A new synthesis of all four stereoisomers of 2-(2,3- dihydroxypropyl)piperidine via iterative asymmetric dihydroxylation to cause enantiomeric enhancement. Application to asymmetric synthesis of naturally occurring piperidine-related alkaloids

Article abstract of DOI:10.1021/jo991034w

Both enantiomers of 2-(2-propenyl)piperidine 1 (76-88% ee), prepared via the first asymmetric dihydroxylation (AD) of 5-hexenyl azide, underwent the second AD to provide all four of the stereoisomeric 2-(2,3- dihydroxypropyl)piperidines 2 with enantiomeric enhancement.(>98% ee). An asymmetric synthesis, starting from 2, of several 2-(2- hydroxyalkyl)piperidine alkaloids [(-)halosaline, (+)-N-methylallosedridine, (+)-8-ethylnorlobelol, (+)-sedridine, (+)-allosedridine, (-)allosedridine, and (+)-N-methylsedridine] and the ant defense alkaloids [(+)-tetraponerine-3 (T-3), T-4, T-7, and T-8] is demonstrated.

Full text of DOI:10.1021/jo991034w

8594
J . Org. Chem. 1999, 64, 8594-8601
A New Syn th esis of All F ou r Ster eoisom er s of
2-(2,3-Dih yd r oxyp r op yl)p ip er id in e via Iter a tive Asym m etr ic
Dih yd r oxyla tion To Ca u se En a n tiom er ic En h a n cem en t.
Ap p lica tion to Asym m etr ic Syn th esis of Na tu r a lly Occu r r in g
P ip er id in e-Rela ted Alk a loid s
Hiroki Takahata,*,† Minoru Kubota,† and Nobuo Ikota‡
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630,
Toyama 930-0194, J apan, and National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku,
Chiba 263-8555, J apan
Received J une 28, 1999
Both enantiomers of 2-(2-propenyl)piperidine 1 (76-88% ee), prepared via the first asymmetric
dihydroxylation (AD) of 5-hexenyl azide, underwent the second AD to provide all four of the
stereoisomeric 2-(2,3-dihydroxypropyl)piperidines 2 with enantiomeric enhancement (>98% ee).
An asymmetric synthesis, starting from 2, of several 2-(2-hydroxyalkyl)piperidine alkaloids [(-)-
halosaline, (+)-N-methylallosedridine, (+)-8-ethylnorlobelol, (+)-sedridine, (+)-allosedridine, (-)-
allosedridine, and (+)-N-methylsedridine] and the ant defense alkaloids [(+)-tetraponerine-3 (T-
3), T-4, T-7, and T-8] is demonstrated.
In tr od u ction
improve the stereoselectivity (ee) on the basis of the
following consideration: The first AD (AD-mix-R) reaction
produces the major (S) and minor (R) enantiomers. After
the introduction of the terminal olefin followed by the
second AD (AD-mix-R), four products result: (S,S)-,
(S,R)-, (R,S)-, and (R,R)-isomers. The relationship be-
tween the desired (S,S)-isomer and the undesired (S,R)-
and (R,S)-isomers is diastereomeric. Very little of the
mirror image (R,R)-isomer is formed, and therefore the
enantiomeric purity of the desired (S,S)-isomer will be
high. On the other hand, the diastereomer of a mixture
of (S,R)- and (R,S)-isomers could show low ee.7
We now describe our findings that additional AD of 1
and ent-1 afforded all four stereoisomers of 2-(2,3-
dihydoxypropyl)piperidine (2) with enantiomeric enhance-
ment, and demonstrate the synthetic utility of 2 by an
expeditious asymmetric synthesis of the 2-(2-hydroxy-
alkyl)piperidine alkaloids such as (-)-halosaline, (+)-N-
methylallosedridine, (+)-8-ethylnorlobelol-I, (+)-sedri-
dine, (+)-allosedridine, (-)-allosedridine, and (+)-N-
methylsedridine and the ant defense alkaloids (+)-
tetraponerine-3 (T-3), T-4, T-7, and T-8 (Chart 1) in short
steps.8
Biologically active alkaloids of the substituted piperi-
dine ring system have been the target of considerable
synthetic efforts.1 The development of methods for the
asymmetric synthesis of 2-substituted piperidines re-
mains an area of substantial interest.2 During our
continuing studies on asymmetric synthesis of piperidine
alkaloids,3 we recently achieved a new asymmetric
synthesis of both enantiomers of 2-(2-propenyl)piperidine
1 via the Sharpless asymmetric dihydroxylation (AD) of
5-hexenyl azide, the design leading to 2-substituted
piperidine and related alkaloids (Scheme 1).4 However,
the precedented AD established by the Sharpless group
suggested that enantiomeric excess (ee) in the case of
terminal olefins might be modest except for arylvinyls
such as styrene.5 In practice, the ees of 1 and ent-1 were
76-88%.4 Our interest in this field has been focused on
the synthetic application of the double AD to cause
enantiomeric enhancement (or amplification).6 We an-
ticipate that repeated AD for the terminal olefins might
† Toyama Medical and Pharmaceutical University.
‡ National Institute of Radiological Sciences.
(1) (a) Elbein, A. D.; Molyneux, R. In Alkaloids; Chemical and
Biological perspectives; Pelletier, S. W., Ed.; J ohn Wiley and Sons: New
York, 1987; Vol. 57, p 1. (b) O’Hagen, D. Nat. Prod. Rep. 1997, 14,
637.
Resu lts a n d Discu ssion
(2) (a) Sterino, C.; Stehle, N.; Park, Y. S.; Florio, S.; Beak, P. J . Org.
Chem. 1999, 64, 1160. (b) Pilli, R. A.; de Fatima Alves, C.; Bockelmann,
M. A.; Mascarenhas, Y. P.; Nery J . G.; Vencato, I. Tetrahedron Lett.
1999, 40, 2891. (c) Katritzky, A. R.; Qiu, G.; Yang, B.; Steel, P. J . J .
Org. Chem. 1998, 63, 6699. (d) Reding, M. T.; Buchwald, S. L. J . Org.
Chem. 1998, 63, 6344. (e) Weymann, M.; Pfrengle, W.; Schollmeyer,
D.; Kuntz. H. Synthesis 1997, 1151. (f) Munchhof, J . M.; Meyers, A. I.
J . Org. Chem. 1995, 60, 7084.
Syn th esis of All F ou r Ster eoisom er s of 2-(2-Hy-
d r oxya lk yl)p ip er id in e via Iter a tive Asym m etr ic
Dih yd r oxyla tion . An asymmetric synthesis of 2-(2-
propenyl)piperidines 1 and ent-1 via the first AD (PYR
ligand) reaction of 5-hexenyl azide has been performed
by us.4 On the basis of the above principle, the second
AD [(DHQ)2PYR ligand]9 reaction of the terminal olefin
(3) (a) Takahata, H.; Bandoh, H.; Hanayama, M.; Momose, T.
Tetrahedron: Asymmetry 1992, 3, 607. (b) Takahata, H.; Inose, K.;
Momose, T. Heterocycles 1994, 38, 269.
(4) Takahata, H.; Kubota, M.; Takahashi, S.; Momose, T. Tetrahe-
dron: Asymmetry 1996, 7, 3047.
(5) For an excellent review, see: Kolb, H. C.; VanNieuwenhze, M.
S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483.
(6) (a) Takahata, H.; Takahashi, S.; Kouno S.; Momose, T. J . Org.
Chem. 1998, 63, 2224. (b) Takahata, H.; Kouno S.; Momose, T.
Tetrahedron: Asymmetry 1995, 6, 1085.
(7) Baba, S. E.; Sartor, K.; Poulin, J .-C.; Kagan, H. B. Bull. Soc.
Chim. Fr. 1994, 131, 525.
(8) A part of this work has been published as a preliminary
communication. Takahata, H.; Kubota, M.; Momose, T. Tetrahedron
Lett. 1997, 38, 3451.
(9) Crispino, G. A.; J eong, K.-S.; Kolb, H. C.; Wang, Z.-M.; Xu, D.;
Sharpless, K. B. J . Org. Chem. 1993, 58, 3785.
10.1021/jo991034w CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/21/1999

Synthesis of 2-(2,3-Dihydroxypropyl)piperidines
J . Org. Chem., Vol. 64, No. 23, 1999 8595
Sch em e 1a
a
Conditions: (a) cat. K2OsO4‚2H2O/cat. (DHQ)2PYR,/K3Fe(CN)6,/K2CO3; (b) cat. K2OsO4‚2H2O/cat. (DHQD)2PYR,/K3Fe(CN)6,/K2CO3,
ref 4; (a) epoxidation (1, CH3C(OCH3)3/PPTS; 2, CH3COBr; 3, K2CO3); (b) vinylmagnesium bromide/CuBr-(CH3)2S; (c) MsCl/pyridine; (d)
Ph3P/THF/H2O; (e) CbzCl/K2CO3.
Ch a r t 1
of 5 to an atmosphere of hydrogen in the presence of Pd-
(OH)2 as a catalyst in MeOH caused simultaneous
reduction of its double bond and debenzyloxycarbonyla-
tion to give the desired (-)-4 {[R]D -19.0° (EtOH), lit.11b
[R]D -19.5° (EtOH)} in quantitative yield.
Two [2R-(2S)]-2-(2-hydroxyalkyl)piperidines, (+)-N-
methylallosedridine (6),12 isolated from Sedum sarmen-
tosum, and (+)-8-ethylnorlobelol-I (7),13 produced by
Loberia inflata, are found. So far, an asymmetric syn-
thesis of these alkaloids, to our knowledge, has not been
reported. We began with the synthesis of 6. Reduction
of the epoxide [2R-(2R)]-3 with LiAlH4 gave 6 {[R]D +78°
(EtOH), lit.12b [R]D +67° (96% EtOH)}as a single product
in 89% yield. Its spectral data were identical with those
reported.14 Treatment of [2R-(2R)]-3 with lithium di-
methylcuprate resulted in the cleavage of the epoxide
ring to provide the alcohol 8, which was converted into
[2R-(2S)]-7 {mp 53-4 °C; [R]D +10.2° (EtOH)} by hydro-
genolysis in 82% overall yield. Surprisingly, both its
melting point and specific rotation were obviously dif-
ferent from the reported values {mp 87 °C; [R]22D +22.3°
(EtOH)}.13 We considered the absolute configuration of
natural (+)-8-ethylnorlobelol-I could be 2S-(2S) on the
basis of the following speculation. Since halosarine (4)
of [2R-(2R)] configuration appears levorotatory, both [2R-
(2R)]-7 and [2S-(2R)]-7 will be levorotatory. Accordingly,
only [2S-(2S)] remains among three possible configura-
tions. In fact, it is known that sedridine (9) of [2S-2(S)]
configuration is dextrorotatory.15 In practice, [2S-2(S)]-
7 was synthesized from the epoxide [2S-2(R)]-3 via 10
in 1 was carried out to afford a readily separable mixture
of the major diastereomer [2R-(2S)]-2 (>98% ee) and the
minor diastereomer [2R-(2R)]-2 (54% ee). These results
containing three other examples are shown in Table 1.
Since the enantioselectivities of four all of the major
diastereomers of 2 were found to be more than 98% ee,
the enantiomeric enhancement by repeated AD was
exemplified.
Asym m etr ic Syn th esis of 2-(2-Hyd r oxya lk yl)p ip -
er id in e Alk a loid s. With all four homochiral 2-(2,3-
dihydroxypropyl)piperidines 2 in hand, we focused our
attention on their transformation into biologically active
2-(2-hydroxyalkyl)piperidine alkaloids. Our synthesis
began with the epoxidation of 2. The four diols 2 were
converted into the four epoxides 3 by the Sharpless one-
pot procedure (1, CH3C(OCH3)3/PPTS; 2, CH3COBr; 3, K2-
CO3)10 in good yields (Scheme 2). Having obtained these
results, the first asymmetric synthesis of (-)-halosarine
(4),11 isolated from Haloxylon salicornicum, was under-
taken. The regioselective cleavage of the epoxide ring in
[2R-(2S)]-3 with vinylmagnesium bromide in combination
with a cuprous bromide-dimethyl sulfide complex was
performed to yield the alcohol 5 in 95% yield. Exposure
(12) (a) Marion, L.; Chaput, M. Can. J . Res. 1949, 27, 215. (b)
Beyerman, H. C.; Bordes, B. S. L.; Maat, L.; Warnaar, F. M. Recl. Trav.
Chim. Pays-Bas 1972, 91, 1441. (c) Kim, J . H.; T’Hart, H.; Stevens, J .
F. Phytochemistry 1996, 41, 1319.
(13) Scho¨pf, C.; Kauffmann, T. J ustus Liebigs Ann. Chem. 1957, 608,
88.
(14) Schneider, M. J .; Brendze, S.; Montali, J . A. Phytochemistry
1995, 39, 1387.
(15) (a) Beyerman, H. C.; Maat, L.; Van Veen, A.; Zweistra, A.; von
Philipsborn, W. Recl. Trav. Chim. Pays-Bas 1965, 84, 1367. (b)
Murahashi, S. Imada, Y.; Kohno, M.; Kawakami, T. Synlett 1993, 395.
(c) Louis, C.; Hootele´, C. Tetrahedron: Asymmetry 1997, 8, 109. (d)
Littler, B. J .; Gallagher, T.; Boddy, I. K.; Riordan, P. Synlett 1997, 22.
(10) Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48, 10515.
(11) (a) Micel, K.-H.; Sandberg, F.; Haglid, F.; Norin, T. Acta Pharm.
Suec. 1967, 4, 97. (b) Micel, K.-H.; Sandberg, F.; Haglid, F.; Norin, T.;
Chan, R. P. K.; Craig, J . C. Acta Chem. Scand. 1969, 23, 3479.

8596 J . Org. Chem., Vol. 64, No. 23, 1999
Ta ble 1. AD Rea ction of Both En a n tiom er s of 1
Takahata et al.
substrate 1
ligand
major compd 2
yield (%)
(ee (%))
minor compd 2
yield (%)
(ee (%))
1
1
(DHQ)2PYRa
(DHQD)2PYRb
(DHQ)2PYR
[2R-(2S)]-2
[2R-(2R)]-2
[2S-(2S)]-2
[2S-(2R)]-2
70
69
70
74
(>98)
(>98)
(>98)
(>98)
[2R-(2R)]-2
[2R-(2S)]-2
[2S-(2R)]-2
[2S-(2S)]-2
21
22
22
14
(54)
(54)
(72)
(47)
ent-1
ent-1
(DHQD)2PYR
a
(DHQ)2PYR ) hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether. b (DHQD)2PYR ) hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl
diether.
Sch em e 2a
a
Conditions: (a) (1) (MeO)3CMe/PPTS; (2) MeCOBr; (3) K2CO3/MeOH; (b) vinylmagnesium bromide/Me2S-CuBr; (c) H2/Pd(OH)2; (d)
LiAlH4; (e) Me2CuLi; (f) Super-Hydride.
by the analogous procedure described for [2R-(2S)]-7.
Both the melting point (mp 88-89 °C) and the specific
rotation {[R]D +25.8° (EtOH)} are almost identical with
those reported (vide supra).13 It is thus concluded that
the absolute configuration of natural (+)-8-ethylnorlo-
belol-I is 2S-(2S).16
Next, an asymmetric synthesis of [2S-(2S)]-2-(2-hy-
droxypropyl)piperidine, (+)-sedridine (9),15a isolated from
Sedum acre, was performed. Super-Hydride-induced
reduction of [2S-2(R)]-3 resulted in only ring-cleavage to
yield the alcohol [2S-(2S)]-11, which was hydrogenated
to give 9 {[R]D +28.4° (EtOH), lit.15b [R]D +28.5° (EtOH)}
in 95% yield. Its spectral data were in agreement with
those reported.15 In a similar fashion, the synthesis of
both enantiomers (12 and ent-12) of allosedridine,17,18
isolated from Sedum nudum, was achieved from [2R-
(2R]- and [2S-(2S)]-3, respectively, using a two-step
sequence. Finally, N-methylsedridine (13),14,18 isolated
from Sedum polytrichoides, was synthesized by reduction
of [2S-2(R)]-3 with LiAlH4 in 99% yield. Its spectral data
were consistent with those reported.14
Asym m etr ic Syn th esis of An t Defen se Alk a loid s.
Eight toxic alkaloids with an original tricyclic structure
are found in New Guinean ant venom: tetraponerine-1
to tetraponerine-8 (T-1 to T-8) isolated from Tetraponera
sp. by Braekman et al.19 So far, the synthesis of T-8 has
been reported several times in both racemic and chiral
forms,20 whereas asymmetric synthesis of others except
(17) (a) Scho¨pf, C.; Gams, E.; Koppernock, F.; Rausch, R. Wallbe,
R. Liebigs Ann. Chem. 1970, 732, 181. (b) Stevens, J . F.; T’Hart, H.;
Hendriks, H.; Malingre´, T. M. Phytochemistry 1992, 31, 3917.
(18) The absolute configurations of both allosedridine (12) and
N-methylsedridine (13) remain unknown.
(19) (a) Merlin, P.; Breakman, J .-C.; Daloze, D.; Pasteels, J .-M. J .
Chem. Ecol. 1988, 14, 517. (b) Breakman, J .-C.; Daloze, D.; Pasteels,
J .-M.; Vanhecke, P.; Declercq, J .-P.; Sinnwell, V.; Franke, W. Z.
Naturforsch. 1987, 42C, 627.
(16) Recently, the same correction of the absolute configuration of
(+)-8-ethylnorlobelol-I was proposed. Mill, S.; Durant, A.; Hootele´, C.
Liebigs Ann. 1996, 2083.

Synthesis of 2-(2,3-Dihydroxypropyl)piperidines
J . Org. Chem., Vol. 64, No. 23, 1999 8597
Sch em e 3a
Sch em e 4
T-7 {[R]25D +30.9° (CHCl3)} in 51% overall yield from 19.
In an analogous way, (+)-T-8 {[R]25D +98.2° (CHCl3)} was
obtained from [2R-(2S)]-3 in 35% four-step yields.
Since all four tricyclic diaza compounds are isolated
as single diastereomers, these reductive cyclizations
proceed highly stereoselectively. The formation of the
compounds can be explained as follows: a hydrogenolysis
of N-Cbz followed by condensation of the resulting
secondary amine with the imide occurred to provide
tricyclic iminium compound A, which was reduced by
hydrogen to give the lactam; alternatively, both the
hydrogenolysis of N-Cbz and a reduction of imide pro-
ceeded to give a secondary amino acyliminium intermedi-
ate, B, which was cyclized to afford the lactam (Scheme
4).
Con clu sion
We developed a general access to synthetically useful
homochiral 2-(2,3-dihydroxypropyl)piperidines 2 via it-
erative asymmetric dihydroxylation starting from an
achiral 5-hexenyl azide. The two stereogenic centers of
2 were constructed with high enantiomeric enhancement
in a sequence of two AD reactions. In practice, we
demonstrated the synthetic utility of 2 as chiral synthons
by the first asymmetric synthesis of several 2-(2-hydroxy-
alkyl)piperidine alkaloids except for 9. In addition, the
asymmetric synthesis of the ant defense alkaloids [(+)-
T-3, (+)-T-4, (+)-T-7, and (+)-T-8] has been performed.
Extension of this methodology (the enantiomeric en-
hancement via the 2-fold or more AD reactions) toward
asymmetric synthesis of other biologically active com-
pounds is under investigation.
a
Conditions: (a) vinylmagnesium bromide/CuBr-Me2S; (b)
succinimide/Ph3P/DEAD; (c) H2/10% Pd-C/4 atm; (d) LiAlH4; (e)
Bu2CuLi; (f) H2/Pd(OH)2/4 atm.
for T-7 (twice) has been reported only once. Among them,
the synthesis of (+)-T-3,4,7,-8 was performed from the
epoxides [2R-(2S)]- and [2R-(2R)]-3. Our synthesis of (+)-
T-3 began with the cleavage of [2R-(2R)]-3 with the
Grignard reagent. According to the method described for
5, the treatment of [2R-(2R)]-3 with vinylmagnesium
bromide in the combination with a cuprous bromide-
dimethyl sulfide complex afforded the alcohol 14 in 90%
yield (Scheme 3). The Mitsunobu reaction of 14 with
succinimide provided the imide 15 in 70% yield. Catalytic
reduction of 15 using 10% palladium carbon under
hydrogen atmosphere at 4 atm resulted in conversion in
a single step into the tricyclic lactam 16 as a single
isomer in 82% yield.21 Finally, reduction of the lactam
Exp er im en ta l Section
Gen er a l P r oced u r es. Column chromatography was per-
formed on silica gel (Fuji-Division BW-200 or Merck 60 (no.
9385)) with a medium-pressure apparatus, and a mixture of
ethyl acetate/hexane was used as eluent unless otherwise
specified. The extracts were dried over Na2SO4 unless other-
wise specified.
16 with LiAlH4 gave (+)-T-3 {[R]25 +34.6° (CHCl3)}
D
(80%), identical in all respects with those reported.20f
Similarly, the synthesis of (+)-T-4 {[R]25D +107.3° (CHCl3)}
was achieved in a three-step sequence from 5 in 43%
overall yield. Next, we initiated the synthesis of (+)-T-
7. The regioselective cleavage of [2R-(2R)]-3 with lithium
dibutylcuprate afforded the alcohol 19 in 79% yield,
which was transformed in a three-step sequence into (+)-
[2R-(2S)]- a n d [2R-(2R)]-1-Ben zyloxyca r bon yl-2-(2,3-
d ih yd r oxyp r op yl)p ip er id in e [[2R-(2S)]- a n d [2R-(2R)]-2].
(R)-1-Benzyloxycarbonyl-2-(2-propenyl)piperidine 1 (270 mg,
1.04 mmol) was added to a mixture of AD-mix (1.35 g),
prepared from K2OsO4‚2H2O (0.7 mg), (DHQ)2PYR (8.7 mg),
K3Fe(CN)6 (945 mg), and K2CO3 (220 mg) by a known
procedure,9 tert-BuOH (5 mL), and H2O (5 mL) at 0 °C. After
the reaction mixture was stirred for 24 h at the same
temperature, sodium sulfite (1.5 g) was added to the mixture.
After being stirred for 30 min, the mixture was filtered through
a Celite pad. The organic layer was separated, and the aqueous
layer was extracted with ethyl acetate three times. The
combined organic layers were washed with brine, dried, and
evaporated. The residue was chromatographed using 50%
ethyl acetate-hexane as eluent to yield major diastereomer
[2R-(2S)]-2 (213 mg, 70%) and minor diastereomer [2R-(2R)]-
2 (64 mg, 21%) as oils. The enantiomeric purities were
(20) Racemic form: (a) Merlin, P.; Breakman, J .-C.; Daloze, D.
Tetrahedron Lett. 1988, 29, 1691. (b) J ones, T. H. Tetrahedron Lett.
1990, 31, 1535. (c) J ones, T. H. Tetrahedron Lett. 1990, 31, 4543. (d)
Barluenga, J . Toma´s, M.; Kouznetsov, V.; Rubio, E. J . Org. Chem. 1994,
59, 3699. Chiral form: (e) Yue, C.; Gauthier, I.; Royer, J .; Husson, H.-
P. J . Org. Chem. 1996, 61, 4949. (f) Marcours, P.; Breakman, J .-C.;
Daloze, D. Tetrahedron 1995, 51, 1415.
(21) Under an atmosphere of hydrogen, only the hydrogenolysis of
N-Cbz proceeded to give no cyclized product. Cf. Scovill, J . P.;
Burckhalter, J . H. J . Heterocycl. Chem. 1980, 17, 23.

8598 J . Org. Chem., Vol. 64, No. 23, 1999
Takahata et al.
determined by HPLC analysis (column, DAICEL CHIRALPAC
AS), 40 °C, eluent hexane-2-propanol (9:1); flow rate 0.4 mL/
min. The results are shown in Table 1.
77%) as an oil: [R]25D +38.21° (c 1.150, CHCl3); IR (neat) 2936,
1
1694, 1423, 1259 cm-1; H NMR (500 MHz, CDCl3) δ 1.38-
1.72 (7 H, m), 2.00 (1 H, qui, J ) 7.32 Hz), 2.43 (1 H, br s),
2.67 (1 H, br s), 2.88 (2 H, br d, J ) 10.90 Hz), 4.09 (1 H, d,
J ) 10.04 Hz), 4.57 (1 H, s), 5.14 (2 H, ABq, J ) 31.73, 12.50
Hz), 7.28-7.37 (5 H, m); 13C NMR (125 MHz, CDCl3) δ 19.0,
25.5, 28.6, 33.0, 39.4, 46.7, 48.9, 5.2, 67.0, 127.8, 127.9, 128.5,
137.0, 155.5. Anal. Calcd for C16H21NO3: N, 5.09; C, 69.79; H,
7.69. Found: N, 4.80; C, 69.82; H, 7.69.
Da ta for [2R-(2S)]-2: [R]25 +23.15° (c 1.310, CHCl3); IR
D
(neat) 3418, 3032, 2937, 2866, 1667, 1586, 1498, 1427, 1264,
1175, 1092 cm-1; 1H NMR (500 MHz, CDCl3) δ 1.29 (1 H, ddd,
J ) 14,11, 10.90, 3.21 Hz), 1.42-1.65 (5 H, m), 1.76-1.81 (1
H, m), 1.91-1.97 (1 H, m), 2.425 (1 H, d, J ) 4.91 Hz), 2.77 (1
H, td, J ) 13.46, 2.78 Hz), 3.47-3.60 (3 H, m), 4.065 (1 H, d,
J ) 12.61 Hz), 4.44 (1 H, br s), 4.54 (1 H, d, J ) 12.18 Hz),
5.15 (2 H, s), 7.32-7.40 (5 H, m); 13C NMR (125 MHz, CDCl3)
δ 19.03, 25.37, 29.30, 33.21, 39.31, 47.19, 66.34, 67.53, 68.49,
[2S-(2S)]-1-Ben zyloxyca r bon yl-2-(2,3-ep oxyp r op yl)p i-
p er id in e [[2S-(2S)]-3]. By a procedure similar to that for the
preparation of [2R-(2S)]-3, [2S-(2S)]-2 (144 mg, 0.49 mmol))
was converted in a three-step sequence [(1) PPTS (1.0 mg, 3.9
mmol, trimethyl orthoacetate (73 mL, 0.59 mmol), CH2Cl2 (1.4
mL); (2) acetyl bromide (44 mL, 0.59 mmol); (3) K2CO3 (88 mg,
0.63 mmol), MeOH (1.6 mL)] to [2S-(2S)]-3 (95 mg, 70%) as
127.84, 128.09, 128.51, 136.36, 156.87; HRMS calcd for C16H23
-
NO4 (M+) 293.1627, found 293.1605.
Da ta for [2R-(2R)]-2: IR (neat) 3421, 2936, 1684, 1430
cm-1; 1H NMR (500 MHz, CDCl3) δ 1.41-1.46 (1 H, m), 1.50-
1.64 (6 H, m), 1.83-1.85 (1 H, m), 2.18 (1 H, br d, J ) 9.40
Hz), 2.92 (2 H, td, J ) 13.03, 1.50 Hz), 3.45 (1 H, br s), 3.68 (2
H, br d, J ) 20.08 Hz), 4.06 (1 H, m), 5.13 (2 H, ABq, J )
25.32, 12.28 Hz), 7.31-7.39 (5 H, m); 13C NMR (75 MHz,
CDCl3) δ 18.9, 25.5, 28.7, 33.6, 39.7, 48.5, 66.8, 67.3, 70.3,
128.0, 128.2, 128.7, 136.8, 156.0. HRMS calcd for C16H23NO4
(M+) 293.1627, found 293.1670.
[2R-(2R)]- a n d [2R-(2S)]-1-Ben zyloxyca r bon yl-2-(2,3-
d ih yd r oxyp r op yl)p ip er id in e [[2R-(2R)]- a n d [2R-(2S)]-2].
The AD reaction was performed on a 15.4 mmol scale with
AD-mix-â [used (DHQD)2PYR as ligand] as described in the
typical procedure (vide supra). [2R-(2R)]- and [2R-(2S)]-2 were
obtained in 69% and 22% yields, respectively. [R]25D [[2R-(2R)]-
2] +39.53° (c 1.575, CHCl3).
an oil: [R]25 -38.43° (c 1.390, CHCl3).
D
[2S-(2R)]-1-Ben zyloxyca r bon yl-2-(2,3-ep oxyp r op yl)p i-
p er id in e [[2S-(2R)]-3]. By a procedure similar to that for the
preparation of [2R-(2S)]-3, [2S-(2R]-2 (1.65 g, 5.6 mmol)) was
converted in a three-step sequence [(1) PPTS (11.3 mg, 0.045
mmol, trimethyl orthoacetate (0.83 mL, 6.7 mmol), CH2Cl2
(16.5 mL); (2) acetyl bromide (0.54 mL, 6.7 mmol); (3) K2CO3-
(1.0 g, 7.3 mmol), MeOH (18.7 mL)] to [2S-(2R)]-3 (1.2 g, 77%)
as an oil: [R]25 -36.14° (c 5.520, CHCl3).
D
[2R-(2R)]-1-Ben zyloxyca r bon yl-2-(2-h yd r oxy-4-p en ten -
yl)p ip er id in e (5). To a slurry of CuBr-Me2S (14.4 mg, 0.07
mmol) in THF (1.4 mL) was added a 1 M vinylmagnesium
bromide-THF solution (1.10 mL, 1.10 mmol) at -78 °C with
stirring. After the reaction mixture was stirred for 30 min, a
solution of [2R-(2S)]-3 (200 mg, 0.73 mmol) in THF (0.78 mL)
was slowly added to it. The mixture was gradually warmed to
-30 °C, stirred for 1.5 h, and quenched with saturated NH4-
Cl. The mixture was diluted with ether, washed with brine,
dried, and evaporated. The residue was chromatographed
using 13% EtOAc-hexane as eluent to give 5 (210 mg, 95%)
as an oil: [R]25D +39.19° (c 2.650, CHCl3); IR (neat) 3447, 3069,
2938, 2864, 1668, 1424, 1353, 1262, 1174, 698 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.10-1.20 (1 H, m), 1.30-1.66 (6 H, m),
1.93 (1 H, t, J ) 13.19 Hz), 2.05-2.21 (2 H, m), 2.60-2.70 (1
H, m), 3.30 (1 H, br s), 3.96 (1 H, br d, J ) 13.19 Hz), 4.03 (1
H, m), 4.42-4.46 (1 H, m), 4.95-5.10 (4 H, m), 5.72-5.80 (1
H, m), 7.18-7.27 (5 H, m); 13C NMR (75 MHz, CDCl3) δ 19.2,
25.5, 29.4, 37.0, 39.3, 41.2, 47.2, 47.3, 47.5, 47.5, 66.9, 67.1,
67.5, 116.8, 127.9, 128.2, 128.4, 128.5, 128.6, 135.5, 136.6,
[2S-(2S)]- a n d [2S-(2R)]-1-Ben zyloxyca r bon yl-2-(2,3-
d ih yd r oxyp r op yl)p ip er id in e [[2S-(2S)]- a n d [2S-(2R)]-2].
The AD reaction was performed on a 0.79 mmol scale using
(S)-1-Benzyloxycarbonyl-2-(2-propenyl)piperidine 1 with AD-
mix-R [used (DHQ)2PYR as ligand] as described in the typical
procedure (vide supra). [2S-(2S)]- and [2S-(2R)]-2 were ob-
tained in 70% and 22% yields, respectively. [R]25 [[2S-(2S)]-
D
2] -40.41° (c 1.440, CHCl3).
[2S-(2R)]- a n d [2S-(2S)]-1-Ben zyloxyca r bon yl-2-(2,3-
d ih yd r oxyp r op yl)p ip er id in e [[2S-(2R)]- a n d [2S-(2S)]-2].
The AD reaction was performed on a 2.08 mmol scale with
AD-mix-â [used (DHQD)2PYR as ligand] as described in the
typical procedure (vide supra). [2S-(2R)]- and [2S-(2S)]-2 were
obtained in 74% and 14% yields, respectively. [R]25D [[2S-(2R)]-
2] -23.82° (c 1.135, CHCl3).
[2R-(2S)]-1-Ben zyloxyca r bon yl-2-(2,3-ep oxyp r op yl)p i-
p er id in e [[2R-(2S)]-3]. Trimethyl orthoacetate (0.83 mL, 6.7
mmol) was added to a solution of [2R-(2S)]-2 (1.64 g, 5.6 mmol)
and PPTS (11.3 mg, 0.045 mmol)) in CH2Cl2 (8.25 mL). After
being stirred for 4 h, the reaction mixture was evaporated,
and then CH2Cl2 (8.25 mL) and acetyl bromide (0.54 mL, 6.7
mmol) were successively added to the resulting residue. After
being stirred for 45 min, the mixture was evaporated. To a
solution of the resulting residue in methanol (18.7 mL) was
added K2CO3 (1.0 g, 7.3 mmol), and the reaction mixture was
stirred for 2 h. The reaction was quenched with saturated NH4-
Cl and extracted with CH2Cl2. The extract was washed with
brine, dried, and evaporated. The residue was chromato-
graphed using 25% EtOAc-n-hexane as eluent to yield [2R-
(2S)]-3 (1.17 g, 76%) as an oil: [R]25D +35.46° (c 2.335, CHCl3);
156.9; HRMS calcd for
303.1814.
C
18H25NO3 (M+) 303.1834, found
(-)-Ha losa r in e (4). A suspension of 5 (237 mg, 0.78 mmol)
and palladium hydroxide (Pd(OH)2) (240 mg) in MeOH (4.4
mL) under a hydrogen atmosphere was stirred for 4 h. The
mixture was filtered through a Celite pad, and the filtrate was
evaporated. The residue was chromatographed on Al2O3 using
25% hexane-CH2Cl2 as eluent to give 4 (134 mg, 100%) as a
solid: mp 83 °C (diisopropyl ether); [R]25 -18.98° (c 0.975,
D
EtOH), lit.11b [R]25D -19.5° (c 0.6, EtOH); IR (KBr) 3313, 2930,
1
2857, 1456 cm-1; H NMR (300 MHz, CDCl3) δ 0.91 (3 H, t,
J ) 6.89 Hz), 1.26-1.59 (12 H, m), 1.78-1.80 (1 H, m), 2.55
(1 H, td, J ) 11.54, 2.75 Hz) 2.81-2.88 (1 H, m), 3.00-3.05 (1
H, m), 3.84-3.90 (1 H, m); 13C NMR (75 MHz, CDCl3) δ 14.3,
19.2, 24.9, 26.2, 31.7, 40.2, 42.2, 47.0, 54.8, 68.9; HRMS calcd
for C10H21NO (M+) 171.1623, found 171.1635.
IR (neat) 2938, 2862, 1694, 1423, 1265 cm-1 1H NMR (500
;
MHz, CDCl3) δ 1.35-1.65 (7 H, m), 1.85 (1 H, br s), 2.355 (1
H, dd, J ) 5.02, 2.67 Hz), 2.58 (1 H, br s), 2.775 (1 H, t, J )
12.93 Hz), 2.85 (1 H, br s), 4.06 (1 H, br s), 4.55 (1 H, br s),
5.11 (2 H, br s), 7.26-7.35 (5 H, m); 13C NMR (125 MHz,
CDCl3) δ 19.0, 25.6, 29.2, 33.4, 39.5, 46.8, 49.1, 50.4, 67.2,
128.1, 128.1, 128.6, 137.0, 155.6. Anal. Calcd for C16H21NO3:
N, 5.09; C, 69.79; H, 7.69. Found: N, 5.25; C, 69.30; H, 7.46.
[2R-(2R)]-1-Ben zyloxyca r bon yl-2-(2,3-ep oxyp r op yl)p i-
p er id in e [[2R-(2R)]-3]. By a procedure similar to that for the
preparation of [2R-(2S)]-3, [2R-(2R)]-2 (1.6 g, 5.45 mmol) was
converted in a three-step sequence [(1) PPTS (11 mg, 0.044
mmol), trimethyl orthoacetate (0.81 mL, 6.54 mmol), CH2Cl2
(16 mL); (2) acetyl bromide (0.49 mL, 6.54 mmol); (3) K2CO3-
(981 mg, 7.10 mmol), MeOH (18 mL)] to [2R-(2R)]-3 (1.16 g,
(+)-N-Meth yla llosed r id in e (6). To a suspension of LiAlH4
(19 mg, 3.12 mmol) in THF (9.3 mL) was added a solution of
[2R-(2R]-3 (430 mg, 1.56 mmol) in THF (9.3 mL) at 0 °C. After
being stirred for 1 h at room temperature, the reaction mixture
was refluxed for 15 h. To the mixture were successively added
H2O (0.12 mL), 2 N NaOH (0.12 mL), H2O (0.36 mL), and
anhydrous K2CO3 with ice cooling, and the resulting mixture
was stirred for 30 min at room temperature. The mixture was
filtered through a Celite pad, and the filtrate was evaporated
at room temperature. The residue was chromatographed using
5% MeOH-CH2Cl2 as eluent to yield 6 (217 mg, 89%) as an
oil: [R]25 +78.53° (c 2.840, EtOH), lit.12b [R]25 +67° (c 0.9,
D
D
EtOH 96%); IR (neat) 3384, 2934, 2856, 2794 cm-1; H NMR
1
(500 MHz, CDCl3) δ 1.13 (3 H, d, J ) 6.20 Hz), 1.19 (1 H, ddd,

Synthesis of 2-(2,3-Dihydroxypropyl)piperidines
J . Org. Chem., Vol. 64, No. 23, 1999 8599
J ) 14.32, 5.13, 2.56 Hz), 1.22-1.27 (1 H, m), 1.36-1.45 (2 H,
m), 1.48-1.54 (1 H, m), 1.59-1.70 (2 H, m), 1.81 (1 H, ddd,
J ) 14.31, 10.26, 8.76 Hz), 2.36 (3 H, s), 2.38-2.43 (1 H, m),
2.57 (1 H, tdd, J ) 7.69, 7.69, 3.85 Hz), 2.94 (1 H, ddd, J )
9.84, 6.84, 3.20 Hz), 3.91 (1 H, dqd, J ) 10.25, 6.20, 2.56 Hz);
13C NMR (125 MHz, CDCl3) δ 21.2, 22.8, 24.3, 26.5, 39.5, 40.3,
52.2, 60.9, 68.0; HRMS calcd for C9H19NO (M+) 157.1467, found
157.1467.
ice were added to it. After the reaction mixture was stirred
for an additional 15 min at room temperature, excess CH2Cl2
was added to it. The organic solvent was washed with brine,
dried, and evaporated. The residue was chromatographed
using 20% EtOAc-hexane as eluent to yield [2S-(2S)]-11 (286
mg, 95%) as an oil: [R]25 -28.52° (c 2.920, CHCl3); IR (neat)
D
3447, 2935, 1670, 1425, 1260, 1176 cm-1; 1H NMR (500 MHz,
CDCl3) δ 1.19 (3 H, d, J ) 6.20 Hz), 1.21-1.27 (1 H, m), 1.40-
1.63 (5 H, m), 1.72-1.75 (1 H, m), 1.995 (1 H, t, J ) 13.14
Hz), 2.76 (1 H, td, J ) 10.58, 6.73 Hz), 3.53 (1 H, br s), 4.045
(1 H, br d, J ) 12.82 Hz), 4.17 (1 H, s), 4.52 (1 H, br d, J )
10.25 Hz), 5.145 (2 H, ABq, J ) 22.11, 9.83 Hz), 7.30-7.39 (5
H, m); 13C NMR (125 MHz, CDCl3) δ 19.2, 22.6, 25.5, 29.4,
39.4, 47.5, 63.4, 67.6, 128.0, 128.2, 128.6, 136.6, 157.0. Anal.
Calcd for C16H23NO3: N, 5.05; C, 69.28; H, 8.36. Found: N,
5.03; C, 68.86; H, 8.19.
[2R-(2S)]-1-Ben zyloxyca r bon yl-2-(2-h yd r oxybu tyl)p i-
p er id in e (8). A 1 M MeLi-Et2O solution (2.82 mL, 2.82 mmol)
was injected into a suspension of CuI (269 mg, 1.41 mmol) in
Et2O (7.2 mL) at -20 °C, and the reaction mixture resulted
in a clear solution. A solution of [2R-(2R)]-3 (260 mg, 0.94
mmol) in Et2O (4.3 mL)was added to the lithium dimethylcu-
prate solution at -20 °C, and the mixture was stirred for 0.5
h. The reaction was warmed to 0 °C, stirred for 0.5 h, diluted
with Et2O, and quenched with saturated NH4Cl. The organic
solvent was washed with H2O and brine, dried, and evapo-
rated. The residue was chromatographed using 20% EtOAc-
(+)-Sed r id in e (9). A suspension of [2S-(2S)]-11 (220 mg,
0.79 mmol) and Pd(OH)2 (22 mg) in MeOH (5 mL) under a
hydrogen atmosphere was stirred for 12 h. The mixture was
filtered through a Celite pad, and the filtrate was evaporated
to give 9 (113 mg, 100%) as a solid: mp 84-85 °C (isopropyl
ether-petroleum ether), lit.15b mp 83-84 °C; [R]25D +28.36° (c
hexane as eluent to yield 8 (228 mg, 83%) as an oil: [R]25
D
+48.65° (c 1.825, CHCl3); IR (neat) 3446, 2935, 2865, 1674,
1
1425, 1350, 1262, 1172, 1148, 698 cm-1; H NMR (300 MHz,
CDCl3) δ 0.83 (3 H, t, J ) 7.42 Hz), 1.28-1.72 (9 H, m), 2.02
(1 H, br s), 2.77-2.86 (2 H, m), 3.44 (1 H, br s), 3.96 (1 H, br
d, J ) 13.19 Hz), 4.33-4.38 (1 H, m), 5.04 (2 H, ABq, J )
15.93, 12.64 Hz), 7.18-7.28 (5 H, m); 13C NMR (75 MHz,
CDCl3) δ 10.1, 19.1, 25.5, 25.6, 29.2, 29.2, 30.5, 37.7, 39.7, 49.0,
67.3, 67.4, 71.5, 128.0, 128.1, 128.2, 128.3, 128.4, 128.4, 128.6,
137.0, 156.0. Anal. Calcd for C17H25NO3: N, 4.81; C, 70.07; H,
8.65. Found: N, 4.52; C, 69.85; H, 8.58.
1.130, EtOH), lit.15b [R]24 +28.5° (c 2.32, EtOH); IR (KBr)
D
3277, 3166, 2968, 2856, 2811, 1474, 1453, 1370, 1340, 1158,
1110, 1093, 1054 cm-1; 1H NMR (500 MHz, CDCl3) δ 1.175 (3
H, d, J ) 6.41 Hz), 1.34-1.48 (4 H, m), 1.55-1.61 (3 H, m),
1.80-1.82 (1 H, m), 2.58 (1 H, td, J ) 11.86 Hz, 2.78 Hz), 2.86-
2.90 (1 H, m), 2.97 (2 H, br s), 3.04-3.07 (1 H, m), 4.125 (1 H,
dqd, J ) 9.40, 6.20, 3.20 Hz); 13C NMR (125 MHz, CDCl3) δ
23.8, 24.9, 26.2, 31.4, 43.8, 47.1, 55.0, 65.3. Anal. Calcd for
C8H17NO: N, 9.78; C, 67.09; H, 11.96. Found: N, 9.72; C,
66.63; H, 11.95.
[2R-(2S)]-2-(2-Hyd r oxybu tyl)p ip er id in e [[2R-(2S)]-7]. A
suspension of 8 (224 mg, 0.77 mmol) and Pd(OH)2 (22 mg) in
MeOH (4.4 mL) under a hydrogen atmosphere was stirred for
4 h. The mixture was filtered through a Celite pad, and the
filtrate was evaporated. The residue was chromatographed on
Al2O3 using 25% hexane-CH2Cl2 as eluent to give 4 (121 mg,
[2R-(2S)]-1-Ben zyloxyca r bon yl-2-(2-h yd r oxyp r op yl)p i-
p er id in e (11). Into a solution of [2R-(2R)]-3 (100 mg, 0.39
mmol) in THF (1.9 mL) was injected a 1 M Super-Hydride-
THF solution (1.56 mL, 1.56 mmol) at 0 °C. After the reaction
mixture was stirred for 15 min, a few pieces of ice were added
to it. After the reaction mixture was stirred for an additional
15 min at room temperature, excess CH2Cl2 was added to it.
The organic solvent was washed with brine, dried, and
evaporated. The residue was chromatographed using 20%
EtOAc-hexane as eluent to yield 11 (83 mg, 82%) as an oil:
100%) as a solid: mp 53-4 °C (Et2O); [R]25 +10.21° (c 1.080,
D
EtOH); IR (KBr) 3302, 2925, 1453, 1324, 1121, 906, 793 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.90 (3 H, t, J ) 7.69 Hz), 1.92-
1.65 (9 H, m), 1.77-1.84 (1 H, m), 2.52-2.62 (1 H, m), 2.69 (1
H, tt, J ) 10.99, 2.75 Hz), 2.98-3.05 (1 H, m), 3.68-3.77 (1
H, m); 13C NMR (75 MHz, CDCl3) δ 10.0, 24,7, 27.6, 31.0, 34.6,
42.1, 46.2, 58.4, 74.6. Anal. Calcd for C9H19NO: N, 8.91; C,
68.74; H, 12.18. Found: N, 8.91; C, 68.66; H, 12.18.
[R]25 +52.23° (c 1.740, CHCl3); IR (neat) 3446, 2934, 1684,
D
1560, 1424 cm-1; H NMR (500 MHz, CDCl3) δ 1.19 (3 H, br
1
[2S-(2S)]-1-Ben zyloxyca r b on yl-2-(2-h yd r oxyb u t yl)p i-
p er id in e (10). By a procedure similar to that for the prepara-
tion of 8, [2S-(2R)]-3 (402 mg, 2.11 mmol) was converted with
lithium dimethylcuprate prepared by MeLi (4.21 mmol) and
s), 1.41-1.63 (7 H, m), 1.83-1.87 (1 H, m), 2.91 (1 H, t, J )
12.93 Hz), 3.81 (1 H, br s), 4.05 (1 H, br s), 4.43 (1H, d, J )
5.34 Hz), 5.13 (2 H, ABq, J ) 20.51, 12.39 Hz), 7.29-7.37 (5
H, m); 13C NMR (125 MHz, CDCl3) δ 19.1, 23.8, 25.6, 29.5,
39.7, 40.1, 49.0, 66.4, 67.3, 128.0, 128.1, 128.6, 136.9, 156.1.
Anal. Calcd for C16H23NO3: N, 5.05; C, 69.28; H, 8.36. Found:
N, 4.77; C, 68.83; H, 8.41.
CuI (402 mg, 2.11 mmol) to 10 (260 mg, 85%) as an oil: [R]25
D
-30.83° (c 1.435, CHCl3); IR (neat) 3447, 2935, 1670, 1424,
1259, 697 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.83 (3 H, t, J )
7.14 Hz), 1.05-1.16 (1 H, m), 1.26-1.66 (8 H, m), 1.86-1.96
(1 H, m), 2.60-2.70 (1 H, td, J ) 12.64, 2.75 Hz), 3.11-3.13
(1 H, m), 3.93-3.97 (2 H, m), 4.41-4.46 (1 H, m), 5.06 (2 H,
ABq, J ) 22.80, 11.81 Hz), 7.20-7.28 (5 H, m); 13C NMR (75
MHz, CDCl3) δ 10.5, 19.1, 25.4, 29.4, 29.6, 37.1, 39.2, 47.2,
67.3, 68.4, 127.6, 127.9, 128.3, 136.4, 156.5; HRMS calcd for
(+)-Allosed r id in e (12). A suspension of 11 (229 mg, 0.83
mmol) and Pd(OH)2 (23 mg) in MeOH (4.7 mL) under a
hydrogen atmosphere was stirred for 12 h. The mixture was
filtered through a Celite pad, and the filtrate was evaporated
to give 12 (119 mg, 100%) as a solid: mp 61 °C, lit.17a mp 62-
63 °C; [R]25 +17.10° (c 1.550, MeOH), lit.17a [R]29 +16.2° (c
D
D
C
17H25NO3 (M+) 291.1834, found 291.1829.
4.01, MeOH); IR (KBr) 3691, 3676, 2924, 1655, 1438, 1367,
1331, 1054, 790 cm-1; 1H NMR (500 MHz, CDCl3) δ 1.03-1.09
(1 H, m), 1.11 (3 H, d, J ) 5.98 Hz), 1.21-1.31 (2 H, m), 1.41-
1.52 (2 H, m), 1.56-1.62 (2 H, m), 1.77-1.80 (1 H, m), 2.56 (1
H, td, J ) 13.89, 2.99 Hz), 2.69 (1 H, t, J ) 10.68 Hz), 3.02 (1
H, d, J ) 13.67 Hz), 3.50 (2 H, br s), 3.98 (1 H, dqd, J ) 10.26,
6.20, 2.14 Hz); 13C NMR (125 MHz, CDCl3) δ 24.0, 24.6, 27.3,
34.3, 44.4, 46.1, 58.1, 69.2. Anal. Calcd for C8H17NO: N, 9.78;
C, 67.09; H, 11.96. Found: N, 9.54; C, 67.18; H, 11.90.
[2S-(2R)]-1-Ben zyloxyca r bon yl-2-(2-h yd r oxyp r op yl)p i-
p er id in e (en t-11). By a procedure similar to that for the
preparation of [2R-(2S)]-11, [2S-(2S)]-3 (105 mg, 0.39 mmol)
was converted with Super-Hydride (LiEt3BH, 1.0 M in THF)
(1.6 mL, 1.6 mmol) in THF (1.9 mL) to ent-11 (85 mg, 84%):
(+)-8-Eth yln or loben ol-I [[2S-(2S)]-7]. By a procedure
similar to that for the preparation of [2R-(2S)]-7, 10 (120 mg,
0.77 mmol) was converted with Pd(OH)2 (12 mg) in MeOH (2.4
mL) to [2S-(2S)]-7 (121 mg, 100%): mp 89-90 °C (Et2O), lit.13
mp 87 °C; [R]25 +25.79° (c 1.380, EtOH), lit.13 [R]25 +22.3°
D
D
(c 1.56, EtOH); IR (KBr) 3272, 3148, 2992, 2926, 2832, 1452,
1342, 1156, 1102, 972 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.91
(3 H, t, J ) 7.42 Hz), 1.30-1.61 (9 H, m), 1.79-1.81 (1 H, m),
2.55 (1 H, td, J ) 11.81, 2.75 Hz), 2.83-3.05 (4 H, m), 3.75-
3.82 (1 H, m); 13C NMR (75 MHz, CDCl3) δ 10.4, 25.0, 26.3,
30.8, 31.6, 41.7, 47.1, 55.0, 70.7; HRMS calcd for C9H19NO (M+)
157.1593, found 157.1568.
[2S-2(S)]-1-Ben zyloxyca r bon yl-2-(2-h yd r oxyp r op yl)p i-
p er id in e [[2S-(2S)]-11]. Into a solution of [2S-(2R)]-3 (300
mg, 1.09 mmol) in THF (5.7 mL) was injected a 1 M Super-
Hydride-THF solution (4.36 mL, 4.36 mmol) at 0 °C. After
the reaction mixture was stirred for 15 min, a few pieces of
[R]25 -52.37° (c 1.275, CHCl3).
D
(-)-Allosed r id in e (en t-12). By a procedure similar to that
for the preparation of 12, [2S-(2R)]-11 was converted with Pd-
(OH)2 (8 mg) in MeOH (6 mL) to ent-12 (119 mg, 95%) as a

8600 J . Org. Chem., Vol. 64, No. 23, 1999
Takahata et al.
solid: mp 60-61 °C, lit.17a mp 62-63 °C; [R]25 -16.18° (c
+31° (c 3.1, CHCl3); IR (neat) 2928, 2858, 2800, 2748, 1457,
1389, 1353, 1130, 1117 cm-1; 1H NMR (500 MHz, C6D6) δ 0.93
(3 H, t, J ) 7.26 Hz), 1.07 (1 H, br d, J ) 12.6 Hz), 1.15-1.18
(1 H, m), 1.27-1.81 (14 H, m), 1.89-1.95 (1 H, m), 1.98-2.03
(1 H, m), 2.74-2.81 (3 H, m), 3.17-2.19 (1 H, m), 3.27 (1 H,
dd, J ) 5.13, 2.35 Hz); 13C NMR (125 MHz, C6D6) δ 14.4, 14.5,
20.6, 22.1, 25.0, 26.3, 30.4, 32.0, 33.1, 33.1, 33.9, 50.6, 50.8,
52.8, 56.7, 75.5, 75.6; HRMS calcd for C14H26N2 (M+) 222.2096,
found 222.2087.
D
1.550, MeOH), lit.17a [R]29 +16.2° (c 4.01, MeOH) for 12.
D
(-)-N-Meth ylsed r id in e (13). By a procedure similar to
that for the preparation of 6, [2S-(2R)]-3 (195 mg, 0.71 mmol)
was converted with LiAlH4 (53.8 mg, 1.42 mmol) in THF (4.2
mL) to 13 (116 mg, 100%) as an oil: [R]25 -32.99° (c 0.675,
D
EtOH), lit.12b [R]23 -31° (c 1.05, 96% EtOH); IR (neat) 3383,
D
2932, 2856, 2792, 1456 cm-1
;
1H NMR (500 MHz, CDCl3) δ
1.155 (3 H, d, J ) 6.20 Hz), 1.23-1.33 (2 H, m), 1.48-1.62 (3
H, m), 1.69-1.78 (2 H, m), 1.93-2.00 (2 H, m), 2.16-2.19 (1
H, m), 2.34 (3 H, s), 2.90 (1 H, br s, J ) 11.54 Hz), 4.225 (1 H,
dqd, J ) 10.68, 5.98, 2.99 Hz); 13C NMR (125 MHz, CDCl3) δ
23.8, 24.7, 26.0, 29.9, 38.9, 44.3, 57.6, 63.1, 65.4; HRMS calcd
for C9H19NO (M+) 157.1466, found 157.1479.
[2R-(2S)]-P h en ylm et h yl 2-(2-(2,5-Dioxop yr r olid in yl)-
p en t-4-en yl)p ip er id in eca r boxyla te (17). By a procedure
similar to that for the preparation of 15, 5 (164 mg, 0.54 mmol)
was converted by the Mitsunobu reaction using PPh3 (425 mg,
1.62 mmol), DEAD (255 mL, 1.62 mmol), and succinimide (161
mg, 1.62 mmol) to 17 (134 mg, 65%) as an oil: [R]25 +42.70°
D
[2R-(2S)]-P h en ylm et h yl 2-(2-H yd r oxyp en t -4-en yl)p i-
p er id in eca r boxyla te (14). By a procedure similar to that for
the preparation of 5, [2R-(2R)]-3 (149 mg, 0.54 mmol)) was
converted with a 1 M vinylmagnesium bromide-THF solution
(0.81 mL, 0.81 mmol) in the presence of CuBr‚SMe2 (11 mg,
(c 1.470, CHCl3); IR (neat) 2937, 1772, 1700, 1425, 1370, 1256,
1187, 1135, 698 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.35-1.67
(6 H, m), 1.82-1.91 (1 H, m), 2.32-2.60 (6 H, m), 2.61-2.84
(2 H, m), 3.96-4.04 (1 H, m), 4.08-4.18 (2 H, m), 4.96-5.14
(4 H, m), 5.52-5.66 (1 H, m), 7.27-7.39 (5 H, m); 13C NMR
(75 MHz, CDCl3) δ 19.2, 25.7, 28.1, 28.7, 36.3, 39.8, 48.9, 50.1,
67.3, 77.4, 117.9, 128.0, 128.6, 134.5, 137.0, 155.3, 177.7;
HRMS calcd for C22H28O4N2 (M+) 384.2049, found 384.2059.
0.54 mmol) to 14 (147 mg, 90%) as an oil: [R]25 +44.05° (c
D
2.250, CHCl3); IR (neat) 3446, 2936, 1674, 1427, 1354, 1264,
1171, 1074, 698 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.35-1.71
(7 H, m), 1.77-1.87 (1 H, m), 2.04-2.34 (2 H, m), 2.80-2.95
(2 H, m), 3.66 (1 H, br s), 4.02-4.06 (1 H, m), 4.44-4.48 (1 H,
m), 5.06-5.13 (4 H, m), 5.76-5.79 (1 H, m), 4.28-7.36 (5 H,
m); 13C NMR (75 MHz, CDCl3) δ 19.2, 25.7, 29.2, 29.2, 29.3,
37.3, 37.4, 39.7, 42.1, 48.8, 67.2, 68.9, 68.9, 69.0, 69.0, 69.1,
69.1, 69.1, 69.2, 117.8, 117.9, 118.02, 127.9, 128.0, 128.5, 134.8,
136.8, 155.7; HRMS calcd for C18H25O3N (M+) 303.1834, found
303.1841.
(2R,7S,9R)-1.6-Diaza-7-pr opyltr icyclo[7.4.0.02,6]tr idecan -
5-on e (18). By a procedure similar to that for the preparation
of 16, 17 (42 mg, 0.11 mmol) was converted with reduction
using 10% Pd/C (42 mg) to 18 (19 mg, 73%) as a solid: mp
58-60 °C; [R]25D +80.94° (c 1.015, CHCl3); IR (neat) 2956, 2930,
2856, 2757, 1702, 1439, 1421, 1278 cm-1; 1H NMR (500 MHz,
CDCl3) δ 0.94 (3 H, t, J ) 7.26 Hz), 1.26-1.45 (5 H, m), 1.54-
1.64 (3 H, m), 1.69-2.00 (6 H, m), 2.07-2.14 (1 H, m), 2.24-
2.31 (1H, m), 2.40-2.50 (2 H, m), 2.97-2.99 (1 H, m), 3.15-
3.19 (1 H, m), 3.51 (1 H, t, J ) 6.20 Hz); 13C NMR (75 MHz,
CDCl3) δ 14.43, 19.78, 23.95, 24.37, 25.54, 31.34, 32.66, 34.00,
38.34, 49.55, 56.97, 61.83, 80.36, 174.74; HRMS calcd for
[2R-(2R)]-P h en ylm eth yl 2-(2-(2,5-Dioxop yr r olid in yl)-
p en t-4-en yl)p ip er id in eca r boxyla te (15). To a solution of
14 (145 mg, 0.48 mmol) and PPh3 (375 mg, 1.43 mmol) in THF
(4.8 mL) was added dropwise a solution of diethyl azodicar-
boxylate (DEAD) (225 mL, 1.43 mmol) in THF (4.8 mL) at -20
°C. Succinimide (142 mg, 1.43 mmol) was added to the mixture.
Then the reaction mixture was slowly warmed to 0 °C and
stirred for 4 h. The organic solvent was evaporated. The
residue was chromatographed using 20% EtOAc-hexane as
C
14H24ON2 (M+) 236.1888, found 236.1821.
(+)-Tetr a p on er in e-4 (T-4). By a procedure similar to that
for the preparation of T-3, 18 (46 mg, 0.19 mmol) was
converted with LiAlH4 (72 mg, 1.9 mmol) in THF (5 mL) to
eluent to yield 15 (130 mg, 70%) as an oil: [R]25 +65.74° (c
T-4 (38 mg, 90%) as an oil: [R]25 +107.25° (c 1.155, CHCl3),
D
D
1.510, CHCl3); IR (neat) 2937, 1773, 1700, 1474, 1430, 1374,
1254, 1171, 699 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.25-1.69
(6 H, m), 2.14-2.41 (4 H, m), 2.52-2.71 (4 H, m), 2.73-2.82
(1 H, m), 4.02-4.27 (3 H, m), 4.95-5.08 (4 H, m), 5.61-5.72
(1 H, m), 7.26-7.39 (5 H, m); 13C NMR (75 MHz, CDCl3) δ
19.55, 25.98, 28.41, 28.74, 30.32, 37.39, 39.47, 47.40, 48.20,
67.31, 117.98, 127.90, 128.49, 134.55, 136.95, 155.30, 178.30;
HRMS calcd for C22H28O4N2 (M+) 384.2049, found 384.2036.
lit.20e [R]20 +105° (c 0.3, CHCl3); IR (neat) 2932, 2857, 2790,
D
1378, 1338, 1191, 1157 cm-1; 1H NMR (500 MHz, C6D6) δ 0.88
(3 H, t, J ) 7.16 Hz), 1.15-1.54 (11 H, m), 1.59-1.74 (7 H,
m), 1.97-2.02 (1 H, m), 2.06-2.11 (1 H, m), 2.27-2.30 (1H,
m), 2.80-2.82 (1 H, m), 3.11 (1 H, ddd, J ) 8.12, 8.12, 2.56
Hz); 13C NMR (125 MHz, C6D6) δ 14.78, 18.64, 20.14, 25.04,
25.16, 29.64, 32.91, 36.83, 37.88, 48.90, 48.99, 51.48, 61.15,
62.62, 85.48, 85.55; HRMS calcd for C14H26N2 (M+) 222.2096,
found 222.2077.
(2R,7R,9R)-1.6-Diaza-7-pr opyltr icyclo[7.4.0.02,6]tr idecan -
5-on e (16). A suspension of 15 (60 mg, 0.16 mmol) and 10%
Pd/C (60 mg) in MeOH (228 mL) was stirred under hydrogen
at 4 atm for 100 h. The mixture was filtered through a Celite
pad, and the filtrate was evaporated. The residue was chro-
matographed using 1% MeOH-CH2Cl2 as eluent to give 16
[2R-(2S)]-P h en ylm et h yl 2-(2-H yd r oxyh ep t yl)p ip er i-
d in eca r boxyla te (19). To a suspension of CuI (415 mg, 2.18
mmol) in Et2O (5.5 mL) was added a 1.6 M n-butyllithium-
hexane solution (2.7 mL, 4.36 mmol) at -45 °C. A solution of
[2R-(2R)]-3 (300 mg, 1.09 mmol) in Et2O (1.1 mL) was added
to the reaction mixture at -70 °C. After being stirred for 2 h,
the reaction was quenched with saturated NH4Cl and ex-
tracted with Et2O. The extract was washed with brine, dried,
and evaporated. The residue was chromatographed using 13%
EtOAc-hexane as eluent to give 19 (287 mg, 79%) as an oil:
(31 mg, 82%) as a solid: mp 39-40 °C; [R]25 +5.95° (c 1.695,
D
CHCl3); IR (neat) 2933, 2859, 2799, 1690, 1421, 1305, 1274,
1090 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.91 (3 H, t, J ) 7.14
Hz), 1.18-1.88 (14 H, m), 2.12-2.50 (4 H, m), 2.91 (1 H, br d,
J ) 10.99 Hz), 3.78 (1 H, t, J ) 6.04 Hz), 4.19 (1 H, q, J )
7.14 Hz); 13C NMR (75 MHz, CDCl3) δ 14.28, 19.76, 24.62,
25.50, 29.96, 32.95, 33.02, 35.00, 46.88, 49.78, 56.49, 73.62,
77.40, 172.87; HRMS calcd for C14H24ON2 (M+) 236.1888, found
236.1867.
[R]25 +41.97° (c 1.215, CHCl3); IR (neat) 3446, 2931, 2857,
D
1669, 1425, 1261, 1171, 697 cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.88 (3 H, t, J ) 6.87 Hz), 1.25-1.81 (16 H, m), 2.85-2.94 (2
H, m), 3.60-3.61 (1 H, m), 4.04 (1 H, br d, J ) 12.09 Hz), 4.43-
4.46 (1 H, m), 5.12 (2 H, ABq, J ) 13.74, 12.64 Hz), 7.29-7.36
(5 H, m); 13C NMR (75 MHz, CDCl3) δ 14.24, 19.09, 22.81,
25.51, 25.62, 29.12, 31.99, 37.67, 37.99, 39.66, 48.90, 67.14,
69.96, 127.77, 127.86, 128.39, 136.74, 155.64; HRMS calcd for
(+)-Tetr a p on er in e-3 (T-3). To a suspension of LiAlH4 (78
mg, 2.1 mmol) in THF (5.3 mL) was added a solution of 16 (49
mg, 0.21 mmol) in THF (2.7 mL) at 0 °C. After being stirred
for 1 h at room temperature, the reaction mixture was refluxed
for 6 h. To the mixture were successively added excess EtOAc
and 10% NH4OH with ice cooling. The organic layer was
separated, and the aqueous layer was extracted with CH2Cl2.
The combined solvents were washed with brine, dried with
anhydrous K2CO3, and evaporated. The residue was chromato-
graphed using 1% MeOH-CH2Cl2 as eluent to yield T-3 (37
C
20H31O3N (M+) 333.2304, found 333.2290.
[2R-(2R)]-P h en ylm eth yl 2-(2-(2,5-Dioxop yr r olid in yl)-
h ep tyl)p ip er id in eca r boxyla te (20). By a procedure similar
to that for the preparation of 15, 19 (130 mg, 0.39 mmol) was
converted by the Mitsunobu reaction using Ph3P (307 mg, 1.17
mmol), DEAD (184 mL, 1.17 mmol), and succinimide (116 mg,
1.17 mmol) in THF (3.9 mL) to 20 (129 mg, 80%) as an oil:
mg, 80%) as an oil: [R]25D +34.57° (c 0.505, CHCl3), lit.20e [R]20
D

Synthesis of 2-(2,3-Dihydroxypropyl)piperidines
J . Org. Chem., Vol. 64, No. 23, 1999 8601
[R]25D +76.52° (c 2.58, CHCl3); IR (neat) 2931, 2858, 1772, 1700,
[2R-(2S)]-P h en ylm et h yl 2-(2-(2,5-Dioxop yr r olid in yl)-
h ep tyl)p ip er id in eca r boxyla te [2R-(2S)]-20. By a procedure
similar to that for the preparation of 15, [2R-(2R)]-19 (167 mg,
0.50 mmol) was converted by the Mitsunobu reaction with
PPh3 (393 mg, 1.50 mmol), DEAD (236 mL, 1.50 mmol), and
succinimide (149 mg, 1.50 mmol) to [2R-(2S)]-20 (171 mg, 83%)
as an oil: [R]25D +24.98° (c 1.70, CHCl3); IR (neat) 2930, 2859,
1772, 1698, 1425, 1371, 1262, 1185 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.83 (3 H, t, J ) 6.59 Hz), 1.10-1.58 (13 H, m), 1.77-
1.86 (1 H, m), 1.92-1.96 (1 H, m), 2.27-2.55 (5 H, m), 2.74-
2.83 (1 H, m), 3.99-4.12 (3 H, m), 5.02-5.11 (2 H, m), 7.29-
7.42 (5 H, m); 13C NMR (75 MHz, CDCl3) δ 14.3, 19.2, 22.8,
25.7, 26.4, 28.2, 28.7, 31.6, 31.7, 32.1, 39.8, 48.9, 48.9, 50.9,
67.2, 67.3, 77.4, 128.0, 128.0, 128.5, 136.9, 155.2, 177.9; HRMS
calcd for C24H34O4N2 (M+) 414.2518, found 414.2530.
(2R,7S,9R)-1,6-Diaza-7-pen tyltr icyclo[7.4.0.02,6]tr idecan -
5-on e (2R,7S,9R)-21. A suspension of [2R-(2S)]-20 (63 mg,
0.152 mmol) in MeOH (206 mL) was stirred under hydrogen
at 5 atm in the presence of Pd(OH)2 (12.6 mg) for 100 h. The
mixture was filtered through a Celite pad, and the filtrate was
evaporated. The residue was chromatographed using 1%
MeOH-CH2Cl2 as eluent to give (2R,7S,9R)-21 (22 mg, 55%)
as an oil: [R]25D +63.50° (c 1.055, CHCl3); IR (neat) 2931, 2856,
2799, 2758, 1700, 1420, 1377, 1341, 1276 cm-1; 1H NMR (300
MHz, CDCl3) δ 0.86 (3 H, t, J ) 6.59 Hz), 1.24-2.48 (22 H,
m), 2.96 (1 H, br d, J ) 10.99 Hz), 3.11-3.20 (1 H, m), 3.49 (1
H, t, J ) 6.59 Hz); 13C NMR (75 MHz, CDCl3) δ 14.4, 23.0,
24.0, 24.4, 25.5, 26.3, 31.3, 31.8, 32.2, 32.6, 38.3, 49.5, 57.1,
61.8, 80.3, 174.7; HRMS calcd for C16H28ON2 (M+) 264.2202,
found 264.2206.
1472, 1429, 1373, 1254, 1171, 698, 668 cm-1 1H NMR (300
;
MHz, CDCl3) δ 0.85 (3 H, t, J ) 6.59 Hz), 1.24-1.79 (12 H,
m), 2.16-2.29 (4 H, m), 2.64 (4 H, br s), 2.73-2.78 (1 H, m),
4.00-4.18 (3 H, m), 4.99-5.05 (2 H, m), 7.29-7.36 (5 H, m);
13C NMR (75 MHz, CDCl3) δ 14.24, 19.50, 22.70, 25.97, 26.36,
28.47, 28.73, 30.53, 31.76, 32.84, 39.41, 47.32, 48.88, 67.23,
127.83, 128.43, 136.93, 155.25, 178.42; HRMS calcd for
C24H34O4N2 (M+) 414.2519, found 414.2487.
(2R,7R,9R)-1.6-Diaza-7-pen tyltr icyclo[7.4.0.02,6]tr idecan -
5-on e (21). By a procedure similar to that for the preparation
of 16, 20 (60 mg, 0.145 mmol) was converted with reduction
using 10% Pd/C (60 mg) in CH3OH (206 mL) to 21 (30 mg,
79%) as an oil: [R]25 +3.15° (c 1.525, CHCl3); IR (neat) 2931,
D
2857, 2798, 1694, 1421, 1276 cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.85 (3 H, t, J ) 6.59 Hz), 1.18-1.86 (18 H, m),2.15-2.43 (4
H, m), 2.90 (1 H, br d, J ) 10.99 Hz), 3.77 (1 H, br t, J ) 6.04
Hz), 4.14-4.16 (1 H, m); 13C NMR (75 MHz, CDCl3) δ 14.3,
22.8, 24.6, 25.5, 26.1, 29.9, 30.8, 32.0, 32.9, 34.9, 47.1, 49.7,
50.4, 73.6, 77.4, 172.8; HRMS calcd for C16H28ON2 (M+)
264.2201, found 264.2222.
(+)-Tetr a p on er in e-7 (T-7). By a procedure similar to that
for the preparation of T-3, 21 (63 mg, 0.24 mmol) was
converted with reduction using LiAlH4 (90 mg, 2.4 mmol) in
THF (3.5 mL) to T-7 (48 mg, 80%) as an oil: [R]25 +30.91° (c
D
1.1350, CHCl3), lit.20e [R]20D +30° (c 2.8, CHCl3); IR (neat) 2931,
2857, 2798, 1694, 1421, 1276 cm-1; 1H NMR (500 MHz, C6D6)
δ 0.92 (3 H, t, J ) 7.05 Hz), 1.10 (1 H, br d, J ) 2.35 Hz),
1.11-1.82 (19 H, m), 1.93 (1 H, ddd, J ) 12.81, 12.81, 5.55
Hz), 2.02-2.05 (1 H, m), 2.76-2.82 (3H, m), 3.15-3.18 (1 H,
m), 3.31 (1 H, dd, J ) 4.70 Hz, 2.78 Hz); 13C NMR (125 MHz,
C6D6) δ 14.38, 22.16, 23.19, 25.18, 26.46, 27.35, 30.46, 31.02,
32.15, 32.46, 34.17, 50.58, 50.93, 53.25, 56.68, 75.42, 75.46;
HRMS calcd for C16H30N2 (M+) 250.2409, found 250.2404.
[2R-(2R)]-P h en ylm et h yl 2-(2-H yd r oxyh ep t yl)p ip er i-
d in eca r boxyla te [[2R-(2R)]-19]. By a procedure similar to
that for the preparation of 19, [2R-(2S)]-3 (300 mg, 1.09 mmol)
was converted with n-Bu2CuLi (2.18 mmol) to [2R-(2R)]-19
(+)-Tetr a p on er in e-8 (T-8). By a procedure similar to that
for the preparation of T-3, (2R,7S,9R)-21 (40 mg, 0.15 mmol)
was converted with reduction using LiAlH4 (57 mg, 1.51 mmol)
in THF (4.3 mL) to T-8 (32 mg, 85%) a solid: mp 38-40 °C,
lit.20e mp 40 °C; [R]25D +98.18° (c 0.70, CHCl3), lit.20e [R]20D +99°
(c 0.6, CHCl3); IR (neat) 2930, 2857, 2789, 2704, 2509, 1377,
1
1338 cm-1; H NMR (500 MHz, C6D6) δ 0.89 (3 H, t, J ) 7.05
Hz), 1.16-1.77 (22 H, m), 2.01-2.14 (2 H, m), 2.29-2.32 (1H,
m), 2.83 (1 H, br d, J ) 9.61 Hz), 3.13-3.17 (1H, m); 13C NMR
(125 MHz, C6D6) δ 14.3, 20.2, 23.1, 25.1, 25.2, 26.2, 29.7, 32.8,
32.9, 34.6, 37.9, 49.0, 51.5, 61.3, 62.6, 85.6; HRMS calcd for
(326 mg, 90%) as an oil: [R]25 +25.12° (c 1.0550, CHCl3); IR
D
(neat) 3462, 2933, 2858, 1670, 1430, 1353, 1258, 1174, 697
cm-1; 1H NMR (300 MHz, CDCl3) δ 0.89 (3 H, t, J ) 6.87 Hz),
1.15-1.80 (15 H, m), 1.95-2.05 (1 H, m), 2.70-2.79 (1 H, m),
3.27 (1 H, br s), 4.04-4.05 (2 H, m), 4.51-4.55 (1 H, m), 5.15
(2 H, ABq, J ) 28.02 Hz, 12.09 Hz), 7.29-7.40 (5 H, m); 13C
NMR (75 MHz, CDCl3) δ 14.3, 19.3, 22.9, 25.6, 26.0, 29.5, 32.1,
36.9, 37.7, 39.4, 47.4, 67.3, 67.5, 127.8, 128.1, 128.5, 136.6,
C
16H30N2 (M+) 250.2409, found 250.2398.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
156.7; HRMS calcd for
333.2279.
C
20H31O3N (M+) 333.2304, found
J O991034W