76
J. S. Clark et al. / Tetrahedron 62 (2006) 73–78
loaded on a silica flash column. Elution (n-pentane/diethyl
ether, 10:1) afforded the desired compound as a colourless
liquid (3.27 g, 94%). The product was used in the next
reaction without further purification: [a]2D9 K49.6 (cZ2.65,
CHCl3); nmax (CHCl3) 2973, 2932, 2865, 1646, 994, 941,
CHCl3); nmax (CHCl3) 3117, 2973, 2930, 2863, 2109, 1639,
995, 914 cmK1 1H NMR (400 MHz, CDCl3) d 5.92
;
(ddt, 1H, JZ17.2, 10.4, 5.6 Hz, CH]CH2), 5.29–5.23 (br,
1H, CHN2), 5.28 (ddt, 1H, JZ17.2, 1.6, 1.5 Hz, CH]CH2
trans), 5.17 (ddt, 1H, JZ10.4, 1.6, 1.4 Hz, CH]CH2 cis),
4.06 (dddd, 1H, JZ12.7, 5.6, 1.5, 1.4 Hz, CH2CH]CH2),
3.90 (dddd, 1H, JZ12.7, 5.6, 1.5, 1.4 Hz, CH2CH]CH2),
3.56–3.47 (m, 1H, CH3CH), 2.51–2.38 (m, 2H, CH2C]O),
1.92–1.73 (m, 2H, CH2CH2C]O), 1.18 (d, 3H, JZ6.1 Hz,
CH3CH); 13C NMR (100.6 MHz, CDCl3) d 195.0 (C), 135.2
(CH), 116.5 (CH2), 73.8 (CH), 69.4 (CH2), 54.2 (CH), 36.7
(CH2), 31.6 (CH2), 19.5 (CH3); LRMS (ES) m/z 205
(MCCNa, 100), 183 [(MCCH, 10)]; HRMS (ES) for
C9H14N2O2Na [MCCNa] calcd 205.0953, found 205.0946.
1
915, 875 cmK1; H NMR (400 MHz, CDCl3) d 5.94 (ddt,
1H, JZ17.2, 10.4, 5.6 Hz, CH]CH2), 5.30 (dddd, 1H,
JZ17.2, 1.6, 1.5, 1.4 Hz, CH]CH2 trans), 5.19 (dddd, 1H,
JZ10.4, 1.6, 1.5, 1.4 Hz, CH]CH2 cis), 4.13–4.08 (m, 1H,
CH2CH]CH2), 3.98–3.93 (m, 1H, CH2CH]CH2),
3.71–3.66 (m, 1H, CH3CH), 3.60–3.47 (m, 2H, CH2Br),
2.14–2.05 (m, 1H, CH2CH2Br), 1.99–1.90 (m, 1H,
CH2CH2Br), 1.20 (d, 3H, JZ6.1 Hz, CH3CH); 13C NMR
(100.6 MHz, CDCl3) d 135.2 (CH), 116.7 (CH2), 72.6 (CH),
69.7 (CH2), 40.0 (CH2), 30.4 (CH2), 19.4 (CH3).
4.1.6.
(2R,6R)-2-Allyl-6-methyldihydro-2H-pyran-
4.1.4. (R)-4-(Allyloxy)pentanoic acid (8). A crystal of
iodine was added to a suspension of magnesium turnings
(392 mg, 16.3 mmol) in dry THF under gentle heating
(water bath). The bromide 7 (3.00 g, 15.5 mmol) was then
added dropwise to the suspension causing an exotherm.
After addition was complete, the mixture was heated at
50 8C for 30 min, before being cooled to K78 8C. Solid
carbon dioxide (2 g, 3 equiv) was then added in one portion
to the solution and the mixture was allowed to warm to room
temperature. The resulting white suspension was stirred for
1 h and 1 M aqueous HCl was added until the pH of the
aqueous layer was acidic. The aqueous layer was extracted
with ethyl acetate and combined organic extracts were dried
(MgSO4), filtered and evaporated. The residue was purified
by flash column chromatography on silica gel (petrol 40–60/
ethyl acetate, 1:1) to afford the carboxylic acid 8 as a
colourless liquid (2.25 g, 92%): [a]2D5 K31 (cZ0.45,
CHCl3); nmax (CHCl3) 3174, 2972, 2931, 2864, 1745,
3(4H)-one (2) and (2S,6R)-2-allyl-6-methyldihydro-2H-
pyran-3(4H)-one (9). A solution of diazo ketone 3 (0.30 g,
1.6 mmol) in dichloromethane (5 mL) was added dropwise
to a solution of Cu(tfacac)2 (25 mg, 5 mol%) in dichloro-
methane (10 mL) at reflux. The mixture was stirred under
reflux for 20 min and the solvent was evaporated. Flash
column chromatography (petrol 40–60/diethyl ether, 10:1)
of the residue afforded a mixture of the ketones 2 and 9
(91:9) as a colourless liquid (0.15 g, 60%). Ketone 2. [a]D23
C157 (cZ0.65, CHCl3); nmax (CHCl3) 2976, 2936, 2873,
1722, 1642, 997, 915 cmK1; 1H NMR (400 MHz, CDCl3) d
5.83 (ddt, 1H, JZ17.1, 10.2, 6.9 Hz, CH]CH2), 5.15 (dq,
1H, JZ17.1, 1.5 Hz, CH]CH2) 5.19–5.10 (m, 1H,
CH]CH2), 4.21–4.12 (m, 1H, CH3CH), 4.10 (dd, 1H, JZ
8.3, 5.6 Hz, OCHC]O), 2.59–2.46 (m, 4H, CH2C]O,
CH2CH]CH2), 2.18–2.09 (m, 1H, CH2CH2C]O),
1.88–1.76 (m, 1H, CH2CH2C]O), 1.29 (d, 3H, JZ
6.2 Hz, CH3CH); 13C NMR (100.6 MHz, CDCl3) d 210.6
(C), 133.6 (CH), 117.6 (CH2), 78.9 (CH), 66.6 (CH), 35.6
(CH2), 34.4 (CH2), 31.1 (CH2), 20.5 (CH3); HRMS (EI) for
C9H14O2 [MC] calcd 154.0994, found 154.0978. Ketone 9.
[a]2D3 K67 (cZ0.60, CHCl3); nmax (CHCl3) 2977, 2927,
1
1710, 995, 943, 914 cmK1; H NMR (400 MHz, CDCl3) d
5.92 (dddd, 1H, JZ17.2, 10.4, 5.7, 5.5 Hz, CH]CH2), 5.27
(ddt, 1H, JZ17.2, 1.6, 1.4 Hz, CH]CH2 trans), 5.16 (ddt,
1H, JZ10.4, 1.6, 1.4 Hz, CH]CH2 cis), 4.06 (ddt, 1H, JZ
12.6, 5.5, 1.4 Hz, CH2CH]CH2), 3.92 (ddt, 1H, JZ12.6,
5.7, 1.4 Hz, CH2CH]CH2), 3.58–3.48 (m, 1H, CH3CH),
2.51–2.45 (m, 2H, CH2C]O), 1.85–1.79 (m, 2H,
CH2CH2C]O), 1.18 (d, 3H, JZ6.2 Hz, CH3CH); 13C
NMR (100.6 MHz, CDCl3) d 179.7 (C), 135.1 (CH), 116.7
(CH2), 73.8 (CH), 69.5 (CH2), 31.3 (CH2), 30.2 (CH2), 19.4
(CH3); LRMS (ES) m/z 181 (MCCNa, 100); HRMS (ES)
for C8H14O3Na [MCCNa] calcd 181.0841, found
181.0842.
1
2855, 1722, 1642, 996, 908 cmK1; H NMR (500 MHz,
CDCl3) d 5.83 (dddd, 1H, JZ17.1, 10.2, 6.9, 6.8 Hz,
CH]CH2), 5.13 (dddd, 1H, JZ10.2, 1.6, 1.4, 1.3 Hz,
CH]CH2) 5.07 (dddd, 1H, JZ17.1, 1.6, 1.4, 1.3 Hz,
CH]CH2), 3.91–3.86 (m, 2H, CH3CH, OCHC]O), 2.59
(dddt, 1H, JZ14.6, 6.9, 4.5, 1.3 Hz, CH2CH]CH2), 2.55
(ddd, 1H, JZ16.0, 6.3, 3.5 Hz, CH2C]O), 2.45 (dddd, 1H,
JZ16.0, 11.3, 7.0, 0.8 Hz, CH2C]O), 2.34 (dddt, 1H,
JZ14.6, 8.0, 6.8, 1.4 Hz, CH2CH]CH2), 2.08 (dddd,
1H, JZ13.6, 7.0, 3.5, 3.0 Hz, CH2CH2C]O), 1.88 (dddd,
1H, JZ13.6, 11.3, 10.5, 6.3, Hz, CH2CH2C]O), 1.30 (d,
3H, JZ6.2 Hz, CH3CH); 13C NMR (125.8 MHz, CDCl3) d
208.7 (C), 134.4 (CH), 117.2 (CH2), 82.4 (CH), 72.6 (CH),
37.7 (CH2), 34.1 (CH2), 33.5 (CH2), 21.4 (CH3); HRMS
(EI) for C9H14O2 [MC] calcd 154.0994, found 154.1000.
4.1.5. (R)-5-(Allyloxy)-1-diazohexan-2-one (3). Oxalyl
chloride (0.29 mL, 3.3 mmol) was added to a solution of
the carboxylic acid 8 (0.40 g, 2.5 mmol) in dichloromethane
(5 mL), followed by two drops of dry DMF. The mixture
was stirred at room temperature for 6 h and transferred to an
ethereal solution of diazomethane at 0 8C. The mixture was
stirred at room temperature for 3 h and excess diazomethane
was quenched by careful addition of acetic acid (2 mL). The
ether solution was washed with saturated aqueous NaHCO3
(20 mL) and the aqueous layer was back-extracted with
diethyl ether (20 mL). The combined organic layers and
extracts were dried (MgSO4), filtered and evaporated to give
a yellow oil. Purification by flash column chromatography
(hexane/diethyl ether, 2:1) afforded the diazo ketone 3 as a
bright yellow liquid (0.33 g, 72%): [a]2D5 K28 (cZ0.43,
4.1.7. (2R,3R,6R)-2-Allyl-6-methyltetrahydro-2H-pyran-
3-ol (10). A solution of L-Selectridew (4.7 mL of a 1 M
solution in THF, 4.7 mmol) was added dropwise to a
solution of ketone 2 (0.24 g, 1.6 mmol) in THF (20 mL) at
K78 8C. The mixture was stirred at K78 8C for 3 h and
H2O2 (4 mL of a 30% aqueous solution) was added,
followed by 2 M NaOH until pH ~10. The biphasic
mixture was stirred vigorously at room temperature for 1 h
and the layers separated. The aqueous layer was extracted