Synthetic Studies on Pandanus Alkaloids
with CH2Cl2 (25 mL) and filtered through a short path of silica 1.68 (qn, J ϭ 6.6 Hz, 2 H, 3Ј,3Ј-H), 1.96 (s, 3 H, CH3), 2.36 (q,
FULL PAPER
gel. The solvent was evaporated under reduced pressure to furnish
aldehyde 10 (1.62 g, 5.0 mmol, 92% yield) which proved to be un-
stable and was used for the next reaction without further purifi-
J ϭ 7.7 Hz, 2 H, 2Ј,2Ј-H), 3.67 (t, J4Ј,3Ј ϭ 5.9 Hz, 2 H, 4Ј,4Ј-H),
5.57 (t, J1Ј,2Ј ϭ 8.6 Hz, 1 H, 1Ј-H), 7.25 (m, 1 H, 4-H), 7.37 (m, 6
H, Ph), 7.63 (m, 4 H, Ph). 13C NMR (62.5 MHz, ppm): δ ϭ 10.7
cation. 1H NMR (250 MHz, ppm): δ ϭ 1.01 (s, 9 H, tBu), 1.88 (m, (CH3), 19.2 (tBu-C), 22.6 (C-3Ј), 26.9 (tBu-CH3), 32.3 (C-2Ј), 62.4
2 H, 3-H), 2.57 (td, J2,3 ϭ 9.0, J2,1 ϭ 1.6 Hz, 2 H, 2-H), 3.67 (t,
J4,3 ϭ 6.1 Hz, 2 H, 4-H), 7.38 (m, 6 H, Ph), 7.63 (m, 4 H, Ph). 13
NMR (62.5 MHz, ppm): δ ϭ 19.2 (tBu-C), 25.3 (C-3), 26.8 (tBu-
(C-4Ј), 113.1 (C-1Ј), 130.1 (C-3), 133.7 (C-4), 127.7/129.7/133.8/
135.6 (Ph), 149.0 (C-5), 171.0 (C-2). 14 ϩ 15: EIMS: m/z ϭ 269
(9), 199 (100), 139 (48). C25H30O3Si calcd. C 73.85, H 7.44; found
C
CH3), 40.7 (C-2), 62.9 (C-4), 127.7/129.7/133.6/135.5 (Ph), 202.4 C 73.70, H 7.31.
(C-1).
(Z)- (8) and (E)-5-(4-Mesyloxy-1-butylidene)-3-methyl-2(5H)-
furanone (18): A solution of a 3:1 mixture of olefins 14 and 15
butyl]-3-methyl-2(5H)-furanone (13): A solution of 3-methyl-2(5H)- (200 mg, 0.49 mmol) in dry THF (2.5 mL) at room temperature
threo- (12) and erythro-5-[4-(tert-Butyldiphenylsilyloxy)-1-hydroxy-
furanone (620 µL, 7.15 mmol) and triethylamine (1.0 mL,
7.49 mmol) in dry CH2Cl2 (8 mL) was cooled to 0 °C and treated
with triisopropylsilyl triflate (2.0 mL, 7.49 mmol). The mixture was
stirred at room temperature for 2 days and then concentrated under
vacuum. The resultant crude material was dissolved in CH2Cl2
(60 mL) and aldehyde 10 (2.70 g, 8.28 mmol) was added. The mix-
ture was cooled to Ϫ78 °C, treated with boron trifluorideϪdiethyl
ether (1.0 mL, 8.28 mmol) and stirred at this temperature for 3 h.
After this time, the reaction mixture was quenched with brine and
allowed to warm to room temperature. The organic phase was sepa-
rated and the aqueous one was extracted with CH2Cl2. The organic
extracts were combined and concentrated under vacuum. Purifi-
was treated with 1.0 TBAF (590 µL, 0.59 mmol). The mixture
was stirred at room temperature for 3 h and then concentrated un-
der vacuum to yield a crude material which, after purification by
flash chromatography (hexanes/diethyl ether, 1:1), afforded a 3:1
mixture of two diastereomeric alcohols 16 and 17 (70 mg,
0.42 mmol, 86% yield) as an oil, which was used in the next reac-
tion without further purification: 1H NMR (250 MHz, ppm): δ
(major isomer) ϭ 1.72 (m, 2 H, 3Ј,3Ј-H), 1.97 (s, 3 H, CH3), 2.45
(q, J ϭ 7.5 Hz, 2 H, 2Ј-H), 3.66 (m, 2 H, 4Ј,4Ј-H), 5.15 (t, J1Ј,2Ј
ϭ
8.0 Hz, 1 H, 1Ј-H), 6.96 (m, 1 H, 4-H); δ (minor isomer, observable
signals) ϭ 1.98 (s, 3 H, CH3), 2.35 (q, J ϭ 7.3 Hz, 2 H, 2Ј,2Ј-H),
5.60 (t, J1Ј,2Ј ϭ 8.0 Hz, 1 H, 1Ј-H), 7.30 (m, 1 H, 4-H). 13C NMR
cation of the resultant crude material by flash chromatography (62.5 MHz, ppm): δ (major isomer): 10.4 (CH3), 22.5 (C-3Ј), 32.8
(hexanes/diethyl ether, 2:1) afforded a 7:1 mixture of alcohols 12 (C-2Ј), 61.9 (C-4Ј), 113.7 (C, 1Ј), 129.0 (C-3), 137.7 (C-4), 148.6 (C-
and 13 (2.61 g, 6.15 mmol, 82% yield). 12 ϩ 13: 1H NMR 5), 171.1 (C-2); δ (minor isomer, observable signals) ϭ 10.7 (CH3),
(250 MHz, ppm): δ (threo isomer 12) ϭ 1.03 (s, 9 H, tBu),
22.5 (C-3Ј), 32.1 (C-2Ј), 61.2 (C-4Ј), 113.0 (C-1Ј), 130.2 (C-3), 133.8
1.50Ϫ1.83 (m, 4 H, 2Ј,2Ј,3Ј,3Ј-H), 1.92 (d, J ϭ 1.7 Hz, 3 H, CH3), (C-4), 149.0 (C-5). EIMS: m/z ϭ 186 (100) [M ϩ 18]ϩ, 169 (14) [M
2.80 (d, J ϭ 4.8 Hz, 1 H, OH), 3.67 (m, 3 H, 1Ј,4Ј,4Ј-H), 4.82 (m, ϩ 1]ϩ. A solution of a freshly prepared 3:1 mixture of the former
1 H, 5-H), 7.00 (qn, J ϭ 1.7 Hz, 1 H, 4-H), 7.38 (m, 6 H, Ph), 7.63
alcohols 16 and 17 (90 mg, 0.54 mmol) in dry CH2Cl2 (5 mL) at 0
(m, 4 H, Ph); δ (erythro isomer 13, observable signals) ϭ 3.28 (d, °C was treated with freshly distilled pyridine (64 µL, 0.64 mmol)
J ϭ 4.7 Hz, 1 H, OH), 4.75 (m, 1 H, 5-H), 7.18 (qn, J ϭ 1.5 Hz, 1
and mesyl chloride (91 µL, 1.2 mmol) and the mixture was stirred
H, 4-H). 13C NMR (62.5 MHz, ppm): δ (threo isomer 12) ϭ 10.8 overnight. It was then washed with brine (2 mL) and a saturated
(CH3), 19.2 (tBu-C), 26.8 (tBu-CH3), 28.4/29.8 (C-2Ј/C-3Ј), 63.8 Na2CO3 solution (2 mL) and concentrated under vacuum to yield
(C-4Ј), 71.9 (C1Ј), 83.8 (C-5), 131.3 (C-3), 127.7/129.7133.4/135.5 a mixture of mesylates 8 and 18 which, when purified by flash
(Ph), 145.9 (C-4), 173.9 (C-2); δ (erythro isomer 13, observable sig-
chromatography (hexanes/ethyl acetate, 3:1), afforded 8 (44 mg,
nals) ϭ 30.8/31.5 (C-2Ј/C-3Ј), 64.1 (C-4Ј), 72.1 (C-1Ј), 83.4 (C-5), 0.18 mmol, 33% yield) and 18 (54 mg, 0.22 mmol, 41% yield).
131.3 (C-3), 146.6 (C-4). EIMS: m/z ϭ 442 (66) [M ϩ 18]ϩ, 424
(16) [M]ϩ, 346 (100). C25H32O4Si: calcd. C 70.72, H 7.60; found C
70.53, H 7.73.
These sulfonates were unstable even at low temperature and were
used in the next reaction without further purification. 8 ϩ 18: H
1
NMR (250 MHz, ppm): δ (major isomer 8) ϭ 1.92 (m, 2 H, 3Ј,3Ј-
H), 2.01 (s, 3 H, CH3), 2.49 (q, J ϭ 7.4 Hz, 2 H, 2Ј,2Ј-H), 3.01 (s,
3 H, CH3OSO2), 4.22 (m, 2 H, 4Ј,4Ј-H), 5.11 (t, J1Ј,2Ј ϭ 8.0 Hz, 1
H, 1Ј-H), 6.97 (m, 1 H, 4-H); δ (minor isomer 18, observable sig-
nals) ϭ 2.35 (q, J ϭ 7.3 Hz, 2 H, 2Ј,2Ј-H), 2.99 (s, 3 H, CH3OSO2),
5.54 (t, J1Ј,2Ј ϭ 8.4 Hz, 1 H,1Ј- H), 7.28 (m, 1 H, 4-H).
(Z)- (14) and (E)-5-[4-(tert-Butyldiphenylsilyloxy)-1-butylidene]-3-
methyl-2(5H)-furanone (15): TMSCl (3.0 mL, 24.2 mmol) was ad-
ded to a solution of a 7:1 mixture of alcohols 12 and 13 (4.1 g,
9.66 mmol) in dry CHCl3 (60 mL), the mixture was stirred at room
temperature for 1 h and then treated with freshly distilled DBU
(7.2 mL, 48.3 mmol). The resultant hot solution was allowed to
cool to room temperature and stirred for 1 h. It was then diluted
with CHCl3 (40 mL), washed with 10% HCl (2 ϫ 40 mL) and brine
(40 mL), and concentrated under vacuum to yield an oil which,
Ethyl (2S,1ЈS)- (20) and (2S,1ЈR)-2-Oxiranylpyrrolidine-1-carb-
oxylate (21): A solution of 55% m-CPBA (1.53 g, 4.88 mmol) in
chloroform (10 mL) was dried with anhydrous Na2SO4, filtered,
and added to a solution of 19[14] (0.550 g, 3.25 mmol) in chloro-
after purification by flash chromatography (hexanes/diethyl ether, form (10 mL). The mixture was then diluted with CHCl3 (20 mL)
3:1), afforded a 3:1 mixture of olefins 14 and 15 as an oil (3.71 g, and washed with a saturated NaHCO3 solution (2 ϫ 25 mL) and
9.1 mmol, 94% yield). A second chromatographic procedure en- brine (25 mL). The organic phase concentrated under vacuum
abled the separation of the isomers. 14: 1H NMR (250 MHz, ppm):
yielded an approximately 1.5:1 mixture of 20 and 21 as oil. Separ-
δ ϭ 1.03 (s, 9 H, tBu-CH3), 1.70 (qn, J ϭ 6.9 Hz, 2 H, 3Ј,3Ј-H), ation by flash chromatography (hexanes/ethyl acetate 4:1) afforded
1.96 (d, J ϭ 0.6 Hz, 3 H, CH3), 2.51 (q, J ϭ 7.5 Hz, 2 H, 2Ј-H), pure 20 (0.310 g, 1.68 mmol, 51% yield) and 21 (0.160 g,
3.67 (t, J4Ј,3Ј ϭ 6.2 Hz, 2 H, 4Ј,4Ј-H), 5.09 (t, J1Ј,2Ј ϭ 7.9 Hz, 1 H, 0.86 mmol, 26% yield). 20: [α]2D0 ϭ Ϫ13 (c ϭ 1.3, ethanol). IR
1Ј-H), 6.90 (m, 1 H, 4-H), 7.37 (m, 6 H, Ph), 7.63 (m, 4 H, Ph).
13C NMR (62.5 MHz, ppm): δ ϭ 10.5 (CH3), 19.2 (tBu-C), 22.8 1110 cmϪ1
(C-3Ј), 26.9 (tBu-CH3), 32.0 (C-2Ј), 63.2 (C-4Ј), 114.2 (C-1Ј), 129.0 7.0 Hz) ϩ 1.24 (t, J ϭ 7.0 Hz) (3 H, CH3CH2O), 1.78Ϫ1.97 (m, 4
(C-3), 127.6/129.6/133.9/135.6 (Ph), 137.6 (C-4), 148.4 (C-5), 171.1 H, 3,3,4,4-H), 2.67 (m) ϩ 2.78 (m) (1 H, 2Ј-H), 2.82 (m, 1 H, 2Ј-
(C-2). 15: H NMR (250 MHz, ppm): δ ϭ 1.05 (s, 9 H, tBu-CH3), H), 2.87 ϩ 2.95 (1 H, 1Ј-H), 3.25Ϫ3.45 (m, 2 H, 5,5-H), 3.48 (m)
(KBr): ν˜ ϭ 2973, 2931, 2882, 1701, 1546, 1419, 1384, 1342, 1187,
.
1H NMR (400 MHz, 260 K, ppm): δ ϭ 1.20 (t, J ϭ
1
Eur. J. Org. Chem. 2004, 48Ϫ53
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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