3410
P. Laurent et al. / Tetrahedron 57 -2001) 3403±3412
mixture of 14a and 14b .0.085 g, 0.262 mmol, 73%). The
diastereomers were then separated by chromatography on a
silica gel Lobarw .Merck) pre-packed column .hexane/
AcOEt 9:1). This yielded 14a .0.109 g) as a white solid
and 14b .0.041g) as a yellow oil .de 45%).
4.1.7. ꢀ1)-[2H11]Adaline [ꢀ1)-15]. Compound 14b
.0.040 g, 0.124 mmol) in methanol .10 mL) was hydro-
genated in the presence of 10% Pd±C as for 14a to afford
.1)-15 .0.021g, 0.094 mmol, 76%) as a yellow oil.
20
.1)-15. [a]D 19.3 .c 1.3, CHCl3). Otherwise, the spec-
14a. Mp 55±588C, HREIMS m/z 324.3096 .52, M1z, calcd
troscopic properties of .1)-15 were identical to those of its
enantiomer.
2
for C21H20 H11NO 324.3096), 309 .15), 281 .27), 274 .6),
260.1966 .23, calcd for C17H202H3NO 260.1968), 239 .8),
225 .6), 219 .21), 205 .5), 191 .6), 177 .29), 170 .6), 163
.17), 156 .20), 105 .100), 91 .7), 79 .26), 69 .12), IR .KBr)
2937, 2205, 2100, 1697, 1638, 1605, 1463, 1404, 1287,
4.1.8. ꢀ^)-cis- and ꢀ^)-trans-N-Methoxycarbonyl-2-
acetonyl-6-pentylpiperidines [ꢀ^)-17a) and ꢀ^)-17b].
N-Methoxycarbonyl-2-pentylpiperidine [.^)-16] .0.200 g,
0.94 mmol) and tetraethylammonium p-toluenesulfonate
.0.200 g, 0.66 mmol) in MeOH .14.8 mL) were submitted
to an anodic oxidation as described previously.7 After
4 Faraday/mol had been consumed, a few drops of
NH4OH were added, and the solvent was evaporated
under reduced pressure. Water was then added and the
mixture extracted three times with CHCl3. The organic
extracts were pooled, dried over MgSO4 and the solvent
removed in vacuo. Flash chromatography of the residue
on a silica gel column .hexane±AcOEt, 95:5) afforded
0.180 g of N-methoxycarbonyl-2-methoxy-6-pentylpiper-
idine .78%). To a solution of the latter compound
.0.040 g, 0.16 mmol) in CH2Cl2 .3.5 mL) at 2788C under
a nitrogen atmosphere were added trimethylsilyloxypropene
.0.025 g, 0.181 mmol) and TMSOTf .3 mL, 0.016 mmol).
This mixture was then stirred at 2788C for 1h. After addi-
tion of a saturated aqueous solution of NaHCO3, the mixture
was extracted with CHCl3 .3£10 mL) and the solvent
evaporated under reduced pressure. The residue was puri-
®ed by ¯ash chromatography on a silica gel column
.hexane/AcOEt, 8:2), to afford a 96:4 mixture of .^)-17a
and .^)-17b, in a 74% yield.
1
1178, 1095, 751, 693 cm21, H NMR .CDCl3) 1.4±1.8 .m,
6H); 1.5 .d, 6.9, 3H); 2.32 .AB, 16.8, 2H); 2.4 .ABX, 16.8,
7.3, 0, 2H); 3.35 .m, 1H); 4.52 .q, 6.9, 1H); 7.2±7.5 .m, 5H).
14b. EIMS m/z 324.3096 .52, M1z, calcd for C21H20 H11NO
2
324.3096), 309 .12), 281 .20), 274 .5), 260.1967 .17, calcd
for C17H202H3NO 260.1968), 242 .3), 239 .6), 219 .14), 214
.5), 191 .6), 177 .15), 170 .5), 163 .11), 156 .16), 105
.100), 79 .20), 77 .16), IR .®lm) 2937, 2205, 2100, 1705,
1
1454, 1362, 1295, 1237, 1186, 1028, 760, 701 cm21, H
NMR .CDCl3) 1.4±1.7 .m, 6H); 1.55 .d, 6.9, 3H); 1.96
.m, 2H); 2.3 .s, 2H); 3.4 .ms, 1H); 4.52 .q, 6.9, 1H); 7.2±
7.5 .m, 5H).
4.1.6. ꢀ2)-[2H11]Adaline [ꢀ2)-15]. Compound 14a .0.107
g, 0.330 mmol) in methanol .10 mL) was hydrogenated in
the presence of 10% Pd±C and one drop of 60% HClO4 at
atmospheric pressure and room temperature for 48 h. The
mixture was ®ltered through Celite and the ®ltrate was
concentrated in vacuo. The residue was taken up in a
5 mL of 20% aqueous NaOH and extracted with ®ve
10 mL portions of diethyl ether. The combined organic
layers were dried .MgSO4) and evaporated in vacuo to
give a residue which was puri®ed by ¯ash chromatography
on a silica gel column .AcOEt/MeOH/NH4OH 95:5:1) to
afford .2)-15 .0.059 g, 0.270 mmol, 82%) as a yellow oil.
.^)-17a. HREIMS m/z 269.1991 .2, M1z, calcd for
C15H27NO3 269.1992), 212.1652 .8, calcd for C12H22NO2
212.1652), 210 .10), 198 .22), 166 .11), 140 .100), 95 .9),
81 .15), 67 .8), 55 .14), IR .®lm) 2955, 2870, 1717, 1694,
1448 cm21, 1H NMR .CDCl3) 0.89 .t, 6.6, 3H); 1.2±1.7 .m,
14H); 2.18 .s, 3H); 2.55 .dd, 18.0, 4.0, 1H); 2.75 .dd, 18.0,
11.0, 1H); 3.69 .s, 3H); 4.10 .m, 1H); 4.65 .m, 1H).
.2)-15. GC .OV 1701, injector temperature 2208C, iso-
thermal 2008C, detector temperature 2308C): tR8.13 min,
20
KI1949, [a]D 29.45 .c 1.99, CHCl3). HREIMS m/z
2
220.2468 .50, C13H12 H11NO) [calcd for C13H12 H11NO
2
2
220.2470], 219.2396 .17, C13H11 H11NO) [calcd for
4.1.9. ꢀ^)-cis- and ꢀ^)-trans-N-Methoxycarbonyl-2-[1-
ꢀ2-hydroxypropyl)]-6-pentylpiperidine [ꢀ^)-18a) and
ꢀ^)-18b]. To the 96:4 mixture of .^)-17a and .^)-17b
.0.143 g, 0.53 mmol) in THF .9 mL) was added LiAl.Ot-
Bu)3H .0.271g, 1.06 mmol). The mixture was stirred at
room temperature for 9 h upon which a few droplets of
water were added. The solvent was then evaporated in
vacuo, diluted NH4OH .10 mL) was added and the solution
was extracted with CHCl3 .3£10 mL). The CHCl3 extracts
were pooled, dried over MgSO4 and evaporated to afford a
residue which was puri®ed by ¯ash chromatography on a
silica gel column .hexane/AcOEt, 65:35) to afford .^)-18a
.0.117 g, 80%) and .^)-18b .0.011 g, 8%).
2
C13H11 H11NO 219.2392], 191.2077 .17, C11H7 H11NO)
2
2
[calcd for C11H7 H11NO 191.2079], 186 .10), 178.1984
2
2
.27, C10H6 H11NO) [calcd for C10H6 H11NO 178.2000],
177 .66), 176 .12), 171 .12), 170 .36), 163.2130 .62,
2
2
C10H7 H11N) [calcd for C10H7 H11N 163.2130], 162 .13),
161 .11), 157 .49), 156.1343 .100, C9H122H3NO) [calcd
for C9H122H3NO 156.1342], 154 .21), 149 .11), 138 .14),
128 .13), 115 .10), 114 .18), 113 .67), 112 .10), 100 .15), IR
.®lm) 3314, 2937, 2205, 2100, 1705, 1463, 1404, 1354,
1
1287, 1237, 1170, 1061 cm21, H NMR .CDCl3) 1.4±1.75
.m, 6H); 2.19 .d, 16.5, 2H); 2.47 .ABX, 16.5, 6.9, 0, 2H);
3.68 .bs, 1H).
1
.2)-15´HCl: H NMR .CDCl3) 1.5±2.1 .m, 6H); 2.57 .B
.^)-18a. HREIMS m/z 271.2147 .3, M1z, calcd for
C15H29NO3 271.2147), 213 .18), 212 .99), 200 .100), 182
.28), 168 .8), 156 .14), 142 .100), 140 .88), 126 .13), 114
.10), 102 .12), 95 .15), 88 .13), 81 .30), 69 .15), 67 .15), 59
.14), 55 .34), IR .®lm) 3452, 2944, 2860, 1665, 1453,
part of ABX, 17.0, ,1.0, 1H); 2.64 .B part of AB, 17.0, 1H);
2.78 .A part of AB, 17.0, 1H); 3.10 .A part of ABX, 17.0,
6.0, 1H); 4.1 .X part of ABX, bs, 1H), 13C NMR .CDCl3)
17.2, 29.1, 34.6, 43.5, 48.7, 51.6, 60.2, 205.3 .deuterium-
bearing carbons were not detected in this experiment).
1
1105 cm21, H NMR .CDCl3) 0.89 .t, 6.5, 3H); 1.19 .d,