Synthesis of (+)- and (-)-dihydropinidine by diastereoselective dimethylzinc promoted allylation of 2-methyltetrahydropyridine-N-oxide with an allylboronic ester

Article abstract of DOI:10.1016/j.tetasy.2006.03.033

The enantiomers of the naturally occurring alkaloid dihydropinidine 1, potential antifeedants against the pine weevil, Hylobius abietis, were prepared by diastereoselective, dimethylzinc mediated addition of pinacolyl 2-propenylboronate 14 to nitrones (R)

Full text of DOI:10.1016/j.tetasy.2006.03.033

Tetrahedron: Asymmetry 17 (2006) 1074–1080
Synthesis of (+)- and (ꢀ)-dihydropinidine by diastereoselective
dimethylzinc promoted allylation of 2-methyltetrahydropyridine-
N-oxide with an allylboronic ester
Carina Eriksson,a,* Kristina Sjo¨din,a Fredrik Schlyterb and Hans-Erik Ho¨gberga
aDepartment of Natural Sciences, Mid Sweden University, SE-851 70 Sundsvall, Sweden
bChemical Ecology, Department of Crop Sciences, Swedish University of Agricultural Sciences, PO Box 44, SE-230 53 Alnarp, Sweden
Received 3 March 2006; accepted 27 March 2006
Abstract—The enantiomers of the naturally occurring alkaloid dihydropinidine 1, potential antifeedants against the pine weevil, Hylobius
abietis, were prepared by diastereoselective, dimethylzinc mediated addition of pinacolyl 2-propenylboronate 14 to nitrones (R)- and (S)-
2-methyl tetrahydropyridine-N-oxide 3, prepared from D- and L-alanine, respectively.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Numerous approaches to enantiomerically enriched
asymmetric 2,6-dialkylpiperidines are described in the
literature.6 Several enantioselective approaches to dihydro-
pinidine are also described.7
The piperidine alkaloid dihydropinidine 1 (Fig. 1) has been
found in needles of Picea pungens1 and in the bark and
needles of Picea sitchensis2 (absolute configuration not
reported). In a preliminary study, we found that the hydro-
chloride salt of rac-1 displayed high antifeedant activity
against the pine weevil, Hylobius abietis, which is a major
pest of newly planted conifer trees.3 To verify this result,
the synthesis and further biological testing of the com-
pound are required. Because enantiomers can have anta-
gonistic biological effects,4 both the enantiomers of
dihydropinidine have to be synthesised and tested individ-
ually. Another alkaloid, pinidine 2 (Fig. 1), present in var-
ious tissues of several Pinus and Picea species,5 was also
considered as a synthetic target suitable for biological
testing.
Vinylboronic esters of pinacol can, according to Pandya
et al., readily be added to nitrones in the presence of di-
methylzinc, forming N-allylic hydroxylamines.8 Although
the nitrones prepared in that work are quite different from
those required for making pinidines, these results inspired
us to explore the potential of using this method for the
preparation of the enantiomers of dihydropinidine 1 and
pinidine 2 (Scheme 1). Thus, both enantiomers of nitrone
3 were required as the substrate for a similar addition reac-
tion. Both enantiomers of 3 can be prepared starting from
either D- or L-alanine.9
2. Results and discussion
H
N
H
N
The nitrones, (S)- and (R)-2-methyl tetrahydropyridine-N-
oxide 3 and ent-3, were prepared as described by Chackala-
mannil and Wang9 with some modifications (Scheme 2).
The synthetic sequence started with either (S)- or (R)-N-
carbobenzyloxyalanine methyl ester (4 or ent-4), which
was prepared in two steps from L- and D-alanine, respec-
tively.10 Diisobutylaluminium hydride reduction of carb-
amate ester 4 gave the corresponding aldehyde 5 (Scheme
2). A Wittig reaction of 5 with the commercially available
1
2
Figure 1. Dihydropinidine 1 and pinidine 2.
*
Corresponding author. Tel.: +46 60 148577; fax: +46 60 148802; e-mail:
carina.s.eriksson@miun.se
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.03.033

C. Eriksson et al. / Tetrahedron: Asymmetry 17 (2006) 1074–1080
1075
O
B
O
O-
N+
OH
N
OH
N
11
NH2
R
R
Me2Zn
+
+
or
COOH
O
B
D- or L-Alanine
12 , R=
13 , R=
16 , R=
3
O
15 , R=
14
H
N
R
1, R=
2, R=
Scheme 1. Planned synthesis of dihydropinidine 1 and pinidine 2.
O
O
P+Ph3 Br-
6
NHCOOCH2Ph
NHCOOCH2Ph
CHO
a)
b)
COOMe
4
5
NH2
NHOCOPh
1
NHCOOCH2Ph
c)
d)
e)
4
2
O
O
O
O
3
O
O
7
8
9
O-
N+
NHOH
f)
O
O
3
10
Scheme 2. Synthesis of nitrone 3. Reagents and conditions: (a) DIBAL-H (2.0 equiv), CH2Cl2, ꢀ78 ꢁC, 96%. (b) (1) 6 (1.38 equiv), THF, KO-t-Bu
(1.38 equiv); (2) addition of 5, rt, 51%. (c) H2, Pd/C, EtOH/EtOAc, 99%. (d) (PhCO)2O2 (2.0 equiv), CH2Cl2, NaHCO3/NaOH buffer (pH 10.5), 56%. (e)
LiOH (2 M, aq), THF/MeOH, 95%. (f) HCl (2 M aq), 15 min.
[2-(1,3-dioxolan-2-yl)ethyl]triphenylphosphonium bromide
6 gave Z-alkene 7 as a single isomer. The Z-configuration
of the alkene moiety was confirmed by an observed NOE
between H4 and H1, which would not have been observed
for the E-isomer; also, the coupling constant of H2–H3
(ꢁ9–10 Hz) was in the range for a Z-alkene. Compound
7 was subjected to palladium catalysed hydrogenation
resulting in a-methyl-1,3-dioxolan-2-butanamine 8 which
in turn was transformed to the corresponding hydroxyl-
amine benzoate 9 by oxidation with benzoyl peroxide.11

1076
C. Eriksson et al. / Tetrahedron: Asymmetry 17 (2006) 1074–1080
O-
N+
OH
OH
N
N
various
conditions
O
B
+
+
O
3
11
12
13
Scheme 3. Addition of 1-propenyl pinacolyl boronate 11 to nitrone 3.
Hydrolysis of the resulting benzoate 9 using LiOH9 gave
the corresponding hydroxylamine 10. Acetal removal using
aqueous HCl12 yielded nitrone 3, which was used immedi-
ately in the addition reaction (Scheme 3).
obtained as virtually equimolar mixtures of 12 and 13,
which in turn were equimolar mixtures of the E- and Z-
1-propenyl isomers. Attempts to separate the four isomers
by chromatography were unsuccessful. Thus, the synthesis
of pinidine was not accomplished via any of these methods.
In our first attempt to prepare pinidine 2, 1-propenyl pina-
colyl boronate 1113 was added to nitrone 3 following the
procedure developed by Pandya et al.,8 for the addition
of boronic esters to other nitrones (2.5 equiv dimethylzinc,
DMF, 60 ꢁC) (Scheme 3). Due to the low conversion of the
nitrone, only trace amounts of hydroxylamine products 12
and 13 were detected. Thus, in order to increase the yield of
the hydroxylamine products, the reaction conditions were
modified: choice of solvent, replacement of dimethylzinc
with diethylzinc, and variation of the reaction temperature.
Moreover, if an alkyl/vinyl exchange on zinc was a prere-
quisite for the reaction to proceed, the addition order of
the reagents was altered, that is, dialkylzinc and boronic
ester were mixed before the addition of nitrone. Despite
these efforts, no appreciable conversion of nitrone could
be achieved.
Pinacolyl allylboronate 14 (Table 1) was prepared in a sim-
ilar way to that used for vinylboronate 11.13 The 1H NMR
spectrum of 14 was in good agreement with that reported
earlier.14 When dimethylzinc mediated addition of boro-
nate 14 to nitrone 3 was attempted using the general reac-
tion conditions developed by Pandya et al.,8 complete
conversion of nitrone was observed (Table 1, entry 1).
However, a major part (47% of the addition products) con-
sisted of diastereomeric products resulting from methyl
addition. In order to increase the yields of the desired allyl
adducts, 15 and 16, and to investigate if the diastereoselec-
tivity could be directed in favour of 15, the reaction condi-
tions were varied (Table 1). When CH2Cl2 was used as a
solvent and the addition of dimethylzinc (2 equiv) was
performed at ꢀ78 ꢁC, the lowest yield of alkyl adduct
and the highest yield of the desired 15 (dr: 71/29) was
obtained (Table 1, entry 8). Chromatographic separation
of diastereomeric hydroxylamines 15 and 16 gave the
desired cis-isomer 15 in 31% isolated yield, based on
hydroxylamine 10.
When, however, the latter was reacted with either di-1-
propenylzinc (prepared in situ) or 1-propenylmagnesium
bromide, full conversion of nitrone was obtained. Unfortu-
nately, the hydroxylamine products were, in both cases,
Table 1. Optimisation of reaction conditions for addition of boronic ester 14 to nitrone 3
O-
N+
OH
OH
N
N
various
conditions
O
B
+
+
O
3
14
15
16
Entry
Boronic ester 14a
Time (h)
Solvent
Temperature (ꢁC)
Organo-metal reagent
15g (%)
16g (%)
Alkyl adductg (%)
1
2
3
4
5
6
7
8
9
1.2
1.2
1.2
1.2
1.2
1.2b
1.2
1.2
1.2
—
4
6
DMF
DMF
rt!60
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
Me2Znc, 2.5a
Me2Znc, 2.5a
Me2Znc, 2.5a
Me2Znd, 2.5a
Me2Znd, 1.2a
Me2Znd, 2.5a
Me2Znc, 2.5a
Me2Znc, 2.0a
Et2Zne, 2.5a
8.8
11.8
57.7
50.9
38.3
37.3
15.1
67.8
45.9
58.4
44.3
57.9
31.4
21.7
20.8
19.5
22.3
28.0
33.6
41.6
46.9
30.3
10.8
27.4
40.9
43.2
62.5
4.2
12
12
12
12
12
12
12
12
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Et2O
CH2Cl2
CH2Cl2
CH2Cl2
20.5
—
10
n-PrMgBrf, 1.1a
a mol/mol nitrone.
b Boronic ester and zinc reagent mixed before addition of nitrone.
c 2.0 M in toluene.
d 1.0 M in heptane.
e 1.0 M in hexane.
f 2.0 M in Et2O.
g Relative area% (GC), rt = room temperature.

C. Eriksson et al. / Tetrahedron: Asymmetry 17 (2006) 1074–1080
1077
˚
A mechanistic suggestion explaining the observed preferen-
tial formation of cis-hydroxylamine 15 is given in Scheme
4. In polar noncoordinating solvents, dimethylzinc coordi-
nates as a Lewis acid to the nitrone oxygen on the face
opposite to the methyl group. The allyl nucleophile (allyl-
boronate (shown), allylmethylborate or allylmethylzinc
formed via transmetallation)8 approaches from the face
opposite to that blocked by the O-coordinated dimethyl-
zinc yielding the cis-adduct. In polar aprotic solvents,
dimethylzinc is probably coordinated to the solvent rather
than to the nitrone leading to more trans-allylation in
such solvents.
LiAlH4, dimethylformamide (DMF) was dried over 4 A
molecular sieves and distilled under reduced pressure, tetra-
hydrofuran (THF) was distilled from potassium–benzo-
phenone under argon, and dichloromethane (CH2Cl2)
was distilled from calcium hydride. Medium pressure liquid
chromatography (MPLC) was performed on straight phase
silica gel (Merck 60, 230–400 mesh, 0.040–0.063 mm)
employing a gradient with increasing concentrations of
ethyl acetate in cyclohexane as the eluent. The GC-analyses
were performed using a Varian 3400 instrument, equipped
with an EC-1 column (30 m · 0.32 mm i.d., df = 0.25 lm,
carrier gas N2) or using a Varian 3300 instrument,
equipped with a capillary column, chiral phase: Gamma-
DexTM 225 [Supelco, 25% 2,3-di-O-acetyl-6-O-TBDMS-c-
cyclodextrin in SPB-20 poly(205 phenyl/80% di-
methylsiloxane) 30 m · 0.25 mm i.d., df = 0.25 lm, carrier
gas He]. The NMR analyses were carried out using a
Bruker Avance 500 MHz spectrometer (500 MHz 1H
and 125.7 MHz 13C) at 25 ꢁC with CDCl3 as the solvent
and TMS as the internal standard. Optical rotations were
measured in a 1 dm cell using a Perkin–Elmer polarimeter
(model 341). The elemental analyses were performed by
Mikrokemi AB, Uppsala, Sweden.
CH3
H3C
Zn
H
CH3
N
N
O
B
H
O
+
Me2Zn
H
O
O
O
B
O
Scheme 4. Suggested mechanism for addition of the allyl moiety of 14 to
cyclic nitrone 3.
3.2. Experimental procedures
Palladium catalysed hydrogenation of cis-isomer 15 pro-
duced dihydropinidine without epimerisation (Scheme 5).
3.2.1. (S)-Benzyl-(1-methyl-2-oxoethyl)carbamate 5. To a
solution of N-(benzyloxycarbonyl)-L-alanine methyl ester
4 (5.82 g, 24.5 mmol) in CH2Cl2 (230 ml) at ꢀ78 ꢁC, di-
isobutylaluminium hydride in CH2Cl2 (1.0 M, 49.0 mmol)
was added dropwise over a 2 h period. The solution was
stirred at ꢀ78 ꢁC for 5 h, after which any further reaction
was stopped by the addition of HCl (1 M, aq, 50 ml).
The mixture was allowed to reach room temperature. The
organic layer was separated and washed with HCl (1 M,
aq, 50 ml) and water (2 · 50 ml), dried over MgSO4, fil-
tered and concentrated to give crude aldehyde 5 (4.88 g,
96.0%), which was used in the next step without further
purification. 1H NMR d 1.35 (3H, d, J = 7.3 Hz), 4.29
(1H, m), 5.11 (2H, s), 5.50 (1H, br s), 7.35 (5H, m), 9.53
(1H, s).
Dihydropinidine was isolated as its HCl salt: (2S,6R)-
20
dihydropinidine hydrochloride 1ÆHCl: ½aꢂD ¼ ꢀ12:6 (c
20
0.1, EtOH) {lit.7t ½aꢂD ¼ ꢀ13 (c 0.075, EtOH)}. In a similar
way but starting from ent-4, (2R,6S)-dihydropinidine
hydrochloride ent-1ÆHCl was obtained (Schemes 2, 3 and
20
20
7t
5): ½aꢂD ¼ þ12:4 (c 0.1, EtOH) {lit. ½aꢂD ¼ þ13 (c 1.12,
EtOH)}. The enantiomeric purity of each enantiomer was
>97% ee, as determined by GC-analysis of the trifluoro-
acetamides on a capillary column covered with a chiral
liquid phase (see Sections 3.1 and 3.2.11).
OH
N
H*HCl
N
1. H2, Pd/C
The (R)-enantiomer ent-5 was prepared by the same proce-
dure starting from N-(benzyloxycarbonyl)-D-alanine
methyl ester ent-4, H NMR spectral data were identical
2. HCl in Et2O
1
15
1
Scheme 5. Hydrogenation of hydroxylamine 15.
to those of 5.
When tested in micro-feeding assays,15 high antifeedant
activity against H. abietis was found for both (2S,6R)-
and (2R,6S)-dihydropinidine hydrochlorides (1ÆHCl and
ent-1ÆHCl, respectively), as well as for the hydrochloride
salts of some other naturally occurring piperidine
alkaloids.16
3.2.2. (S)-Benzyl-[(2Z)-4-(1,3-dioxolan-2-yl)-1-methylbut-2-
en-1-yl]carbamate 7. Phosphonium bromide 6 (Aldrich)
(3.81 g, 8.6 mmol) was dissolved in dry THF (38 ml).
Potassium tert-butoxide (0.96 g, 8.6 mmol) was added
and the resulting orange mixture was stirred at room tem-
perature for ꢁ1 h. A solution of aldehyde 5 (1.29 g,
6.23 mmol) from the previous step dissolved in dry THF
(13 ml) was added slowly. The mixture was stirred for 1 h
and saturated ammonium chloride (aq, 40 ml) added. The
mixture was extracted with ether (3 · 50 ml) and the result-
ing organic phase was dried over MgSO4, filtered and con-
centrated. The crude product was purified by MPLC
(EtOAc in cyclohexane, 1.25%!20%), yielding 7 as a single
isomer (0.93 g, 51.3%, 93.1% purity according to GC). IR
[mmax(neat)/cmꢀ1]: 3334, 3031, 2967, 2886, 1709, 1525,
3. Experimental
3.1. Chemicals and instruments
Unless otherwise stated, commercially available chemicals
were used as received from the suppliers without further
purification. Diethyl ether (Et2O) was distilled from

1078
C. Eriksson et al. / Tetrahedron: Asymmetry 17 (2006) 1074–1080
1454, 1376, 1234, 1051, 699 (this peak and the absence of a
3.2.5. (S)-5-(1,3-Dioxolan-2-yl)-N-hydroxypentan-2-amine
10. Hydroxylamine benzoate 9 (0.57 g, 2.04 mmol) was
dissolved in THF–MeOH (6.2 ml, 1:1 v/v) and LiOH
(2 M, aq, 6.2 ml) was added dropwise. The mixture was
stirred for 2 h at room temperature. Et2O (25 ml) was
added and the phases were separated. The aqueous phase
was extracted with Et2O (3 · 25 ml) and the combined
organic phases were dried over MgSO4, filtered and concen-
trated in vacuo to yield hydroxylamine 10 (0.34 g, 95%). IR
[mmax(neat)/cmꢀ1]: 3281, 3056, 2917, 2849, 1662, 1368,
1140, 736. ½aꢂD ¼ ꢀ5:0 (c 0.12, CHCl3). H NMR d 1.10
(3H, d, J = 6.4 Hz), 1.30–1.55 (3H, m), 1.59–1.71 (3H,
m), 3.00 (1H, m), 3.800–4.01 (4H, m), 4.86 (1H, t,
J = 4.7 Hz), 5.84 (2H, br). 13C NMR d 17.5, 20.4,
33.4, 33.9, 57.2, 64.9 (2C), 104.4. Anal. Calcd for
C9H17NO: C, 54.8; H, 9.8; N, 8.0. Found: C, 54.9; H,
9.8; N, 7.8.
strong one at 970–960 cmꢀ1 indicate a cis-double bond).
20
1
½aꢂD ¼ þ50:3 (c 0.61, CHCl3). H NMR d 1.22 (3H, d,
J = 6.6 Hz), 2.54 (2H, m), 3.82 (2H, m), 3.94 (2H, m),
4.50 (1H, m), 4.91 (2H, m), 5.08 (2H, s), 5.41 (1H, dd
(app t), J = 9.0, 10.4 Hz), 5.51 (1H, m), 7.30 (5H, m). 13C
NMR d 21.7, 32.5, 44.6, 64.9, 65.0, 66.5, 103.5, 124.5,
128.02, 128.04 (2C), 128.5 (2C), 134.5, 136.6, 155.5.
Starting from (R)-benzyl-(1-methyl-2-oxoethyl)carbamate
ent-5, the (R)-enantiomer ent-7 was prepared using the
20
1
same procedure. The purity was 87% according to GC.
20
½aꢂD ¼ ꢀ45:1 (c 0.73, CHCl3). The NMR spectral data
were identical to those of 7.
3.2.3. (S)-5-(1,3-Dioxolan-2-yl)pentan-2-amine 8. Com-
pound 7 (2.32 g, 7.97 mmol) was dissolved in EtOH/EtOAc
(1:2, v/v, 41 ml), 10% palladium on charcoal (0.3 g) was
added and the mixture was hydrogenated at room temper-
ature and ambient pressure overnight. Filtration through a
pad of Celite and concentration in vacuo yielded free amine
8 (1.26 g, 99.3%, 98.5% purity according to GC) as a pale
yellow oil. IR [mmax(neat)/cmꢀ1]: 3286, 2953, 2873, 1617,
Starting from (R)-N-(benzoyloxy)-5-(1,3-dioxolan-2-yl)-
pentan-2-amine ent-9, the (R)-enantiomer ent-10 was
20
prepared using the same procedure. ½aꢂD ¼ þ5:0 (c 0.12,
CHCl3). The NMR spectral data were identical to those
of 10.
20
1
1461, 1378, 1142. ½aꢂD ¼ þ1:9 (c 0.78, CHCl3). H NMR
d 1.09 (3H, d, J = 6.3 Hz), 1.37–1.54 (4H, m), 1.64–1.71
(2H, m), 1.97 (2H, m), 2.92 (1H, m), 3.82–3.98 (4H, m),
4.86 (1H, t, J = 4.8 Hz). 13C NMR d 20.8, 23.4, 33.8,
39.5, 46.9, 64.9 (2C), 104.4.
3.2.6. (S)-2-Methyl-2,3,4,5-tetrahydropyridine 1-oxide 3.
To hydroxylamine 10 (1 g, 5.71 mmol) was added 2 M
HCl (aq, 10 ml). The solution was stirred at room temper-
ature for 25 min after which water (30 ml) was added and
the pH adjusted to ꢁ11 with Na2CO3. The reaction mix-
ture was extracted with Et2O (2 · 50 ml) and CHCl3
(5 · 50 ml). The combined CHCl3 phases were filtered
through MgSO4 and the filtrate evaporated to give nitrone
3 (yellow oil), which was used immediately in the next step.
Starting from (R)-benzyl-[(2Z)-4-(1,3-dioxolan-2-yl)-1-
methylbut-2-en-1- yl]carbamate (ent-7), the (R)-enantiomer
ent-8 was prepared by the same procedure. The purity was
20
97.9% according to GC. ½aꢂD ¼ ꢀ1:3 (c 0.79, CHCl3). The
NMR spectral data were identical to those of 8.
In the same way, enantiomer ent-3 was prepared, starting
from hydroxylamine ent-10, and used immediately in the
next step.
3.2.4.
(S)-N-(Benzoyloxy)-5-(1,3-dioxolan-2-yl)pentan-2-
amine 9. Amine 8 (0.58 g, 3.64 mmol) was dissolved in
an aqueous buffer [pH 10.5, 18.2 ml, prepared from
NaHCO3 (0.75 M, aq) and NaOH (1.5 M, aq)].11 Benzoyl
peroxide (25% w/w in H2O, 2.35 g, 7.28 mmol) dissolved
in CH2Cl2 (18.2 ml) was added dropwise at ambient tem-
perature and the resulting mixture stirred vigorously for
24 h. The phases were separated and the aqueous phase
was extracted with CH2Cl2 (2 · 30 ml). The combined
organic layers were dried over Na2SO4, filtered and the
solvent was evaporated off. The crude product was purified
by chromatography on silica gel (EtOAc in cyclohexane,
3.2.7. (2S,6S)-2-Allyl-6-methylpiperidin-1-ol 15. To allyl
boronic ester 14 (1.15 g, 6.85 mmol) at ꢀ78 ꢁC, nitrone 3
(5.71 mmol) in CH2Cl2 (20 ml) was added. Dimethylzinc
(2.0 M in toluene, 5.71 ml, 11.4 mmol) was added slowly
after which the mixture was allowed to reach room temper-
ature and stirred overnight. The mixture was cooled in an
ice bath and water (5 ml) was added slowly. The mixture
was filtered through a pad of Celite and the filtrate evapo-
rated. The crude product was purified by MPLC on
silica gel (EtOAc–c-hexane, 0%!100%) yielding 2-(S)-
1%!25%) yielding product 9 (0.57 g, 56.1%). IR [mmax
-
(neat)/cmꢀ1]: 3236, 3063, 2950, 2878, 1718, 1451, 1271,
20
1
733, 710. ½aꢂD ¼ ꢀ1:5 (c 0.4, CH2Cl2). H NMR d 1.20
(3H, d, J = 6.4 Hz), 1.44–1.61 (3H, m), 1.70 (3H, m),
3.23 (1H, m), 3.84 (2H, m), 3.95 (2H, m), 4.85 (1H, m),
7.46 (2H, m), 7.58 (1H, m), 8.02 (2H, m). 13C NMR d
17.9, 20.4, 24.0, 33.82, 33.84, 56.7, 64.8, 64.9, 104.3,
104.5, 128.46, 128.51, 129.3, 133.3, 166.8. Calcd for
C15H21NO4: C, 64.5; H, 7.6; N, 5.0. Found: C, 64.2; H,
7.9; N, 4.6.
allyl-6-(S)-methylpiperidin-1-ol 15 (0.3 g, 33.8%). IR [mmax-
20
(neat)/cmꢀ1]: 3375, 3077, 2935, 2862, 996, 919. ½aꢂD ¼ ꢀ7:8
(c 0.32, CHCl3). 1H NMR d 1.10 (3H, d, J = 6.4 Hz), 1.21–
1.35 (3H, m), 1.55–1.85 (3H, m), 2.17 (1H, m), 2.47 (2H,
m), 2.69 (1H, m), 4.95–5.10 (3H, m), 5.84 (1H, m). 13C
NMR d 20.5, 23.7, 31.2, 34.2, 38.6, 63.3, 67.0, 116.4,
136.1. Anal. Calcd For C9H17NO: C, 69.6; H, 11.0; N,
9.0. Found: C, 69.4; H, 10.9; N, 8.8.
1
Starting from (R)-5-(1,3-dioxolan-2-yl)pentan-2-amine ent-
trans-Isomer 16 (0.15 g, 17.0%): H NMR d 5.78 (1H, m),
8, the (R)-enantiomer ent-9 was prepared by the same pro-
5.05 (2H, m), 3.30 (1H, m), 2.98 (1H, m), 2.68 (1H, m),
2.20 (1H, m), 1.30–1.95 (5H, m), 1.20 (1H, m), 1.15 (3H,
d, J = 5.7 Hz).
20
cedure. ½aꢂD ¼ þ1:5 (c 0.4, CH2Cl2). The NMR spectral
data were identical to those of 9.

C. Eriksson et al. / Tetrahedron: Asymmetry 17 (2006) 1074–1080
1079
(2R,6R)-Enantiomer ent-15 was prepared following the
Acknowledgements
20
same procedure starting from nitrone ent-3. ½aꢂD ¼ þ7:5
(c 0.32, CHCl3). The NMR spectral data were identical
to those of 15.
The authors would like to thank Ms. Rebecka From, for
technical assistance and Dr. Tessa Pocock, for valuable
comments on the manuscript. Financial support from
MISTRA (The Foundation for Strategic Environmental
Research, ‘Pheromones and kairomones for control of pest
insects’, http://biosignal.org.) and EU, Objective 1 the
Region of South Forest Counties, is also warmly
acknowledged.
3.2.8. (2S,6R)-Dihydropinidine hydrochloride 1–HCl.
Hydroxylamine 15 (0.096 g, 0.62 mmol) was dissolved in
EtOAc (1 ml) and EtOH (2 ml). Palladium on charcoal
(10%, 0.013 g) was added and the mixture was hydro-
genated at ambient pressure for 10 days, after which time
the palladium was filtered off and HCl (0.62 ml, 1.0 M in
Et2O) was added to the filtrate. The solvents were evapo-
rated and the residue purified by crystallisation (MeOH–
References
Et2O), yielding (2S,6R)-dihydropinidine hydrochloride
20
(1ÆHCl) (0.07 g, 60%). ½aꢂD ¼ ꢀ12:6 (c 0.1, EtOH), lit.7t
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20
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20
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