8952
I. McCort et al. / Tetrahedron 58 (2002) 8947–8955
was taken up in water (55 mL) and extracted with CH2Cl2
(3£130 mL). The organic layer was dried over Na2SO4,
evaporated then purified by column chromatography
(cyclohexane/EtOAc, 2:1 then 1:1), providing 8 (0.625 g,
7%) as a foam, and 9 (3.58 g, 58%) and 10 (0.49 g, 8%) as
solids.
4.3.1.1. (1S,10S)-2,3-Bis(1-hydroxy-2-p-toluenesul-
fonyloxy-ethyl)quinoxaline (8). Rf 0.49 (cyclohexane/
EtOAc, 1:1); [a]D20¼28.5 (c 1.0, CHCl3). 1H NMR
(CDCl3) d 2.35 (s, 6H, CH3), 3.91 (d, 3J¼7.5 Hz, 2H,
D2O exchangeable, OH), 4.43 (ABX, JAB¼10.5 Hz,
JAX¼6.1 Hz, JBX¼5.2 Hz, Dd¼0.05, 4H, CH2), 5.31
(ABX, JAX¼JBX¼5.8 Hz, 3J¼7.3 Hz, 2H, CH), 7.17 (d,
3J¼8.2 Hz, 4H, HaromTs), 7.64 (d, 3J¼8.2 Hz, 4H, HaromTs),
7.7–7.9 (m, 2H, Harom), 7.9–8.1 (m, 2H, Harom); 13C NMR
(CDCl3) d 21.6 (CH3), 68.0 (CH), 72.6 (CH2), 127.8, 128.8,
129.8, 130.8 (CHarom), 132.3, 140.7, 145.0, 150.9 (Cqarom);
FABþ m/z: 559 (MHþ, 100%).
4.3.2.1. (1S,10S)-2-(1-Hydroxy-2-p-toluenesulfonyl-
oxyethyl)-3-(2-hydroxy-1-p-toluenesulfonyloxyethyl)-
1
quinoxaline (11). Rf 0.38 (cyclohexane/EtOAc, 1:1); H
NMR (CDCl3) d 2.38, 2.44 (2s, 6H, CH3), 2.86 (m, 1H,
CH2OH), 3.61 (d, 3J¼5.5 Hz, 1H, CHOH), 4.0–4.4 (m, 2H,
2
3
CH2OH), 4.60 (dd, J¼10.8 Hz, J¼7.4 Hz, 1H, CH2OTs),
2
3
4.80 (dd, J¼10.8 Hz, J¼3.3 Hz, 1H, CH2OTs), 5.49 (m,
3
1H, CHOH), 6.18 (dd, J¼5.8, 4.7 Hz, 1H, CHOTs), 7.13,
3
7.33, 7.68, 7.84 (4d, J¼8.1 Hz, 8H, HaromTs), 7.7–8.1 (m,
4H, Harom); 13C NMR dept (CDCl3) d 21.7 (CH3), 63.9
(CH2OH), 68.7 (CHOH), 72.2 (CH2OTs), 78.7 (CHOTs),
127.8, 128.0, 128.8, 129.1, 129.6, 129.9, 130.7, 131.0
(CHarom); FABþ m/z: 559 (MHþ, 100%).
4.4. Reaction of ditosylate 8 with sodium azide
Ditosylate 8 (1.27 g, 2.27 mmol) in DMF (40 mL) was
treated with sodium azide (1.18 g, 18.16 mmol). After
stirring at 708C for 4 h, the solvent was removed in vacuo.
CH2Cl2 (60 mL) and water (12 mL) were added and the
mixture extracted with CH2Cl2 (3£60 mL). The extracts
were dried over Na2SO4, evaporated then purified by
column chromatography (cyclohexane/EtOAc, 2:8 to 1:1),
affording 12 (464 mg, 68%) and 13 (70 mg, 12%) as solids.
4.3.1.2. (1S,4S)-4-Hydroxy-1-(p-toluenesulfonyloxy-
methyl)-3,4-dihydro-1H-pyrano[3,4-b]quinoxaline (9).
Rf 0.23 (cyclohexane/EtOAc, 1:1), mp 1318C; [a]2D0¼þ81
(c 1.0, CH2Cl2). 1H NMR (CDCl3) d 2.37 (s, 3H, CH3), 3.26
(d, 3J¼5.0 Hz, 1H, D2O exchangeable, OH), 4.12 (dd,
3
2
2J¼12.3 Hz, J¼3.9 Hz, 1H, CHax), 4.26 (dd, J¼12.3 Hz,
3J¼3.9 Hz, 1H, CHeq), 4.66 (dd, J¼10.8 Hz, J¼5.6 Hz,
2
3
1H, CH2OTs), 4.86 (m, 1H, CHOH), 4.91 (dd, 2J¼10.9 Hz,
4.4.1. (1R,10R)-2,3-Bis(1-hydroxy-2-azido-ethyl)quinoxa-
line (12). Rf 0.6 (cyclohexane/EtOAc, 1:1), mp 988C;
[a]2D0¼þ195.5 (c 1.0, CH2Cl2). 1H NMR (CDCl3) d 3.75 (d,
3J¼5.5 Hz, 4H, CH2), 4.15 (d, 3J¼7.8 Hz, 2H, D2O
exchangeable, OH), 5.26 (dt, 3J¼7.8, 5.5 Hz, 2H, CH),
7.7–7.9 (m, 2H, Harom), 8.0–8.2 (m, 2H, Harom); 13C NMR
(CDCl3) d 56.5 (CH2), 69.8 (CH), 128.8, 131.0 (CHarom),
140.8, 151.6 (Cqarom); HRMS calcd for C12H13N8O2 (MHþ)
301.1161, found 301.1155.
3J¼2.3 Hz, 1H, CH2OTs), 5.11 (dd, J¼5.5, 2.3 Hz, 1H,
3
OCH), 7.20 (d, 3J¼8.0 Hz, 2H, HaromTs), 7.68 (d,
3J¼8.0 Hz, 2H, HaromTs), 7.7–8.0 (m, 3H, Harom), 8.0–8.2
(m, 1H, Harom); 13C NMR (CDCl3) d 21.4 (CH3), 66.9
(CHOH), 68.9, 70.6 (CH2), 76.2 (OCH), 127.6, 128.6,
128.9, 129.5, 130.2 (CHarom), 132.5, 141.2, 141.5, 144.6,
148.5, 150.6 (Cqarom); FABþ m/z: 387 (MHþ, 100%).
4.3.1.3. (1R,4S)-4-Hydroxy-1-(p-toluenesulfonyloxy-
methyl)-3,4-dihydro-1H-pyrano[3,4-b]quinoxaline (10).
Rf 0.34 (cyclohexane/EtOAc, 1:1), mp 1138C; [a]2D0¼þ15
(c 1.0, CH2Cl2). 1H NMR (CDCl3) d 2.34 (s, 3H, CH3), 3.70
(dd, 2J¼11.2 Hz, 3J¼9.8 Hz, 1H, CHax), 4.22 (brs, 1H, D2O
4.4.2. (1R,4S)-1-Azidomethyl-4-hydroxy-3,4-dihydro-
1H-pyrano[3,4-b]quinoxaline (13). Rf 0.4 (cyclohexane/
EtOAc, 1:1), mp 898C; [a]2D0¼þ115 (c 1.0, CH2Cl2).1H
NMR (CDCl3) d 3.27 (brs, 1H, D2O exchangeable, OH),
4.02 (ABX, JAB¼13.0 Hz, JAX¼6.2 Hz, JBX¼3.1 Hz,
2
3
exchangeable, OH), 4.45 (dd, J¼11.3 Hz, J¼6.0 Hz, 1H,
2
3
CHeq), 4.61 (dd, J¼10.7 Hz, J¼5.1 Hz, 1H, CH2OTs),
2
3
2
3
4.79 (dd, J¼10.7 Hz, J¼2.4 Hz, 1H, CH2OTs), 5.0 (dd,
Dd¼0.08, 2H, CH2N3), 4.19 (dd, J¼12.4 Hz, J¼3.0 Hz,
1H, CH2O), 4.38 (dd, 2J¼12.4 Hz, 3J¼3.5 Hz, 1H, CH2O),
4.91 (m, 1H, CHOH), 5.09 (ABX, JAX¼6.2 Hz,
JBX¼3.1 Hz, 1H, CHO), 7.7–7.9 (m, 2H, Harom), 8.0–8.2
(m, 2H, Harom); 13C NMR (CDCl3) d 53.6 (CH2N3), 67.5
(CH), 69.0 (CH2O), 78.0 (CHOH), 129.0, 129.1, 130.4
130.7 (CHarom), 141.7, 142.1, 149.9, 150.5 (Cqarom); CIMS
(NH3) m/z: 258 (MHþ, 100%).
2J¼9.7 Hz, 3J¼6.0 Hz, 1H, CHOH), 5.07 (dd, 3J¼5.1,
3
2.3 Hz, 1H, OCH), 7.15 (d, J¼8.0 Hz, 2H, HaromTs), 7.62
(d, 3J¼8.0 Hz, 2H, HaromTs), 7.7–7.9 (m, 3H, Harom),
8.0–8.2 (m, 1H, Harom); 13C NMR (CDCl3) d 21.6
(CH3), 65.9 (CHOH), 68.6, 71.0 (CH2), 77.2 (OCH),
127.9, 128.6, 129.0, 129.7, 130.2 (CHarom), 132.8, 141.0,
141.5, 144.7, 148.5, 152.7 (Cqarom); FABþ m/z: 387 (MHþ,
100%).
4.5. Reaction of diazidodiol 12 with triphenylphosphine
4.3.2. Through organotin derivative in catalytic con-
ditions. To a suspension of tetraol 7 (2.08 g, 8.31 mmol) in
dry THF (40 mL) was added (CH3)2SnCl2 (36.5 mg,
0.166 mmol) and K2CO3 (4.6 g, 33.24 mmol). A solution
of tosyl chloride (3.25 g, 17.03 mmol) in THF (10 mL) was
added under argon at 08C. After stirring the mixture 4 h at
this temperature then overnight at room temperature, water
was added (30 mL) and the residue extracted with CH2Cl2
(50 mL). The combined organic layers were washed with a
saturated aqueous NH4Cl solution, dried (Na2SO4) and
concentrated in vacuo. Purification by column chromato-
graphy (cyclohexane/EtOAc, 1:1) afforded 8 (3.48 g, 75%)
and 11 (0.87 g, 19%) as foams.
A solution of diazidodiol 12 (0.233 g, 0.776 mmol) and
triphenylphosphine (0.407 g, 1.552 mmol) in dry THF
(12 mL) was stirred and refluxed under argon until complete
transformation of the bis-iminophosphorane into the NH-
bis-aziridine (monitored by TLC using EtOH/CH2Cl2, 7:3
as eluent with Rf 0.0 and Rf 0.25, respectively). After
evaporation to dryness, the crude residue containing 4a was
protected without further purification.
4.6. Protection with di-tert-butyldicarbonate
To a solution of the above residue 4a (0.776 mmol) in THF