D. Declerck et al. / Tetrahedron 68 (2012) 1145e1152
1151
(C4), 73.4 (C5), 71.9 (C
D
), 67.8 (CH2Ph), 52.7 (C3), 32.6 (NCH3), 26.8
a]imidazole])] (9a). Compound 9a has been prepared starting from
100 mg of 5a (0.27 mmol), 130 L of Ti(Oi-Pr)3Me, 370 L of
EtMgBr (1.5 M), 70 L of BF3$Et2O, and 1.5 mL of THF and obtained
as syrup in 21% yield after purification with cyclohexane/EtOAc
(CH3), 26.3 (CH3), 11.2 (CH2D), 10.7 (CH2D); ES-HRMS for
m
m
C26H31N2O4 [MþH]þ calcd 435.2284, found 435.2282.
m
20
4.8.2. Spiro[3-deoxy-1,2-isopropylidene-5-O-methyl-
anose-3,30-(30-hydro-40-methyl-50-phenyl-spiro[cyclopropane-1,20-
pyrrolo[1,2-a]imidazole])] (8b). Compound 8b has been prepared
starting from 201 mg of 3b (0.58 mmol), 208
a
-
D
-ribofur-
75:25. [
1454, 734, 704 cmꢀ1
5H, C6H5), 5.43 (d, 1H, H1, J¼3.5), 4.55 (d, 1H, H2, J¼3.5), 4.53e4.45
a
]
ꢀ48.5 (c 1.05, CHCl3); IR (ATR):
n
2987, 1631, 1512,
D
;
1H NMR (CDCl3, 300 MHz):
d
7.36e7.26 (m,
mL of Ti(Oi-Pr)3Me,
(m, 3H, H4þCH2Ph), 4.12 (t, 1H, H5a, J¼9.0), 3.88 (dd, 1H, H5b
,
440 L of EtMgBr (2.0 M), 150 L of BF3$Et2O, and 7.5 mL of THF
m
m
J¼4.2e9.0), 3.65 (td, 1H, CH2, J¼2.8e8.5), 3.45 (q, 1H, CH2, J¼8.5),
2.66e2.51 (m, 1H, CH2), 2.12e2.03 (m, 2H, CH2), 1.89e1.82 (m, 2H,
CH2þ1H, CH2D), 1.58 (s, 3H, CH3), 1.40e1.34 (m, 1H, CH2D), 1.33 (s,
3H, CH3), 1.28e1.17 (m, 1H, CH2D), 0.77e0.69 (m, 1H, CH2D); 13C
and obtained as syrup in 32% yield after purification with EtOAc.
[
a]
16 ꢀ22.3 (c 1.00, CHCl3); IR (ATR):
n
2947, 1618, 1599, 1499, 1458,
D
1371, 1086, 1067, 775, 710 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
d
7.48e7.45 (m, 2H, C6H5), 7.39e7.37 (m, 3H, C6H5), 5.43 (d, 1H, H1,
NMR (CDCl3, 75 MHz):
128.6e128.1 (CH, C6H5), 113.5 (Ciso), 102.9 (C1), 83.5 (C2), 74.0
(CH2Ph), 73.6 (C4), 71.4 (C3), 67.0 (C5), 52.6 (C ), 45.4 (CH2), 26.6
d , C6H5),
176.5 (NeC]N), 137.6 (CIV
J¼3.4), 4.61 (d, 1H, H4, J¼4.2), 4.59 (d, 1H, H2, J¼3.4), 3.88e3.85 (m,
2H, H5), 3.37 (s, 3H, OCH3), 2.98 (s, 3H, NCH3), 1.57 (s, 3H, CH3),
1.33 (s, 3H, CH3), 1.32e1.19 (m, 1H, CH2D), 1.13e1.10 (m, 1H, CH2D),
0.90e0.84 (m, 1H, CH2D), 0.77e0.71 (m, 1H, CH2D); 13C NMR
D
(CH3), 26.3 (CH3), 25.2 (CH2), 23.7 (CH2), 8.8 (CH2D), 6.8 (CH2D);
ES-MS [MþH]þ m/z 385.
(CDCl3, 75 MHz):
(CH, C6H5), 112.9 (Ciso), 103.2 (C1), 84.7 (C4), 76.5 (C2), 71.8 (C3),
d
165.7 (NeC]N), 131.2 (CIV, C6H5), 129.7e128.3
4.8.6. Spiro[5-O-tert-butyldimethysilyl-3-deoxy-1,2-isopropylidene-
a-D
-ribofuranose-3,30-(30,50,60,70-tetrahydrospiro[cyclopropane-1,20-
70.4 (C5), 59.3 (OCH3), 52.6 (C
D), 32.6 (NCH3), 26.7 (CH3), 26.3
(CH3), 11.2 (CH2D), 10.7 (CH2D); ES-HRMS for C20H27N2O4 [MþH]þ
pyrrolo[1,2-a]imidazole])] (9c). Compound 9c has been prepared
starting from 252 mg of 5c (0.64 mmol), 227 L of Ti(Oi-Pr)3Me,
355 L of EtMgBr (2.7 M), 160 L of BF3$Et2O, and 25 mL of THF and
calcd 359.1971, found 359.1960.
m
m
m
4.8.3. Spiro[5-O-tert-butyldimethylsilyl-3-deoxy-1,2-isopropylidene-
obtained as syrup in 11% yield after purification with cyclohexane/
a
-
D
-ribofuranose-3,30-(30-hydro-40-methyl-50-phenyl-spiro[cyclopro-
EtOAc 85:15. [
a
]
20 ꢀ45.2 (c 0.72, CHCl3); IR (ATR):
n
3017,1375, 1187,
pane-1,20-pyrrolo[1,2-a]imidazole])] (8c). Compound 8c has been
prepared starting from 200 mg of 3c (0.45 mmol), 160 L of Ti(Oi-
Pr)3Me, 340 L of EtMgBr (2.0 M), 115 L of BF3$Et2O, and 20 mL of
THF and obtained as syrup in 26% yield after purification with
1094, 1073 cmꢀD1
; d 5.46 (d, 1H, H1,
1H NMR (CDCl3, 300 MHz):
m
J¼3.5), 4.63 (d, 1H, H2, J¼3.5), 4.41 (dd, 1H, H4, J¼4.1e8.0), 4.27 (dd,
1H, H5a, J¼8.0e10.5), 3.97 (dd, 1H, H5b, J¼4.1e10.5), 3.84 (td, 1H,
CH2, J¼3.7e8.2), 3.62 (q, 1H, CH2, J¼8.2), 2.92 (ddd, 1H, CH2,
J¼4.7e8.6e19.0), 2.82e2.65 (m, 1H, CH2), 2.42e2.33 (m, 2H, CH2),
1.89e1.70 (m, 1H, CH2D), 1.62 (s, 3H, CH3), 1.54e1.41 (m, 1H, CH2D),
1.37 (s, 3H, CH3), 1.21e1.09 (m, 1H, CH2D), 0.94 (s, 9H, OTBDMS),
0.79e0.68 (m, 1H, CH2D), 0.14 (s, 3H, OTBDMS), 0.11 (s, 3H,
m
m
20
cyclohexane/EtOAc 6:4. [
2988, 1581, 1517, 1455, 1114, 743, 698 cmꢀ1
300 MHz): 7.51e7.48 (m, 2H, C6H5), 7.39e7.37 (m, 3H, C6H5),
5.43 (d, 1H, H1, J¼3.5), 4.60 (d, 1H, H2, J¼3.5), 4.54 (t, 1H, H4,
a
]
ꢀ23.7 (c 1.00, CHCl3); IR (ATR):
n
D
;
1H NMR (CDCl3,
d
J¼5.4), 4.13 (dd, 1H, H5a
,
J¼5.4e11.5), 4.05 (dd, 1H, H5b
,
OTBDMS); 13C NMR (CDCl3, 75 MHz):
102.7 (C1), 83.9 (C2), 76.5 (C4), 70.8 (C3), 60.1 (C5), 45.4 (CH2), 29.7
d 175.2 (NeC]N), 113.4 (Ciso),
J¼5.4e11.5), 3.01 (s, 3H, NCH3), 1.60 (s, 3H, CH3), 1.35 (s, 3H, CH3),
1.25e1.07 (m, 2H, CH2D), 0.95e0.80 (m, 1H, CH2D), 0.86 (s, 9H,
OTBDMS), 0.75e0.65 (m, 1H, CH2D), 0.07 (s, 3H, OTBDMS), 0.05 (s,
(CD), 26.6 (CH3), 26.2 (CH3), 26.0 (OTBDMS), 25.4 (CH2), 23.7 (CH2),
18.5 (CIV, OTBDMS), 8.0 (CH2D), 7.2 (CH2D); ES-HRMS for
C21H37N2O4Si [MþH]þ calcd 409.2523, found 409.2513.
3H, OTBDMS); 13C NMR (CDCl3, 75 MHz):
d
165.6 (NeC]N), 131.2
(CIV, C6H5), 129.7e128.3 (CH, C6H5), 112.7 (Ciso), 103.0 (C1), 85.3
(C2), 78.6 (C4), 71.8 (C3), 61.2 (C5), 52.8 (C
D
), 32.8 (NCH3), 26.7
4.8.7. Spiro[3-deoxy-1,2:5,6-di-O-isopropylidene-a-D-allofuranose-
(CH3), 26.4 (CH3), 26.0 (CH3, OTBDMS), 18.4 (CIV, OTBDMS), 11.3
(CH2D), 10.9 (CH2D); ES-HRMS for C25H39N2O4Si [MþH]þ calcd
459.2679, found 459.2663.
3,30-(30,50,60,70-tetrahydrospiro[cyclopropane-1,20-pyrrolo[1,2-a]imid-
azole])] (9d). Compound 9d has been prepared starting from
500 mg of 5d (1.42 mmol), 510
EtMgBr (2.2 M), 360 L of BF3$Et2O, and 30 mL of THF and obtained
as syrup in 28% yield after purification with cyclohexane/EtOAc
mL of Ti(Oi-Pr)3Me, 1.0 mL of
m
4.8.4. Spiro[3-deoxy-1,2:5,6-di-O-isopropylidene-a-D-allofuranose-
3,30-(30-hydro-40-methyl-50-phenyl-spiro[cyclopropane-1,20-pyrrolo
[1,2-a]imidazole])] (8d). Compound 8d has been prepared starting
20
75:25. [
a
]
ꢀ59.4 (c 1.05, CHCl3); IR (ATR):
n 3025, 1626,
D
1065 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
d
5.41 (d, 1H, H1, J¼3.3),
from 1.0 g of 3d (2.49 mmol), 900
mL of Ti(Oi-Pr)3Me, 1.7 mL of
4.68 (dt, 1H, H5, J¼6.5e9.4), 4.56 (d,1H, H2, J¼3.3), 4.17 (dd,1H, H6a
,
EtMgBr (2.2 M), 630 L of BF3$Et2O, and 50 mL of THF and ob-
m
J¼6.5e8.5), 4.11 (d, 1H, H4, J¼9.4), 3.80 (dd, 1H, H6b, J¼6.5e8.5),
3.75e3.70 (m, 1H, CH2), 3.55 (q, 1H, CH2, J¼8.5), 2.85 (dt, 1H, CH2,
J¼6.2e18.6), 2.66e2.59 (m, 1H, CH2), 2.34e2.27 (m, 2H, CH2),
1.87e1.82 (m, 1H, CH2D), 1.55 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.33 (s,
3H, CH3), 1.32 (m, 4H, CH3þ1H, CH2D), 1.19e1.13 (m, 1H, CH2D),
tained as syrup in 60% yield after purification with cyclohexane/
EtOAc 3:7. [
a
]
20 ꢀ34.8 (c 0.70, CHCl3); IR (ATR):
n
2985, 1371, 1063,
729, 700 cmꢀD1
; d 7.44e7.41 (m, 2H,
1H NMR (CDCl3, 300 MHz):
C6H5), 7.35e7.32 (m, 3H, C6H5), 5.31 (d, 1H, H1, J¼3.4), 4.70 (td, 1H,
H5, J¼6.4e8.9), 4.58 (d, 1H, H2, J¼3.4), 4.29 (d, 1H, H4, J¼8.9), 4.14
(dd, 1H, H6a, J¼6.4e8.5), 3.85 (dd, 1H, H6b, J¼6.4e8.5), 2.91 (s, 3H,
NCH3), 1.55 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.30 (s,
3H, CH3), 1.23e1.16 (m, 2H, CH2D), 0.83e0.71 (m, 2H, CH2D); 13C
0.82e0.77 (m, 1H, CH2D); 13C NMR (CDCl3, 75 MHz):
d 177.1
(NeC]N), 113.6 (Ciso), 109.9 (Ciso), 103.0 (C1), 82.9 (C2), 76.4 (C4),
71.4 (C ), 71.5 (C5), 68.6 (C6), 52.5 (C3), 45.3 (CH2), 26.6 (CH3), 26.5
D
(CH3), 26.2 (CH3), 25.5 (CH2), 24.6 (CH2), 23.8 (CH2), 8.61 (CH2D),
6.5 (CH2D); ES-HRMS for C19H28N2O5Na [MþNa]þ calcd 387.1896,
found 387.1898.
NMR (CDCl3, 75 MHz):
129.3e128.3 (CH, C6H5), 113.1 (Ciso), 109.6 (Ciso), 102.9 (C1), 81.1
(C2), 77.0 (C4), 72.2 (C5), 71.8 (C ), 68.6 (C6), 52.4 (C3), 32.5 (NCH3),
d
166.6 (NeC]N), 131.9 (CIV, C6H5),
D
26.9 (CH3), 26.6 (CH3), 26.3 (CH3), 25.4 (CH3), 10.2 (CH2D), 9.9
(CH2D); ES-HRMS for C23H31N2O5 [MþH]þ calcd 415.2233, found
415.2236.
4.8.8. Spiro[5-O-tert-butyldimethysilyl-3-deoxy-1,2-isopropylidene-
a-D
-ribofuranose-3,30-(30,50,60,70-tetrahydro-20-ethylidene-pyrrolo
[1,2-a]imidazole)] (10c). Compound 10c has been prepared start-
ing from 252 mg of 5c (0.64 mmol), 227 L of Ti(Oi-Pr)3Me, 355
of EtMgBr (2.7 M), 160 L of BF3$Et2O, and 25 mL of THF and ob-
tained as syrup in 9% yield after purification with cyclohexane/
m
mL
4.8.5. Spiro[5-O-benzyl-3-deoxy-1,2-isopropylidene-
a
-
D
-ribofur-
m
anose-3,30-(30,50,60,70-tetrahydrospiro[cyclopropane-1,20-pyrrolo[1,2-