A. P. John Pal, P. Gupta, Y. Suman Reddy, Y. D. Vankar
FULL PAPER
mL solution in tBuOH, 0.02 mL, 0.002 mmol). The reaction mix-
ture was stirred for 24 h and then treated with Na2S2O5 (127.1 mg,
0.669 mmol). The reaction mixture was stirred for another 1 h and
extracted with EtOAc (3ϫ40 mL). The organic layer was washed
with 1 n HCl, water, and finally with brine. Usual workup there-
after gave a crude product, which was purified by column
chromatography to give diol 24 as a major product. Yield: 86%
(297 mg), oil. Rf = 0.3 (hexane/ethyl acetate, 1:1). [α]2D8 = +26.67 (c
N-{[(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-(benzyloxymethyl)-
2-vinyltetrahydro-2H-pyran-2-yl]methyl}acrylamide (27): Com-
pound 27 was prepared by general procedure C. Yield: 56 %
(520 mg), liquid. Rf = 0.30 (hexane/ethyl acetate, 3:2). [α]2D8 = +35.0
(c = 0.7, CH Cl ). IR (neat): ν = 3418, 2917, 1661, 1626, 1453 cm–1.
˜
2
2
1H NMR (500 MHz, CDCl3): δ = 7.33–7.19 (m, 20 H, Ar-H), 6.17–
6.13 (m, 2 H), 5.90–5.97 (m, 2 H), 5.48–5.42 (m, 2 H), 5.21 (dd, J
= 0.9, 10.7 Hz, 1 H), 4.93–4.82 (m, 4 H, 2 PhCH2), 4.65–4.49 (m,
4 H, 2 PhCH2), 3.90 (t, J = 9.2 Hz, 1 H), 3.83–3.57 (m, 6 H), 3.50
= 0.45, CH Cl ). IR (neat): ν = 3442, 3031, 2923, 1700, 1453,
˜
2
2
1422 cm–1. 1H NMR (500 MHz, CDCl3, mixture of rotamers 1:1 (t, J = 9.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.0,
ratio): δ = 7.33–7.14 (m, 50 H, Ar-H), 5.10 (d, J = 12.3 Hz, 1 H),
5.06 (s, 2 H), 4.97 (d, J = 12.3 Hz, 1 H), 4.92 (d, J = 10.9 Hz, 1
H), 4.88 (d, J = 11.2 Hz, 1 H), 4.86 (d, J = 10.8 Hz, 1 H), 4.83–
4.77 (m, 5 H), 4.68 (d, J = 11.2 Hz, 2 H), 4.59 (d, J = 12.0 Hz, 1
H), 4.58 (d, J = 10.9 Hz, 1 H), 4.52 (d, J = 12.3 Hz, 1 H), 4.51 (d,
J = 10.3 Hz, 1 H), 4.45–4.40 (m, 3 H), 4.22–4.11 (m, 5 H), 3.97 (d,
J = 15.2 Hz, 1 H), 3.87 (dd, J = 4.8, 14.6 Hz, 1 H), 3.78 (dd, J =
2.8, 10.9 Hz, 1 H), 3.75–3.58 (m, 7 H), 3.50 (d, J = 9.7 Hz, 1 H),
3.39 (dd, J = 4.0, 10.9 Hz, 1 H), 3.34–3.30 (m, 3 H), 3.21 (dd, J =
6.9, 14.6 Hz, 1 H), 3.15 (d, J = 15.2 Hz, 1 H), 2.77 (dd, J = 10.6,
17.15 Hz, 1 H), 2.61–2.04 (m, 4 H), 1.61 (d, J = 13.7 Hz, 1 H,
-OH), 1.52 (d, J = 14.3 Hz, 1 H, -OH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 157.3, 155.9, 138.5–138.1 (m, Ar-C), 136.8, 136.2,
128.6–127.7 (m, Ar-C), 86.0, 85.8, 83.8, 83.6, 78.7, 78.6, 78.3, 78.2,
76.1, 75.6, 75.0, 74.8, 73.5, 73.4, 72.4, 72.1, 69.7, 69.6, 69.2, 69.0,
67.9, 67.4, 67.1, 66.6, 51.1, 50.5, 47.9, 47.0, 41.6, 41.4 ppm. HRMS:
calcd. for C47H51NO9 [M + H]+ 774.3642; found 774.3641.
138.7, 138.6, 138.4, 138.2, 138.0, 130.9, 128.6–127.6 (m, Ar-C),
126.0, 116.2, 81.2, 80.7, 78.1, 76.1, 74.4, 74.2, 73.5, 72.8, 71.7, 70.1,
37.2 ppm. HRMS: calcd. for C40H43NO6 [M + H]+ 634.3169;
found 634.3165.
N-{[(2R,3R,4S,5R,6R)-2-Allyl-3,4,5-tris(benzyloxy)-6-(benzyloxy-
methyl)tetrahydro-2H-pyran-2-yl]methyl}acrylamide (28): Com-
pound 28 was prepared by general procedure C. Yield: 63 %
(550 mg), solid. Rf = 0.30 (hexane/ethyl acetate, 3:2). [α]2D8 = +50.0
(c = 0.55, CH Cl ). IR (neat): ν = 3318, 3030, 2917, 2864, 1663,
˜
2
2
1
1628, 1453 cm–1. H NMR (400 MHz, CDCl3): δ = 7.37–7.19 (m,
20 H, Ar-H), 6.15–6.10 (m, 2 H, -NH, -CH=CH2), 5.91–5.84 (m,
1 H, -CH=CH2), 5.72 (dd, J = 10.2, 16.8 Hz, 1 H, -CH=CHaHb),
5.42 (dd, J = 1.2, 10.2 Hz, 1 H, -CH=CHaHb), 5.12 (br. d, J =
10.2 Hz, 1 H, -CH=CHaHb), 5.03 (br. d, J = 17.0 Hz, 1 H,
-CH=CHaHb), 4.88 (2 d, J = 11.2 Hz, 2 H, PhCH2), 4.81 (2 d, J =
11.0 Hz, 2 H PhCH2), 4.65 (d, J = 11.2 Hz, 1 H, PhCH), 4.59–4.51
(m, 3 H, 3 PhCH), 3.88 (t, J = 9.2 Hz, 1 H), 3.81–3.52 (m, 6 H),
3.39 (t, J = 9.5 Hz, 1 H), 2.50 (dd, J = 5.1, 14.6 Hz, 1 H,
-CHaHbCH=CH2), 2.35 (dd, J = 9.0, 14.6 Hz, 1 H, -CHaHb-
CH=CH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.7, 140.1,
140.0, 139.9, 139.7, 135.0, 132.8, 130.3–129.2 (m, Ar-C), 127.9,
120.7, 86.4, 83.2, 80.8, 79.6, 77.6, 77.1, 76.9, 75.4, 74.8, 71.5, 41.8,
41.3 ppm. HRMS: calcd. for C41H45NO6 [M + H]+ 648.3325;
found 648.3322.
(2R,3S,4S,5R,6R,10R,11S)-2-(Hydroxymethyl)-1-oxa-8-azaspiro[5.6]-
dodecane-3,4,5,10,11-pentaol (25): The benzyl-protected spiro sugar
(75 mg, 0.269 mmol) was dissolved in MeOH (10 mL) and 20%
Pd(OH)2/C (50 mg) and trifluoroacetic acid (0.5 mL) were added.
The reaction mixture was stirred under 50 psi H2 pressure for 3–4 d
at room temperature. The catalyst was filtered off through Celite,
concentrated, and the filtrate was passed through Dowex (50X)
basic resin column to obtain polyhydroxylated spiro azepane 25.
Yield: 76% (21 mg), liquid. [α]2D8 = –60.0 (c = 0.3, MeOH). 1H
NMR (500 MHz, D2O): δ = 4.09 (br. d, J = 9.1 Hz, 1 H), 3.87 (br.
s, 1 H), 3.71–3.69 (m, 1 H), 3.58–3.51 (m, J = 2H Hz), 3.42 (td, J
= 3.0, 9.5 Hz, 1 H), 3.27–3.17 (m, 2 H), 3.14 (dd, J = 2.7, 9.5 Hz,
1 H), 3.01–2.98 (m, 1 H), 2.83–2.78 (m, 2 H), 2.57–2.52 (m, 1 H)
1.38 (d, J = 14.5 Hz, 1 H) ppm. 13C NMR (125 MHz, D2O): δ =
77.2, 76.9, 73.7, 73.1, 72.9, 70.1, 67.7, 61.1, 51.6, 47.9, 39.4 ppm.
HRMS: calcd. for C11H21NO7 [M + H]+ 280.1396; found 280.1398.
(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-2-(benzyloxymethyl)-1-
oxa-8-azaspiro[5.5]undec-10-en-9-one (29): To a stirred solution of
compound 27 (180 mg, 0.284 mmol) in dry CH2Cl2 (3–4 mL) at
room temperature was added the Grubbs 2nd generation catalyst
(12 mg, 0.014 mmol). The mixture was heated at reflux for 24 h,
and after completion of the reaction, the solvent was evaporated
and the residue was purified by column chromatography. Yield:
67% (115 mg), liquid. Rf = 0.20 (hexane/ethyl acetate, 2:3). [α]2D8
+24.0 (c = 0.5, CH Cl ). IR (neat): ν = 3383, 3030, 2922, 2852,
=
˜
2
2
(2R,3R,4S,5R,6R,10R,11S)-2-(Acetoxymethyl)-8-acetyl-1-oxa-8-aza-
spiro[5.6]dodecane-3,4,5,10,11-pentayl pentaacetate (26): Com-
pound 26 was prepared by general procedure B: Yield: 79 %
(32 mg), light yellow oil. Rf = 0.20 (hexane/ethyl acetate, 1:9).
1685, 1619, 1453 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.32–7.13
(m, 20 H, Ar-H), 6.22 (d, J = 9.9 Hz, 1 H, -CH=CH-), 6.0 (d, J =
9.9 Hz, 1 H, -CH=CH-), 5.67 (br. s, 1 H, -NH), 4.83 (m, 2 H,
PhCH2), 4.79 (d, J = 10.7 Hz, 1 H, PhCH), 4.76 (d, J = 11.1 Hz,
1 H, PhCH), 4.64 (d, J = 10.7 Hz, 1 H, PhCH), 4.59 (d, J =
12.3 Hz, 1 H, PhCH), 4.53 (d, J = 10.3 Hz, 1 H, PhCH), 4.49 (d,
J = 12.2 Hz, 1 H, PhCH), 3.84 (d, J = 13.8 Hz, 1 H), 3.72–3.58
(m, 7 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.6, 143.1,
138.2, 138.0, 137.9, 137.5, 128.7–127.8 (m, Ar-C), 127.1, 83.1, 82.8,
78.1, 75.7, 75.6, 75.1, 73.7, 73.5, 72.7, 68.8, 41.3 ppm. HRMS:
calcd. for C38H39NO6 [M + H]+ 606.2856; found 606.2859.
[α]2D8 = +16.0 (c = 0.5, CH Cl ). IR (neat): ν = 2923, 2852, 1746,
˜
2
2
1656, 1370 cm–1. 1H NMR (500 MHz, CDCl3): δ = 5.49 (br. s, 1
H, H-10), 5.33 (t, J = 10.1 Hz, 1 H, H-4), 5.25–5.23 (m, 1 H, H-
11), 5.00 (d, J = 10.0 Hz, 1 H, H-5), 4.99 (t, J = 9.6 Hz, 1 H, H-
3), 4.85 (d, J = 15.1 Hz, 1 H, H-7a), 4.38–4.36 (m, 1 H, H-2), 4.15
(dd, J = 5.0, 12.3 Hz, 1 H, CHOAc), 4.02 (dd, J = 5.9, 15.1 Hz, 1
H, H-9a), 3.97 (dd, J = 2.2, 12.3 Hz, 1 H, CHOAc), 3.26 (dd, J =
5.5, 15.1 Hz, 1 H, H-9b), 3.06 (d, J = 15.1 Hz, 1 H, H-7b), 2.28–
2.23 (m, 1 H, H-7a), 1.77 (d, J = 14.2 Hz, 1 H, H-7a), 2.15 (s, 3
H, COCH3), 2.09 (s, 3 H, COCH3), 2.08 (s, 3 H, COCH3), 2.06 (s,
3 H, COCH3), 2.01 (s, 3 H, COCH3), 1.99 (s, 3 H, COCH3), 1.97
(s, 3 H, COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 171.2,
170.8, 170.2, 169.9, 169.8, 169.7, 169.5, 75.9, 74.8, 71.6, 69.9, 69.5,
(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-2-(benzyloxymethyl)-1-
oxa-8-azaspiro[5.6]dodec-10-en-9-one (30): A procedure similar to
that described for the synthesis of 29 was employed. Yield: 75%
(350 mg, from 488 mg, 0.754 mmol of 28), liquid. Rf = 0.30 (hex-
ane/ethyl acetate, 1:1). [α]2D8 = +29.28 (c = 0.7, CH2Cl2). IR (neat):
68.8, 67.9, 50.4, 45.1, 38.8, 22.1, 21.0–20.7 (m, 6 COCH3) ppm. ν = 3290, 2923, 2854, 2852, 1669, 1621, 1454 cm–1 1H NMR
.
˜
HRMS: calcd. for C25H35NO14 [M + H]+ 574.2136; found
574.2136.
(500 MHz, CDCl3): δ = 7.35–7.13 (m, 20 H, Ar-H), 6.24–6.19 (m,
1 H, CH=CH-), 5.99 (br. s, 1 H, -NH), 5.94 (d, J = 12.0 Hz, 1 H,
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Eur. J. Org. Chem. 2010, 6957–6966