K. Kodama et al. / Tetrahedron 72 (2016) 1387e1394
1393
22
NaHCO3 until the pH became 8e9. The resulting mixture was
extracted with CHCl3 (100 mLꢁ3) and the organic phase was dried
over anhydrous Na2SO4. The solvent was removed under reduced
pressure and the residue was purified by silica gel column chro-
matography (hexane/EtOAc¼10:1). Further recrystallization from
ethanol gave rac-1d (2.12 g, 6.81 mmol, 40%) as colorless needle-
shaped crystals. Mp: 113e114 ꢀC. 1H MNR (400 MHz, CDCl3):
1006, 804, 762, 729, 700, 610 cmꢂ1. [
a
]
D
¼55.9 (c 0.8, EtOH). (R)-1c:
Mp: 87.8e89.5 ꢀC. IR (KBr): nmax¼3343, 3281, 2575, 1596, 1454,
22
1407, 1276, 1251, 1006, 762, 700, 61s0 cmꢂ1. [
a
]
¼ꢂ47.0 (c 1.0,
D
EtOH). (R)-1d$9: Mp: 176.5e178.0 ꢀC. IR (KBr): nmax¼3429, 2959,
22
1717, 1624, 1479, 1453, 1267, 1117, 713 cmꢂ1. [
a
]
¼ꢂ49.0 (c 1.0,
D
EtOH). (R)-1d: Mp: 105.0e107.0 ꢀC. IR (KBr): nmax¼3295, 2957,
1600, 1480, 1442, 1361, 1251, 1231, 973, 883, 756, 698 cmꢂ1
.
22
d
11.6 (br, 1H), 7.41e7.32 (m, 4H), 7.31e7.26 (m, 1H), 7.22 (d, 1H,
J¼2.4 Hz), 6.64 (d, 1H, J¼2.4 Hz), 5.31 (s, 1H), 2.24 (br, 2H), 1.44 (s,
9H), 1.19 (s, 9H). 13C NMR (100 MHz, CDCl3):
154.5, 143.4, 140.2,
[a
]
¼ꢂ77.0 (c 1.0, EtOH).
D
d
4.6. Asymmetric addition reaction of diethylzinc to benzal-
dehyde catalyzed by enantiopure 1
136.7, 128.8, 127.6, 127.0, 125.5, 123.4, 123.2, 60.6, 35.1, 34.1, 31.6,
29.7. IR (KBr): nmax¼3378, 3290, 2956, 1573, 1478, 1440, 1362, 1252,
1231, 1203, 961, 903, 878, 754, 703, 649 cmꢂ1. Elemental analysis:
calcd for C21H29NO: C 80.98%, H 9.38%, N 4.51%; found: C 80.81%, H
9.54%, N 4.39%.
To a solution of 1 (0.1 mmol) in dry toluene (1.5 mL) was added
Et2Zn (0.77 Mhexane solution, 3.25 mL, 2.50 mmol) dropwise at
0 ꢀC under N2 atmosphere, and the mixture was stirred for 30 min.
A solution of benzaldehyde (106 mg, 1.00 mmol) in dry toluene
(2.0 mL) was added dropwise to the mixture and the reaction
mixture was stirred for 24 h at 0 ꢀC. The reaction was quenched by
the addition of 1N HClaq (5 mL) and water (20 mL). The aqueous
layer was extracted with EtOAc (20 mLꢁ3). The extracts was dried
over anhydrous Na2SO4 and concentrated under reduced pressure.
The crude product was purified by preparative scale TLC (hexane/
EtOAc¼7:3) and its enantiopurity was determined by an HPLC
analysis (Daicel ChiralPak OD-3, hexane/2-propanol¼9:1,
1.0 mL minꢂ1, tr(R)¼11.8 min; tr(S)¼13.4 min).
4.4. General procedure for the diastereomeric resolution of
rac-1
The mixture of
1 (0.4 mmol) and each resolving agent
(0.4 mmol) were dissolved in MeOH. After concentration, the di-
astereomeric salts were recrystallized from an appropriate solvent.
When 1d was used, some insoluble solid 11 was filtered off before
cooling. The precipitated salt was collected by filtration and dried
under reduced pressure. The yield was calculated based on a half
amount of rac-1 initially used. A part of the salt was added in 1N
NaOHaq and extracted with EtOAc. The organic phase was dried
over anhydrous Na2SO4. After removal of the solvent, 1 was ob-
tained as a solid. The enantiomeric excess was determined by an
HPLC analysis (1c: Daicel ChiralPak OD-3, hexane/2-propanol¼9:1,
0.8 mL minꢂ1, tr(S)¼23.9 min; tr(R)¼43.8 min, 1d: ChiralPak OD-3,
4.7. Single crystal X-ray analyses
X-ray crystallographic data were collected on a Bruker Smart
APEX II diffractometer with graphite monochromated Mo-Ka ra-
diation. The structures were solved by a direct method using SIR
hexane/2-propanol¼9:1, 1.0 mL minꢂ1
,
tr(S)¼7.7 min; tr(R)¼
2004 and refined by SHELXL-2013 program.18 Crystal data for rac-
12.5 min).
1d:
C21H29NO,
M¼311.45,
orthorhombic,
a¼17.203(3),
11: Mp: 189e191 ꢀC (decomp.). 1H NMR (400 MHz, CDCl3):
d
8.18
ꢀ
3
ꢀ
b¼18.271(3), c¼5.9332(9) A, V¼1864.9(5) A , T¼150 K, space group
Pna21, Z¼4, 8584 reflections measured, 3093 independent re-
(s, 2H), 7.34e7.20 (m, 12H), 6.86 (d, 2H, J¼2.4 Hz), 4.87 (d, 2H,
J¼5.6 Hz), 3.19 (t, 1H, J¼6.4 Hz), 1.44 (s, 18H), 1.27 (s, 18H). 13C NMR
flections (Rint¼0.1168), The final R1 was 0.0634 (I>2
s(I)) and wR(F2)
(100 MHz, CDCl3):
d 152.3, 141.9, 141.2, 136.8, 128.8, 127.6, 127.6,
was 0.1677 (I>2s(I)), CCDC: 1435690. Crystal data for (R)-
125.3, 124.7, 123.3, 63.5, 34.9, 34.3, 31.7, 29.9. IR (KBr): nmax¼3507,
2959, 2869, 1604, 1479, 1447, 1391, 1362, 1240, 1201, 1161, 1123, 881,
825, 756, 700 cmꢂ1. MS (MALDI-TOF, matrix; dithranol): m/z calcd
for [MþH]þ: 606.43, found: 606.49.
1c$4$0.5H2O: C27H28NO4.5, M¼438.50, monoꢀclinic, a¼26.870(6),
3
ꢀ
ꢀ
b¼5.4794(13), c¼15.955(4) A,
b
¼102.335(3) , V¼2294.9(9) A ,
T¼200 K, space group C2, Z¼4, 5512 reflections measured, 3765
independent reflections (Rint¼0.1244), The final R1 was 0.0608
(I>2s(I)) and wR(F2) was 0.1367 (I>2s(I)), CCDC: 1435691. Crystal
4.5. Preparation of enantiopure 1c and 1d
data for (S)-1c$9$3H2O: C31H33NO12, M¼611.58, monoclinic,
ꢀ
a¼12.908(2), b¼7.7688(12), c¼15.594(3) A,
b
¼109.440(2)ꢀ,
3
ꢀ
The mixture of 1c (2.00 g, 10.0 mmol) and 9 (3.60 g, 10.0 mmol)
was dissolved in MeOH. After removal of the solvent, the salt was
recrystallized seven times from 50% EtOH to afford diastereopure
salt (S)-1c$9 (0.54 g, 0.96 mmol, 19%) as colorless crystals. The fil-
trates of the first and second recrystallization were collected and
the solvent was removed. The salt was decomposed to recover
enantio-enriched (R)-1c (1.23 g, 6.17 mmol, 55 %ee), which was
mixed with an equimolar amount of 4 (1.42 g, 6.18 mmol). The salt
1c$4 was recrystallized from 50% EtOH twice to afford diaster-
eopure salt (R)-1c$4 (1.12 g, 2.6 mmol, 42%) as colorless crystals.
The salts were decomposed to afford enantiopure 1c quantitatively.
Similarly, recrystallization of the salt between 1d (0.80 g,
2.57 mmol) and 9 (1.84 g, 5.14 mmol) from 50% EtOH three times
afforded diastereopure (R)-1d$9 (210 mg, 0.49 mmol, 30%) as
a white solid. The composition ratio of the solid was 1d:9¼3:2 and
(R)-1d was quantitatively recovered by decomposition of the salt.
(S)-1c$9: Mp: 174e175 ꢀC (decomp.). IR (KBr): nmax¼3509, 3164,
V¼1474.7(4) A , T¼150 K, space group P21, Z¼2, 7042 reflections
measured, 4957 independent reflections (Rint¼0.0712), The final R1
was 0.0551 (I>2s(I)) and wR(F2) was 0.1254 (I>2s(I)), CCDC:
1435692. Detailed data is summarized in the Supplementary data
(Table S1). Crystallographic data for the structures in this paper
can be obtained free of charge from The Cambridge Crystallo-
Supplementary data
Supplementary data (Crystal structure of 11 (Fig. S1), powder
XRD patterns of the compounds (Fig. S2), TGA chart of (S)-1c$9
(Fig. S3), crystal structure of 1c$10 (Fig. S4), summary of crystal-
lographic data (Table S1), copies of 1H NMR, 13C NMR, and IR spectra
of the reported compounds) associated with this article can be
1715,1602,1499, 1461, 1335,1270,1119, 761, 715, 617, 566, 514 cmꢂ1
.
22
[
a]
¼ꢂ70.7 (c 1.0, EtOH). (R)-1c$4: Mp: 127.5e129.0 ꢀC. IR (KBr):
D
References and notes
nmax¼3060, 1606, 1558, 1462, 1386, 1363, 1269, 1229, 1031, 856, 814,
757, 695 cmꢂ1. [
a
]
¼ꢂ1.6 (c 1.0, EtOH). (S)-1c: Mp: 88.5e90.0 ꢀC. IR
22
D
€
(KBr): nmax¼3343, 3281, 2572, 1595, 1455, 1407, 1276, 1251, 1094,