PAPER
Efficient Route to Deoxy-2-ulosonic Acids
1203
3
(m, 1 H, H-5), 3.90–4.10 (m, 3 H, H-7, H-7¢, H-6), 4.43 (dd, 1 H,
3J4,3 = 7.9 Hz, 3J4,5 = 1.1 Hz, H-4), 5.44 (t, 1 H, 3J3,2 = 3J3,4 = 7.9 Hz,
H-3), 5.91 (d, 1 H, 3J2,3 = 7.9 Hz, H-2).
Hz, 3J4,5 = 2.3 Hz, H-4), 4.45 (ddd, 1 H, 3J6,5 = 7.4 Hz, J6,7b = 6.2
Hz, 3J6,7a = 5.1 Hz, H-6), 4.48 (ddd, 1 H, 3J3,2a = 7.9 Hz, 3J3,2b = 6.0
Hz, 3J3,4 = 5.9 Hz, H-3).
13C NMR (62.8 MHz, CDCl3): d = 16.6 (SCH3), 17.1 (SCH3), 24.3
(CH3), 25.2 (CH3), 26.5 (CH3), 26.8 (CH3), 66.7 (C-7), 70.4 (C-6),
75.5 (C-3), 76.1 (C-4), 76.5 (C-5), 108.3 [C(CH3)2], 109.2
[C(CH3)2], 125.7 (CH=), 138.7 [=C(SMe)2].
13C NMR (62.8 MHz, CDCl3): d = 24.6 (CH2), 25.5 (CH3), 26.1
(CH3), 26.2 (SCH2), 26.9 (CH3), 27.0 (SCH2), 27.7 (CH3), 39.5 (C-
2), 66.8 (C-7), 69.9 (C-3), 71.0 (C-4), 72.0 (C-5), 74.3 (C-6), 85.6
(C-1), 109.2 [C(CH3)2], 109.3 [C(CH3)2].
MS (EI): m/z (%) = 350 [M+], 303, 277, 162, 133 (100), 101.
MS (EI): m/z (%) = 362 [M+], 347, 289, 273, 106, 58 (100).
Anal. Calcd for C15H26O5S2 (350.50): C, 51.40; H, 7.48. Found: C,
51.62; H, 7.46.
Anal. Calcd for C16H26O5S2 (362.51): C, 53.01; H, 7.23. Found: C,
53.09; H, 7.13.
2-(1¢-Deoxy-2¢,3¢,5¢-tri-O-benzyl-D-arabinit-1-ylidene)-1,3-
dithiane (7)
1,2-Dideoxy-3,4:6,7-di-O-isopropylidene-1,1-bis(methylsulfa-
nyl)-D-manno-heptopyranose (4b)
Flash chromatography: PE–EtOAc (90:10).
2,3,5-Tri-O-benzyl-b-D-arabinofuranose was dried by recrystalliza-
tion from a mixture of PE–EtOAc (95:5), followed by co-evapora-
tion with toluene. The reaction with D-arabinose derivative required
the use of 2 equiv of silyl reagent and n-BuLi. Flash chromatogra-
phy: PE–EtOAc (80:20).
Yield: 168 mg (76%); colorless oil; [a]D23 +134.0 (c 0.57, CHCl3).
IR (film): 2985, 1455, 1370, 1058, 510 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.36 (s, 3 H, CH3), 1.39 (s, 3 H,
CH3), 1.45 (s, 3 H, CH3), 1.51 (s, 3 H, CH3), 2.09 (s, 3 H, SCH3),
2.14 (s, 3 H, SCH3), 2.15 (dd, 1 H, 2J2a,2b = 14.6 Hz, 3J2a,3 = 6.1 Hz,
Yield: 1.05 g (83%); colorless oil; [a]D23 –39.1 (c 0.55, CHCl3).
IR (film): 3468 (OH), 3029, 2911, 1578, 1454 cm–1.
2
H-2a), 2.35 (dd, 1 H, J2b,2a = 14.6 Hz, 3J2b,3 = 7.8 Hz, H-2b), 4.03
1H NMR (250 MHz, CDCl3): d = 2.10–2.20 (m, 2 H, CH2 dithiane),
2.70–2.80 (m, 1 H, SCH2), 2.80–2.95 (m, 4 H, 3 H of SCH2 and
OH), 3.55–3.60 (m, 3 H, H-3¢, H-5¢, H-5¢¢), 3.95–4.05 (m, 1 H, H-
2
(dd, 1 H, J7a,7b = 8.8 Hz, J7a,6 = 5.1 Hz, H-7a), 4.05 (dd, 1 H,
3
3
2
3J5,6 = 6.3 Hz, J5,4 = 2.3 Hz, H-5), 4.10 (dd, 1 H, J7b,7a = 8.8 Hz,
3J7b,6 = 6.3 Hz, H-7b), 4.17 (dd, 1 H, J4,3 = 6.1 Hz, J4,5 = 2.3 Hz,
H-4), 4.38 (dt, 1 H, 3J6,7b = 3J6,5 = 6.3 Hz, 3J6,7a = 5.1 Hz, H-6), 4.46
(dt, 1 H, 3J3,2 = 7.8 Hz, 3J3,2¢ = 3J3,4 = 6.1 Hz, H-3).
3
3
2
4¢), 4.39 (d, 1 H, JH,H = 11.8 Hz, OCH2), 4.45–4.55 (m, 4 H, 2
2
OCH2), 4.63 (d, 1 H, JH,H = 11.6 Hz, OCH2), 4.74 (dd, 1 H,
3J2¢,1¢ = 9.1 Hz, 3J2¢,3¢ = 3.8 Hz, H-2¢), 6.03 (d, 3J1¢,2¢ = 9.1 Hz, H-1¢),
7.27–7.31 (m, 15 Harom).
13C NMR (62.8 MHz, CDCl3): d = 11.6 (SCH3), 13.1 (SCH3), 25.5
(CH3), 26.0 (CH3), 26.8 (CH3), 27.9 (CH3), 38.4 (C-2), 66.5 (C-7),
70.6 (C-3, C-4), 71.6 (C-5), 74.5 (C-6), 93.5 (C-1), 109.1
[C(CH3)2], 109.1 [C(CH3)2].
13C NMR (62.8 MHz, CDCl3): d = 24.5 (CH2 dithiane), 29.3
(SCH2), 29.7 (SCH2), 70.5 (C-4¢), 70.9 (OCH2), 71.2 (C-5¢), 73.4
(OCH2), 74.1 (OCH2), 75.5 (C-2¢), 80.4 (C-3¢), 127.6–128.6 (15
CHarom), 128.8 (CH=), 133.1 [=C(SR)2], 138.5 (3 Carom).
MS (EI): m/z (%) = 349 [M+ – 1], 302, 287, 229, 169, 114 (100).
Anal. Calcd for C15H26O5S2 (350.50): C, 51.40; H, 7.48. Found: C,
51.41; H, 7.34.
Anal. Calcd for C30H34O4S2 (522.72): C, 68.93; H, 6.56. Found: C,
68.56; H, 6.86.
1,2-Dideoxy-3,4,5-tri-O-benzyl-1,1-dithianyl-D-arabino-
hexopyranose (8)
Dithioortho Esters 4a,b; General Procedure
To a solution of the ketene dithoacetal 3a,b (0.55 mmol) in anhyd
CH2Cl2 (2.5 mL) was added pyridinium p-toluenesulfonate (PPTS,
0.11 mmol, 0.2 equiv). The resulting mixture was stirred (1.5 h for
3a and 48 h for 3b) at r.t. and extracted with Et2O. The Et2O extract
was washed with aq NaHCO3, brine and dried (MgSO4). After re-
moval of the solvent, the crude product was purified by flash chro-
matography.
A solution of the ketene dithioacetal 7 (200 mg, 0.38 mmol) in 1,2-
dichloroethane (10 mL) was refluxed for 3 h. After cooling, the sol-
vent was evaporated in vacuo. The crude residue was chromato-
graphed over silica gel to give pure dithioortho ester 8. Flash
chromatography: PE–EtOAc (90:10).
Yield: 170 mg (85%); colorless oil; [a]D22 +83.9 (c 0.53, CHCl3).
IR (film): 2913, 1605, 1586, 1496, 1453 cm–1.
1,2-Dideoxy-3,4:6,7-di-O-isopropylidene-1,1-dithianyl-D-man-
no-heptopyranose (4a)
Flash chromatography: PE–EtOAc (85:15).
1H NMR (250 MHz, CDCl3): d = 1.76–1.90 (m, 1 H, H-2a), 1.84
(m, 1 H, 2J2¢ax,2¢eq = 14.0 Hz, H-2¢ax), 2.01 (m, 1 H, 2J2¢eq,2¢ax = 14.0
Hz, H-2¢eq), 2.46 (m, 1 H, H-1¢eq), 2.49 (dd, 1 H, 2J2b,2a = 13.2 Hz,
22
Yield: 177 mg (89%); colorless solid; mp 81 °C; [a]D +110.2
(c 0.55, CHCl3).
2
3J2b,3 = 5.2 Hz, H-2b), 2.59 (m, 1 H, J3¢eq,3¢ax = 14.0 Hz, H-3¢eq),
2.93 (ddd, 1 H, 2J1¢ax,1¢eq = 14.0 Hz, 3J1¢ax,2¢eq = 2.5 Hz, H-1¢ax), 3.42
3
2
(t, 1 H, J4,3 = 3J4,5 = 9.5 Hz, H-4), 3.43 (ddd, 1 H, J3¢ax,3¢eq = 14.0
Hz, H-3¢ax), 3.69 (d, 2 H, 3J6a,5 = 3J6b,5 = 9.5 Hz, H-6a, H-6b), 3.92–
4.00 (m, 2 H, H-3, H-5), 4.47–4.60 (m, 5 H, 3 CH2O), 4.82 (d, 1 H,
2JH,H = 10.9 Hz, CH2O), 7.19–7.28 (m, 15 Harom).
IR (KBr): 2992, 1458, 1375, 1243 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.36 (s, 3 H, CH3), 1.40 (s, 3 H,
CH3), 1.47 (s, 3 H, CH3), 1.51 (s, 3 H, CH3), 1.97 (dtt, 1 H,
2J2¢ax,2¢eq = 14.0 Hz, 3J2¢ax,1¢ax = 3J2¢ax,3¢ax = 12.8 Hz, 3J2¢ax,3¢eq = 3.1 Hz,
13C NMR (62.8 MHz, CDCl3): d = 25.2 (CH2 dithiane), 25.8 (CH2
dithiane), 27.4 (CH2 dithiane), 42.5 (C-2), 69.3 (CH2Ph), 71.9
(CH2Ph), 73.2 (CH2Ph), 74.7 (CH), 74.9 (C-6), 77.1 (CH), 78.5
(CH), 86.0 (C-1), 127.5–128.4 (15 CHarom), 138.1–138.6 (Carom).
2
3J2¢ax,1¢eq = 3.0 Hz, H-2¢ax), 2.04 (dd, 1 H, J2a,2b = 14.3 Hz,
2
3J2a,3 = 7.9 Hz, H-2a), 2.13 (dquint, 1 H, J2¢eq,2¢ax = 14.0 Hz,
3J2¢eq,1¢ax = 3J2¢eq,1¢eq = 3J2¢eq,3¢ax = 3J2¢eq,3¢eq = 2.8 Hz, H-2¢eq), 2.16 (dd,
2
3
1 H, J2b,2a = 14.3 Hz, J2b,3 = 6.0 Hz, H-2b), 2.60 (dt, 1 H,
2J1¢eq,1¢ax = 14.0 Hz, 3J1¢eq,2¢ax = 3J1¢eq,2¢eq = 3.0 Hz, H-1¢eq), 2.66 (dt, 1
Anal. Calcd for C30H34O4S2 (522.72): C, 68.93; H, 6.56. Found: C,
68.71; H, 6.94.
2
3
H, J3¢eq,3¢ax = 14.0 Hz, J3¢eq,2¢ax = 3J3¢eq,2¢eq = 3.1 Hz, H-3¢eq), 3.00
(ddd, 1 H, 2J1ax,1¢eq = 14.0 Hz, 3J1¢ax,2¢ax = 12.8 Hz, 3J1¢ax,2¢eq = 2.6 Hz,
2
H-1¢ax), 3.40 (ddd, 1 H, J3¢ax,3¢eq = 14.0 Hz, J3¢ax,2¢ax = 12,8 Hz,
3
Lactones 5 and 6; General Procedure
3J3¢ax,2¢eq = 2.7 Hz, H-3¢ax), 3.97 (dd, 1 H, J5,6 = 7.4 Hz, 3J5,4 = 2.3
3
CaCO3 (0.83 mmol, 3 equiv) and I2 (0.83 mmol, 3 equiv) were add-
ed successively to a solution of the dithioortho ester (0.28 mmol) in
a mixture of THF–H2O (4:1, 5 mL). The mixture was stirred at r.t.
Hz, H-5), 4,08 (dd, 1 H, 2J7a,7b = 8.6 Hz, 3J7a,6 = 5.1 Hz, H-7a), 4.16
(dd, 1 H, 2J7b,7a = 8.6 Hz, 3J7b,6 = 6.2 Hz, H-7b), 4.20 (dd, 3J4,3 = 5.9
Synthesis 2006, No. 7, 1200–1204 © Thieme Stuttgart · New York