=
=
the alcohol as a 1 : 1 mixture of diastereomers (2.13 g, 80%). IR
(CH2Cl2, cast) 3490, 2986, 2953, 2892, 1456, 1418 cm−1; 1H NMR
(CDCl3, 300 MHz) d 3.81–3.95 (3H, m, CH2OC + CHOC), 1.44
(3H, s, C(CH3)2), 1.38 (3H, s, C(CH3)2), 1.14 (3H, s, CH3COH)
1.07 (1H, d, J = 14.7 Hz, CH2Si), 0.93 (1H, d, J = 14.7 Hz, CH2Si),
0.87 (1H, d, J = 14.7 Hz, CH2Si), 0.72 (1H, d, J = 14.7 Hz, CH2Si),
0.1 (9H, s, Si(CH3)3), 0.07 (9H, s, Si(CH3)3); 13C NMR (CDCl3,
100 MHz) d 109.4, 109.3, 83.3, 83.2, 72.2, 65.3 (2C), 30.2, 27.4,
26.7, 26.5, 25.5, 25.4, 24.5, 0.6 (3C), 0.5 (3C); HRMS (ES +ve)
calcd for [M + Na]+ C11H24O3SiNa 255.1387, found 255.1386.
300 MHz) d 5.18 (m, 1H, C CH2), 5.03 (m, 1H, C CH2), 2.88
(t, 1H, J = 4.2 Hz, CHCH2), 2.73 (dd, 1H, J = 5.3 Hz, 2.7 Hz,
13
=
CHCH2), 2.47 (m, 1H, CHCH2), 1.64 (s, 3H, C CCH3); C NMR
(CDCl3, 125 MHz) d 141.5, 114.6, 54.5, 46.8, 16.2; HRMS (EI)
calcd for [M+ ] C5H8O 84.0575, found 84.0563, 69 (35%).
•
(2S)-[2-2H1]-Isopentenol43
To a stirring solution of (R)-2-isopropenyl oxirane, sodium
cyanoborodeuteride (167 mg, 2.54 mmol) and a small amount
bromocresol green (5 mg) in Et2O (5 ml) was added dropwise a
BF3–etherate solution until the color of the solution was observed
to be yellow. The resulting mixture was stirred at room temperature
for 5 h and additional amounts of BF3–etherate were added
periodically to keep the solution acidic. The solution was diluted
with brine and extracted with Et2O (3 × 15 mL). The combined
ethereal extracts were◦dried over MgSO4 and evaporation of the
solvent in vacuo at 0 C gave the deuterio alcohol as a colorless
liquid. The volatile alcohol was partially characterized and used
(2R)-3-Methyl-3-butene-1,2-diol (14)
A
stirring solution of (2S)-3-(trimethylsilyl)methyl-1,2,3-
butanetriol-1,2-acetonide (1.19 g, 5.12 mmol) in EtOH (16 mL)
was treated with 3 M HCl (0.5 mL) and the mixture was refluxed
for 2 h. After cooling to room temperature the solution was
neutralized with the slow addition of solid NaHCO3. The
precipitated solids were filtered, washed with EtOH, and the
filtrate was concentrated in vacuo. The resulting residue was
re-dissolved in MeOH and treated with Et2O (50 mL). The
precipitated solids were filtered and the solvent was evaporated
in vacuo which afforded the title compound 14 as a colorless oil
(390 mg, 75%). [a]D20 = −15.7◦ (c 1.4, CH2Cl2); IR (CH2Cl2, cast)
3373, 3075, 2970, 2879, 1652, 1444; cm−1; 1H NMR (CDCl3,
1
in the next step without further purification. H NMR (CDCl3,
500 MHz) d 4.87 (m, 1H, C CH2), 4.79 (m, 1H, C CH2), 3.72 (m,
2H, CH2OH), 2.29 (m, 1H, CHDCH2), 1.76 (m, 3H, C CCH3).
=
=
=
(2S)-[2-2H1]-Isopentenyl tosylate (16)41
A stirring solution of (2S)-[2-2H1]-isopentenol and tosyl chloride
(67 mg, 1.91 mmol) in CH2Cl2 (5 mL) was treated with Et3N
(0.27 mL, 1.91 mmol) and DMAP (10 mg (136 mg, 1.11 mmol).
The resulting mixture was stirred at room temperature for 12 h,
at which time Et2O (50 mL) was added. Precipitated solids were
removed by filtration, and the filtrate was concentrated in vacuo.
Purification of the crude tosylate by flash column chromatography
(SiO2, hexane–EtOAc, 10 : 1) afforded the tosylate 16 as an
oil (80 mg, 26% for three steps). [a]2D0 = −0.4◦ (c 1.0, CH2Cl2);
=
=
300 MHz) d 5.06 (m, 1H, C CH2), 4.96 (m, 1H, C CH2), 4.18
(dd, 1H, J = 7.2 Hz, 3.4 Hz, CHOH), 3.70 (dd, 1H, J = 11.2 Hz,
3.5 Hz, CH2OH), 3.55 (dd, 1H, J = 11.2 Hz, 7.3 Hz, CH2OH),
2.58 (b, 2H, OH), 1.75 (m, 3H, C CCH3); 13C NMR (CDCl3,
125 MHz) d 144.1, 112.0, 75.7, 65.2, 18.9; HRMS (EI) calcd for
C5H10O2 [M+ ] 102.0681, found 102.0679, 84 (44%), 71 (100%).
=
•
(2R)-3-Methyl-3-butene-1,2-diol-1-yl tosylate (15)
1
To a stirring solution of diol 14 (225 mg, 2.20 mmol) in pyridine
IR (CH2Cl2, cast) 3078, 2971, 1652, 1495, 1177 cm−1; H NMR
(5 mL) at 0 ◦C was added freshly recrystallized tosyl chloride
(CDCl3, 300 MHz) d 7.79 (m, 2H, Ar), 7.34 (m, 2H, Ar), 4.79 (m,
◦
=
=
(462 mg, 2.42 mmol) in pyridine (10 mL) and stirred at 0 C for
1H, C CCH2), 4.68 (m, 1H, C CCH2), 4.12 (m, 2H, CH2OS),
2.45 (s, 3H, ArCH3), 2.34 (m, 1H, CHDCH2), 1.66 (m, 3H,
18 h. The solution was then poured onto ice-water and extracted
with Et2O (3 × 15 mL). The combined ethereal extracts were
washed with 1 M HCl followed by a saturated NaHCO3 solution,
water and brine, and dried over MgSO4. Evaporation of the solvent
C CCH3); 2H NMR (CHCl3, 61.4 MHz) d 2.36; 13C NMR
=
(CDCl3, 125 MHz) d 144.8, 140.1. 133.2, 129.8, 127.9, 113.2, 66.8,
•
36.4 (t, J = 19.5 Hz), 22.3, 21.7; HRMS (EI) calcd for [M+ ]
afforded the tosylate 15 as a colorless oil (564 mg, 71%). [a]D20
=
C12H15DO3S 241.0883, found 241.0877, 155 (52%), 91 (79%).
−13.3◦ (c 1.2, CH2Cl2); IR (CH2Cl2, cast) 3533, 3069, 2951, 2921,
1
1652, 1495, 1190 cm−1; H NMR (CDCl3, 500 MHz) d 7.81 (m,
(2S)-[2-2H1]-Isopentenyl diphosphate (9)41
=
2H, Ar), 7.36 (m, 2H, Ar), 5.06 (m, 1H, C CH2), 4.97 (m, 1H,
A similar procedure was employed as that described for the prepa-
ration of 6. The reaction of (2S)-[2-2H1]-isopentenyl tosylate (16)
(10 mg, 0.041 mmol) in MeCN (2 mL) with tris-n-butylammonium
hydrogen diphosphate gave the crude labelled IPP. The reaction
was worked up as previously described. Purification of the crude
product using HPLC (Vydac 259VHP reverse phase polymer
column; 4.6 × 150 mm; 10% MeCN, 90% 100 mM NH4HCO3
20 min, 10–50% MeCN over 5 min, 50% MeCN 10 min, 50–90%
MeCN over 1 min, 90% MeCN 20 min, tR 44.0 min) afforded the
title compound 9 as a white solid (11 mg, 87%). IR (lscope) 2707
(b), 1685, 1430 cm−1; 1H NMR (D2O–ND4OD, 400 MHz) d 4.99
=
C CH2), 4.31 (dd, 1H, J = 7.6 Hz, 3.2 Hz, CHOH), 4.12 (dd, 1H,
J = 10.6 Hz, 3.3 Hz, CH2OS), 3.97 (dd, 1H, J = 10.3 Hz, 7.7 Hz,
CH2OS), 2.46 (s, 3H, ArCH3), 2.06 (b, 1H, OH) 1.70 (m, 3H,
C CCH3); 13C NMR (CDCl3, 100 MHz) d 145.1, 142.0, 132.8,
=
129.9 (2C), 128.0 (2C), 113.7, 73.0, 72.4, 21.7, 18.6; HRMS (ES
+ve) calcd for [M + Na]+ C12H16O4SNa 279.0662, found 279.0660.
(R)-Isopropenyl oxirane42
Finely powdered KOH (1.0 g, 17.8 mmol) was added to tosylate
15 (325 mg, 1.27 mmol) and heated to 60 ◦C for 1 h. After
cooling to room temperature, the residue was dissolved in Et2O and
filtered through a mini-pad of Celiteꢀ to remove solid impurities.
This compound was partially characterized and used without
further purification for the subsequent reaction. 1H NMR (CDCl3,
=
(m, 2H, C CH), 4.18 (m, 2H, CH2OP), 2.53 (m, 1H, CHDCH2),
R
1.91 (s, 3H, C CCH3); 13C NMR (D2O–ND4OD, 100 MHz) d
=
145.2, 112.8, 67.1 (d, 2JP–P = 5.8 Hz), 39.2 (1JC–D = 22 Hz), 23.1;
31P NMR (D2O–ND4OD, 162 MHz) d −9.05 (m, 1P), −5.05 (m,
736 | Org. Biomol. Chem., 2006, 4, 730–742
This journal is
The Royal Society of Chemistry 2006
©