Enantioselective synthesis of 5-substituted pipecolic acids using an intramolecular allylsilane-iminium ion cyclization

Article abstract of DOI:10.1016/S0957-4166(00)00361-X

The application of the intramolecular allylsilane-iminium ion cyclization reaction for the enantioselective synthesis of piperidine derivatives is described. The synthetic potential of this methodology is demonstrated by the enantioselective synthesis of

Full text of DOI:10.1016/S0957-4166(00)00361-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 3913–3919
Enantioselective synthesis of 5-substituted pipecolic acids
using an intramolecular allylsilane-iminium ion cyclization
Muriel Cellier,a Yvonne Gelas-Mialhe,a,* Henri-Philippe Husson,b Bertrand Perrina and
Roland Remusona
aLaboratoire de Chimie des Substances Naturelles, UMR 6504, Universite´ Blaise Pascal (Clermont-Ferrand), 63177,
Aubie`re Cedex, France
bLaboratoire de Chimie The´rapeutique associe´ au CNRS et a` l’Universite´ Rene´ Descartes (UMR 8638),
Faculte´ des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l’Observatoire, 75270 Paris Cedex 06, France
Received 18 July 2000; accepted 12 September 2000
Abstract
The application of the intramolecular allylsilane-iminium ion cyclization reaction for the enantioselec-
tive synthesis of piperidine derivatives is described. The synthetic potential of this methodology is
demonstrated by the enantioselective synthesis of 5-substituted pipecolic acids. © 2000 Elsevier Science
Ltd. All rights reserved.
1. Introduction
The piperidine ring is a structural subunit found in a large number of naturally occurring
alkaloids. The stereoselective synthesis of functionalized piperidines has received considerable
attention due to the biological activities possessed by these compounds.1–3 Substituted pipecolic
acids are the subject of many current investigations.1,2,4,5 They have been used as key intermedi-
ates in the synthesis of different types of piperidine-like natural products and, as constrained
a-amino acids, they have been used as building blocks in the synthesis of peptidomimetics. We
report herein the enantioselective synthesis of 5-substituted pipecolic acids via a short sequence
of reactions, which should prove to be a general method for the synthesis of piperidine
derivatives. The key reaction in the sequence is an intramolecular allylsilane-iminium ion
addition. This type of Mannich intramolecular cyclization reaction has previously been used to
prepare piperidines possessing unsaturation.6–8 Our approach relies on chiral N-cyanomethyl-4-
phenyloxazolidine 1, which is efficiently prepared from (R)-(−)-phenylglycinol. Compound 1
represents a precursor of an iminium ion by opening of the oxazolidine ring whereas the cyano
* Corresponding author. E-mail: gelas@chisg1.univ-bpclermont.fr
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00361-X

3914
M. Cellier et al. / Tetrahedron: Asymmetry 11 (2000) 3913–3919
group can be transformed into a carboxylic acid function to obtain pipecolic acids. Further-
more, it provides the first stereogenic center used for the enantioselective elaboration of the
piperidine ring.
2. Synthesis and structural analysis
(R)-Cyanomethyloxazolidine 1 was prepared as previously described.9 Nickel catalyzed cou-
pling of trimethylsilylmethyl magnesium chloride with 2,3-dihydrofuran according to the
methodology described10,11 gave homoallylic alcohol 2.12 According to the literature procedure,9
1 was alkylated with iodide 4 to afford a 3:1 mixture of the allylsilyl diastereomers 5 and 6 in
75% yield (Scheme 1). These isomers were separated by flash chromatography. The (S) absolute
configuration was assigned to the new stereogenic center (C-6) of the major isomer 5 on the
basis of the chemical shift of H-6, by analogy with previous work.12
Scheme 1.
The intramolecular cyclization reaction (Scheme 2) was performed by treating the oxazolidine
with trimethylsilyl trifluoromethanesulfonate (TMSOTf). Treatment of allylsilyl substituted
oxazolidine 5 with TMSOTf resulted in conversion to piperidine 8 in 96% yield via the iminium
1
ion intermediate 7. The H NMR spectrum of 8 showed it to be a 9:1 mixture of two isomers
(8a and 8b, respectively), each displaying characteristic eight peak signals for the alkene
hydrogen H-7 at l 5.77 and 6.07 ppm. These diastereomers could not be separated by flash
chromatography. Alkylation product 6 was also reacted with TMSOTf to give piperidine 9 in
62% isolated yield after flash chromatography. This intramolecular cyclization proceeded with
excellent diastereoselectivity (>92%), as the C-5 diastereomer of 9 was only detected as a minor
component in the crude reaction mixture. The small coupling constants exhibited by proton H-2
for the piperidines 8a, 8b and 9 are consistent with an axial disposition of the cyano group.
Scheme 2.

M. Cellier et al. / Tetrahedron: Asymmetry 11 (2000) 3913–3919
3915
Stirring a solution of 2-cyanopiperidine 8 in a 1 M solution of HCl gas in ethyl acetate at
room temperature for 24 h afforded a 4:1 mixture of lactones 10 and 11 in 77% yield, which
1
were separated by flash chromatography. The 400 MHz H NMR spectrum of 10 showed H-2
as a double doublet with J=11.3 and 2.7 Hz, indicative of an axial position of this atom. The
two H-6 signals are indicative of an equatorial orientation of H-5 and hence of a cis
stereochemistry of the 2,5-disubstituted piperidine ring, with a 2S,5R absolute configuration.
The minor diastereomer 11 was assigned the trans stereochemistry, with a 2S,5S absolute
1
configuration. This structural assignment followed from its H NMR spectrum: Proton H-2
showed a large J1,2 value (11.5 Hz) due to a trans diaxial coupling. The axial orientation of H-5
was inferred from the large J value due to geminal and trans diaxial coupling exhibited by the
axial H-6 hydrogen. Similar reaction of 9 gave lactone 12 in 60% isolated yield. For this
diastereomer the values of the coupling constants for H-2 and H-6 indicated an axial orientation
for H-2 and H-5 and hence a trans stereochemistry of the piperidine ring, and a 2R,5R absolute
configuration.
Lactones 10, 11 and 12 were quantitatively converted to the corresponding pipecolic acid
derivatives 13, 14 and 15 respectively, upon cleavage of the lactone ring and hydrogenolysis of
the benzylic CꢀN bond in the presence of Pearlman’s catalyst. The structural assignments of
1
acids 13, 14 and 15 were confirmed by their H NMR spectra analysis.
3. Conclusion
In conclusion, we have developed a concise method for the synthesis of enantiomerically pure
5-substituted pipecolic acids, starting from readily available materials. The key step in the
synthesis is a stereoselective intramolecular cyclization which involves the formation of a CꢀC
skeletal bond. The other steps are functional group transformations. The work described herein
also provides a useful entry to enantiopure 5-substituted 2-cyanopiperidines which are consid-
ered to be valuable building blocks in the synthesis of 2-aminomethylpiperidines used in the
preparation of several pharmaceuticals.13–17

3916
M. Cellier et al. / Tetrahedron: Asymmetry 11 (2000) 3913–3919
4. Experimental
4.1. General
NMR spectra were recorded on a Bruker AC 400 spectrometer operating at 400.13 MHz for
1H NMR and 100.61 MHz for 13C NMR. Chemical shifts were recorded as l values (ppm) and
1
coupling constants were expressed in hertz (Hz). H and 13C NMR assignments were confirmed
by 2D-COSY spectra. A Perkin–Elmer 377 instrument was used to effect IR spectra. TLC
analyses were performed on Merck 60 F254 silica gel plates and were visualized using iodine.
Flash column chromatography was carried out using Merck silica gel (grade 60, 230–400 mesh).
4.2. N-(1-Cyano-6-trimethylsilylhex-4-enyl)-4-phenyloxazolidines 5 and 6
A solution of cyanomethyloxazolidine 19 (3.27 g, 0.017 mol) in THF (25 mL) was added to
a stirring solution of LDA–HMPA (1:1, 1.25 equiv.) in THF (50 mL) under argon at −78°C and
the stirring was continued for 30 min. Iodide 4 (5.1 g) was then added and the mixture was
stirred at room temperature overnight. It was then hydrolyzed with saturated aqueous ammon-
ium chloride and extracted with ether. The combined extracts were dried, concentrated and the
residue chromatographed on silica gel (hexane–ethyl acetate 95:5 as eluent) to give 3.2 g of 5 and
1.05 g of 6 (75% overall yield).
1
Compound 5: oil; [h]D −162 (c 0.99, CHCl3); IR (cm−1) 1695, 2220; H NMR (CDCl3) 0.00
(9H, s, SiMe3), 1.45 (2H, d, H-11, J=8.7), 1.75 (2H, q, H-7, J=7.7), 2.15 (2H, m, H-8), 3.62
(1H, t, H-6, J=8.0), 3.72 (1H, t, H-4, J=8.3), 4.01 (1H, dd, H-5, J=7.4, 8.3), 4.31 (1H, t, H-5,
J=7.4), 4.49 (1H, d, H-2, J=2.5), 4.83 (1H, d, H-2, J=2.5), 5.13 (1H, m, H-9), 5.45 (1H, m,
H-10), 7.30–7.40 (5H, m, Ph); 13C NMR (CDCl3) −1.7, 18.9, 23.3, 32.9, 50.6, 65.4, 74.4, 82.4,
117.1, 124.2, 127.7, 128.1, 128.5, 128.9, 137.2; anal. calcd for C19H28N2OSi: C, 69.46; H, 8.59; N,
8.53; Si, 8.55. Found: C, 69.52; H, 8.64; N, 8.58; Si, 8.25.
1
Compound 6: oil; [h]D −103 (c 0.9, CHCl3); IR (cm−1) 1645, 2220; H NMR (CDCl3) 0.00
(9H, s, SiMe3), 1.43 (2H, m, H-11), 1.60 (2H, q, H-7, J=7.3), 2.02 (2H, m, H-8), 3.71 (1H, dd,
H-4, J=6.2, 8.4), 3.81 (1H, t, H-6, J=7.8), 4.24 (1H, dd, H-5, J=6.2, 7.5), 4.42 (1H, t, H-5,
J=8.1), 4.58 (1H, d, H-2, J=4.4), 4.78 (1H, d, H-2, J=4.4), 5.06 (1H, m, H-9), 5.48 (1H, m,
H-10), 7.25–7.45 (5H, m, Ph); 13C NMR (CDCl3) −1.7, 18.5, 23.0, 32.9, 53.8, 63.1, 75.1, 87.3,
118.8, 124.3, 126.8, 127.7, 128.2, 128.8, 141.8; anal. calcd for C19H28N2OSi: C, 69.46; H, 8.59; N,
8.53; Si, 8.55. Found: C, 69.58; H, 8.88; N, 8.18; Si, 8.40.
4.3. N-(1-Phenyl-2-hydroxyethyl)-2-cyano-5-vinylpiperidines 8 and 9
Trimethylsilyl trifluoromethanesulfonate (1.2 equiv., 71 mL) was added to a stirred 0.3 M
solution of oxazolidine 5 (0.1 g, 0.30 mmol) in anhydrous methylene chloride (1 mL) at −40°C
under argon. The solution was stirred for 30 min at −40°C and for 3 h at room temperature.
After concentration, the residue was chromatographed over silica gel (eluted with ethyl
acetate–hexane 5:5) to give 0.075 g (96% yield) of a mixture of piperidines 8a and 8b (8a/8b 9:1):
oil; [h]D −83 (c 0.21, CHCl3); IR (cm−1) 3630, 3610, 3500, 2230, 1650, 1620; anal. calcd for
C16H20N2O: C, 74.96; H, 7.86; N, 10.93; O, 6.24. Found: C, 74.56; H, 8.12; N, 10.25; O, 6.76.
1
Compound 8a: H NMR (CDCl3) l 1.40–1.60 (1H, m, H-4), 1.70–1.90 (3H, m, H-3a, H-3e,
H-4), 2.30–2.40 (2H, m, H-5, H-6), 3.21 (1H, m, H-6), 3.57 (1H, dd, H-9, J=5.3, 4.1), 3.62 (1H,

M. Cellier et al. / Tetrahedron: Asymmetry 11 (2000) 3913–3919
3917
t, H-2, J=3.3), 3.82 (1H, dd, H-10, J=11.5, 4.1), 3.92 (1H, dd, H-10, J=11.5, 5.3), 5.04 (1H,
d, H-8, J=10.4), 5.10 (1H, d, H-8, J=17.1), 5.77 (1H, ddd, H-7, J=17.1, 10.4, 6.3), 7.25–7.50
(5H, m, Ph); 13C NMR (CDCl3) 26.6 (C-4), 28.5 (C-3), 40.1 (C-5), 51.0 (C-2), 51.9 (C-6), 64.0
(C-10), 69.5 (C-9), 115.2 (C-8), 116.9 (CN), 128.3, 128.4, 129.0 and 140.0 (Ph), 140.3 (C-7).
1
Compound 8b: H NMR (CDCl3) l 2.55 (1H, dd, J=12.2, 3.1), 2.65 (1H, d, J=12.2), 4.33
(1H, broad s, H-2), 6.03 (1H, ddd, H-7, J=17.2, 10.5, 6.4); 13C NMR (CDCl3) 25.6 (C-4), 26.6
(C-3), 36.9 (C-5), 51.5 (C-2), 51.6 (C-6), 64.2 (C-10), 69.8 (C-9), 115.3 (C-8), 117.2 (CN), 128.3,
128.7, 128.8 and 140.0 (Ph), 140.3 (C-7).
Compound 9 was prepared as described for 8. Oxazolidine 6 (0.3 g, 0.91 mmol) in anhydrous
methylene chloride (3 mL) gave 0.145 g of pure piperidine 9 (62% yield): mp 58–60°C; [h]D −47
1
(c 0.78, CHCl3); IR (cm−1) 3600, 3480, 2220, 1640, 1610; H NMR (CDCl3) l 1.45 (1H, qd,
H-4a, J=13.0, 4.3), 1.80 (1H, broad d, H-4e, J=13.0), 1.90–2.10 (3H, m, H-3a, H-3e, H-6),
2.12–2.22 (1H, m, H-5), 2.66 (1H, dd, H-6, J=11.7, 3.0), 3.58 (1H, t, H-9, J=5.0), 3.78 (1H, dd,
H-10, J=12.0, 5.0), 3.88, (1H, dd, H-10, J=12.0, 4.0), 4.36 (1H, broad s, H-2), 4.93 (1H, d, H-8,
J=10.0), 4.97 (1H, d, H-8, J=17.0), 5.58 (1H, ddd, H-7, J=17.0, 10.5, 6.7), 7.30–7.50 (5H, m,
Ph); 13C NMR (CDCl3) 26.5 (C-4), 28.7 (C-3), 39.8 (C-5), 50.2 (C-2), 52.1 (C-6), 64.2 (C-10),
69.3 (C-9), 114.5 (C-8), 117.2 (CN), 127.9, 128.4, 128.8 and 138.9 (Ph), 139.7 (C-7).
4.4. 4-Phenyl-7-vinylhexahydropyrido[2,1c][1,4]oxazin-1-one 10, 11 and 12
A mixture of piperidines 8a and 8b (0.6 g, 0.23 mmol) was dissolved in a 1 M solution of HCl
gas in ethyl acetate (18.7 mL) and SiO2 (6 g) was added.18 The mixture was stirred for 24 h,
neutralized with saturated aqueous K2CO3, filtered and extracted with ethyl acetate. The
combined extracts were dried and concentrated to give a 4:1 mixture of lactones 10 and 11 (0.46
g, 77% yield) which were separated by chromatography on silica gel (hexane–ethyl acetate 8:2 as
eluent).
1
Compound 10: white solid, mp 148°C; [h]D −114 (c 0.355, CHCl3); IR (cm−1) 1760, 1640; H
NMR (CDCl3) l 1.60–1.70 (1H, m, H-4), 1.85–1.95 (2H, m, H-3, H-4), 2.0 (1H, dd, H-6a,
J=11.4, 3.8), 2.20–2.35 (2H, m, H-3, H-5), 2.76 (1H, dd, H-6e, J=11.4, 2.2), 3.00 (1H, dd,
H-2a, J=11.3, 2.7), 3.57 (1H, dd, H-9, J=11.1, 3.8), 4.23 (1H, dd, H-10, J=11.1, 3.8), 4.33 (1H,
t, H-10, J=10.8), 5.05 (1H, d, H-8, J=17.3), 5.09 (1H, d, H-8, J=10.5), 6.15 (1H, ddd, H-7,
J=6.8, 10.5, 17.3); 13C NMR (CDCl3) l 23.9 (C-3), 29.2 (C-4), 36.4 (C-5), 56.4 (C-6), 64.2 (C-9),
64.7 (C-2), 72.7 (C-10), 114.5 ((C-8), 128.3, 128.5, 128.8 and 136.2 (Ph), 140.4 (C-7), 169.2
(CꢁO); anal. calcd for C16H19NO2: C, 74.68; H, 7.44; N, 5.44; O, 12.44. Found: C, 74.54; H,
7.12; N, 5.76; O, 12.02.
1
Compound 11: oil; [h]D −70 (c 1.89, CHCl3); IR (cm−1) 1760, 1640; H NMR (CDCl3) l 1.10
(1H, tdd, H-4a, J=13.0, 11.9, 4.0), 1.75 (1H, tdd, H-3a, J=13.0, 11.5, 3.9), 1.85–1.92 (1H, m,
H-4e), 1.97 (1H, t, H-6a, J=11.6), 2.15–2.30 (2H, m, H-3e, H-5a), 2.82 (1H, ddd, H-6e, J=11.6,
3.8, 1.8), 3.12 (1H, dd, H-2a, J=11.5, 3.2), 4.0 (1H, t, H-9, J=4.0), 4.51 (1H, dd, H-10, J=11.0,
4.0), 4.69 (1H, dd, H-10, J=11.0, 4.0), 4.91 (1H, ddd, H-8, J=10.3, 1.5, 1.3), 4.94 (1H, ddd,
H-8, J=17.2, 1.5, 1.3), 5.54 (1H, ddd, H-7, J=17.2, 10.3, 6.8), 7.40–7.80 (5H, m, Ph); 13C NMR
(CDCl3) l 26.8 (C-3), 30.2 (C-4), 38.0 (C-5), 56.2 (C-6), 58.4 (C-2), 59.1 (C-9), 73.1 (C-10), 114.5
(C-8), 128.5, 128.8 and 134.5 (Ph), 140.1 (C-7), 170.2 (CꢁO).
Compound 12 was prepared from 9 (0.145 g, 0.566 mmol) as described previously. The crude
product was purified by chromatography on silica gel (hexane–ethyl acetate 8:2 as eluent) to give
piperidinolactone 12 (0.087 g, 60% yield): oil; [h]D −118 (c 1.485, CHCl3); IR (cm−1) 1760, 1640;

3918
M. Cellier et al. / Tetrahedron: Asymmetry 11 (2000) 3913–3919
1H NMR (CDCl3) l 1.20 (1H, qd, H-4a, J=13.0, 4.1 Hz), 1.49 (1H, t, H-6a, J=11.2), 1.69 (1H,
tdd, H-3a, J=13.1, 11.4, 3.8), 1.89 (1H, d large, H-4e, J=12.7), 2.10–2.22 (1H, m, H-5a), 2.41
(1H, d large, H-3e, J=13.1), 2.72 (1H, ddd, H-6e, J=11.2, 3.7, 1.5), 2.88 (1H, dd, H-2a,
J=11.4, 2.5), 3.57 (1H, dd, H-9, J=10.6, 3.8), 4.15 (1H, dd, H-10, J=11.1, 3.8), 4.22 (1H, t,
H-10, J=10.9), 4.82 (IH, d, H-8, J=11.5Hz), 4.88 (1H, d, H-8, J=17.5Hz), 5.49 (1H, ddd, H-7,
J=17.2, 10.6, 6.8), 7.20–7.45 (5H, m, Ph); 13C NMR (CDCl3) l 27.6 (C-3), 30.2 (C-4), 39.2
(C-5), 57.2 (C-6), 64.1 (C-2), 64.3 (C-9), 72.7 (C-10), 114.1 (C-8), 128.5, 128.6, 128.9 and 136.1
(Ph), 139.9 (C-7), 169.1 (CꢁO).
4.5. (2S,5S)-5-Ethylpipecolic acid 13
The piperidinolactone 10 (54 mg, 0.21 mmol) was dissolved in ethanol (14 mL), acetic acid
(0.35 mL) and water (1.4 mL) and Pearlman’s catalyst (80 mg) was added. The resultant mixture
was stirred under 4 atm of hydrogen at room temperature for 48 h in a Parr apparatus. Removal
of the catalyst by filtration through a Celite pad followed by evaporation of the solvent in vacuo
furnished the free amino acid in a quantitative yield: white solid, mp 205–210°C; [h]D −13 (c 1.3,
1
H2O); H NMR (D2O) l 0.96 (3H, t, H-8, J=7.4), 1.20–1.34 (1H, m, H-4), 1.35–1.50 (2H, m,
H-7), 1.65–1.80 (1H, m, H-5), 1.82–1.94 (1H, m, H-4), 1.95–2.05 (1H, m, H-3), 2.22–2.40 (1H,
m, H-3), 3.08 (1H, dd, H-6a, J=10.2, 12.7), 3.32 (1H, dd, H-6e, J=3.8, 12.7), 3.95 (1H, t, H-2,
J=4.6); 13C NMR (D2O) l 12.8 (C-8), 26.6 (C-3), 27.8 (C-7), 27.9 (C-4), 36.2 (C-5), 48.8 (C-6),
59.2 (C-2), 176.4 (CꢁO); anal. calcd for C8H15NO2: C, 61.12; H, 9.62; N, 8.91. Found: C, 61.56;
H, 9.21; N, 8.58.
4.6. (2S,5R)-5-Ethylpipecolic acid 14
The piperidinolactone 11 (52 mg, 0.20 mmol) was dissolved in ethanol (5 mL) and Pearlman’s
catalyst (80 mg) was added. The resultant mixture was stirred under 4 atm of hydrogen at room
temperature for 48 h in a Parr apparatus. Removal of the catalyst by filtration through a Celite
pad followed by evaporation of the solvent in vacuo furnished the free amino acid (29 mg, 92%
1
yield): oil; [h]D +18 (c 1.35, H2O); H NMR (D2O) l 1.00 (3H, t, H-8, J=7.4), 1.22–1.50 (3H,
m, H-7, H-4e), 1.62–1.80 (2H, m, H-3a, H-5a), 2.00 (1H, d large, H-4e, J=13.2), 2.35 (1H, dq,
H-3e, J=3.2, 14.3), 2.75 (1H, t, H-6a, J=12.5), 3.50 (1H, dd, H-6e, J=2.8, 12.5), 3.70 (1H, dd,
H-2a, J=3.2, 12.8); 13C NMR (D2O)) l 12.8 (C-8), 28.3 (C-7), 29.3 (C-3), 31.1 (C-4), 37.1 (C-5),
50.8 (C-6), 62.1 (C-2), 177.4 (C=O); anal. calcd for C8H15NO2: C, 61.12; H, 9.62. Found: C,
61.42; H, 10.06.
4.7. (2R,5S)-5-Ethylpipecolic acid 15
Hydrogenolysis of the piperidinolactone 12 (80 mg, 0.31 mmol) was performed as described
1
above to furnish the free amino acid in a quantitative yield: oil; [h]D −17 (c 2.0, H2O); H NMR
(D2O) l 1.00 (3H, t, H-8, J=7.4), 1.22–1.50 (3H, m, H-7, H-4e), 1.62–1.80 (2H, m, H-3a, H-5a),
2.00 (1H, d large, H-4e, J=13.2), 2.35 (1H, dq, H-3e, J=3.2, 14.3), 2.75 (1H, t, H-6a, J=12.5),
3.50 (1H, dd, H-6e, J=2.8, 12.5), 3.70 (1H, dd, H-2a, J=3.2, 12.8); 13C NMR (D2O) l 12.8
(C-8), 28.3 (C-7), 29.3 (C-3), 31.1 (C-4), 37.1 (C-5), 50.8 (C-6), 62.1 (C-2) 177.4 (CꢁO); anal.
calcd for C8H15NO2: C, 61.12; H, 9.62; N, 8.91. Found: C, 60.68; H, 9.28; N, 8.60.

M. Cellier et al. / Tetrahedron: Asymmetry 11 (2000) 3913–3919
3919
Acknowledgements
The authors wish to thank Professor Jean-Claude Gramain for helpful discussions.
References
1. Strunz, G. M.; Findlay, J. A. In The Alkaloids; Brossi, A., Ed. Pyridine and Piperidine alkaloids. Academic Press:
New York, 1985; Vol. 26, pp. 89.
2. Angle, S. R.; Breitenbucher, J. G. In Studies in Natural Products; Atta-ur-Rahman, Ed. Recent Progress in the
Synthesis of Piperidine and Indolizidine Alkaloids. Elsevier Science: Amsterdam, 1995; Vol. 16, pp. 453.
3. Bailey, P. D.; Millwood, P. A.; Smith, P. D. J. Chem. Soc., Chem. Commun. 1998, 633–640.
4. Couty, F. Amino Acids 1999, 16, 297–320.
5. Zaparucha, A.; Danjoux, M.; Chiaroni, A.; Royer, J.; Husson, H.-P. Tetrahedron Lett. 1999, 40, 3699–3700.
6. Grieco, P. A.; Fobare, W. F. Tetrahedron Lett. 1986, 27, 5067–5070.
7. Agami, C.; Bihan, D.; Morgentin, R.; Puchot-Kadouri, C. Synlett 1997, 799–800.
8. Wu, X.-D.; Khim, S.-K.; Zhang, X.; Cederstrom, E. M.; Mariano, P. S. J. Org.Chem. 1998, 63, 841–859.
9. Marco, J. L.; Royer, J.; Husson, H.-P. Tetrahedron Lett. 1985, 26, 3567–3570.
10. Wenkert, E.; Michelotti, E. L.; Swindell, C. S.; Tingoli, M. J. Org. Chem. 1984, 49, 4894–4899.
11. Kocienski, P. J.; Pritchard, M.; Wadman, S. N.; Whitby, R. J.; Yeates, C. L. J. Chem. Soc., Perkin Trans. 1 1992,
3419–3429.
12. Hiemstra, H.; Sno, M. H. A. M.; Vijn, R. J.; Speckamp, W. N. J. Org. Chem. 1985, 50, 4014–4020.
13. Perumattam, J.; Shearer, B. G.; Confer, W. L.; Mathew, R. M. Tetrahedron Lett. 1991, 32, 7183–7186.
14. Compernolle, F.; Saleh, M.-A.; Toppet, S.; Hoonaert, G. J. Org. Chem. 1991, 56, 5192–5196.
15. Murray, P. J.; Starkey, I. D. Tetrahedron Lett. 1996, 37, 1875–1878.
16. Froelich, O.; Desos, P.; Bonin, M.; Quirion, J.-C.; Husson, H.-P. J. Org. Chem. 1996, 61, 6700–6705.
17. Nazabadioko, S.; Perez, R. J.; Brieva, R.; Gotor, V. Tetrahedron: Asymmetry 1998, 9, 1597–1604.
18. Agami, C.; Couty, F.; Mathieu, H. Tetrahedron Lett. 1996, 37, 4001–4002.
.
.