The Journal of Organic Chemistry
Article
(isomeric mixture, 60:40 dr, CDCl3, 125 MHz) δ = 27.7 (s), 28.2 (s),
28.4 (s), 28.7 (s), 28.8 (s), 29.3 (s), 45.7 (s), 47.6 (s), 52.8 (t, 2 C),
55.9 (p, 2 C), 56.06 (p), 56.09 (p), 60.5 (t), 63.1 (t), 108.3 (t), 108.7
(t), 111.42 (t), 111.44 (t), 118.5 (q), 119.8 (q), 125.7 (q), 125.9 (q),
129.2 (q), 129.5 (q), 147.4 (q), 147.5 (q), 147.7 (q), 147.9 (q);
HRMS (C15H18N2O2Na), [M + Na]+ calcd for 281.1266, found
281.1265. Anal. Calcd for C15H18N2O2 (258.31): C, 69.74; H, 7.02; N,
10.84. Found C, 68.55; H, 7.03; N, 10.08.
300 K, transients = 456) δ = 1.20−1.50 (m, 2 H), 1.54 (d, 3JPH = 15.8
Hz, 9 H), 1.63−1.69 (m, 1 H), 2.00−2.07 (m, 1 H), 2.10−2.22 (m, br,
1 H), 2.30−2.40 (m, br, 1 H), 2.50−2.60 (m, br, 1 H), 2.70−2.74 (m,
1 H), 3.25−3.35 (m, br, 1 H), 3.45 (s, 3 H), 3.47 (s, 3 H), 3.70−3.90
(m, br, 1 H), 4.90−5.05 (m, br, 1 H), 6.22 (s, 1 H), 6.26 (s, 1 H), 7.35
(td, 3JHH = 7.6 Hz, 4JPH = 2.8 Hz, 2 H), 8.54−8.58 (m, 3 H); 13C NMR
(C6D6, 125 MHz, NS = 1693) δ = 21.9 (s), 24.3 (s), 25.4 (p), 32.0 (s),
1
36.4 [q, d, JPH = 75.0 Hz], 45.8 (s), 52.2 (s), 55.3 (p), 55.5 (p), 60.0
2
(t), 109.8 (t), 111.5 (t), 123.6 (q), 125.1 (q), 127.1 [t; (d, JPH = 11.0
(−)-Crispine A·(−)-O,O′-Dibenzoyl-L-tartaric Acid·Ethanol,
(−)-14. To a solution of 0.33 g (1.41 mmol) of a partially resolved
mixture of (−)-crispine A (90:10 er) in 10 mL of ethanol was added
0.52 g (1.45 mmol) of (−)-O,O′-dibenzoyl-L-tartaric acid monohy-
drate. The solution was heated to reflux, and the homogeneous
solution was allowed to cool to room temperature slowly. The
precipitate was then filtered over a sintered glass funnel to give 0.60 g
(81% based on isomer content) of (−)-crispine A·(−)-O,O′-dibenzoyl-
L-tartaric acid·ethanol as colorless crystals which were analyzed by
X-ray diffraction: mp = 152−154 °C; [α]22D −54 (c 1.0, CHCl3, ≥98:2
dr); 1H NMR (CDCl3, 300 MHz) δ = 1.20 (t, J = 7.0 Hz, 3 H), 1.75−
1.90 (m, 2 H), 1.91−2.08 (m, 1 H), 2.40−2.50 (m, 1 H), 2.60−2.75
(m, 1 H), 2.82−3.10 (m, 3 H), 3.38−3.50 (m, 1 H), 3.68 (q, J = 7.0
Hz, 2 H), 3.76 (s, 3 H), 3.80 (s, 3 H), 4.70−4.80 (m, 1 H), 5.83 (s, 2
H), 6.44 (s, 1 H), 6.47 (s, 1 H), 7.33 (t, J = 7.5 Hz, 4 H), 7.47 (t, J =
7.4 Hz, 2 H), 8.03 (d, J = 7.2 Hz, 4 H); 13C NMR (CDCl3, 75 MHz)
δ = 18.3 (p), 22.3 (s), 24.3 (s), 32.5 (s), 46.4 (s), 52.9 (s), 55.9 (p),
56.0 (p), 58.4 (s), 60.7 (t), 73.0 (t), 108.9 (t), 110.8 (t), 123.3 (q),
124.0 (q), 128.2 (t), 129.7 (q), 130.0 (t), 133.0 (t), 148.36 (q), 148.46
(q), 165.6 (q), 170.4 (q); HRMS (C14H20NO2), [M]+ calcd for
234.1494, found 234.1486. Anal. Calcd for C34H39NO11 (637.25): C,
64.04; H, 6.16; N, 2.20. Found: C, 63.82; H, 6.23; N, 2.07.
(S)-(−)-Crispine A from the Tartrate Salt (−)-14. To a stirred
aqueous 10% NaOH solution (10 mL) was added 0.20 g (0.31 mmol)
of tartrate salt (−)-14. The mixture was stirred at ambient temperature
for 5 min before diethyl ether (20 mL) was added, whereupon the
solution was stirred for another 30 min period. The aqueous layer was
separated and extracted twice with 10 mL of diethyl ether. The organic
layers were washed with 10 mL of water, dried over magnesium sulfate,
and concentrated under reduced pressure to afford 0.065 g (89%) of
(−)-crispine A: [α]22D −97 [c 1.02, CHCl3, ≥98:2 er] [lit.6b [α]22D = +100
(c = 1.5, CHCl3)]; this value is referred to the R enantiomer.
Hz)], 129.6 [t; (d, 4JPH = 2.4 Hz)], 133.4 [t; (d, 3JPH = 9.2 Hz)], 139.1
1
[q; (d, JPH = 90.0 Hz)], 149.0 (q), 149.2 (q); 31P NMR (C6D6, 121
MHz) δ = 82.14.
(+)-Crispine A (85:15 er)·(+)-15: 1H NMR (C6D6, 400 MHz,
295 K) δ = 1.60−1.80 (m, H-1a, H-2a and H-2b, 3H), 2.00−2.10
(m, H-1b, 1 H), 2.38 (m, H-3a, 1 H), 2.47−2.60 (m, H-5a and H-6a, 2
3
H), 2.90−3.07 (m, H-3b, H-6b and H-5b, 3 H), 3.32 (t, J = 7.15 Hz,
H-10b, 1 H), 3.44 (s, MeO-9, 3 H), 3.48 (s, MeO-8, 3 H), 6.49 (s, H-
7, 1 H), 6.56 (s, H-10, 1 H); 13C NMR (C6D6, 100 MHz, 295 K) δ =
22.3 (C-2), 28.5 (C-6), 30.5 (C-1), 48.5 (C-5), 53.1 (C-3), 55.50
(CH3−O-9), 55.70 (CH3−O-8), 63.2 (C-10b), 110.3 (C-10), 112.7
(C-7), 126.7 (C-6a), 131.7 (C-10a), 148.34 (C-8), 148.44 (C-9).
(R)-(+)-Crispine A·(+)-15: (R)-(+)-Crispine A (130 μmol) and
C6D6 (0.7 mL) were mixed in a 5 mm NMR tube, and (+)-15
(149 μmol) was added. The 13C and 1H NMR data were collected on
a 400 MHz spectrometer. The chemical shifts (ppm) were internally
1
referenced to the TMS signal (0 ppm): H NMR (C6D6, 400 MHz,
3
295 K) δ = 1.10−1.30 (m, H-1a and H-2a, 2H), 1.42 (d, JHP = 15.8
Hz, 9 H), 1.50−1.60 (m, H-2b, 1 H), 1.90−2.00 (m, H-1b, 1 H),
2.18−2.30 (m, H-3a and H-6a, 2 H), 2.40−2.50 (m, H-5a, 1 H), 2.70−
2.80 (m, H-6b, 1 H), 3.05−3.15 (m, H-5b, 1 H), 3.34 (s, MeO-9, 3
H), 3.38 (s, MeO-8, 3 H), 3.60−3.70 (m, H-3b, 1 H), 4.50−4.60
(m, H-10b, 1 H), 6.04 (s, H-10, 1 H), 6.20 (s, H-7, 1 H), 7.10−7.20
(m, 3 H), 8.30−8.35 (m, 2 H); 13C NMR (C6D6, 100 MHz, 295 K)
δ = 21.9 (C-2), 24.5 (C-6), 25.4 (C-CH3-t-Bu), 31.8 (C-1), 36.2 (d,
1JCP = 75.0 Hz, C-CH3-t-Bu), 45.8 (C-5), 52.1 (C-3), 55.34 (CH3−
O-8), 55.42 (CH3−O-9), 59.9 (C-10b), 109.8 (C-10), 111.5 (C-7),
2
123.6 (C-6a), 125.1 (C-10a), 126.8 (d, JPH = 11.0 Hz, Cm), 129.3
4
3
1
(d, JPH = 2.4 Hz, Cp), 133.2 (d, JPH = 9.2 Hz, Co), 139.5 (d, JPH
=
90.0 Hz, Ci), 148.94 (C-8), 149.03 (C-9).
rac-Crispine A·(+)-15: rac-Crispine A (140 μmol) and C6D6
(0.7 mL) were mixed in a 5 mm NMR tube, and (+)-15 (145
μmol) was added. The 13C and 1H NMR data were collected on a 400
MHz spectrometer. The chemical shifts (ppm) were internally
(R)-(+)-Crispine A. The syntheses were as reported for (−)-crispine
A but starting from α-aminonitrile (−)-4 to afford (+)-11, [α]22
D
+23.0 [c 1.0, CHCl3, 85 (R,R):15 (S,R) dr]; (+)-12, [α]22D +26 [c 1.0,
CHCl3, 85 (R):15 (S) er], and (+)-crispine A as a beige solid:
1
referenced to the TMS signal (0 ppm): H NMR (C6D6, 500 MHz,
[α]22 +72 [c 1.0, CHCl3, 85 (R):15 (S) er].
300 K, transients = 136) δ = 1.20−1.45 (m, 2 H), 1.54 (d, 3JHP = 15.8
Hz, 9 H), 1.60−1.80 (m, 1 H), 2.00−2.17 (m, 1 H), 2.25−2.45 (m, br,
2 H), 2.50−2.60 (m, br, 1 H), 2.75−2.81 (m, 0.5 H), 2.87−2.91
(m, 0.5 H), 3.17−3.30 (m, br, 1 H), 3.45 (s, 1.5 H), 3.48 (s, 3 H), 3.50
(s, 1.5 H), 3.70−3.90 (m, br, 1 H), 4.60−4.70 (m, br, 0.5 H), 4.85−
4.95 (m, br, 0.5 H), 6.17 (s, 0.5 H), 6.29 (s, 0.5 H), 6.30 (s, 0.5 H),
6.32 (s, 0.5 H), 7.24−7.27 (m, 1 H), 7.35 (td, 3JHH = 7.6 Hz, 4JHP = 2.8
Hz, 2 H), 8.54−8.58 (m, 2 H); 13C NMR [C6D6, 125 MHz, 300 K,
transients =664, splitting signals are indicated with an asterisk (*)] δ =
[22.0 (s), 22.1 (s)]*, [24.5 (s), 24.7 (s)]*, 25.6 (p), [31.9 (s), 32.1
D
(+)-Crispine A·(+)-O,O′-Dibenzoyl-D-tartaric Acid·Ethanol,
(+)-14. To a solution of 0.26 g (1.11 mmol) of a mixture [85(R):15
(S)] of (+)-crispine A and (−)-crispine A in 10 mL of ethanol was
added 0.40 g (1.11 mmol) of (+)-O,O′-dibenzoyl-D-tartaric acid
monohydrate. The solution was heated to reflux, and the
homogeneous solution was allowed to cool to room temperature
slowly. The precipitate was then filtered over a sintered glass funnel to
give 0.47 g (78% based on isomer content) of (+)-crispine A·(+)-O,O′-
dibenzoyl-D-tartaric acid·ethanol ((+)-14): colorless crystals; mp =
152−154 °C; [α]22D +48 (c 1.0, CHCl3, ≥98:2 dr). Spectral properties
(1H and 13C) are identical to those reported for tartrate (−)-14.
(R)-(+)-Crispine A from Tartrate Salt (+)-14. A basic treatment
1
(s)]*, 36.5 [q, (d, JCP = 75.0 Hz)], 45.8 (s), 52.2 (s), [55.40 (p),
55.43 (p), 55.50 (p)*, 55.57 (p)]*, [59.95 (t), 60.03 (t)]*, [109.81
(t), 109.88 (t)]*, [111.55 (t), 111.61 (t)]*, [123.8 (q), 123.9 (q)]*,
[125.36 (q), 125.43 (q)]*, 127.1 [t; (d, 3JCP = 11.0 Hz)], 129.3 [t; (d,
(10% NaOH) of tartrate salt (+)-14 afforded (+)-crispine A: [α]22
+
D
98 (c 1.0, CHCl3, ≥98:2 er) in 87% yield; 1H NMR (C6D6, 400 MHz)
δ = 1.60−1.80 (m, 3 H), 2.00−2.10 (m, 1 H), 2.34−2.41 (m, 1 H),
2.48−2.60 (m, 2 H), 2.90−3.08 (m, 3 H), 3.32 (t, J = 8.5 Hz, 1 H),
3.45 (s, 3 H),3.48 (s, 3 H), 6.49 (s, 1 H), 6.56 (s, 1 H); 13C NMR
(CDCl3, 75 MHz) δ = 22.3 (s), 28.5 (s), 30.5 (s), 48.5 (s), 53.1 (s),
55.5 (p), 55.7 (p), 63.2 (t), 110.3 (t), 112.7 (t), 126.7 (q), 131.7 (q),
148.34 (q), 148.44 (q).
2
1
4JCP = 2.4 Hz), 133.4 [t; (d, JPH = 8.9 Hz), 139.9 [q, (d, JPH = 88.5
Hz)], [149.0 (q), 149.1 (q), 149.2 (q)]*.
Crystal Data, X-ray Data Collection, and Refinement Results of
Tartrate (−)-14. C34H39NO11, M = 637.66, monoclinic, space group
P21, a = 9.3851(6) Å, b = 11.1429(7) Å, c = 15.4073(11) Å, α = 90,
β = 97.742(2), γ = 90°, V = 1596.57(18) Å−3, Z = 2, Dx = 1.326 Mg
m−3, μ = 0.99 cm−1, λ (Mο Kα) = 0.71073 Å, F(000) = 676, T =
100(2) K. The sample (0.28 × 0.24 × 0.13 mm) was studied on a
diffractometer with graphite-monochromatized Mo Kα radiation. The
data collection (Θmax = 27.48°, range of HKL: H −10→12, K −14→
13, L −20→20) gave 14460 reflections with 3846 unique reflections
from which 3606 with I > 2.0σ(I). The structures were solved by direct
(S)-(−)-Crispine A·(+)-15. (S)-(−)-Crispine A (50 μmol, ≥98:2 er)
and C6D6 (0.7 mL) were mixed in a 5 mm NMR tube, and (+)-15
(60 μmol) was added. The 13C and 1H NMR data were collected on a
500 MHz spectrometer. The chemical shifts (ppm) were internally
1
referenced to the TMS signal (0 ppm): H NMR (C6D6, 500 MHz,
9730
dx.doi.org/10.1021/jo2017982|J. Org. Chem. 2011, 76, 9720−9732