The Journal of Organic Chemistry
NOTE
(Q = TBS, R = H) (2.0 g, 5.1 mmol) and TBAF (2.0 g, 7.62 mmol) in
20 mL of THF was allowed to react for 1 h, quenched with 10 mL of
water, extracted tree times with ethyl acetate (50 mL), and processed as
usual. The crude reaction was used as is in the following reaction.
Respective 1,3- aminoalcohol (1 g, 3.58 mmol) was dissolved in 10 mL
of CH2Cl2 at 0 °C, and acetic acid (0.10 g, 1.78 mmol) and acetic
anhydride (0.73 g, 7.15 mmol) were slowly added. The reaction mixture
was allowed to react for 3 h. The reaction mixture was treated with a
saturated aqueous solution of NaHCO3 (5 mL), extracted three times
with ethyl acetate (100 mL), and processed as usual. Flash chromatog-
raphy on silica gel (eluent: hexane/ethyl acetate 2/1) gave 0.7 g of 5 (Q =
acetyl, R = H) in 60% yield. [R]D = þ192 (c 1.0, CHCl3). 1H NMR (400
MHz, CDCl3) δ: 1.35 (s, 3H), 1.53 (s, 3H), 2.0 (s, 3H), 2.88 (dd, J = 10.0,
4.4 Hz, 1H), 3.75 (d, J = 13.2 Hz, 1H), 3.87 (ddd, J = 10.0, 5.6, 2.0 Hz,
1H), 3.95 (d, J = 13.2 Hz, 1H), 4.13 (dd, J = 12.0, 5.6 Hz, 1H), 4.39 (dd, J
= 12.0, 2.0 Hz, 1H), 4.58 (t, J = 4.0 Hz, 1H), 5.79 (d, J = 4.0 Hz, 1H),
7.23ꢀ7.36 (m, 5H). NMR 13C (400 MHz, CDCl3) δ: 20.8, 26.4, 26.6,
51.8, 60.6, 63.6, 76.7, 77.8, 104.6, 112.0, 127.1, 128.0, 128.3, 139.8, 170.9.
FAB-HRMS m/z 322.1654 [M þ H]þ calcd for C17H24N1O5: 322.1701.
Synthesis of 2-epi-(ꢀ)-Jaspine B.
water, and the organic phase was extracted three times with ethyl acetate
(50 mL) and concentrated under reduced pressure. The reaction was
highly quantitative, and compound 11 was submitted to the next
reaction. [R]D = þ77.5 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3)
δ: 0.87 (t, J = 6.4 Hz, 3H), 1.25 (broad-s, 26H), 3.03 (apparent-t, J = 8.0
Hz, 1H), 3.5 (dd, J = 5.2, 1.6 Hz, 1H), 3.67 (d, J = 12.8 Hz, 1H), 3.71 (d,
J = 10.4 Hz, 1H), 3.75 (s, 2H), 4.05 (m, 1H), 4.34 (d, J = 12.0 Hz, 1H),
4.61 (d, J = 12.0 Hz, 1H), 7.26ꢀ7.35 (m, 10H). 13C NMR (100 MHz,
CDCl3) δ: 14.1, 22.7, 25.8, 29.4, 29.4, 29.5,29.6, 29.7, 32.0, 34.9, 52.5,
62.0, 63.9, 71.3, 79.8, 80.0, 83.4, 127.1, 127.9,128.0, 128.1, 128.4, 128.5,
137.7, 140.0.
(2S,3R,4R,5S)-N-Benzyl-4-(benzyloxy)-tetrahydro-2-(methyl-
N-phthalimidyl)-5-tetradecylfuran-3-amine (12). To a solution of
amine 12 (0.350 g, 0.686 mmol) and triphenylphosphine (0.361 g, 1.37
mmol) in 20 mL of THF at 0 °C were added N-hydroxyphthalimide (0.145 g,
0.896 mmol) and subsequently DEAD (0.25 g, 1.24 mmol). The resultant
solution was warmed to room temperature and allowed to react for 1 h. The
reaction mixture was concentrated under reduced pressure, and the residue
was purified by column chromatography on silica gel (eluent: 4:1 hexane/
ethyl acetate) to give 0.37 g of 12 in 81% yield. [R]25 = þ31.7 (c 1.0,
D
CHCl3). 1H NMR (400 MHz, CDCl3) δ: 0.88 (t, J = 6.8 Hz, 3H), 1.22
(broad-s, 6H), 1.25 (broad-s, 18H), 1.95 (broad, 2H), 3.04 (dd, J = 9.2, 5.52
Hz, 1H), 3.50 (dd, J= 5.6, 2.4 Hz, 1H), 3.68 (d, J=13.2Hz, 1H), 3.77(d, J=
13.2 Hz, 1H) 3.92 (t, J = 5.6 Hz, 1H), 4.0 (t, J = 7.2 Hz, 1H), 4.24 (dd, J =
11.6, 6.0 Hz, 1H), 4.33 (d, J = 11.6 Hz, 1H), 4.46 (dd, J = 10.8, 2.0 Hz, 1H),
4.56 (d, J= 12.0 Hz, 1H), 7.22ꢀ7.35(m, 10H), 7.72(m, 2H), 7.81(m, 2H).
13C NMR (100 MHz, CDCl3) δ: 14.1, 22.7, 25.6, 29.3, 29.4, 29.5, 29.6, 29.7,
31.9, 34.6, 52.5, 60.5, 71.4, 78.7, 79.3, 80.1, 83.4, 123.3, 127.1, 127.9, 128.0,
128.1, 128.3, 128.4, 129.0, 134.1, 137.7, 140.3, 163.3. FAB-HRMS m/z
655.4285 [M þ H]þ calcd for C41H54N2O5: 655.4211.
(2S,3R,4R,5S)-5-Allyl-N-benzyl-4-(benzyloxy)-tetrahydro-
2-(methyl-tert-butyldimethylsilyloxy)furan-3-amine (8). To a
solution of trans-6 (1 g, 2.64 mmol) and NaH (0.127 g, 5.29 mmol) in
30 mL of THF at 0 °C was added benzyl bromide (0.90 g, 5.29 mmol).
The reaction mixture was stirred for 2 h at reflux and then quenched with
5 mL of water. The organic phase was extracted three times with ethyl
acetate (50 mL) and processed as usual. Flash chromatography on silica
gel (eluent: hexane/ethyl acetate 5/1) gave 1.15 g of 8 in 93% yield.
[R]25D = þ48.1 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ: 0.05 (s,
3H), 0.06 (s, 3H), 0.88 (s, 9H), 2.22 (m, 2H), 3.14 (dd, J = 7.6, 5.2 Hz,
1H), 3.61 (dd, J = 5.6, 2.8 Hz, 1H), 3.65 (m, 1H), 3.67 (s, 2H),
3.73ꢀ3.79 (m, 2H), 4.09 (td, J = 6.4, 2.8 Hz, 1H), 4.33 (d, J = 11.2 Hz,
1H), 4.54 (d, J = 11.6 Hz, 1H), 5.03ꢀ5.08 (m, 2H), 5.80 (m, 1H),
7.21ꢀ7.36 (m, 10 H). 13C NMR (100 MHz, CDCl3) δ: ꢀ5.4, ꢀ5.3,
18.4, 26.0, 39.0, 52.5, 59.0, 63.2, 71.5, 80.0, 81.3, 83.1, 117.2, 127.0,
127.8, 128.0, 128.1, 128.3, 128.4, 134.5, 138.0, 140.5. FAB-HRMS m/z
468.2968 [M þ H]þ calcd for C28H42N1O3 Si1: 468.2954.
(3R,4R,5S)-N-Benzyl-4-(benzyloxy)-tetrahydro-5-tetra-
decylfuran-3-amine (13). To a boiled solution of phthalimide 12
(50 mg, 0.076 mmol) and catalytic amounts of AIBN (15 mg) in 30 mL
of toluene was added slowly (30 min) Bu3SnH (19 mg, 0.061 mmol)
dissolved in 20 mL of toluene. The reaction mixture was stirred for 2 h
and evaporated under reduced pressure. The residue was purified by
column chromatography on silica gel (eluent: hexane/ethyl acetate 5/1)
to give 31 mg of 13 in 85% yield. 1H NMR (400 MHz, CDCl3) δ: 0.87
(t, J = 6.4 Hz, 3H), 1.25 (broad, 19H), 1.42 (broad, 2H), 1.62 (broad, 4H),
3.26 (dd, J = 8.0, 6.0 Hz, 1H), 3.55ꢀ3.61 (m, 2H), 3.71 (d, J = 13.2 Hz,
1H), 3.75 (d, J = 13.2 Hz, 1H), 3.99 (dd, J = 8.43.99 (dd, J = 8.4, 6.4 Hz,
1H), 4.42 (d, J = 11.6 Hz, 1H), 4.57 (d, J = 11.6 Hz, 1H), 7.22ꢀ7.35
(m, 10H). 13C NMR (100 MHz, CDCl3) δ: 14.1, 22.2, 22.7, 25.2, 25.9,
29.3, 29.6, 29.7, 31.9, 34.3, 34.5, 52.3, 59.2, 70.8, 71.7, 80.9, 82.9, 127.0,
127.9, 128.1, 128.4, 128.5, 137.8, 140.2. FAB-HRMS m/z 479.3763
[M þ H]þ calcd for C32H49N1O2: 479.3801
(2S,3R,4R,5S)-N-Benzyl-4-(benzyloxy)-tetrahydro-2-(methyl-
tert-butyldimethylsilyloxy)-5-tetradecylfuran-3-amine (10). In
an oven-dried two-neck 100 mL round flask, equipped with a magnetic stir
bar and a rubber septum and reflux column, was added catalytic amount of
second generation HoveydaꢀGrubbs catalyst (0.219 g, 0.350 mmol) in
30 mL of toluene. The reaction mixture was stirred for 10 min, and then
compound 8 (0.820 g, 1.75 mmol) and 1-trideceno (1.91 g, 10.5 mmol)
were added. The reaction mixture was stirred at reflux for 1 h, the solids were
filtered off, and the liquid mother solution was evaporated under reduced
pressure. The residue was dissolved in 20 mL of methanol and treated with
Pd(OH)2 (0.10 mg) under a hydrogen atmosphere for 1 h. The solids were
filtered off, and the filtrate was concentrated under reduced pressure. Flash
chromatography on silica gel (eluent: hexane/ethyl acetate 7/1) gave 0.77 g
of 10 in 70% yield. [R]25D = þ10.5 (c 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3) δ: 0.04 (s, 3H), 0.05 (s, 3H), 0.88 (s, 9H), 0.89 (t, J = 6.8 Hz, 3H),
1.25 (broad-s, 24H), 1.63 (broad, 2H), 3.15 (dd, J = 7.6, 5.6 Hz, 1H), 3.57
(dd, J = 5.6, 3.2 Hz, 1H), 3.65 (m, 1H), 3.68 (s, 2H), 3.73ꢀ3.78 (m, 2H),
4.0 (m, 1H), 4.36 (d, J = 11.6 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H), 7.26ꢀ7.37
(m, 10H). 13C NMR (100 MHz, CDCl3) δ: ꢀ5.4, ꢀ5.3, 14.1, 18.4, 22.7,
25.8, 26.0, 29.3, 29.5, 29.6, 29.7, 31.9, 34.6, 52.4, 59.0, 63.3, 71.5, 80.5, 81.8,
82.9, 126.9, 127.8, 127.9, 128.1, 128.3, 128.4, 137.9, 140.6. FAB-HRMS m/z
623.4734 [M þ H]þ calcd for C39H65N1O3 Si1: 623.4741
2-epi-(ꢀ)-Jaspine B (7). To a solution of amine 13 (20 mg, 0.041
mmol) and acetic acid (two drops) in 3 mL of methanol was added an
excess of Pd(OH)2 (40 mg) under a hydrogen atmosphere. The reaction
was stirred for 3 days, solids were filtered off, the filtrate was evaporated,
and the residue was purified by column chromatography to give 7 in 80%
yield. [R]25 = ꢀ8.2 (c 1.0, CHCl3); [lit.8b [R]25 = ꢀ9.6 (c 1.1,
D
D
CHCl3)]. 1H NMR (400 MHz, CDCl3) δ: 0.87 (t, J = 6.8 Hz, 3H), 1.25
(s, 26H) 3.61ꢀ3.75 (m, 5H), 4.03 (t, J = 6 Hz, 1H), 4.14 (dd, J = 9.6, 6.4,
Hz, 1H,). 13C NMR (100 MHz, CDCl3) δ: 13.9, 20.7, 21.8, 25.5, 29.6,
31.8, 32.9, 51.8, 66.0, 73.0, 84.3
’ ASSOCIATED CONTENT
(2S,3R,4R,5S)-3-(Benzylamino)-4-(benzyloxy)-tetrahydro-
5-tetradecylfuran-2-yl)methanol (11). A solution of amine 10
(0.630 g, 1.03 mmol) and TBAF (0.39 g, 1.51 mmol) in 10 mL of THF
was allowed to react for 1 h. When consumption of starting material was
completed, the reaction mixture was quenched by addition 10 mL of
S
Supporting Information. Experimental procedures,
b
NMR data, and copies of H and 13C spectra for new com-
1
pounds. This material is available free of charge via the Internet at
5470
dx.doi.org/10.1021/jo200639t |J. Org. Chem. 2011, 76, 5466–5471