniel Seidel*
Department of Chemistry and Chemical Biology
Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 (USA)
Supporting Information
General Information: Reagents and solvents were purchased from commercial sources and
were used as received unless stated otherwise. Toluene was freshly distilled from sodium
under nitrogen prior to use. Reactions were run under a nitrogen atmosphere. Purification of
reaction products was carried out by flash chromatography using Sorbent Technologies
Standard Grade silica gel (60 Å, 230–400 mesh). Analytical thin layer chromatography was
performed on EM Reagent 0.25 mm silica gel 60 F254 plates. Melting points were recorded
on a Thomas Hoover capillary melting point apparatus and are uncorrected. Infrared spectra
were recorded on an ATI Mattson Genesis Series FT-Infrared spectrophotometer. Proton
1
nuclear magnetic resonance spectra ( H-NMR) were recorded on a Varian VNMRS–500 or
4
00 MHz instrument and are reported in ppm using solvent as an internal standard (CDCl
3
at
7
.26 ppm and (CD SO at 2.50 ppm. Data are reported as app = apparent, s = singlet, d =
3 2
)
doublet, t = triplet, dd = doublet of doublets, m = multiplet, comp = complex, br s= broad
singlet; integration; coupling constant(s) in Hz. Proton-decoupled carbon nuclear magnetic
1
3
resonance spectra ( C-NMR) spectra were recorded on a Varian VNMRS–500 MHz
instrument and are reported in ppm using solvent as an internal standard (CDCl at 77.0 ppm
and (CD SO at 39.5 ppm ). Mass spectra were recorded on a Finnigan LCQ-DUO mass
3
3 2
)
spectrometer or on a Finnigan 2001 Fourier Transform Ion Cyclotron Resonance Mass
Spectrometer. HPLC analysis was carried out on an Agilent 1100 series instrument with auto
sampler and multiple wavelength detectors. Optical rotations were measured using a 1 mL
cell with a 1 dm path length on a Jasco P–2000 polarimeter at 589 nm and at 20 °C. Racemic
1
1
1
3
3
2
3
3
1
1
,2-diaryl-1,2-diaminoethanes 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h, and 7i were prepared
based on literature methods. 1,2-Diaryl-1,2-diaminoethanes, catalyst 1, DMAP and benzoic
anhydride were purified by recrystallization prior to use.
D
The absolute configuration of 9f ([α] 20 +24.9, c 0.5, CHCl
3
, 65% ee) was assigned by
comparison with the bis(2,2,2-trichloroethyl) ((1R,2R)-1,2-diphenylethane- 1,2-
D
diyl)dicarbamate ([α] 20 –40.8, c 0.5, CHCl
3
) synthesized from commercially available
(
9
1R,2R)-(+)-1,2-diphenylethylenediamine. The absolute configuration of products (8a–8i,
a–9e and 9g–9i) was assigned by analogy.
4
Conversions and s-factors were calculated in accord with standard procedures.
S 1

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General Procedure for the Resolution and Protection of Racemic Diamines:
A flame dried round bottom flask was charged with benzoic anhydride (22.6 mg, 0.1 mmol,
.5 equiv.) and powdered 4Å MS (100 mg). Freshly distilled toluene (10 mL) and N,N-
0
dipropylpyridine-4-amine (3.6 mg, 0.02 mmol, 0.1 equiv.) in 1 mL of toluene was added.
The resulting mixture was cooled to –78 °C over 15 min and a solution of catalyst 1 (12.5
mg, 0.02 mmol, 0.1 equiv.) in 6 mL of toluene was added. After 15 min, a solution of
diamine (0.2 mmol) in 3 mL of toluene was added slowly along the inner side of the flask and
the reaction mixture was stirred at –78 °C. When benzoic anhydride could no longer be
detected by TLC analysis, an ethanolic ammonia solution (2 M, 2 mL) was added. The
reaction mixture was allowed to warm to rt, diluted with 10 mL of a 1:1 water/brine mixture
and extracted with EtOAc (5 x 30 mL). After drying with anhydrous sodium sulfate, the
2 2
organic layer was concentrated under reduced pressure and dissolved in 10 mL of CH Cl .
The solution was cooled to 0 °C and Hünig's base and Troc-Cl were added slowly. After
completion of the reaction, the resulting mixture was concentrated under reduced pressure
and purified by flash chromatography.
The conversion, CHPLC, for each catalytic reaction was calculated using the following
equation:
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ꢀꢁꢂꢃꢀ
ꢄ
ꢅꢅ ꢈ ꢅꢅ
ꢂ
ꢆꢇ
p
Where ee is the enantiomeric excess of the amide product and eeSM is the enantiomeric
excess of the recovered amine.
The s-factor was calculated using the calculated conversion and ee from either the product,
p
ee , or recovered starting material, eeSM, following the equation:
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ꢂ
ꢉ ꢄ
ꢊꢋꢌꢍꢎ ꢏ ꢀꢁꢂꢃꢀꢐꢍꢎ ꢈ ꢅꢅ ꢐꢑ
ꢂ
ꢊꢋꢌꢍꢎ ꢏ ꢀꢁꢂꢃꢀꢐꢍꢎ ꢏ ꢅꢅꢆꢇꢐꢑ
ꢉ ꢄ
ꢊꢋꢌꢍꢎ ꢏ ꢀꢁꢂꢃꢀ ꢐꢍꢎ ꢈ ꢅꢅꢆꢇꢐꢑ
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Characterization Data of Products
2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-bis(4-chlorophenyl)ethyl)carbamate (8a):
Following the general procedure, compound 8a was obtained as a
white solid in 44% yield (49 mg); mp = 222–224 °C; R = 0.21
, 83% ee);
IR (KBr) 3334, 3053, 2947, 2364, 1713, 1640, 1529, 1492, 1277,
f
D
(
Hexanes/EtOAc 6:1 v/v); [α] 20 –29.2 (c 0.5, CHCl
3
-
1 1
1
148, 1094, 1015, 820, 729 cm ; H NMR (500 MHz, CDCl
.75 (d, J = 7.7 Hz, 2H), 7.65–7.32 (comp, 6H), 7.31–7.25 (m,
H), 7.22 (d, J = 7.5 Hz, 1H), 7.06 (app t, J = 7.1 Hz, 3H), 6.20
3
) δ
7
1
(
1
d, J = 8.0 Hz, 1H), 5.45 (app t, J = 9.2 Hz, 1H), 5.16–4.93 (m, 1H), 4.74 (d, J = 12.0 Hz,
1
3
H), 4.55 (d, J = 12.0 Hz, 1H); C NMR (125 MHz, CDCl
3
) δ 167.8, 155.5, 137.2, 136.8,
1
33.3, 132.1, 132.0, 129.1, 129.0, 128.7, 127.1, 122.4, 122.2, 95.1, 74.6, 60.5, 59.1; m/z(ESI-
+
MS) 561.9 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 97/3, Flow rate = 1
mL/min, UV = 230 nm, t = 10.5 min (major) and t = 8.4 min (minor).
R
R
Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-bis(4-chlorophenyl)ethane-1,2-diyl)dicarbamate
9a): Following the general procedure, compound 9a was obtained
as a white solid in 46% yield (58.0 mg); mp = 205–207 °C; R
(
f
=
D
0
.48 (Hexanes/EtOAc 6:1 v/v); [α] 20 +36.7 (c 0.5, CHCl
3
, 86%
ee); IR (KBr) 3330, 2952, 1710, 1537, 1278, 1144, 1093, 820, 721
-
1 1
cm ; H NMR (500 MHz, CDCl
3
) δ 7.22 (d, J = 8.4 Hz, 4H), 7.03
(
4
d, J = 8.4 Hz, 4H), 5.91 (br s, 2H), 4.97 (dd, J = 5.6, 2.4 Hz, 2H),
.82 (d, J = 12.0 Hz, 2H), 4.63 (d, J = 12.0 Hz, 2H); C NMR
1
3
(
6
125 MHz, CDCl
3
) δ 155.0 136.1, 134.3, 129.1 128.6, 95.2, 74.7, 60.4; m/z (ESI-MS)
+
33.4[M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 98/2, Flow rate = 0.5
R R
mL/min, UV = 230 nm, t = 20.6 min (major) and t = 27.5 min (minor). Calculated
conversion = 51; s = 30.
2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-bis(4-bromophenyl)ethyl)carbamate (8b):
Following the general procedure, compound 8b was obtained as a
white solid in 41% yield (53 mg); mp = 218–219 °C; R = 0.20
, 83% ee); IR
KBr) 3334, 3055, 2950, 2362, 1715, 1642, 1531, 1492, 1280,
f
D
(
(
Hexanes/EtOAc 6:1 v/v); [α] 20 –27.8 (c 0.5, CHCl
3
-
1 1
1148, 1097, 1015, 822, 728 cm ; H NMR (500 MHz, (CD
3
)
2
SO) δ
8.82 (d, J = 9.5 Hz, 1H), 8.59 (d, J = 9.5 Hz, 1H), 7.75 (d, J = 7.7
Hz, 2H), 7.60–7.50 (comp, 2H), 7.49–7.37 (comp, 5H), 7.36–7.20
comp, 4H), 5.64–5.55 (m, 1H), 5.32–5.23 (m, 1H), 4.78 (d, J = 12.5 Hz, 1H), 4.66 (d, J =
(
1
3
1
2.5 Hz, 1H); C NMR (125 MHz, (CD
3 2
) SO) δ 166.0, 154.1, 139.2, 139.1, 134.1, 131.6,
1
31.5, 131.4, 129.0, 128.8, 128.3, 128.0, 127.9(7), 127.2, 96.0, 73.3, 58.4, 56.3; m/z (ESI-
+
MS) 650.4 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 95/5, Flow rate = 1
mL/min, UV = 230 nm, t
R
R
= 8.4 min (major) and t = 5.8 min (minor).
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Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-bis(4-bromophenyl)ethane-1,2-diyl)dicarbamate
9b): Following the general procedure, compound 9b was
obtained as a white solid in 42% yield (60 mg); mp = 208–210 °C;
(
D
R
f
= 0.45 (Hexanes/EtOAc 6:1 v/v); [α] 20 +19.3 (c 0.5, CHCl
3
,
7
0% ee); IR(KBr) 3330, 3058, 2954, 1716, 1529, 1489, 1248,
-
1 1
1148, 1075, 1011, 818, 725, 568 cm ; H NMR (500 MHz, CDCl
3
)
δ 7.37 (d, J = 8.3 Hz, 4H), 6.97 (d, J = 8.3 Hz, 4H), 5.95 (br s, 2H),
1
3
5
.06–4.91 (m, 2H), 4.81 (d, J = 12.0 Hz, 2H), 4.64 (d, J = 12.0 Hz, 2H); C NMR (125 MHz,
+
CDCl
HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 95/5, Flow rate = 1 mL/min, UV = 230 nm,
= 5.4 min (major) and t = 6.4 min (minor). Calculated conversion = 46; s = 22.
3
) δ 154.9, 136.6, 132.0, 128.9, 126.4,, 95.2, 74.7, 60.3; m/z (ESI-MS) 721.9 [M+H] ;
t
R
R
2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-bis(4-fluorophenyl)ethyl)carbamate (8c):
Following the general procedure, compound 8c was obtained as a
white solid in 40% yield (42 mg); mp = 211–213 °C; R
f
= 0.19
, 83% ee); IR
KBr) 3332, 3056, 2366, 1715, 1640, 1532, 1490, 1148, 1097, 827
D
(Hexanes/EtOAc 6:1 v/v); [α] 20 –31.3 (c 0.5, CHCl
3
(
-
1 1
cm ; H NMR (500 MHz, CDCl
7
6
3
) δ 7.76 (d, J = 7.4 Hz, 2H), 7.57–
.48 (m, 1H), 7.48–7.37 (comp, 2H), 7.21–7.07 (comp, 4H), 7.01–
.84 (comp, 4H), 6.19 (d, J = 8.1 Hz, 1H), 5.47 (dd, 10.7, 8.1 1H),
1
3
5
.05 (dd, 10.7, 8.1 Hz, 1H), 4.74 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 12.0 Hz, 1H); C NMR
(125 MHz, CDCl
3
) δ 167.8, 155.5, 134.3, 133.8, 133.4, 131.9, 129.1(5), 129.1(2), 129.0(9),
1
29.0(6), 128.6, 127.0, 115.8 (d, JC-F = 21.0 Hz), 115.7 (d. JC-F = 21.0 Hz), 95.1, 74.5, 60.6,
+
59.2; m/z (ESI-MS) 528.3 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 97/3,
R R
Flow rate = 1 mL/min, UV = 230 nm, t = 10.5 min (major) and t = 8.0 min (minor).
Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-bis(4-fluorophenyl)ethane-1,2-diyl)dicarbamate
9c): Following the general procedure, compound 9c was obtained
as a white solid in 45% yield (54 mg); mp = 202–203 °C; R = 0.41
, 78% ee);
IR(KBr) 3331, 3055, 2952, 1714, 1530, 1490, 1248, 1148, 820, 725
(
NHTroc
NHTroc
f
D
(
Hexanes/EtOAc 6:1 v/v); [α] 20 +29.4 (c 0.5, CHCl
3
F
-
1 1
cm ; H NMR (500 MHz, CDCl
3
) δ 7.11–7.01 (comp, 4H), 6.98–
6
1
.87 (comp, 4H), 5.89 (br s, 2H), 5.00–4.91 (m, 2H), 4.82 (d, J =
2.0 Hz, 2H), 4.63 (d, J = 12.0 Hz, 2H); C NMR (125 MHz,
F
1
3
3
CDCl ) δ 163.3, 161.3, 155.0, 133.6, 129.0, 128.9, 115.13(d, JC-F = 21.8 Hz), 95.2, 74.7, 60.5;
+
m/z (ESI-MS) 600.2 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 95/5, Flow
rate = 1 mL/min, UV = 230 nm, t
R
R
= 7.0 min (major) and t = 8.7 min (minor). Calculated
conversion = 48; s = 25.
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2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-di-p-tolylethyl)carbamate (8d):
Following the general procedure, compound 8d was obtained as a
D
white solid in 44% yield (45 mg); mp = 229–231 °C; [α] 20 –21.5
(
(
c 0.5, CHCl
KBr) 3336, 3060, 1720, 1630, 1542, 1261, 1152, 730 cm ; H
) δ 7.78 (d, 7.6 Hz, 2H), 7.53–7.47 (m,
H), 7.45-7.39 (comp, 2H), 7.19–7.06 (comp, 4H), 7.05–6.97
comp, 4H), 6.05 (d, J = 8.1 Hz, 1H), 5.54–4.47 (m, 1H), 5.10–
.03 (m, 1H), 4.71 (d, J = 12.0 Hz, 1H), 4.54 (d, J = 12.0 Hz, 1H), 2.27 (s, 3H), 2.25 (s, 3H);
3 f
, 69% ee); R = 0.21 (Hexanes/EtOAc 6:1 v/v); IR
-
1
1
NMR (500 MHz, CDCl
1
(
3
5
1
3
C NMR (125 MHz, CDCl
3
) δ = 167.6, 155.4, 137.8, 137.6, 135.5, 135.1, 133.8, 131.7,
1
29.3(5), 129.3, 128.5, 127.4, 127.3, 117.6, 95.2, 74.5, 60.8, 59.2, 21.0(8), 21.0(7); m/z (ESI-
+
MS) 520.5 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 97/3, Flow rate = 1
mL/min, UV = 210 nm, t = 6.8 min (major) and t = 5.1 min (minor).
R
R
Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-di-p-tolylethane-1,2-diyl)dicarbamate
Following the general procedure, compound 9d was obtained as a
white solid in 44% yield (51 mg); mp = 165–168 °C; R = 0.44
, 67% ee); IR
(9d):
f
D
(
(
Hexanes/EtOAc 6:1 v/v); [α] 20 +17.3 (c 0.5, CHCl
KBr) 3318, 3061, 1706, 1636, 1541, 1257, 1152, 732 cm ; H
) δ 7.03 (d, J = 7.6 Hz, 4H), 6.98 (d, J =
.6 Hz, 4H), 5.82 (br s, 2H), 5.03–4.96 (m, 2H), 4.80 (d, J = 12.0
3
-
1
1
NMR (500 MHz, CDCl
7
3
1
3
Hz, 2H), 4.63 (d, J = 12.0 Hz, 2H), 2.27 (s, 6H); C NMR (125
MHz, CDCl
3
) δ 154.9, 137.8, 134.9, 129.3, 127.2, 95.4, 74.6, 60.5, 21.1; m/z (ESI-MS) 592.2
+
[M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 97/3, Flow rate = 1 mL/min, UV
=
230 nm, t = 7.0 min (major) and t = 8.9 min (minor). Calculated conversion = 49; s = 11.
R
R
2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-bis(4-methoxyphenyl)ethyl)carbamate
8e): Following the general procedure, compound 8e was
obtained as a white solid in 45% yield (49 mg); mp = 210–213
(
D
°
C; R
f
= 0.10 (Hexanes/EtOAc 6:1 v/v); [α] 20 –15.5 (c 0.5,
CHCl
3
, 70% ee); IR (KBr) 3330, 2950, 2831, 1718, 1637, 1515,
-
1 1
1
7
2
3
250, 1176, 1028, 827, 731 cm ; H NMR (500 MHz, CDCl ) δ
.82–7.78 (comp, 2H), 7.51–7.46 (m, 1H), 7.45–7.38 (comp,
H), 7.17–7.07 (comp, 2H), 6.84–6.78 (comp, 4H), 6.70–6.60
(
comp, 2H), 6.54 (d, J=10.0 Hz, 1H), 5.89–5.82 (m, 1H), 5.52–5.45 (m, 1H), 4.63 (d, J = 12,0
1
3
Hz, 1H), 4.57 (d, J = 12.0 Hz, 1H), 3.97 (s, 3H), 3.93 (s, 3H); C NMR (125 MHz, CDCl
3
) δ
1
1
67.7, 159.2, 159.0, 155.4, 133.8, 131.7, 130.9, 130.3, 128.7, 128.6, 128.5(3), 128.5(2),
+
27.1, 114.0, 95.2, 74.5, 60.6, 59.1, 55.2.; m/z (ESI-MS) 552.6 [M+H] ; HPLC: Daicel
= 20.3 min
Chiralpak OJ-H, hexane/i-PrOH = 93/7, Flow rate = 1 mL/min, UV = 230 nm, t
major) and t = 16.3 min (minor).
R
(
R
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Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-bis(4-methoxyphenyl)ethane-1,2-diyl)dicarbamate
9e): Following the general procedure, compound 9e was
obtained as a white solid in 44% yield (55mg); mp = 170–172
(
D
°
C; R
f
= 0.20 (Hexanes/EtOAc 6:1 v/v); [α] 20 +22.4 (c 0.5,
, 80% ee); IR (KBr) 3331, 2953, 2836, 1701, 1614, 1516,
CHCl
1
3
-
1 1
250, 1180, 1031, 831, 733 cm ; H NMR (500 MHz, CDCl
3
) δ
7.01 v (d, J = 8.5 Hz, 4H), 6.75 (d, J = 8.5 Hz, 4H), 5.81 (br s,
2
H), 5.02–4.91 (m, 2H), 4.81 (d, J = 12.0 Hz, 2H), 4.63 (d, J = 12.0 Hz, 2H), 3.75 (s, 6H);
1
3
C NMR (125 MHz, CDCl
3
) δ 159.2, 154.9, 130.0, 128.5, 114.0, 95.4, 74.6, 60.4, 55.2; m/z
ESI-MS) 623.8 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 95/5, Flow rate =
mL/min, UV = 230 nm, t = 11.5 min (major) and t = 9.9 min (minor). Calculated
conversion = 53; s = 14.
+
(
1
R
R
2
,2,2-Trichloroethyl ((1R,2R)-2-benzamido-1,2-diphenylethyl)carbamate (8f): Following
the general procedure, compound 8f was obtained as a white solid in
4
0% yield (39 mg); mp = 187–190 °C; R
f
= 0.19 (Hexanes/EtOAc 6:1
D
v/v); [α] 20 –24.0 (c 0.5, CHCl
717, 1653, 1637, 1528, 1144, 1082, 1027, 821, 735 cm ; H NMR
500 MHz, CDCl ) δ 7.78 (d, J = 7.8 Hz, 2H), 7.54–7.47 (m, 1H),
.46–7.39 (comp, 2H), 7.29–7.13 (comp, 10H), 6.15 (d, J = 8.2 Hz,
3
, 72% ee); IR (KBr) 3333. 3053, 2925,
-
1
1
1
(
7
3
1
1
1
4
2
H), 5.58–5.49 (m, 1H), 5.18–5.06 (m, 1H), 4.73 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 12.0 Hz,
H); C NMR (125 MHz, CDCl ) δ 167.7, 155.5, 138.5, 138.0, 133.8, 131.8, 128.7(2),
3
13
28.6(8), 128.6, 128.2, 128.0, 127.5, 127.4, 127.1, 95.2, 74.5, 61.3, 59.8.; m/z (ESI-MS)
+
93.2 [M+H] ; Daicel Chiralpak AD-H, hexane/i-PrOH = 95/5, Flow rate = 1 mL/min, UV =
R R
30 nm, t = 11.0 min (major) and t = 8.8 min (minor).
Bis(2,2,2-trichloroethyl)
Following the general procedure, compound 9f was obtained as a white
solid in 42% yield (47 mg); mp = 147–150 °C; R = 0.41
, 65% ee); IR
KBr) 3329, 3061, 2955, 1705, 1541, 1254, 1148, 1082, 1027, 820, 733
((1S,2S)-1,2-diphenylethane-1,2-diyl)dicarbamate(9f):
f
D
(
Hexanes/EtOAc 6:1 v/v); [α] 20 +24.9 (c 0.5, CHCl
3
(
-
1 1
cm ; H NMR (500 MHz, CDCl
3
) δ 7.25–7.16 (comp, 6H), 7.15–7.01
(
comp, 4H), 5.93 (br s, 2H), 5.09–4.98 (m, 2H), 4.82 (d, J = 12.0 Hz,
1
3
2
9
H), 4.63 (d, J = 12.0, 2H); C NMR (125 MHz, CDCl
3
) δ 154.9, 137.8, 128.7, 128.2, 127.3,
5.3, 74.7, 61.1; m/z (ESI-MS) 564.1 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-
= 6.1 min (major) and t = 7.4 min
+
PrOH = 95/5, Flow rate = 1 mL/min, UV = 230 nm, t
minor). Calculated conversion = 47; s = 12.
R
R
(
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2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-di-o-tolylethyl)carbamate (8g):
Following the general procedure, compound 8g was obtained as a
white solid in 41% yield (43 mg); mp = 220–222 °C; R = 0.24
, 76% ee); IR
f
D
(
(
(
Hexanes/EtOAc 6:1 v/v); [α] 20 –21.0 (c 0.5, CHCl
KBr) 3328, 3061, 1713, 1636, 1541, 1257, 1152, 732 cm ; H NMR
500 MHz, CDCl ) δ 7.79 (d, J = 7.7 Hz, 2H), 7.61–7.47 (comp, 3H),
.46–7.39 (comp, 2H), 7.27–7.17 (comp, 2H), 7.15–7.07 (comp, 3H),
.03–6.93 (comp, 2H), 6.02–5.89 (comp, 2H), 5.52–5.45 (m, 1H), 4.67 (d, J = 12.0 Hz, 1H),
3
-
1 1
3
7
7
4
1
1
1
3
3
.55 (d, J = 12.0 Hz, 1H), 2.08 (s, 3H), 2.03 (s, 3H); C NMR (125 MHz, CDCl ) δ 167.7,
55.7, 136.8, 136.2, 136.6, 136.1, 133.8, 131.8, 130.7, 130.6, 128.6, 128.1, 127.9, 127.1,
26.6, 126.5, 126.4, 126.3, 95.1, 74.5, 56.8, 55.2, 19.3, 19.2(7); m/z (ESI-MS) 520.7
+
[M+H] ; Daicel Chiralpak AD-H, hexane/i-PrOH = 95/5, Flow rate = 1 mL/min, UV = 230
nm, t
R R
= 8.8 min (major) and t = 7.1 min (minor).
Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-di-o-tolylethane-1,2-diyl)dicarbamate
(9g):
Following the general procedure, compound 9g was obtained as a white
D
solid in 44% yield (52 mg); mp = 177–178 °C; [α] 20 +23.1 (c 0.5,
CHCl
3
, 75% ee); R
f
= 0.47 (Hexanes/EtOAc 6:1 v/v); IR (KBr) 3320,
-
1
1
3055, 2950, 1707, 1650, 1527, 1255, 713 cm ; H NMR (500 MHz,
3
CDCl ) δ 7.44 (d, J = 7.5 Hz, 2H), 7.20 (app t, J = 7.4 Hz, 2H), 7.11
(app t, J = 7.4 Hz, 2H), 6.96 (d, J = 7.5 Hz, 2H), 5.92 (br s, 2H), 5.40
(
dd, J = 5.9, 2.3 Hz, 2H), 4.82 (d, J = 12.0 Hz, 2H), 4.64 (d, J = 12.0 Hz, 2H), 2.00 (s, 6H);
1
3
C NMR (125 MHz, CDCl
6.5, 19.2; m/z (ESI-MS) 592.2 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH =
7/3, Flow rate = 1 mL/min, UV = 230 nm, t = 7.2 min (major) and t = 9.0 min (minor).
3
) δ 155.3, 136.7, 136.2, 130.7, 128.1, 126.4, 126.3(7), 95.3, 74.7,
+
5
9
R
R
Calculated conversion = 50; s = 16.
Bis(2,2,2-trichloroethyl)((1R,2R)-1,2-di-m-tolylethane-1,2-diyl)dicarbamate
Following the general procedure, compound 8h was obtained as a
NHTroc white solid in 40% yield (41 mg); mp = 199–201 °C; IR (KBr)
(8h):
NHBz
Me
-
1
3
0
f
337, 3056, 2947, 1718, 1653, 1527, 1254, 711, 568 cm ; R =
D
.24 (Hexanes/EtOAc 6:1 v/v); [α] 20 –14.2 (c 0.5, CHCl
3
, 45%
) 7.79 (d, J= 7.5Hz, 2H), 7.53-
.47 (m, 1H), 7.46–7.38 (comp, 2H), 7.20–7.07 (comp, 4H), 7.06-
.97 (comp, 4H), 6.01 (d, J= 8.4 Hz, 1H), 5.53–5.47 (m, 1H), 5.10-5.04 (m, 1H), 4.71 (d,
1
ee); H NMR (500 MHz, , CDCl
7
3
Me
6
1
3
J=12.0 Hz, 1H), 4.55 (d, J= 12.0 Hz, 1H), 2.26 (s, 3H), 2.27(s, 3H); C NMR (125 MHz, ,
CDCl ) δ 167.7, 155.4, 138.4, 138.3, 138.2(6), 138.0, 133.8, 131.7, 128.8, 128.7, 128.5,
28.4(7), 128.2, 128.0, 127.1, 124.6, 95.2, 74.5, 61.1, 59.5, 21.3, 21.2(8); m/z (ESI-MS)
3
1
5
+
20.8 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 97/3, Flow rate = 1
mL/min, UV = 230 nm, t
R
R
= 8.6 min (major) and t = 5.7 min (minor).
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Bis(2,2,2-trichloroethyl)
((1S,2S)-1,2-di-m-tolylethane-1,2-diyl)dicarbamate
(9h):
Following the general procedure, compound 9h was obtained as a
white solid in 41% yield (48 mg); mp = 190–192 °C; R
f
= 0.46
D
(
(
Hexanes/EtOAc 6:1 v/v); [α] 20 +12.4 (c 0.5, CHCl
KBr) 3318, 3055, 2950, 1707, 1650, 1527, 1255, 713 cm ; H
) δ 7.14–7.07 (comp, 2H), 7.06–6.98
comp, 2H), 6.90 (s, 2H), 6.86 (d, J= 7.4 Hz, 2H), 5.88 (br s, 2H), 5.02–4.96 (m, 2H), 4.82 (d,
3
, 44% ee); IR
-
1
1
NMR (500 MHz, CDCl
3
(
1
3
J = 12.0 Hz, 2H), 4.63 (d, J = 12.0 Hz, 2H), 2.25 (s, 6H); C NMR (125 MHz, CDCl
3
) δ
1
54.9, 138.4, 137.7, 128.9, 128.5, 128.0, 124.5, 95.4, 74.6, 60.8, 21.3; m/z (ESI-MS) 592.2
+
[
M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 98/2, Flow rate = 1 mL/min, UV
230 nm, t = 9.0 min (major) and t = 16.3 min (minor). Calculated conversion = 49; s =
.0.
=
4
R
R
2
,2,2-Trichloroethyl((1R,2R)-2-benzamido-1,2-bis(3-chlorophenyl)ethyl)carbamate (8i):
Following the general procedure, compound 8i was obtained as a
white solid in 39% yield (43 mg); mp = 203–205 °C; R
f
= 0.21
D
(
Hexanes/EtOAc 6:1 v/v); [α] 20 –27.7 (c 0.5, CHCl
3
, 82% ee); IR
-
1
(
KBr) 3336, 3061, 2949, 1714, 1636, 1528, 1252, 1084, 702 cm ;
1
H NMR (400 MHz, (CD
3 2
) SO) δ 8.47 (s, 1H), 7.64 (d, J = 7.2,
2
H), 7.58–7.34 (comp, 10H) 7.37–7.26(m, 1H), 6.82 (br s, 1H),
1
3
5
.17 (d, J = 6.3 Hz, 1H), 4.68 (d, J = 6.3 Hz, 1H), 4.04 (s, 2H); C NMR (100 MHz,
(CD
3
)
2
SO) δ 166.1, 154.1, 142.5, 142.4(8), 134.0, 132.8, 132.7(6), 131.5, 129.9, 128.3,
1
5
27.1, 127.0(9), 127.0, 126.9, 126.8, 125.8, 125.5, 96.0, 73.4, 58.4, 56.3; m/z (ESI-MS)
61.9 [M+H] ; HPLC: Daicel Chiralpak AD-H, hexane/i-PrOH = 97/3, Flow rate = 1
+
R R
mL/min, UV = 230 nm, t = 9.2 min (major) and t = 7.6 min (minor).
Bis(2,2,2-trichloroethyl)((1S,2S)-1,2-bis(3-chlorophenyl)ethane-1,2-diyl)dicarbamate
9i): Following the general procedure, compound 9i was obtained
as a white solid in 43% yield (54 mg); mp = 199–202 °C; R = 0.48
, 70% ee); IR
(
f
D
(
(
Hexanes/EtOAc 6:1 v/v); [α] 20 +25.5 (c 0.5, CHCl
KBr) 3331, 2952, 1709, 1537, 1277, 1144, 1092, 821 cm ; H
SO) δ 8.30 (d, J = 8.2 Hz, 2H), 7.50 (s,
H), 7.36–7.26 (comp, 6H), 5.20 (d, J = 8.1 Hz, 2H), 4.72 (d, J = 12.4 Hz, 2H), 4.68 (d, J =
3
-
1
1
3 2
NMR (500 MHz, (CD )
2
1
1
1
3
2.4 Hz, 2H); C NMR (125 MHz, (CD
25.5, 96.0, 73.4, 58.3; m/z (ESI-MS) 633.4 [M+H] ; HPLC: Daicel Chiralpak AD-H,
= 6.8 min (major) and t
3 2
) SO) δ 154.1, 142.2, 132.9, 130.1, 127.2, 126.7,
+
hexane/i-PrOH = 97/3, Flow rate = 1 mL/min, UV = 230 nm, t
R
R
=
8.0 min (minor). Calculated conversion = 46; s = 21.
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References:
[1] D. C. Braddock, J. M. Redmond, S. A. Hermitage, A. J. White, Adv. Synth. Catal. 2006,
348, 911.
[2] E. J. Corey, F. N. M. Kuhnle, Tetrahedron Lett. 1997, 38, 8631.
[3] E. J. Corey, D. Lee, S. Sarshar, Tetrahedron: Asymmetry 1995, 6, 3.
[4] H. B. Kagan, J. C. Fiaud, Top. Stereochem. 1988, 18, 249.
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HPLC Profile of 8a
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HPLC Profile of 8b
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HPLC Profile of 8c
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HPLC Profile of 8d
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HPLC Profile of 8e
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HPLC Profile of 8f
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HPLC Profile of 8g
S 16

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HPLC Profile of 8h
S 17

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HPLC Profile of 8i
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HPLC Profile of 9a
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HPLC Profile of 9b
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HPLC Profile of 9c
NHTroc
NHTroc
F
F
S 21

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HPLC Profile of 9d
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HPLC Profile of 9e
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HPLC Profile of 9f
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HPLC Profile of 9g
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HPLC Profile of 9h
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HPLC Profile of 9i
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1H NMR of 8a in CDCl3
NHBz
NHTroc
Cl
Cl
330
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13C NMR of 8a in CDCl3
NHBz
NHTroc
Cl
Cl
330
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1
H NMR of 8b in CD SO
(
3)2
NHBz
NHTroc
Br
Br
330
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