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13
Selected Data: (
Z
)-
N
-(1-Deoxy-2,3:4,5-di-
O
-
iso
propylidene-
d
-
xylo
-1-ylidene)-benzylamine-
N
-oxide(7): Colorless solid, mp 95-97 °C (crystalized from hexanes); total yield 20%; [α]D = +41.3 (CHCl3, c 0.22); 1H NMR (400 MHz, CDCl3): δ = 1.36, 1.38, 1.43, 1.48 [4 × s, 4 × 3 H, C(CH3)2], 3.73 (dd, 1 H, J
4,5a = 6.8 Hz, J
5a,5b = 8.6 Hz, H-5a), 3.95 (dd, 1 H, J
2,3 = 5.9 Hz, J
3,4 = 6.7 Hz, H-3), 4.09 (dd, 1 H, J
4,5b = 6.7 Hz, J
5a,5b = 8.8 Hz, H-5b), 4.40 (q, 1 H, J
3,4 = 6.7 Hz, J
4,5a = J
4,5b = 6.7 Hz, H-4), 4.89 (s, 2 H, NCH2Ph), 5.07 (dd, 1 H, J
1,2 = J
2,3 = 6.2 Hz, H-2), 6.81 (d, 1 H, J
1,2 = 6.0 Hz, H-1), 7.41-4.42 (br s, 5 H, NCH2Ph); 13C NMR (125 MHz, CDCl3): δ = 25.8, 26.8, 27.0, 27.4 [C(CH3)2], 66.1 (C-5), 70.1 (NCH2Ph), 73.6 (C-2), 76.8 (C-4), 81.1 (C-3), 110.1, 111.3 [C(CH3)2], 129.4, 129.5, 129.7, 129.8, 130.0, 132.5 (NCH2Ph), 137.4 (C-1). (
Z
)-
N
-(1-Deoxy-2,3-
O
-
iso
propylidene-4-
O
-benzoyl-5-
O
-
tert
-butyldiphenylsilyl-d-
xylo
-1-ylidene)-benzylamine-
N
-oxide(12): Colorless oil, total yield 15%; [α]D = +9.5 (CHCl3, c 0.22); 1H NMR (400 MHz, CDCl3): δ = 1.04 [s, 9 H, OSiC(CH3)3], 1.39, 1.50 [2 × s, 2 × 3 H, C(CH3)2], 3.99 (dd, 1 H, J
4,5a = 5.7 Hz, J
5a,5b = 10.4 Hz, H-5a), 4.10 (dd, 1 H, H-5b, J
4,5b = 6.1 Hz, J
5a,5b = 10.2 Hz, H-5b), 4.50 (dd, 1 H, J
2,3 = 6.7 Hz, J
3,4 = 3.8 Hz, H-3), 4.86 (s, 2 H, NCH2Ph), 5.23 (dd, 1 H, J
1,2 = J
2,3 = 6.3 Hz, H-2), 5.68 (dt, 1 H, J
3,4 = 3.8 Hz, J
4,5a = J
4,5b = 5.8 Hz, H-4), 6.79 (d, 1 H, J
1,2 = 5.6 Hz, H-1), 7.28-8.11 (m, 20 H, NCH2Ph, OSiPh2); 13C NMR (125 MHz, CDCl3): δ = 19.6 [OSiC(CH3)3], 27.0 [C(CH3)2], 27.2 [OSiC(CH3)3], 27.3 [C(CH3)2], 62.9 (C-5), 69.9 (NCH2Ph), 72.9 (C-2), 74.0 (C-4), 78.6 (C-3), 111.0 [C(CH3)2], 128.0-136.1 (NCH2Ph, OSiPh2), 136.9 (C-1), 166.0 (COPh).
14
Kochetkov NK.
Dmitriev BA.
Tetrahedron
1965,
21:
803
15
Dondoni A.
Franco S.
Junquera F.
Merchan FL.
Merino P.
Tejero T.
Synth. Commun.
1994,
24:
2537
16a
Kaulinja LT.
Lidak MJ.
Khim. Geterotsikl. Soedin.
1987,
94
16b
Zhou J.
Shevlin BP.
Synth. Commun.
1997,
27:
3591
16c
Ciapetti P.
Taddei M.
Tetrahedron
1998,
54:
11305
17
Typical Experimental Procedure: A mixture of nitrone and N-vinylated base was stirred in toluene for 12-24 h under reflux. When starting nitrone had been consumed (TLC), the toluene was evaporated under vacuum and the mixture of isomers was separated by flash column chromatography (silica gel, CHCl3:MeOH = 95: 5).
18 Yields of cycloadditions depended on the numbers of equivalents of the dipolarophiles employed, presumably due to the nitrone’s instability. Nitrone 7 in the absence of dipolarophile was completely decomposed after 24 h in toluene at 110 °C.
19
Selected Data: 1-{(3
S
,5
R
)-2-Benzyl-3-[1,2:3,4-di-
O
-
iso
propylidene-d-
xylo
]isoxazolidine-5-yl}uracil(13a): Colorless solid, mp 187-189 °C (from toluene); yield 33%; [α]D = -52.7 (MeOH, c 0.12); 1H NMR (400 MHz, CDCl3): δ = 1.38, 1.40, 1.41, 1.44 [4 × s, 4 × 3 H, C(CH3)2], 2.60 (ddd, 1 H, J
3,4b = 7.3 Hz, J
4a,4b = 13.7 Hz, J
4b,5 = 3.2 Hz, H-4b), 2.91 (dt, 1 H, J
3,4a = 8.5 Hz, J
4a,4b = 14.3 Hz, J
4a,5 = 8.5 Hz, H-4a), 3.19 (ddd, 1 H, J
1
′
,3 = 2.9 Hz, J
3,4a = 6.9 Hz, J
3,4b = 8.9 Hz, H-3), 3.64 (dd, 1 H, J
1
′
,2
′ and J
2
′
,3
′ = 3.4 Hz and 8.6 Hz, H-2′), 3.87 (t, 1 H, J
3
′
,4
′
a = J
4
′
a,4
′
b = 7.9 Hz, H-4′a), 4.00 (dd; 1 H, J
3
′
,4
′
b = 6.7 Hz, J
4
′
a,4
′
b = 8.2 Hz, H-4′b), 4.04 (d, 1 H, NCH2Ph, J = 14.3 Hz), 4.08-4.13 (m, 2 H, H-1′, H-3′), 4.24 (d, 1 H; NCH2Ph, J = 14.0 Hz), 5.70 (dd, 1 H, J
5
′′
,6
′′ = 8.2 Hz, J
5
′′
,NH = 2.1 Hz, H-5′′), 6.28 (dd, 1 H, J
4a,5 = 7.9 Hz, J
4b,5 = 2.9 Hz, H-5), 7.30-7.40 (m, 5 H, NCH2Ph), 7.96 (d, 1 H, J
5
′′
,6
′′ = 8.2 Hz, H-6′′), 8.81 (s, 1 H, NH); 13C NMR (125 MHz, CDCl3): δ = 25.9, 26.5, 27.3, 27.4 [C(CH3)2], 37.3 (C-4), 61.6 (NCH2Ph), 65.3 (C-3), 66.0 (C-4′), 74.7, 75.1 (C-1′, C-3′), 78.6 (C-2′), 83.3 (C-5), 102.1 (C-5′′), 110.2, 110.5 [C(CH3)2], 128.4, 128.9, 129.1, 129.6, 135.9 (NCH2Ph), 141.7 (C-6′′), 151.0, 163.8 (CO). 1-{(3
S
,5
R
)-2-Benzyl-3-[1,2-
O
-
iso
propylidene-3-
O
-benzoyl-4-
O
-
tert
-butyldiphenylsilyl-d-
xylo
]isoxazolidine-5-yl}uracil(14a): Colorless solid, mp 57-60 °C (purified by column chromatography); yield 40%; [α]D = -30.9 (CHCl3, c 0.13); 1H NMR (400 MHz, CDCl3): δ = 1.04 [s, 9 H, OSiC(CH3)3], 1.32, 1.37 [2 × s, 2 × 3 H, C(CH3)2], 2.61 (ddd, 1 H, J
3,4b = 7.0 Hz, J
4a,4b = 14.0 Hz, J
4b,5 = 3.0 Hz, H-4b), 2.91 (ddd, 1 H, J
3,4a = 9.2 Hz, J
4a,4b = 14.0 Hz, J
4a,5 = 8.0 Hz, H-4a), 3.27 (ddd, 1 H, J
1
′
,3 = 2.4 Hz, J
3,4a = 9.4 Hz, J
3,4b = 7.0 Hz, H-3), 3.84 (dd, 1 H, J
1
′
,2
′ = 8.6 Hz, J
1
′
,3 = 2.6 Hz, H-1′), 3.94 (dd, 1 H, J
3
′
,4
′
a = 6.0 Hz, J
4
′
a,4
′
b = 2.4 Hz, H-4′a), 3.99-4.02 (m; 2 H, H-2′, H-4′b), 4.01 (d, 1 H, NCH2Ph, J = 14.8 Hz), 4.10 (d, 1 H, NCH2Ph, J = 14.0 Hz), 5.35 (dt, 1 H, J
3
′
,4
′
a = 6.0 Hz, J
3
′
,4
′
b = 2.7 Hz, H-3′)5.62 (dd, 1 H, J
5
′′
,6
′′ = 8.4 Hz, J
5
′′
,NH = 2.4 Hz, H-5′′), 6.28 (dd, 1 H, J
4a,5 = 7.8 Hz, J
4b,5 = 3.0 Hz, H-5), 7.20-7.70 and 8.07-8.09 (m, 20 H, NCH2Ph, COPh, OSiPh2), 7.99 (d, 1 H, J
5
′′
,6
′′ = 8.4 Hz, H-6′′), 9.03 (d, 1 H, J
5
′′
,NH = 1.6 Hz, NH); 13C NMR (125 MHz, CDCl3): δ = 19.5 [OSiC(CH3)3], 27.1, 27.3 [C(CH3)2, OSiC(CH3)3], 37.5 (C-4), 61.7 (NCH2Ph), 63.3 (C-4′), 65.7 (C-3), 72.1 (C-3′), 74.5 (C-1′), 77.8 (C-2′), 83.3 (C-5), 102.0 (C-5′′), 110.3 [C(CH3)2], 128.2-141.9 (NCH2Ph, COPh, OSiPh2), 151.0 (C-6′′), 163.8, 166.5 (CO). 9-{(3
S
,5
R
)-2-Benzyl-3-[1,2:3,4-di-
O
-
iso
propylidene-d-
xylo
]isoxazolidine-5-yl}adenine(15a): Colorless solid, mp 59-62 °C (purified by column chromatography); yield 59%; [α]D = -69.4 (CHCl3, c 0.16); 1H NMR (400 MHz, CDCl3): δ = 1.31, 1.39, 1.42, 1.46 [4 × s, 4 × 3 H, C(CH3)2], 2.95 (ddd, 1 H, J
3,4b = 6.8 Hz, J
4a,4b = 13.6 Hz, J
4b,5 = 2.4 Hz, H-4b), 3.04 (ddd, 1 H, J
3,4a = 9.2 Hz, J
4a,4b = 13.6 Hz, J
4a,5 = 8.0 Hz, H-4a), 3.25 (ddd, 1 H, J
1
′
,3 = 2.4 Hz, J
3,4a = 9.2 Hz, J
3,4b = 6.8 Hz, H-3), 3.64 (dd, 1 H, J
1
′
,2
′ = 8.8 Hz and J
2
′
,3
′ = 3.2 Hz, H-2′), 3.87 (dd, 1 H, J
3
′
,4
′
a = 7.2 Hz, J
4
′
a,4
′
b = 8.0 Hz, H-4′a), 3.89 [s, 6 H, N(SO2CH3)2], 4.01 (dd; 1 H, J
3
′
,4
′
b = 6.8 Hz, J
4
′
a,4
′
b = 8.0 Hz, H-4′b), 4.08 (dt, 1 H, J
2
′
,3
′ = 3.6 Hz, J
3
′
,4
′
a and J
3
′
,4
′
b = 6.8 Hz, H-3′) 4.16 (d, 1 H, NCH2Ph, J = 14.0 Hz), 4.17 (dd, 1 H, J
1
′
,3 = 2.4 Hz, J
1
′
,2
′ = 8.4 Hz, H-1′), 4.30 (d, 1 H, NCH2Ph, J = 14.0 Hz), 6.61 (dd, 1 H, J
4a,5 = 8.0 Hz, J
4b,5 = 2.4 Hz, H-5), 7.35-7.36 (m, 5 H, NCH2Ph), 8.88, 8.91 (2 × s, 2 × 1 H, H-adenine); 13C NMR (125 MHz, CDCl3): δ = 25.9, 26.5, 27.2, 27.4 [C(CH3)2], 36.9 (C-4), 45.4 [N(SO2CH3)2], 60.7 (NCH2Ph), 64.9 (C-3), 66.0 (C-4′), 74.5 (C-1′, C-3′), 78.6 (C-2′), 81.0 (C-5), 110.2, 110.6 [C(CH3)2], 128.4, 128.9, 130.0, 130.9, 135.6, 146.5, 154.2 (NCH2Ph, C-adenine), 146.3, 152.3 (CH-adenine). 9-{(3
S
,5
S
)-2-Benzyl-3-[1,2:3,4-di-
O
-
iso
propylidene-d-
xylo
]isoxazolidine-5-yl}adenine(15b): Colorless solid, mp 67-70 °C (purified by column chromatography); yield 10%; [α]D = +13.8 (CHCl3, c 0.05); 1H NMR (400 MHz, CDCl3): δ = 1.42, 1.43, 1.45, 1.47 [4 × s, 4 × 3 H, C(CH3)2], 3.23 (ddd, 1 H, J
3,4a = 4.0 Hz, J
4a,4b = 13.6 Hz, J
4a,5 = 7.6 Hz, H-4a), 3.48 (m, 1 H, H-4b), 3.60 (dd, 1 H, J = 4.2 Hz, J = 7.4 Hz, H-2′), 3.68 (m, 1 H, H-3), 3.90 [s, 6 H, N(SO2CH3)2], 3.86-3.93 (m, 1 H, H-4a′), 4.00 (dd, 1 H, J
3
′
,4
′
b = 6.6 Hz, J
4
′
a,4
′
b = 8.2 Hz, H-4′b) 4.18-4.23 (m, 2 H, H-1′, H-3′), 4.19 (d, 1 H, NCH2Ph, J = 12.4 Hz), 4.26 (d, 1 H; NCH2Ph, J = 12.8 Hz), 6.40 (dd, 1 H, J
4a,5 = 7.6 Hz, J
4b,5 = 5.2 Hz, H-5), 7.27-7.31 (m, 5 H, NCH2Ph), 8.27, 8.92 (2 × s, 2 × 1 H, H-adenine); 13C NMR (75 MHz, CDCl3): δ = 25.7, 26.3, 27.0, 27.4 [C(CH3)2], 35.1 (C-4), 45.0 [N(SO2CH3)2], 61.9 (NCH2Ph), 65.4 (C-3), 65.7 (C-4′), 75.6 (C-1′, C-3′), 79.6 (C-2′), 86.0 (C-5), 109.8, 110.3 [C(CH3)2], 128.2-131.5 (NCH2Ph, C-adenine), 146.8, 153.1 (CH-adenine).
20 Crystallographic data for the structure 13a have been deposited with the Cambridge Crystallographic Data Centre; reference number CCDC 178867(13a). Copies of the data can be obtained on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (email: deposit@ccdc.cam.ac.uk).