Iridoids from Carbohydrates via Pauson-Khand Reaction
Hz, 1 H, H-6), 5.35 (d, J 1,9 ) 5.3 Hz, 1 H, H-1), 5.00 (dd, J 3,4
J . Org. Chem., Vol. 64, No. 22, 1999 8309
)
(C-11), 48.8 (C-9), 40.5 (C-5); MS (70 eV) m/z 212 (46), 85 (100).
Anal. Calcd for C10H14O6: C, 52.17; H, 6.13. Found: C, 53.85;
H, 6.47.
10.6 Hz, J 4,5 ) 7.2 Hz, 1 H, H-4), 4.64 (ddd, J 3,11 ) 4.8 Hz,
J 3,11′ ) 2.3 Hz, 1 H, H-3), 4.28 (dd, J 11,11′ ) 12.1 Hz, 1 H, H-11′),
4.16 (dd, 1 H, H-11), 3.93 (t, J 10,10′ ) J 8,10′ ) 8.9 Hz, 1 H, H-10′),
3.86 (dd, J 8,10 ) 3.5 Hz, 1 H, H-10), 2.95-2.74 (m, 3 H, H-5,
H-8, H-9), 2.08, 2.07, 2.01 (s, s, s, 9 H, 3 × OCOCH3), 2.01
(ddd, J 7a,7b ) 14.8 Hz, J 7b,8 ) 7.5 Hz, 1 H, H-7b), 1.91 (d, 1 H,
H-7a); 13C NMR (CDCl3, 50 MHz) δ 170.9, 170.3, 170.1 (3 ×
OCOCH3), 101.3 (C-1), 75.6 (C-6), 71.8 (C-10), 66.4 (C-4), 65.8
(C-3), 63.0 (C-11), 43.1 (C-9), 42.3 (C-8), 41.1 (C-5), 39.8 (C-7),
21.5, 20.8, 20.7 (3 × OCOCH3); MS (70 eV) m/z 222 (19), 43
(100). Anal. Calcd for C16H22O8: C, 56.14; H, 6.48. Found: C,
56.35; H, 6.47.
[1R-(1r,3r,4â,4a r,5â,6r,7a r)]-4,5-(Dia cetoxy)-7b-[(a ce-
toxy)m eth yl]-1,3-(epoxym eth an e)-3,4,4a,5,6,7a-h exah ydr o-
6,7-oxir en o-cyclop en ta [c]p yr a n (13). Following General
Procedure for Acetylation, compound 12 (15 mg, 0.065 mmol)
gave product 13 (20 mg, 87%) after flash chromatography
(hexane/ethyl acetate: 7/3). 13: mp 99-102 °C; [R]25 +7 (c
D
0.23, CHCl3); IR (KBr) ν 1725 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 5.71 (d, J 1,9 ) 7.8 Hz, 1 H, H-1), 5.22 (d, J 5,6 ) 2.2 Hz, 1 H,
H-6), 4.79 (d, J 10,10′ ) 10.6 Hz, 1 H, H-10′), 4.49 (s, 1 H, H-7),
4.39 (t, J 3,11 ) J 3,11′ ) 4.7 Hz, 1 H, H-3), 4.25 (br s, 1 H, H-4),
4.15 (d, 2 H, 2 H-11), 3.86 (d, 1 H, H-10), 2.95 (ddd, J 5,9 ) 5.2
Hz, J 4,9 ) 1.7 Hz, 1 H, H-9), 2.61 (ddd, J 5,4 ) 2.5 Hz, 1 H,
H-5), 2.10, 2.08, 2.02 (s, s, s, 9 H, 3 × OCOCH3); 13C NMR
(CDCl3, 50 MHz) δ 170.7, 170.2, 169.6 (3 × OCOCH3), 98.2
(C-1), 89.5 (C-8), 79.6, 78.6 (C-6, C-7), 74.0 (C-4), 72.4 (C-10),
68.5 (C-3), 65.3 (C-11), 44.7 (C-9), 37.5 (C-5), 21.0, 20.9, 20.8
(3 × OCOCH3); MS (70 eV) m/z 296 (47), 43 (100). Anal. Calcd
for C16H20O9: C, 53.93; H, 5.66. Found: C, 53.88; H, 5.70.
[1R-(1r,3r,4â,4a r,5â,7a r)]-4,5-(Dia cet oxy)-3,7-[(d ia ce-
t oxy)m et h yl]-3,4,4a ,5,7a -p en t a h yd r o-1-m et h oxy-cyclo-
p en ta [c]p yr a n (15). Following General Procedure for Epoxi-
dation (B, MeOH) and Acetylation, compound 8 (mg, mmol)
gave compound 13 (10 mg, 11%) and 15 (35 mg, 34%) after
flash chromatography (hexane/ethyl acetate 85/15). 15: oil;
[4S-(4a r,5â,6r,7a r,7br)]-4,4a ,5,6,7a ,7b-Hexa h yd r o-4,5-
(d ih yd r oxy)-6-[(h yd r oxy)m eth yl]-2H-1,7-d ioxa cyclop en t-
[cd ]in d en e (8). Following General Procedure for Reductions
(NaBH4/CeCl3) and Basic Hydrolysis, compound 2 (85 mg, 0.9
mmol) was transformed into mixture of 8 + 6 (44 mg, in a
3.4/1 ratio, respectively, that we were unable to separate by
flash chromatography (methylene chloride/methanol 98/2).
Following General Procedure for Reductions (DIBAH) and
Basic Hydrolysis, compound 2 (109 mg, 0.37 mmol) was
transformed into pure 8 (36 mg, 45%). 8: oil; [R]25D -50 (c 0.19,
1
MeOH); IR (film) ν 3500-3100 cm-1; H NMR (CD3OD, 300
MHz) δ 5.87-5.85 (m, 1 H, H-7), 5.67-5.63 (m, 1 H, H-6), 5.56
(d, J 1,9 ) 5.0 Hz, 1 H, H-1), 4.72 (dt, J 10,10′ ) 12.9 Hz, J 6,10′
J 7,10′ ) 1.7 Hz, 1 H, H-10′), 4.42 (ddd, J 6,10 ) 1.9 Hz, J 7,10
)
)
[R]25 +51(c 0.47, CHCl3); IR (film) ν 1720 cm-1 1H NMR
;
D
3.7 Hz, 1 H, H-10), 4.17 (dt, J 3,4 ) 6.7 Hz, J 3,11 ) J 3,11′ ) 5.0
(CDCl3, 300 MHz) δ 5.84 (br d, J 6,7 ) 2.8 Hz, 1 H, H-7), 5.75
(dd, J 5,6 ) 6.4 Hz, 1 H, H-6), 4.99 (dd, J 4,5 ) 7.9 Hz, J 3,4 ) 10.3
Hz, 1 H, H-4), 4.80 (dd, J 10,10′ ) 15.6 Hz, J 7,10′ ) 1.4 Hz, 1 H,
H-10′), 4.64 (d, 1 H, H-10), 4.42 (d, J 1,9 ) 8.4 Hz, 1 H, H-1),
4.21 (d, J 3,11 ) 4.1 Hz, 2 H, 2 H-11), 4.04 (dt, 1H, H-3), 3.52 (s,
3 H, OCH3), 3.08 (ddd, J 5,9 ) 7.4 Hz 1 H, H-5), 2.70 (dd, 1 H,
Hz, 1 H, H-3), 4.05 (t, J 4,5 ) 6.7 Hz, 1 H, H-4), 3.86 (d, J 3,11
5.0 Hz, 2 H, 2 H-11), 3.37-3.32 (m, 1 H, H-9), 2.64 (dt, J 5,9
)
)
J 5,6 ) 7.7 Hz, 1 H, H-5); 13C NMR (CD3OD, 50 MHz) δ 147.4
(C-8), 127.1 (C-7), 96.9 (C-1), 86.9 (C-6), 77.6 (C-3), 68.6 (C-4),
65.4 (C-10), 62.6 (C-11), 52.6 (C-9), 43.6 (C-5); MS (70 eV) m/z
165 (31), 79 (100). Anal. Calcd for C10H14O5: C, 56.07; H, 6.59.
Found: C, 55.75; H, 6.47.
H-9), 2.10, 2.09, 2.07, 2.03 (s, s, s, s, 12 H, 4 × OCOCH3); 13
C
NMR (CDCl3, 50 MHz) δ 170.9, 170.4, 170.3, 169.8 (4 ×
OCOCH3), 148.1 (C-8), 125.8 (C-7), 106.1 (C-1), 75.8 (C-6), 72.9
(C-3), 67.4 (C-4), 63.2, 62.0 (C-10, C-11), 56.7 (OCH3), 49.3 (C-
9), 41.2 (C-5), 21.5, 20.8, 20.7 (4 × OCOCH3); MS (70 eV) m/z
192 (62), 43 (100). Anal. Calcd for C19H26O10: C, 55.07; H, 6.32.
Found: C, 55.20; H, 6.44.
[4S-(4ar,5â,6r,7ar,7br)]-4,5-(Diacetyloxy)-6-[(acetyloxy)-
m eth yl]-4,4a ,5,6,7a ,7b-h exa h yd r o-2H-1,7-d ioxa cyclop en t-
[cd ]in d en e (9). Following General Procedure for Reduction
(NaBH4/CeCl3, MeOH, 0 °C) and Acetylation, compound 2 (80
mg, 0.27 mmol) gave recovered 2 (10 mg), 9 (13 mg, 14%), and
a mixture of 9 and 7 (14 mg in a 2.2/1 ratio, determined by 1H
NMR) after flash chromatography (hexane/ethyl acetate 8/2).
[2a S -(3r,4â,4a r,5â,6a ,7a r,7b r)]-4,5-(Dia ce t yloxy)-6-
[(a cetyloxy)m eth yl]-3,4,4a ,5,6,7a ,7b-h ep ta h yd r o-2a ,3-ox-
ir en o-2H-1,7-d ioxa cyclop en t [cd ]in d en e (16). Following
General Procedure for Epoxidation (B, CH2Cl2), compound 9
(81 mg, 0.24 mmol) gave compound 16 (45 mg, 53%) after flash
9: oil; [R]25 -80 (c 0.13, CHCl3); IR (film) ν 1725 cm-1
;
1H
D
NMR (CDCl3, 300 MHz) δ 6.19-6.16 (m, 1 H, H-6), 5.65 (br s,
1 H, H-7), 5.44 (d, 1 H, J 1,9 ) 4.7 Hz, 1 H, H-1), 5.07 (t, J 4,5
)
J 3,4 ) 6.2 Hz, 1 H, H-4), 4.60 (dq, J 10,10′ ) 12.9 Hz, J ) 1.7 Hz,
1 H, H-10′), 4.29 (ddt, J 6,10 ) 2.2 Hz, J 7,10 ) 3.6 Hz, 1 H, H-10),
chromatography (methylene chloride/methanol 99/1). 16: oil;
1
[R]25 - 4.2 (c 0.13, CHCl3); IR (film) ν 1725 cm-1; H NMR
D
4.25-4.07 (m, 3 H, H-3, 2 H-11), 3.40 (dt, J 5,6 ) 6.2 Hz, J 5,9
)
(CDCl3, 300 MHz) δ 5.50 (d, J 1,9 ) 4.5 Hz, 1 H, H-1), 5.48 (d,
J 5,6 ) 6.2 Hz, 1 H, H-6), 5.03 (dd, J 4,5 ) 7.8 Hz, J 3,4 ) 5.8 Hz,
1 H, H-4), 4.35 (m, 1 H, H-3), 4.21 (dd, J 11,11′ ) 12.1 Hz, J 3,11′
) 6.0 Hz, 1 H, H-11′), 4.17 (d, J 10,10′ ) 9.7 Hz, 1 H, H-10′),
4.05 (d, 1 H, H-10), 4.04 (dd, J 3,11 ) 3.0 Hz, 1 H, H-11), 3.61
(s, 1 H, H-7), 3.13 (ddd, J 5,9 ) 8.7 Hz, 1 H, H-5), 2.76 (dd, 1 H,
H-9), 2.11, 2.08, 2.01 (s, s, s, 9 H, 3 × OCOCH3); 13C NMR
(CDCl3, 50 MHz) δ 170.6, 169.7, 169.6 (3 × OCOCH3), 96.9
(C-1), 76.4 (C-8), 73.7 (C-6), 73.0 (C-3), 66.0 (C-4), 64.9 (C-7),
63.2, 63.1 (C-10, C-11), 45.6 (C-9), 41.6 (C-5), 21.0, 20.8 (3 ×
OCOCH3); MS (70 eV) m/z 181 (18), 43 (100). Anal. Calcd for
8.1 Hz, 1 H, H-5), 3.24-3.20 (m, 1 H, H-9), 2.07, 2.04, 2.02 (s,
s, s, 9 H, 3 × OCOCH3); 13C NMR (CD3OD, 50 MHz) δ 170.6,
170.4, 169.9 (3 × OCOCH3), 146.7 (C-8), 122.6 (C-7), 94.9
(C-1), 83.8 (C-6), 72.0 (C-3), 65.2 (C-4), 64.5 (C-10), 62.7
(C-11), 51.9 (C-9), 40.5 (C-5), 21.1, 21.0, 20.2 (3 × OCOCH3),
MS (70 eV) m/z 160 (16), 43 (100). Anal. Calcd for C16H20O8:
C, 56.47; H, 5.92. Found: C, 56.69; H, 5.73.
[1R-(1r,3r,4â,4a r,5â,6r,7a r)]-1,3-(Ep oxym eth a n e)-3,4,-
4a,5,6,7a-h exah ydr o-4,5-(dih ydr oxy)-7â-[(h ydr oxy)m eth yl]-
6,7-oxir en o-cyclop en ta [c]p yr a n (12). Following General
Procedure for Epoxidation (A) + Reduction with Sodium
Borohydride and Basic Hydrolysis, compound 2 (107 mg, 0.36
mmol) gave product 12 (16.2 mg, 19%) after flash chromatog-
raphy (methylene chloride/methanol 96/4). Following General
Procedure for Epoxidation (A) + Reduction with L-Selectride
and Basic Hydrolysis or General Procedure for Epoxidation
(A) + Reduction with DIBALH, compound 12 was obtained in
C
16H20O9: C, 53.93; H, 5.66. Found: C, 53.77; H, 5.89.
Following General Procedure for Basic Hydrolysis, compound
16 (35 mg, 0.098 mmol) gave product 12 (15 mg, 66%) (flash
chromatography: methylene chloride/methanol 95/5). Follow-
ing General Procedure for Acetylation, compound 12 (15 mg,
0.065 mmol) gave product 13 (20 mg, 87%) (flash chromatog-
raphy: hexane/ethyl acetate 7/3).
2-(P r op-2-yn yl)-4,6-di-O-ben zyl-2,3-dideoxy-r-D-er yth r o-
h ex-2-en op yr a n osid e (17). Compound 3 (1.41 g, 7.64 mmol)
was dissolved in dry THF (5 mL, 0.14 M), cooled at 0 °C, and
under argon, sodium hydride (458 mg, 19.1 mmol, 2.5 equiv)
was added. Tetrabutylammonium iodide (cat.) and benzyl
bromide (1.83 mL, 15.3 mmol, 2.01 equiv) were added. The
mixture was stirred at room temperature for 24 h. The reaction
was cooled in an ice-bath, AcOH (10 mL) was slowly added,
the mixture was filtered over Celite-545, the cake was washed
40% and 39% yield, respectively. 12: oil; [R]25 -5 (c 0.38,
D
MeOH); IR (film) ν 3350-3100 cm-1; H NMR (CD3OD, 300
1
MHz) δ 5.81 (d, J 1,9 ) 7.8 Hz, 1 H, H-1), 4.79 (d, J 5,6 ) 1.8 Hz,
1 H, H-6), 4.65 (d, J 10,10′ ) 9.2 Hz, 1 H, H-10′), 4.58 (br s, 1 H,
H-4), 4.25 (t, J 3,11 ) J 3,11′ ) 4.8 Hz, 1 H, H-3), 3.95 (s, 1 H,
H-7), 3.80 (d, 1 H, H-10), 3.75 (d, 2 H, 2 H-11), 2.70 (ddd, J 5,9
) 5.3 Hz, J 4,9 ) 1.8 Hz, 1 H, H-9), 2.54 (ddd, J 5,4 ) 2.5 Hz, 1
H, H-5); 13C NMR (CD3OD, 50 MHz) δ 100.9 (C-1), 86.2 (C-8),
85.1 (C-7), 79.7 (C-6), 75.8 (C-10), 74.9 (C-4), 73.3 (C-3), 64.8