2448
A. Zúñiga et al.
PAPER
(4aR,6S,8aR)-2,2-Di-tert-butyl-6-methyltetrahydropyrano[3,2-
d][1,3,2]dioxasilin-8(8aH)-one (5) and (4aR,6R,8aR)-2,2-Di-tert-
butyl-6-methyltetrahydropyrano[3,2-d][1,3,2]dioxasilin-
8(8aH)-one (6)
The mixture of p-tosylhydrazones (373 mg, 0.79 mmol) was dis-
solved in DMF–sulfolane (1:1; 10 mL), and NaBH3CN (200 mg, 3.2
mmol) and PTSA (42 mg, 0.22 mmol) were added. The mixture was
heated at 140 °C for 6 h, then cooled to r.t. and dissolved in EtOAc
(20 mL). The organic phase was washed with H2O (3 × 20 mL) and
brine (3 × 20 mL), then the organic layer was dried over Na2SO4,
filtered and evaporated. The crude material was purified by flash
chromatography (EtOAc–hexane, 2%), affording 7.
To a solution of CuI (4.6 g, 24.27 mmol) in Et2O (30 mL) cooled to
–20 °C, was slowly added a solution of MeLi (1.5 M in THF, 32.36
mL, 48.54 mmol). TMSCl (2.6 g, 24.27 mmol) was added to the last
mixture cooled to –78 °C and stirred for 10 min. A solution of 2 (2.3
g, 8.09 mmol) in Et2O (30 mL) was added using a cannula and the
mixture was stirred for 1 h, quenched with sat. NH4Cl (50 mL) and
extracted with EtOAc (3 × 30 mL). The combined organic phases
were washed with H2O (3 × 50 mL) and brine (3 × 50 mL), dried
over Na2SO4 and the solvent was evaporated under reduced pres-
sure. The residue was purified by chromatography on silica gel
(EtOAc–hexane, 1%), affording 5 and 6.
Yield: 141 mg (62%); colourless liquid; Rf = 0.68 (EtOAc–hexane,
30%); [a]D24 +10.4 (c 0.58, CHCl3).
IR (NaCl): 2966, 2935, 2881, 2860 cm–1.
1H NMR (CDCl3): d = 4.12 (q, J = 6.5 Hz, 1 H, CH-8), 3.99 (dd,
J = 9.8, 4.5 Hz, 1 H, CH2-5), 3.77 (t, J = 9.8 Hz, 1 H, CH2-5), 3.71
(m, 1 H, CH-1), 3.56 (td, J = 9.5, 4.7 Hz, 1 H, CH-6), 1.93 (m, 2 H,
CH2-9), 1.62 (m, 2 H, CH2-10), 1.29 (d, J = 6.3 Hz, 3 H, CH3-8),
1.04 [s, 9 H, C(CH3)3], 1.00 [s, 9 H, C(CH3)3].
13C NMR (CDCl3): d = 74.72 (CH-6), 69.57 (CH-1), 68.72 (CH-8),
67.80 (CH2-5), 28.97 (CH2-9), 27.50 [C(CH3)3], 27.40 (CH2-10),
27.13 [C(CH3)3], 22.65 [C(CH3)3], 19.92 [C(CH3)3], 16.49 (CH3-8).
6
Yield: 3.1 g (71%); colourless oil; Rf = 0.42 (EtOAc–hexane, 30%);
[a]D24 +100.80 (c 1.96, CHCl3).
IR (NaCl): 2968, 2935, 2889, 2860, 1722 cm–1.
1H NMR (CDCl3): d = 4.51 (q, J = 6.8 Hz, 1 H, CH-8), 4.40 (d,
J = 9.5 Hz, 1 H, CH-1), 4.09 (dd, J = 9.7, 4.2 Hz, 1 H, CH2-5), 3.93
(t, J = 9.8 Hz, 1 H, CH2-5), 3.77 (td, J = 9.6, 4.3 Hz, 1 H, CH-6),
2.85 (dd, J = 13, 6.8 Hz, 1 H, CH2-9), 2.28 (d, J = 13.6 Hz, 1 H,
CH2-9), 1.20 (d, J = 6.8 Hz, 3 H, CH3-8), 1.00 [s, 9 H, C(CH3)3],
0.97 [s, 9 H, C(CH3)3].
13C NMR (CDCl3): d = 202.87 (CO-10), 80.31 (CH-1), 71.73 (CH-
6), 71.24 (CH-8), 67.32 (CH2-5), 46.36 (CH2-9), 27.24 [C(CH3)3],
26.89 [C(CH3)3], 22.65 [C(CH3)3], 20.01 [C(CH3)3], 18.32 (CH3-8).
MS (ESI): m/z (%) = 285 (68), 286 (22) [M]+, 287 (39), 307 (100),
309 (58) [M + Na]+.
HRMS (ESI): m/z calcd for C15H31O3Si: 287.1964; found:
287.2037.
(2R,3S,6R)-2-(Hydroxymethyl)-6-methyltetrahydro-2H-pyran-
3-ol (8)
To a solution of 7 (55 mg, 0.19 mmol) in MeCN (2 mL), was added,
dropwise, HF (48% in H2O) until the reaction was complete. Sat.
NaHCO3 was added and the mixture was extracted with EtOAc. The
organic layer was dried over Na2SO4, filtered and evaporated. The
crude material was purified by flash chromatography (EtOAc–hex-
ane, 50%), to afford 8.
MS (ESI): m/z (%) = 285 (14) [M + 1 – O]+, 301 (100) [M + 1]+.
HRMS (ESI): m/z calcd for C15H29O4Si: 301.1757; found:
301.1829.
Yield: 29 mg (99%); yellow oil; Rf = 0.13 (EtOAc); [a]D24 +28.0 (c
5
1.05, CHCl3).
Yield: 435 mg (10%); colourless oil; Rf = 0.50 (EtOAc–hexane,
30%); [a]D24 +1.2 (c 0.32, CHCl3).
IR (NaCl): 3390, 2924, 2852 cm–1.
IR (NaCl): 2968, 2935, 2889, 2860, 1722 cm–1.
1H NMR (CDCl3): d = 4.04 (m, 1 H, CH2-1¢), 3.74 (m, 2 H, CH-
2,4), 3.56 (m, 2 H, CH2-1¢, CH-1), 1.85 (m, 1 H, CH2-6), 1.74 (m,
2 H, CH2-5,6), 1.57 (m, 1 H, CH2-5), 1.25 (d, J = 6.2 Hz, 3 H, CH3-
4).
13C NMR (CDCl3): d = 74.59 (CH-2), 67.69 (CH-4), 67.38 (CH-
C1), 62.84 (CH2-1¢), 28.38 (CH2-6), 27.20 (CH2-5), 17.80 (CH3-4).
1H NMR (CDCl3): d = 4.43 (d, J = 9.3 Hz, 1 H, CH-1), 4.24 (dd,
J = 10.0, 4.7 Hz, 1 H, CH2-5), 3.99 (t, J = 9.8 Hz, 1 H, CH2-5), 3.88
(m, 1 H, CH-8), 3.57 (td, J = 10.1, 4.5 Hz, 1 H, CH-6), 2.51 (m, 1 H,
CH2-5), 2.42 (m, 1 H, CH2-5), 1.30 (d, J = 5.9 Hz, 1 H, CH3-8), 1.04
[s, 9 H, C(CH3)3], 1.00 [s, 9 H, C(CH3)3].
13C NMR (CDCl3): d = 202.62 (CO-10), 79.95 (CH-1), 77.13 (CH-
6), 74.99 (CH-8), 66.87 (CH2-5), 48.99 (CH2-9), 27.35 [C(CH3)3],
26.98 [C(CH3)3], 22.73 [C(CH3)3], 21.67 [C(CH3)3], 20.13 (CH3-8).
MS (ESI): m/z (%) = 129 (11) [M – OH]+, 169 (100) [M + Na]+.
HRMS (ESI): m/z calcd forC7H14NaO3: 169.0841; found: 169.0835.
MS (ESI): m/z (%) = 285 (14) [M + 1 – O]+, 301 (100) [M + 1]+.
[(2R,3S,6R)-3-Hydroxy-6-methyltetrahydro-2H-pyran-2-
yl]methyl-4-methylbenzenesulfonate (9)
HRMS (ESI): m/z calcd for C15H29O4Si: 301.1757; found:
To a solution of 8 (50 mg, 0.34 mmol) in THF (3 mL) at 0 °C, was
added, dropwise, pyridine (1 mL) and the solution was stirred for 10
min. p-TsCl (72 mg, 0.37 mmol) was added and the solution was
stirred at 0 °C for 4 h. Sat. NaHCO3 (10 mL) was added and the
mixture was extracted with EtOAc (10 mL). The organic layer was
washed with H2O (3 × 10 mL) and brine (3 × 10 mL), then the or-
ganic layer was dried over Na2SO4, filtered and evaporated. The
crude material was purified by flash chromatography (EtOAc–
hexane, 30%) to afford 9.
301.1829.
(4aR,6R,8aS)-2,2-Di-tert-butyl-6-methylhexahydropyrano[3,2-
d][1,3,2]dioxasiline (7)
To a solution of 6 (318 mg, 1.06 mmol) in MeOH (10 mL) was add-
ed p-toluenesulfonylhydrazine (217 mg, 1.16 mmol), PTSA (120
mg, 64 mmol) and 4Å MS (90 mg). The mixture was stirred at r.t.
for 18 h, then the MeOH was evaporated under reduced pressure
and the residue was dissolved in CH2Cl2 (15 mL). The organic
phase was washed with H2O (3 × 15 mL) and brine (3 × 15 mL),
then the organic phase was dried over Na2SO4. Filtration and sol-
vent evaporation afforded a residue that was purified by chromatog-
raphy on silica gel (EtOAc–hexane, 20%), affording a mixture of p-
tosylhydrazones [373 mg, 75%, yellow oil, Rf = 0.33 and 0.26 (30%
EtOAc)].
21
Yield: 86 mg (84%); colourless oil; Rf = 0.53 (EtOAc); [a]D
+21.71 (c 0.91, CHCl3).
IR (NaCl): d = 3433, 3033, 2972, 2937, 2871, 1599, 1358 cm–1.
1H NMR (CDCl3): d = 7.80 (d, J = 8.4 Hz, 2 H, CHo-Ts), 7.34 (d,
J = 8.2 Hz, 2 H, CHp-Ts), 4.30 (dd, J = 10.3, 4.7 Hz, 1 H, CH2-1¢),
4.14 (dd, J = 10.3, 2.9 Hz, 1 H, CH2-1¢), 3.96 (m, 1 H, CH-2), 3.64
(m, 1 H, CH-6), 3.57 (m, 1 H, CH-3), 2.44 (s, 1 H, CH3-Ts), 1.84
Synthesis 2010, No. 14, 2446–2450 © Thieme Stuttgart · New York