(–)-Sparteine-Mediated Synthesis of Kainoids
FULL PAPER
IR (film): ν (cm–1) = 2910–2833, 1707 (CO), 1442, 1407, 1368. H
NMR (300 MHz, CDCl3): δ = 1.09 (s, 9 H, SiC(CH3)3), 1.30 (t, 3
H, 3J = 7.1 Hz, CO2CH2CH3), 1.67 (s, 3 H, CH=C(CH3)), 3.15–
3.21 (m, 2 H, NCH2), 3.48 (m, 1 H, CHCH=CH), 3. 61 (d, 1 H,
3J = 10.1 Hz, CH2Ar), 3.75–3.82 (m, 3 H, CH2OSiPh2 and CH2Ar),
1
chromatography, Rf = 0.45 (SiO2, AcOEt/petroleum ether, 10:90)
affording 15 (1.40 g, 70%) as a pale yellow oil. [α]2D0 = +9.7 (c =
0.37, CHCl3). rac-15 (865 mg, 78%) was obtained by the same pro-
˜
cedure from rac-14 (1.00 g, 1.62 mmol). IR (film): ν (cm–1) = 2976–
˜
1
2856, 1728 (CO), 1474, 1447, 1370. H NMR (600 MHz, CDCl3):
δ = 0.04 (s, 6 H, Si(CH3)2), 0.89 (s, 9 H, SiC(CH3)3), 1.03 (s, 9 H, 3.97 (s, 2 H, CH2Cl), 4.21 (q, 3J = 7.2 Hz, 2 H, 14.0 Hz,
3
3
SiC(CH3)3), 1.30 (t, 3 H, J = 7.2 Hz, CO2CH2CH3), 1.53 (s, 3 H, CO2CH2CH3), 5.56 (t, 1 H, J = 7.3 Hz, C(CH3)=CH), 6.01 (d, 1
CH=C(CH3)), 3.12 (m, 1 H, NCH2), 3.22 (m, 1 H, NCH2), 3.50
H, 3J = 15.0 Hz, CHCH=CH), 7.00 (dd, 1 H, 3J = 7.4, 15.1 Hz,
3
(m, 1 H, CHCH=CH), 3.59 (d, 1 H, J = 10.1 Hz, NCH2Ar) 3.76 CHCH=CH), 7.28–7.46 (m, 11 H, ArH), 7.61 (d, 4 H, 3J = 6.1 Hz,
(m, 2 H, CH2NAr and CH2OSiPh2), 3.88 (m, 1 H, CH2OSiPh2),
ArH). 13C NMR (75 MHz, CDCl3): δ = 14.3 (CH=C(CH3)), 19.2
(CH2CH3), 22.4 (SiC(CH3)3), 26.9 (SiC(CH3)3), 44.6 (NCH2), 51.8
3
3.98 (s, 2 H, CH2OSi(CH3)2), 4.22 (q, 2 H, J = 7.1 Hz, 14.1 Hz,
3
CO2CH2CH3) 5.47 (t, 1 H, J = 7.5 Hz, C(CH3)=CH), 6.01 (d, 1 (CH2Cl), 60.4 (CH2CH3), 61.7 (CHCH=CH), 64.0 (CH2OSiPh2),
H, 3J = 15.1 Hz, CHCH=CH), 7.01 (dd, 1 H, 3J = 15.2, 7.5 Hz,
CHCH=CH), 7.21 (t, 1 H, 3J = 7.1 Hz, ArH), 7.22–7.42 (m, 10 H, 127.8, 128.2, 128.3, 128.4, 128.9, 129.8, 133.2, 133.6, 135.6, 136.3
ArH), 7.63 (d, 4 H, 3J = 6.4 Hz, ArH). 13C NMR (150 MHz,
and 138.5 (Ar), 139.7 (C(CH3)=CH), 145.8 (CHCH=CH), 179.6
CDCl3): δ = –5.3 (Si(CH3)2), 13.7 (CH=C(CH3)), 14.3 (CH2CH3), (CO). ESI-MS, m/z (%) = 612 (50) [M+ + Na], 590 (38) [M+
69.9 (NCH2Ar), 116.2 (C(CH3)=CH), 123.9 (CHCH=CH), 127.0,
+
19.1, 19.5 (SiC(CH3)3), 25.9, 26.8 (SiC(CH3)3), 47.6 (NCH2), 54.8
(NCH2Ar), 60.3 (CH2CH3), 61.5 (CHCH=CH), 63.9 (CH2OS-
H]. HRMS (TOF-CI) C35H44ClNO3Si (589.28): [M+ + H] calcd.
590.2852; found: 590.2844, [M+ + Na] calcd. 612.2671; found
iPh2), 68.3 (CH2OSi(CH3)2), 122.6 (C(CH3)=CH), 123.7 612.2659.
(CHCH=CH), 126.7, 127.7, 128.2, 128.4, 129.7, 133.3, 135.6 and
Ethyl (2E,4S)-4-{Benzyl[(2E)-4-chloro-3-methyl-2-butenyl]amino}-5-
137.2 (Ar), 140.1 (C(CH3)=CH), 146.5 (CHCH=CH), 166.4 (CO).
EI-MS, m/z (%) = 685 (8) [M+ – H], 628 (3) [M+ – H – C(CH3)3],
hydroxy-2-pentenoate (24): To a solution of 17 (50 mg, 0.08 mmol)
in THF (10 mL) was added TBAF (0.17 mL, 0.17 mmol) at room
temperature. After being stirred at the same temperature for 3 h,
the reaction mixture was poured into ether (10 mL) and washed
with H2O several times (5×6 mL). The organic phase was dried
416 (100), 199 (26), 73 (35). ESI-MS, m/z (%) = 709 (10) [M+
+
Na], 686 (100) [M+ + H]. C41H59NO4Si2 (686.08): calcd. (%) C,
71.78, H 8.67, N 2.04; found: C 71.39, H 8.61, N 1.93.
Ethyl (2E,4S)-4-{Benzyl[(2E)-4-hydroxy-3-methyl-2-butenyl]amino}- (MgSO4) and concentrated in vacuo. The crude product 24 was
5-{[tert-butyl(diphenyl)silyl]oxy}-2-pentenoate (16): Pyridinium p-
toluenesulfonate (PPTS) (0.79 g, 3.0 mmol) was added with stirring
at room temperature to a solution of 15 (1.30 g, 1.90 mmol) in ab-
solute ethanol (20 mL). The reaction mixture was stirred for 48 h
at 55 °C and the solvent was evaporated to dryness. The residue
was purified by a short flash chromatography, Rf = 0.37 (SiO2,
AcOEt/petroleum ether, 20:80) affording 16 (1.08 g, 100%) as a col-
orless oil. [α]2D0 = +6.8 (c = 0.74, CHCl3). rac-16 (645 mg, 97%)
was obtained by the same procedure from rac-15 (800 mg,
used in next step without further purification. Crude product rac-
24 was obtained by the same procedure from rac-17 (60 mg,
0.51 mmol). IR (film): ν (cm–1) = 3526–3313 (OH), 2926–2852,
˜
1717 (CO), 1647, 1447, 1365. 1H NMR (400 MHz, CDCl3): δ =
1.27 (t, 3 H, 3J = 7.2 Hz, CO2CH2CH3), 1.68 (s, 3 H, CH=C(CH3)),
2.9 (br. s, 1 H, OH), 3.12–3.22 (m, 2 H, NCH2), 3.35 (m, 1 H,
CHCH=CH), 3.42–3.55 (m, 2 H, CH2OH and NCH2Ar), 3.58 (m,
3
1 H, CH2OH), 3.82 (d, 1 H, J = 10.6 Hz, NCH2Ar), 3.90 (s, 2 H,
CH2Cl), 4.20 (q, 2 H, 3J = 7.2 Hz, 14.0 Hz, CO2CH2CH3), 5.60
1.16 mmol). IR (film): ν (cm–1) = 3553–3298 (OH), 2961–2864, (t, 1 H, 3J = 7.3 Hz, C(CH3)=CH), 5.98 (d, 1 H, 3J = 15.0 Hz,
˜
1
1729 (CO), 1639, 1445, 1410, 1350. H NMR (300 MHz, CDCl3):
CHCH=CH), 7.40 (dd, 1 H, 3J = 6.8, 15.7 Hz, CHCH=CH), 7.48–
δ = 0.98 (s, 9 H, SiC(CH3 )3 ), 1.21 (t, 3 H, 3 J = 7.0 Hz, 7.67 (m, 5 H, ArH). HRMS (TOF-CI) C19H26ClNO3 (351.87): [M+
CO2CH2CH3), 1.48 (s, 3 H, CH=C(CH3)), 3.11 (m, 2 H, NCH2),
3.42 (m, 1 H, CHCH=CH), 3. 55 (d, 1 H, 3J = 10.2 Hz, NCH2Ar),
3.70–3.79 (m, 3 H, NCH2Ar and CH2OSiPh2), 3.88 (m, 2 H,
CH2OH), 4.12 (q, 2 H, 3J = 7.2 Hz, 14.0 Hz, CO2CH2CH3) 5.38
(t, 1 H, 3J = 7.3 Hz, C(CH3)=CH), 5.91 (d, 1 H, 3J = 15.0 Hz,
CHCH=CH), 6.92 (dd, 1 H, 3J = 15.0, 7.5 Hz, CHCH=CH), 7.19–
+ H] calcd. 352.1674; found: 352.1667.
Ethyl (2E,4S)-4-{Benzyl[(2E)-4-chloro-3-methyl-2-butenyl]amino}-
5-[(3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl)oxy]-2-pentenoate
(25): To a solution of 24 (21 mg, 0.06 mmol) in CCl4 (1 mL) were
added three drops of pyridine followed by (R)-(–)-α-methoxy-α-(tri-
fluoromethyl)phenylacetyl chloride (14 μL, 0.07 mmol) at 0 °C. Af-
ter being stirred at room temperature for 4 h, the reaction mixture
was dried (MgSO4) and concentrated in vacuo. The crude product
was purified by flash chromatography, Rf = 0.51 (1:1 Et2O/petro-
leum ether) affording 25 and its epimer as a diastereomeric mixture,
which could not be separated by flash chromatography (29 mg,
65% overall yield) as a pale colorless oil. rac-25 (41 mg, 71%) was
obtained by the same procedure from rac-24 (33 mg, 0.94 mmol).
3
7.40 (m, 11 H, ArH), 7.55 (d, 4 H, J = 6.1 Hz, ArH). 13C NMR
(75 MHz, CDCl3): δ = –5.3 (Si(CH3)2), 13.5 (CH=C(CH3)), 14.3
(CH2CH3), 19.6 (SiC(CH3)3), 27.2 (SiC(CH3)3), 48.4 (NCH2), 55.8
(CH2OH), 60.7 (CH2CH3), 62.7 (CHCH=CH), 64.5 (CH2OSiPh2),
68.9 (NCH2Ar), 123.9 (C(CH3)=CH), 124.6 (CHCH=CH), 127.2,
128.1, 128.6, 128.8, 129.2, 130.1, 133.7, 135.2, 136.0 and 137.5 (Ar),
140.6 (C(CH3)=CH), 146.9 (CHCH=CH), 179.9 (CO). ESI-MS,
m/z (%) = 572 (94) [M + H]. Daughter peaks resulting from m/z
572: 488 (10); 410 (30), 231 (42); 120 (40), 91 (100) [PhCH2+].
HRMS (TOF-CI) C35H45NO4Si (571.82): [M+ + H] calcd.
572.3191; found: 572.3184.
IR (film): ν (cm–1) = 2917–2848, 1752 and 1721 (CO), 1656, 1456,
˜
1
3
1374. H NMR (600 MHz, CDCl3): δ = 1.23 (t, 3 H, J = 7.2 Hz,
CO2CH2CH3), 1.62 (s, 3 H, CH=C(CH3)), 3.11–3.16 (m, 2 H,
3
NCH2), 3.42 (s, 3 H, OMe), 3.50 (d, 1 H, J = 10.2 Hz, NCH2Ar),
Ethyl (2E,4S)-4-{Benzyl[(2E)-4-chloro-3-methyl-2-butenyl]amino}-5- 3.60–3.65 (m, 1 H, CHCH=CH), 3.70 (d, 1 H, 3J = 10.2 Hz,
{[tert-butyl(diphenyl)silyl]oxy}-2-pentenoate (17): Compound 16
(1.59 g, 2.78 mmol) was treated under the conditions described for
10 to produce 17 (1.36 g, 83 %) as a colourless oil after flash
chromatography, Rf = 0.47 (SiO2, AcOEt/petroleum ether, 5:95).
[α]D20 = +5.2 (c = 0.64, CHCl3, Ϸ26% ee). rac-17 (365 mg, 71%) was
obtained by the same procedure from rac-16 (500 mg, 0.88 mmol).
NCH2Ar), 3.96 (s, 2 H, CH2Cl), 4.20 (q, 2 H, 3J = 7.2 Hz, 14.0 Hz,
CO2CH2CH3), 4.30–4.37 (m, 1 H, CHCH2O), 4.51–4.58 (m, 1 H,
CHCH2O), 5.48–5.55 (m, 1 H, C(CH3)=CH), 5.86–5.91 (m, 1 H,
CHCH=CH), 6.80–6.85 (m, 1 H, CHCH=CH), 7.20–7.50 (m, 10
H, ArH). HRMS C29H33ClF3NO5 (568.02): calcd. 568.2078; found:
568.2049.
Eur. J. Org. Chem. 2005, 1427–1443
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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