Enantiospecific syntheses of valienamine and 2-epi-valienamine

Article abstract of DOI:10.1021/jo982024i

Cyclic sulfite 10, readily available from (-)-quinic acid (3) in 10 steps, was ring opened regio- and stereospecifically with azide anion to give (1S,2R,3R,4R)-1-azido-3,4-di-O-benzyl-5-(benzyloxymethyl)cyclohex-5-ene- 2,3,4-triol (11). Deprotection of 11 afforded, for the first time, 2- epivalienamine (2), which was isolated as penta-N,O-acetyl-2-epi-valienamine (14). The configuration of the free hydroxy group in 11 was inverted by a two-step sequence to give the blocked valienamine 19 that was deprotected to give valienamine (1), isolated as penta-N,O-acetylvalienamine (21). This approach furnished (+)-valienamine (1) in 16 steps (7% overall yield) and recorded the first synthesis of 2-epi-valienamine (2) in 13 steps (11% overall yield).

Full text of DOI:10.1021/jo982024i

J . Org. Chem. 1999, 64, 1941-1946
1941
En a n tiosp ecific Syn th eses of Va lien a m in e a n d 2-epi-Va lien a m in e1
Tony K. M. Shing,* Tin Y. Li, and Stanton H.-L. Kok
Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Received October 7, 1998
Cyclic sulfite 10, readily available from (-)-quinic acid (3) in 10 steps, was ring opened regio- and
stereospecifically with azide anion to give (1S,2R,3R,4R)-1-azido-3,4-di-O-benzyl-5-(benzyloxy-
methyl)cyclohex-5-ene-2,3,4-triol (11). Deprotection of 11 afforded, for the first time, 2-epi-
valienamine (2), which was isolated as penta-N,O-acetyl-2-epi-valienamine (14). The configuration
of the free hydroxy group in 11 was inverted by a two-step sequence to give the blocked valienamine
19 that was deprotected to give valienamine (1), isolated as penta-N,O-acetylvalienamine (21).
This approach furnished (+)-valienamine (1) in 16 steps (7% overall yield) and recorded the first
synthesis of 2-epi-valienamine (2) in 13 steps (11% overall yield).
In tr od u ction
Valienamine2 [(1S,2S,3S,4R)-1-amino-5-(hydroxymeth-
yl)cyclohex-5-ene-2,3,4-triol]t (1) is a carbasugar3 pro-
duced by the microbial degradation of validoxylamine A4
with Pseudomonas denitrificans5 or Flavobacterium
saccharophilum.6 The structure of valienamine was
deduced by spectroscopic studies.5 Valienamine demon-
strated R-glucosidase inhibitory activity, inhibiting 50%
activity of maltase and sucrase at a concentration of 3.4
× 10-4 and 5.3 × 10-5 M, respectively.7 Also, it showed
antibiotic activity against Bacillus species.8,9 The absolute
configuration of valienamine (1) is similar to that of R-D-
glucose. Since valienamine is an R-glucosidase inhibitor,
it was expected that the unnatural diastereomer, 2-epi-
valienamine (2), which is structurally related to R-D-
mannose, might be an R-mannosidase inhibitor (Figure
1).
Valienamine is an essential core unit in many kinds
of pseudo-oligosaccharidic R-glucosidase inhibitors, such
as acarbose,10,11 adiposin-2,12 acarviosin,13 and trestatin
B.14 These pseudo-oligosaccharides exhibit stronger en-
F igu r e 1.
zyme inhibitory activities than valienamine itself. Syn-
thesis of partially protected valienamine is warranted for
the subsequent coupling reactions targeting these pseudo-
aminodisaccharides or oligosaccharides. Related car-
baaminosugars (pseudoaminosugars) which show potent
glycosidase activity include valiolamine,15 validamine,16
and hydroxyvalidamine.17
* To whom correspondence should be addressed. Fax: (852)-2603
5057. E-mail: tonyshing@cuhk.edu.hk.
Since the isolation of valienamine 1 in 1972, eight
enantiospecific18-25 syntheses have appeared. The first
(1) (-)-Quinic acid in organic synthesis. 9. Part 8: (a) Shing, T. K.
M.; Tam, E. K. W. J . Org. Chem. 1998, 63, 1547. Part 7: (b) Shing, T.
K. M.; Wan, L. H. J . Org. Chem. 1996, 61, 8468. (c) Shing, T. K. M.;
Wan, L. H. Angew. Chem., Int. Ed. Engl. 1995, 34, 1643.
(2) Horii, S.; Iwasa, T.; Mizuta, E.; Kameda, Y. J . Antibiot. 1971,
24, 59.
(3) For a review see: (a) Suami, T.; Ogawa, S. Adv. Carbohydr.
Chem. Biochem. 1990, 48, 21. For general pseudosugar synthesis,
see: (b) Ogawa, S. J . Synth. Org. Chem. J pn. 1985, 43, 26. (c) Pingli,
L.; Vandewalle, M. Synlett 1994, 228, and references therein.
(4) Iwasa, I.; Yamamoto, H.; Shibata, M. J . Antibiot. 1970, 23, 595.
(5) Kameda, Y.; Horii, S. J . Chem. Soc., Chem. Commun. 1972, 746.
(6) Kameda, Y.; Asano, N.; Teranishi, M.; Matsui, K. J . Antibiot.
1980, 33, 1573.
(7) Kameda, Y.; Asano, N.; Yoshikawa, M.; Matsui, K. J . Antibiot.
1982, 35, 1624.
(8) Kameda, Y.; Asano, N.; Yoshikawa, M.; Takeuchi, M.; Yamagu-
chi, T.; Matsui, K. J . Antibiot. 1984, 37, 1301.
(9) Kameda, Y.; Asano, N.; Yoshikawa, M.; Matsui, K. J . Antibiot.
1980, 33, 1575.
(10) Schmidt, D. D.; Frommer, W.; J unge, B.; Mu¨ller, L.; Wingender,
W.; Truscheit, E.; Schafer, D. Naturwissenschaften. 1977, 64, 535.
(11) J unge, B.; Heiker, F. R.; Kurz, J .; Mu¨ller, L.; Schmidt, D. D.;
Wunsche, C. Carbohydr. Res. 1984, 128, 235.
(14) Yokose, K.; Ogawa, S.; Suzuki, Y.; Buchschacher, P. The 23rd
Symposium on Natural Organic Compounds, Nagaya, J apan, October,
1980, Abstr No. 82.
(15) Kameda, Y.; Asano, N.; Yoshikawa, M.; Takeuchi, M.; Yamagu-
chi, T.; Matsui, K.; Horii, S.; Fukase, H. J . Antibiot. 1984, 37, 1301.
(16) Kameda, Y.; Horii, S. J . Chem. Soc., Chem. Commun. 1972,
746.
(17) Horii, S.; Iwasa, T.; Mizuta, E.; Kameda, Y. J . Antibiot. 1971,
24, 59.
(18) (a) Paulsen, H.; Heiker, F. R. Angew. Chem., Int. Ed. Engl.
1980, 19, 904. (b) Liebigs Ann. Chem. 1981, 2180.
(19) Schmidt, D. D.; Ko¨hn, A. Angew. Chem., Int. Ed. Engl. 1987,
26, 482.
(20) Nicotra, F.; Panza, L.; Ronchetti, F.; Russo, G. Gazz. Chim. Ital.
1989, 119, 577.
(21) Park, T. K.; Danishefsky, S. J . Tetrahedron Lett. 1994, 35, 2667.
(22) Yoshikawa, M.; Cha, B. C.; Okaichi, Y.; Takinami, Y.; Yokoka-
wa, Y.; Kitagawa, I. Chem. Pharm. Bull. 1988, 36, 4236.
(23) Ogawa, S.; Shibata, Y.; Nose, T.; Suami, T. Bull. Chem. Soc.
J pn. 1985, 58, 3357.
(12) Namiki, S.; Kangouir, K.; Nagata, T.; Hara, N.; Sugita, K.;
Omura, S. J . Antibiot. 1982, 35, 1234.
(13) J unge, B.; Heiker, F.; Kurz, J .; Mu¨ller, L.; Schmidt, D. D.;
Wu¨nsche, C. Carbohydr. Res. 1984, 128, 235.
(24) Knapp, S.; Naughton, A. B. J .; Dhar, T. G. M. Tetrahedron Lett.
1992, 33, 1025.
(25) Trost, B. M.; Chupak L. S.; Lu¨bbers T. J . Am. Chem. Soc. 1998,
120, 1732.
10.1021/jo982024i CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/24/1999

1942 J . Org. Chem., Vol. 64, No. 6, 1999
Shing et al.
Sch em e 1
in 5 to furnish the double bond in valiename was our next
objective. Initially, the tribenzyl ether 5 was treated with
POCl3 in pyridine,27 but there was no observable reaction.
The reaction of 5 with Martin sulfurane dehydrating
agent,28 however, gave the undesired enol ether 6 as the
sole product in excellent yield (eq 1). It was speculated
that this pathway was preferred because the cyclohex-
ylidene ring in 5 might block the R-face, thereby prevent-
ing anti-elimination from proceeding at the endocyclic
methylene. The tribenzyl ether 5 was also allowed to
react with thionyl chloride and pyridine in CH2Cl2 at 0
°C,29 but a low yield of the desired alkene 8 was obtained.
The major product was the dimer 7 together with a small
amount of the enol ether 6 (eq 2). Dimer formation was
synthesis was reported by Paulsen et al.,18 on the basis
of transformations from the cyclitol quebrachitol. Four
other syntheses were based on conversions from D-glucose
in which three19-21 involved a Ferrier rearrangement and
one22 employed cyclization of a nitrofuranose as the key
step for the formation of the cyclohexane framework. The
three23-25 remaining constructions took advantage of the
Diels-Alder reaction to fabricate the cyclohexane skel-
eton, which then was functionalized to give the target
molecule. The most recent synthesis was asymmetric and
was achieved via two consecutive palladium-catalyzed
asymmetric alkylations as the key steps.25 However, the
construction of 2-epi-valienamine (2) has not been re-
ported in the literature. In our own quest for a general
and efficient entry to pseudoaminosugars, we previously
described the preparations of validamine and 2-epi-
validamine,26 valiolamine, 1-epi-valiolamine, 2-epi-vali-
olamine, and (1R,2R)-valiolamine using the (-)-quinic
acid approach.1b We herein report the versatility of this
approach for the facile and enantiospecific syntheses of
valienamine (1) and its 2-epimer 2, involving a regiose-
lective cyclic sulfite opening as the key step.
probably due to the tribenzyl ether 5 being in excess
when thionyl chloride was added dropwise to the reaction
mixture. The tribenzyl ether 5 could be regenerated from
the dimer 7 in 90% yield upon solvolysis with sodium
hydroxide in methanol. We therefore modified the elimi-
nation procedure in order to prevent the formation of
dimer 7. This was realized by ensuring that thionyl
chloride was in excess throughout the reaction (reversed
quenching). A solution of 5 in pyridine was therefore
added dropwise to the thionyl chloride solution in CH2Cl2
at 0 °C. In this manner, the desired alkene 8 was
obtained in 70% yield and only a small amount of the
dimer 7 (15%) was produced.
Hydrolysis of the cyclohexylidene blocking group in 8
was carried out using aqueous trifluoroacetic acid (TFA)
in CH2Cl2 to give the diol 9 in 85% yield (Scheme 1). A
second reaction with thionyl chloride in the conventional
way provided the cyclic sulfite30 10 in excellent yield. The
cyclic sulfite proved to be unstable and was used in the
following ring-opening reaction without characterization.
To synthesize valienamine and its 2-epimer, an amino
group must be installed at the allylic position. An azido
group was chosen as the amine precursor, and the
Syn th esis of 2-epi-Va lien a m in e
Our previous work has shown that the diol 4 could be
obtained from (-)-quinic acid (3) in six steps with 34%
overall yield (Scheme 1).1b Then, selective benzylation of
the secondary alcohol in diol 4 with benzyl bromide in
the presence of sodium hydride afforded the tribenzyl
ether 5. Regioselectivity could be achieved because the
secondary hydroxyl group is less hindered than the
tertiary one. Elimination of the tertiary hydroxyl group
(27) Mori, K.; Takigawa, T.; Matsuo, T. Tetrahedron 1979, 35, 933.
(28) (a) Martin, J . C.; Arhart, R. J . J . Am. Chem. Soc. 1971, 93,
4327. (b) Paquette, L. A.; Zhao, M. J . Am. Chem. Soc. 1993, 115, 354.
(29) Schwartz, A.; Madan, P. J . Org. Chem. 1986, 51, 5463.
(30) (a) Lohray, B. B.; Ahuja, J . R. J . Chem. Soc., Chem. Commun.
1991, 95. (b) Hui Shao, H.; Goodman, M. J . Org. Chem. 1996, 61, 2582.
(c) Dauban, P.; Chiaroni A.; Riche C.; Dodd R. H. J . Org. Chem. 1996,
61, 2488.
(26) Shing, T. K. M.; Tai, V. W.-F. J . Org. Chem. 1995, 60, 5332.

Valienamine and 2-epi-Valienamine
J . Org. Chem., Vol. 64, No. 6, 1999 1943
Sch em e 2
Sch em e 3
introduction of the azido group at the allylic position
proceeded via a regiospecific SN2 reaction30 of lithium
azide on the cyclic sulfite 10, affording a single adduct
11 in 97% yield. The regio- and stereochemical assign-
ments were based on 1H NMR spectral analysis of the
azido acetate 12 formed from 11. The coupling constants
of 1.3 Hz between H2-H3 and 7.8 Hz between H1-H2
show that H1 and H2 are anti-disposed and H2 and H3
are syn-disposed. These assignments were confirmed by
spin-decoupling experiments, thus providing evidence
that the nucleophilic opening reactions of the cyclic sulfite
10 by the azido group were stereospecific and occurred
via the â-face.
It has been reported that reduction of an allylic azide
with NaBH4 would cause the azide group to migrate
through a boron-assisted allylic rearrangement.31 Thus,
the reduction of the azido group in 11 was effected with
triphenylphosphine (PPh3), aqueous ammonia, and pyr-
idine,32 furnishing amine 13 in excellent yield. In this
reaction, PPh3 reacts with the azide group to give a
triphenylphosphinimine, which is then hydrolyzed cleanly
to the amine on treatment with aqueous ammonia.
Because the presence of a double bond in 13 precludes
the use of hydrogenolysis, debenzylation of 13 was carried
out using sodium in liquid ammonia at -78 °C to give
2-epi-valienamine (2). This constitutes the first chemical
synthesis of this compound. Peracetylation of 2 to the
corresponding pentaacetyl derivative 14 allowed facile
isolation and characterization. The overall yield of 14
from (-)-quinic acid (3) was 11% in 14 steps.
cinimide. A stronger nucleophile, tetrabutylammonium
acetate, was then employed. Unfortunately, whether
because the basicity of tetrabutylammonium acetate is
too strong or the triflate group is too reactive, elimination
rather than SN2 substitution predominated, and the
aromatic compound 16 was obtained in 50% yield to-
gether with only 27% of the desired azidoacetate 17.
When the triflate group was replaced by the less nucle-
ofugal mesylate group via standard esterification of 11
with mesyl chloride, the elimination reaction of the
resultant mesylate 18 in the presence of tetrabutylam-
monium acetate was minimized to 10%, and the yield of
the desired azidoacetate 17 was greatly improved to 61%
(Scheme 3).
Since the current chirality of all the functional groups
was now established, the next step was to deacetylate
17 to afford 19 using a catalytic amount of potassium
carbonate in methanol. The azido group in 19 was then
reduced readily to the amine 20 using PPh3 and NH4OH
in pyridine. Finally, debenzylation of 20 with sodium in
liquid ammonia at -78 °C afforded valienamine 1.
Acetylation of 1 afforded peracetate 20 for isolation and
characterization. The overall yield of N,O,O,O,O-penta-
cetylvalienamine 20 from (-)-quinic acid was 7% in 17
steps. The spectral data and physical constants, of our
Syn th esis of Va lien a m in e
synthetic compound 20, mp 92-94 °C, [R]20 +20.1 (c )
D
For the synthesis of valienamine 1, the configuration
at C-2 of 11 needs to be inverted. Activation of the free
alcohol at this site as a sulfonate ester was investigated,
and the preparation of a triflate ester was attempted
first. Thus the hydroxy group in 11 was esterified with
trifluoromethanesulfonic anhydride and pyridine in dichlo-
romethane to yield the triflate 15 in excellent yield
(Scheme 2). The triflate 15 was then reacted with
N-hydroxysuccinimide in an attempt to invert the con-
figuration at C-2.33 However, no reaction occurred, prob-
ably due to the weak nucleophilicity of N-hydroxysuc-
0.8, CHCl3), are in close agreement with those reported
in the literature (lit.5 mp 95 °C; lit.23 mp 92.5-95 °C) {lit.5
[R]23 +32.2 (CHCl3); lit.23 [R]21 +20 (c ) 1.04, CHCl3)}.
D
D
Con clu sion s
We have described facile, practical, and enantiospecific
syntheses of (+)-valienamine (1) and (+)-2-epi-valien-
amine (2) in 16 steps (7% overall yield) and 13 steps (11%
overall yield), respectively, from quinic acid (3). The
preparation of (+)-2-epi-valienamine (2) has not been
previously reported. Synthetic intermediates such as
amino alcohols 13 and 20 are possibly valuable substrates
for the coupling reactions that lead to pseudoaminodis-
accharides or oligosaccharides. Research along this line
is under way.
(31) Boivin, J .; Pais, M.; Monneret, C. Carbohydr. Res. 1980, 79,
193.
(32) Mungall, W. S.; Greene, G. L.; Heavnerm G. A.; Letsinger, R.
L. J . Org. Chem. 1975, 40, 1659.
(33) Shing, T. K. M.; Gillhouley, J . G. Tetrahedron 1994, 50, 8685.

1944 J . Org. Chem., Vol. 64, No. 6, 1999
Shing et al.
with CH2Cl2 (2 ×). The combined organic extracts were washed
with brine, dried over MgSO4, and filtered. Concentration of
the filtrate followed by flash chromatography (hexane-diethyl
ether, 5:1) gave the endocyclic alkene 8 (45 mg, 25%) as a white
solid and the exo enol ether 6 (9 mg, 5%) and the sulfite dimer
7 (77 mg, 40%) as colorless oils.
Exp er im en ta l Section
Melting points are reported in degrees Celsius and are
uncorrected. Optical rotations were measured at 589 nm. IR
spectra were recorded on a FT-IR spectrometer as thin films
on KBr disks. Unless otherwise stated, NMR spectra were
measured in solutions of CDCl3 at 250 MHz (1H) or at 62.9
MHz (13C). Spin-spin coupling constants (J ) were measured
directly from the spectra. Carbon and hydrogen elemental
analyses were carried out at either the Shanghai Institute of
Organic Chemistry, The Chinese Academy of Sciences, China,
or the MEDAC Ltd, Department of Chemistry, Brunel Uni-
versity, Uxbridge, U.K. All reactions were monitored by
analytical TLC on aluminum precoated with silica gel 60F254
(E. Merck), and compounds were visualized with a spray of
either 5% w/v dodecamolybdophosphoric acid in ethanol or 5%
v/v concentrated sulfuric acid in ethanol and subsequent
heating. All columns were packed wet using E. Merck silica
gel 60 (230-400 mesh) as the stationary phase and eluted
using flash column chromatographic technique.
Alkene 8: mp 65-68 °C; Rf ) 0.3 (hexane-diethyl ether,
4:1); [R]20 -25.8 (c ) 1.0, CHCl3); IR (film) 2933, 2859 cm-1
;
D
1H NMR δ 1.55-1.63 (10H, m), 3.76 (1H, dd, J ) 7.9, 2.5 Hz),
3.96 and 4.26 (2H, ABq, J ) 12.9 Hz), 4.39 (1H, br d, J ) 7.9
Hz), 4.44 and 4.52 (2H, ABq, J ) 11.8 Hz), 4.50-4.55 (2H,
m), 4.69 and 4.88 (2H, ABq, J ) 10.8 Hz), 4.79 (2H, s), 5.71
(1H, br s), 7.25-7.41 (15H, m); MS (FAB) m/z (relative
intensity) 526 (MH+, 7). Anal. Calcd for C34H38O5: C, 77.54;
H, 7.27. Found: C, 77.52; H, 7.24.
Sulfite dimer 7: Rf ) 0.33 (hexane-diethyl ether, 4:1); [R]20
D
1
+4.5 (c ) 1.3, CHCl3); IR (film) 2934, 2859 cm-1; H NMR δ
1.43-1.73 (20H, m), 1.83-1.94 (2H, m), 2.27-2.40 (2H, m),
3.57 and 3.73 (2H, ABq, J ) 8.9 Hz), 3.62 and 3.78 (2H, ABq,
J ) 9 Hz), 4.00-4.18 (6H, m), 4.23-4.36 (6H, m), 4.58 (2H, d,
J ) 11.3 Hz), 4.63-4.66 (2H, m), 4.74 (2H, d, J ) 11.8 Hz),
4.97 (2H, d, J ) 11.4 Hz), 7.11-7.32 (30H, m); MS (FAB) m/z
(relative intensity) 545 (M+ - C34H37O7S, 27%). Anal. Calcd
for C68H78O13S: C, 71.93; H, 6.92; S, 2.82. Found: C, 71.78;
H, 6.81; S, 2.83.
(b) To a solution of thionyl chloride (0.015 mL, 0.21 mmol)
in dry CH2Cl2 (5 mL) at 0 °C was added dropwise a solution
of the tertiary alcohol 5 (60 mg, 0.11 mmol) in dry CH2Cl2 (5
mL) and pyridine (0.1 mL, 1.24 mmol) within 30 min, and the
mixture was stirred for 5 h at 0 °C. The reaction mixture was
diluted with CH2Cl2 (10 mL) and washed with saturated
NaHCO3 (10 mL). The aqueous layer was extracted with
CH2Cl2 (2 ×). The combined organic extracts were washed with
brine, dried over MgSO4, and filtered. Concentration of the
filtrate followed by flash chromatography (hexane-diethyl
ether, 5:1) gave the alkene 8 (41 mg, 70%) as a white solid
and the dimer 7 (15%).
(1R,2R,3R,4R)-3,4-Di-O-ben zyl-5-(ben zyloxym eth yl)cy-
cloh ex-5-en e-1,2,3,4-tetr a ol (9). To a solution of the alkene
8 (115 mg, 0.22 mmol) in CH2Cl2 (5 mL) was added TFA (0.5
mL) and water (0.1 mL) at room temperature. The mixture
was stirred for 24 h at room temperature and poured into
saturated NaHCO3 (10 mL). The aqueous layer was extracted
with CH2Cl2 (2 ×). The combined organic extracts were washed
with brine, dried over MgSO4, and filtered. Concentration of
the filtrate followed by flash chromatography (hexane-diethyl
ether, 1:2) gave the diol 9 (83 mg, 85%) as a white solid.
(1R,2R,3R,4S,5S)-3,4-Di-O-ben zyl-5-(ben zyloxym eth yl)-
1,2-O-cycloh exyliden e-1,2,3,4,5-cycloh exan epen tol (5). So-
dium hydride (80%, 0.10 g, 3.33 mmol) was washed with dry
n-hexane and suspended in dry THF (5 mL) under nitrogen
at 0 °C. A solution of the diol 41b (0.96 g, 2.11 mmol) in THF
(8 mL) was added dropwise over 30 min at 0 °C, and then the
mixture was stirred for 1 h at 0 °C. Benzyl bromide (0.5 mL,
4.21 mmol) was added dropwise over 30 min at 0 °C followed
n
by the addition of a catalytic amount of Bu4NI. The mixture
was stirred overnight at room temperature. Methanol (3 mL)
was then added slowly to destroy the excess of hydride, and
this was followed by the addition of water (5 mL). Concentra-
tion of the mixture gave a residue that was partitioned
between CH2Cl2 (20 mL) and water (20 mL). The aqueous layer
was extracted with CH2Cl2 (2 ×). The combined organic
extracts were washed with brine, dried over MgSO4, and
filtered. Concentration of the filtrate followed by flash chro-
matography (hexane-diethyl ether, 2:1) gave the tribenzyl
ether 5 (0.98 g, 85%) as a colorless oil: Rf ) 0.25 (hexane-
diethyl ether, 2:1); [R]20 +1.5 (c ) 1.3, CHCl3); IR (film) 3450
D
cm-1; H NMR δ 1.40-2.03 (12H, m), 2.30 (1H, s), 3.21 and
1
3.42 (2H, ABq, J ) 8.6 Hz), 3.97 (2H, m), 4.25-4.33 (2H, m),
4.44 and 4.50 (2H, ABq, J ) 12.0 Hz), 4.54 and 4.93 (2H, ABq,
J ) 10.8 Hz), 4.73 and 4.79 (2H, ABq, J ) 12.1 Hz), 7.22-
7.42 (15H, m); MS (FAB) m/z (relative intensity) 545 (MH+,
6). Anal. Calcd for C34H40O6: C, 74.97; H, 7.40. Found: C,
74.55; H, 7.47.
(1R,2R,3S,4R)-3,4-Di-O-ben zyl-5-(ben zyloxym eth ylen e)-
1,2-O-cycloh exylid en ecycloh ex-5-en e-1,2,3,4-tetr a ol (6).
To a solution of the tertiary alcohol 5 (123 mg, 0.22 mmol) in
dry benzene (15 mL) was added Martin sulfurane dehydrating
agent28 (230 mg, 0.34 mmol) at room temperature. The reaction
mixture was heated under reflux for 3 h under nitrogen, then
concentrated, diluted with CH2Cl2 (20 mL), and washed with
brine (10 mL). The aqueous layer was extracted with CH2Cl2
(2 ×). The combined organic extracts were dried over MgSO4
and filtered. Concentration of the filtrate followed by flash
chromatography (hexane-diethyl ether, 3:2) gave the exocyclic
alkene 6 (104 mg, 88%) as a colorless oil.
Diol 9: mp 79-85 °C; Rf ) 0.16 (hexane-diethyl ether, 1:2);
D
1
[R]20 -75.7 (c ) 1.0, CHCl3); IR (film) 3422 cm-1; H NMR δ
2.83 (1H, br d, J ) 10.6 Hz), 3.33 (1H, br d, J ) 7.6 Hz), 3.85-
3.89 (2H, m), 4.05-4.18 (4H, m), 4.34 and 4.47 (2H, ABq, J )
11.8 Hz), 4.43 and 4.59 (2H, ABq, J ) 11.3 Hz), 4.52 and 4.58
(2H, d, J ) 11.7 Hz), 5.95 (1H, d, J ) 3.5 Hz), 7.21-7.37 (15H,
m); MS (FAB) m/z (relative intensity) 447 (MH+, 2). Anal.
Calcd for C28H30O5: C, 75.31; H, 6.77. Found: C, 75.57; H,
7.01.
(1R,2S,3S,4R)-3,4-Di-O-ben zyl-5-(ben zyloxym eth yl)-1,2-
O,O-su lfon ylcycloh ex-5-en e-1,2,3,4-tetr a ol (10). To a solu-
tion of the diol 9 (455 mg, 1.02 mmol) in CH2Cl2 (10 mL) and
Et3N (0.7 mL) was added a solution of thionyl chloride (0.22
mL, 3.02 mmol) in CH2Cl2 (10 mL) at 0 °C, and the mixture
was stirred for 1 h at 0 °C. The reaction mixture was diluted
with CH2Cl2 (15 mL) and washed with saturated NaHCO3 (10
mL). The aqueous layer was extracted with CH2Cl2 (2 ×). The
combined organic extracts were washed with brine, dried over
MgSO4, filtered, and concentrated to afford the crude cyclic
sulfite 10, which was used directly in the following ring-
opening experiment.
6: Rf ) 0.54 (hexane-diethyl ether, 4:1); [R]20 ) +54.2 (c
D
) 2.0, CHCl3); IR (film) 1682 cm-1; 1H NMR δ 1.33-1.64 (10H,
m), 2.22 (1H, dd, J ) 14.5, 4.6 Hz), 2.58 (1H, dd, J ) 14.5, 3.6
Hz), 3.64 (1H, dd, J ) 6.9, 3.2 Hz), 4.08 (1H, d, J ) 6.9 Hz),
4.24-4.30 (1H, m), 4.38-4.42 (2H, m), 4.52 (1H, d, J ) 11.6
Hz), 4.76-4.87 (4H, m), 6.25 (1H, s), 7.24-7.39 (15H, m);
HRMS (EI) calcd for C34H28O5 526.2719 (M+), found 526.2713.
Dim er 7 a n d (1R,2R,3S,4R)-3,4-Di-O-ben zyl-5-(ben zyl-
oxymethyl)-1,2-O-cyclohexylidenecyclohex-5-ene-1,2,3,4-tetraol
(8). (a ) To a solution of the tertiary alcohol 5 (185 mg, 0.34
mmol) in dry CH2Cl2 (20 mL) and pyridine (0.25 mL, 3.10
mmol) was added dropwise a solution of thionyl chloride (0.04
mL, 0.55 mmol) in dry CH2Cl2 (8 mL) for 30 min at 0 °C, and
the mixture was stirred for 5 h at 0 °C. The reaction mixture
was then diluted with CH2Cl2 (20 mL) and washed with
saturated NaHCO3 (12 mL). The aqueous layer was extracted
(1S,2R,3R,4R)-1-Azid o-3,4-d i-O-b en zyl-5-(b en zyloxy-
m eth yl)cycloh ex-5-en -2,3,4-tr iol (11). The above cyclic sulfite
34
10 was dissolved in DMF (10 mL), and LiN3 (130 mg) was
added. The reaction mixture was stirred for 3 h at 80 °C. The
(34) Hofmann-Bang, N. Acta Chem. Scand. 1957, 11, 581.

Valienamine and 2-epi-Valienamine
J . Org. Chem., Vol. 64, No. 6, 1999 1945
cooled mixture was then diluted with EtOAc (15 mL), washed
with brine, dried over MgSO4, and filtered. Concentration of
the filtrate followed by flash chromatgraphy (hexane-diethyl
ether, 3:1) gave the azide 11 (433 mg, 90%) as a colorless oil.
and 4.52 (2H, ABq, J ) 13.2 Hz), 4.80 (1H, br t, J ) 8.1 Hz),
5.09 (1H, dd, J ) 8.1, 2.4 Hz), 5.19-5.22 (1H, m), 5.34 (1H, d,
J ) 3.9 Hz), 5.82 (1H, m), 6.02 (1H, br d, J ) 8.5 Hz); 13C
NMR δ 20.6, 23.1, 47.3, 63.6, 67.6, 69.4, 69.6, 130.0, 131.2,
169.4, 169.5, 169.9, 170.2, 170.7; MS (L-SIMS) m/z (relative
intensity) 386 (MH+, 0.6). Anal. Calcd for C17H23NO9: C, 52.98;
H, 6.02; N, 3.63. Found: C, 53.18; H, 6.08; N, 3.62.
Azide 11: Rf ) 0.52 (hexane-diethyl ether, 1:1); [R]20 +36
D
(c ) 1.3, CHCl3); IR (film) 3502, 2099 cm-1; H NMR δ 2.26
1
(1H, d, J ) 7.8 Hz), 3.86-3.96 (3H, m), 4.05-4.17 (3H, m),
4.36 and 4.48 (2H, ABq, J ) 11.9 Hz), 4.46 and 4.57 (2H, ABq,
J ) 11.3 Hz), 4.54 and 4.61 (2H, ABq, J ) 11.9 Hz), 5.74 (1H,
s), 7.22-7.38 (15H, m); MS (FAB) m/z (relative intensity) 472
(MH+, 6). Anal. Calcd for C28H29N3O4: C, 71.32; H, 6.20; N,
8.91. Found: C, 71.15; H, 6.26; N, 8.80.
(1S,2R,3S,4R)-1-Azid o-3,4-d i-O-b en zyl-5-(b en zyloxy-
m et h yl)-2-O-t r iflu or om et h a n esu lfon ylcycloh ex-5-en e-
2,3,4-tr iol (15). To a solution of the alcohol 11 (48 mg, 0.10
mmol) in dry CH2Cl2 (10 mL) and pyridine (0.04 mL, 0.5 mmol)
was added dropwise Tf2O (0.04 mL, 0.24 mmol) for 10 min at
0 °C, and the mixture was stirred for 3 h at 0 °C. The mixture
was diluted with CH2Cl2 (20 mL) and washed with saturated
NaHCO3 (10 mL). The aqueous layer was extracted with
CH2Cl2 (2 ×). The combined organic extracts were washed with
brine, dried over MgSO4, and filtered. Concentration of the
filtrate followed by flash chromatography (hexane-diethyl
ether, 3:1) gave the triflate 15 (58.4 mg, 95%) as a colorless
oil.
Triflate 15: IR (film) 2105, 1400 1200 cm-1; 1H NMR δ 3.88
(1H, d, J ) 12.8 Hz), 3.62-4.07 (3H, m), 4.32 (1H, d, J ) 11.4
Hz), 4.35 (1H, d, J ) 11.8 Hz), 4.45-4.46 (2H, m), 4.50-4.51
(2H, m), 4.63 (1H, d, J ) 11.8 Hz), 5.05 (1H, dd, J ) 8.5, 2.2
Hz), 5.58 and 4.72 (2H, ABq, J ) 12 Hz), 5.78 (1H, m), 7.16-
7.36 (15H, m).
(1S,2R,3S,4R)-2-O-Acetyl-1-azido-3,4-di-O-ben zyl-5-(ben -
zyloxym eth yl)cycloh ex-5-en e-2,3,4-tr iol (12). To a solution
of the alcohol 11 (100 mg, 0.21 mmol) in CH2Cl2 (10 mL) was
added Ac2O (0.04 mL, 0.42 mmol), pyridine (0.07 mL, 0.84
mmol), and a catalytic amount of DMAP (1 mg) at room
temperature. The reaction mixture was stirred overnight at
room temperature, then diluted with CH2Cl2 (15 mL), and
washed with saturated Na2CO3. The aqueous layer was
extracted with CH2Cl2 (2 ×). The combined organic extracts
were washed with brine, dried over MgSO4, and filtered.
Concentration of the filtrate followed by flash chromatography
(hexane-diethyl ether, 4:1) gave the acetate 12 (100 mg, 95%)
as a colorless oil.
Acetate 12: Rf ) 0.47 (hexane-diethyl ether, 3:1); [R]20
D
+49.7 (c ) 0.4, CHCl3); IR (film) 2098, 1743 cm-1; H NMR δ
1
(1S,2S,3S,4R)-2-O-Acetyl-1-azido-3,4-di-O-ben zyl-5-(ben -
zyloxym eth yl)cycloh ex-5-en e-2,3,4-tr iol (17). (a ) F r om
Tr ifla te 15. To a solution of the triflate 15 (58 mg, 0.097
mmol) in DMF (5 mL) was added n-Bu4NOAc (90 mg, 0.30
mmol) at room temperature, and the resulting mixture was
stirred overnight at 80 °C. The reaction mixture was diluted
with EtOAc (20 mL) and washed with saturated NaHCO3 (10
mL). The aqueous layer was extracted with EtOAc (2 ×). The
combined organic extracts were washed with brine, dried over
MgSO4, and filtered. Concentration of the filtrate followed by
flash chromatography (hexane-diethyl ether, 4:1) gave the
aromatic compound 16 (20 mg, 50%) as a white solid and the
desired azidoacetate 17 (14 mg, 27%) as a colorless oil.
2.08 (3H, s), 3.90 and 3.10 (2H, ABq, J ) 12.5 Hz), 4.00 (2H,
s), 4.34-4.44 (3H, m), 4.49 (1H, d, J ) 11.9 Hz), 4.53 (1H, s),
4.60 (1H, d, J ) 11.4 Hz), 5.21 (1H, d, J ) 7.7 Hz), 5.75 (1H,
s), 7.25-7.37 (15H, m).
(1S,2R,3R,4R)-1-Am in o-3,4-d i-O-b en zyl-5-(b en zyloxy-
m eth yl)cycloh ex-5-en e-2,3,4-tr iol (13). To a solution of the
alcohol 11 (379 mg, 0.81 mmol) in pyridine (10 mL) and
aqueous NH3 (32%, 2 mL) was added PPh3 (317 mg, 1.21
mmol), and the mixture was stirred overnight at room tem-
perature. The reaction mixture was diluted with CH2Cl2 (20
mL) and washed with brine. The aqueous layer was extracted
with CH2Cl2 (2 ×). The combined organic extracts were dried
over MgSO4 and filtered. Concentration of the filtrate followed
by flash chromatography (CHCl3-MeOH, 10:1) gave the amine
13 (349 mg, 97%) as a white solid.
Compound 16: mp 42-44 °C; Rf ) 0.67 (hexane-diethyl
1
ether, 10:1); IR (film) 1478, 1454, 735, 696 cm-1; H NMR δ
Amine 13: mp 80-82 °C; Rf ) 0.39 (CHCl3-MeOH, 10:1);
4.52 (2H, s), 4.56 (2H, s), 5.03 (2H, s), 5.14 (2H, s), 6.96-7.08
(3H, m), 7.28-7.47 (15H, m); HRMS (EI) calcd for C28H26O3
410.1882 (M), found 410.1871 (M).
[R]20 -9.7 (c ) 1.1, CHCl3); IR (film) 3355, 3289, 3022 cm-1
;
D
1H NMR δ 2.27 (3H, br s), 3.47 (1H, br d, J ) 8.2 Hz), 3.60
(1H, dd, J ) 8.4, 2.3 Hz), 3.82 and 4.10 (2H, ABq, J ) 12.1
Hz), 3.89 (1H, br t, J ) 2.5 Hz), 4.02 (1H, br d, J ) 2.5 Hz),
4.31 (1H, d, J ) 11.8 Hz), 4.43 (2H, t, 11.4 Hz), 4.54 (1H, d, J
) 11.4 Hz), 4.60 (2H, s), 5.70 (1H, s), 7.22-7.33 (15H, m); MS
(FAB) m/z (relative intensity) 446 (MH+, 26). Anal. Calcd for
Acetate 17: Rf ) 0.42 (hexane-diethyl ether, 3:1); [R]20
)
D
+35.6 (c ) 1.0, CHCl3); IR (film) 2103, 1746 cm-1; H NMR δ
2.04 (3H, s), 3.99 (1H, d, J ) 13 Hz), 4.12-4.21 (3H, m), 4.31
(1H, br t, J ) 4.3 Hz), 4.44 and 4.52 (2H, ABq, J ) 11.8 Hz),
4.59 and 4.70 (2H, ABq, J ) 11 Hz), 4.74 and 4.80 (2H, ABq,
J ) 11.4 Hz), 5.09-5.15 (1H, m), 5.84 (1H, d, J ) 4.9 Hz),
7.21-7.37 (15H, m); MS (EI) m/z (relative intensity) 514 (MH+,
10); HRMS (ESI) calcd for C30H31N3O5Na+ 536.2154, found
536.2160.
1
C
28H31NO4: C, 75.48; H, 7.01; N, 3.14. Found: C, 75.21; H,
6.86; N, 3.04.
2-epi-Va lien a m in e (2) a n d (1S,2R,3S,4R)-1-Aceta m id o-
5-(a cetoxym eth yl)-2,3,4-tr i-O-a cetylcycloh ex-5-en e-2,3,4-
tr iol [P en ta -N,O-a cetyl-2-epi-va lien a m in e] (14). To a so-
lution of the amine 13 (276 mg, 0.62 mmol) in dry THF (5 mL)
and liquid NH3 (20 mL) was added sodium (150 mg, 6.52 mmol)
at -78 °C. The reaction mixture was stirred for 4 h at -78
°C. Solid NH4Cl (100 mg) was added to the mixture at -78
°C. After disappearance of the blue color of the mixture, NH3
and solvent were removed under reduced pressure to give
crude 2-epi-valienamine (2). The crude product 2 was dissolved
in pyridine (10 mL), and acetic anhydride (2 mL) containing a
catalytic amount of DMAP (2 mg) was added. The mixture was
stirred overnight at room temperature. The reaction mixture
was diluted with EtOAc (10 mL) and washed with saturated
NaHCO3 (10 mL). The aqueous layer was extracted with
EtOAc (2 ×). The combined organic extracts were washed with
brine, dried over MgSO4, and filtered. Concentration of the
filtrate followed by flash chromatography (hexanes-EtOAc,
1:4) gave the pentaacetate 14 (165 mg, 70%) as white plate
crystals.
(b) F r om Mesyla te 18. To a solution of the mesylate 18
(123 mg, 0.22 mmol) in DMF (5 mL) was added n-Bu4NOAc
at room temperature, and the resultant mixture was stirred
overnight at 80 °C. The cooled reaction mixture was diluted
with EtOAc (20 mL) and washed with saturated NaHCO3 (10
mL). The aqueous layer was extracted with EtOAc (2 ×). The
combined organic extracts were washed with brine, dried over
MgSO4, and filtered. Concentration of the filtrate followed by
flash chromatography (hexane-diethyl ether, 4:1) gave the
acetate 17 (65 mg, 61%) as a colorless oil.
(1S,2R,3S,4R)-1-Azid o-3,4-d i-O-b en zyl-5-(b en zyloxy-
m et h yl)-2-O-m et h a n esu lfon ylcycloh ex-5-en e-2,3,4-t r iol
(18). To a solution of the alcohol 11 (31 mg, 0.07 mmol) in
CH2Cl2 (10 mL) and Et3N (0.04 mL) was added methanesulfo-
nyl chloride (0.01 mL, 0.13 mmol) at 0 °C, and the mixture
was stirred for 1 h at 0 °C. The reaction mixture was then
diluted with CH2Cl2 (15 mL) and washed with saturated
NaHCO3 (10 mL). The aqueous layer was extracted with
CH2Cl2 (2 ×). The combined organic extracts were washed with
brine, dried over MgSO4, and filtered. Concentration of the
Pentaacetate 14: mp 143-146 °C; Rf ) 0.29 (hexanes-
EtOAc, 1:4); [R]20D +11.3 (c ) 1.1, CHCl3); IR (film) 3264, 1733,
1
1665 cm-1; H NMR δ 1.91 (3H, s), 1.92-2.03 (12H, m), 4.38

1946 J . Org. Chem., Vol. 64, No. 6, 1999
Shing et al.
filtrate followed by flash chromatography (hexane-diethyl
4.21 (2H, ABq, J ) 12 Hz), 4.07-4.08 (1H, m), 4.40 and 4.49
(2H, ABq, J ) 11.8 Hz), 4.58 (1H, d, J ) 11 Hz), 4.70-4.77
(2H, m), 4.79 (1H, d, J ) 11.6 Hz), 5.82 (1H, d, J ) 3.1 Hz),
7.22-7.35 (15H, m); MS (FAB) m/z (relative intensity) 446
(MH+, 14). Anal. Calcd for C28H31NO4: C, 75.48; H, 7.01; N,
3.14. Found: C,75.43; H, 7.03; N, 3.12.
ether, 3:1) gave the mesylate 18 (36 mg, 98%) as a colorless
oil.
Mesylate 18: Rf ) 0.43 (hexane-diethyl ether, 2:1); [R]20
D
+27.1 (c ) 1.2, CHCl3); IR (film) 3031, 2105, 1454, 1179 cm-1
;
1H NMR δ 3.06 (3H, s), 3.87 (1H, d, J ) 12.8 Hz), 3.92 (1H, br
d, J ) 3.4 Hz), 4.04 (1H, d, J ) 12.8 Hz), 4.15-4.17 (1H, m),
4.31 (1H, d, J ) 11.3 Hz), 4.34 (1H, d, J ) 11.8 Hz), 4.44-
4.53 (3H, m), 4.72 and 5.58 (2H, ABq, J ) 12 Hz), 4.84 (1H,
dd, J ) 8.4, 2.2 Hz), 5.75-5.76 (1H, m), 7.18-7.36 (15H, m);
MS (ESI) m/z (relative intensity) 549 (M+, 0.45). Anal. Calcd
for C29H31N3O6S: C, 63.37; H, 5.68; N, 7.65; S, 5.83. Found:
C, 63.05; H, 5.88; N, 7.32; S, 5.45.
Va lien a m in e (1) a n d (1S,2S,3S,4R)-1-Aceta m id o-5-(a c-
et oxym et h yl)-2,3,4-t r i-O-a cet ylcycloh ex-5-en e-2,3,4-t r i-
ol [P en ta -N,O-a cetylva lien a m in e] (21). To a solution of the
amine 20 (204 mg, 0.46 mmol) in dry THF (10 mL) and liquid
NH3 (30 mL) was added sodium (80 mg, 3.48 mmol) at -78
°C. The reaction mixture was stirred for 4 h at -78 °C. Solid
NH4Cl (120 mg) was added to the mixture at -78 °C. After
disappearance of the blue color of the mixture, NH3 and solvent
were removed under reduced pressure to give crude valien-
amine (1). The crude product 1 was dissolved in pyridine (20
mL) and acetic anhydride (4 mL) containing a catalytic amount
of DMAP (2 mg). The mixture was stirred overnight at room
temperature. The reaction mixture was diluted with EtOAc
(20 mL) and washed with saturated NaHCO3 (20 mL). The
aqueous layer was extracted with EtOAc (2 ×). The combined
organic extracts were washed with brine, dried over MgSO4,
and filtered. Concentration of the filtrate followed by flash
chromatography (hexane-EtOAc, 1:4) gave pentaacetate 21
(120 mg, 68%) as a white solid.
(1S,2S,3R,4R)-1-Azid o-3,4-d i-O-b en zyl-5-(b en zyloxy-
m eth yl)cycloh ex-5-en e-2,3,4-tr iol (19). To a solution of the
acetate 17 (120 mg, 0.23 mmol) in MeOH (10 mL) was added
a catalytic amount of K2CO3 (3 mg), and the mixture was
stirred for 12 h at room temperature. The reaction mixture
was diluted with EtOAc (10 mL) and washed with saturated
NH4Cl (10 mL). The aqueous layer was extracted with EtOAc
(2 ×). The combined organic extracts were washed with brine,
dried over MgSO4, and filtered. Concentration of the filtrate
followed by flash chromatography (hexane-diethyl ether, 2:1)
gave the alcohol 19 (110 mg, 100%) as a colorless oil.
Alcohol 19: Rf ) 0.24 (hexane-diethyl ether, 2:1); [R]20
D
+37.2 (c ) 1.3, CHCl3); IR (film) 3452, 2104 cm-1; H NMR δ
1
Pentaacetate 21: mp 92-94 °C (lit.5 mp 95 °C) (lit.23 mp
92.5-95 °C); Rf ) 0.29 (hexane-EtOAc, 1:4); [R]20 +20.1 (c
2.99 (1H, d, J ) 6.1 Hz), 3.92-4.05 (3H, m), 4.09-4.21 (3H,
m), 4.42 and 4.50 (2H, ABq, J ) 11.8 Hz), 4.57 and 4.68 (2H,
ABq, J ) 11.2 Hz), 4.67 and 4.75 (2H, ABq, J ) 11.5 Hz), 5.86
(1H, d, J ) 3.6 Hz), 7.23-7.38 (15H, m); MS (EI) m/z (relative
intensity) 470 (M+ - H, 6). Anal. Calcd for C28H29N3O4: C,
71.32; H, 6.20; N, 8.91. Found: C, 71.28; H, 6.20; N, 8.80.
(1S,2S,3R,4R)-1-Am in o-3,4-d i-O-b en zyl-5-(b en zyloxy-
m eth yl)cycloh ex-5-en e-2,3,4-tr iol (20). To a solution of the
alcohol 19 (54 mg, 0.12 mmol) in pyridine (5 mL) and aqueous
NH3 (32%, 1 mL) was added PPh3 (45 mg, 0.17 mmol) at room
temperature, and the mixture was stirred overnight at room
temperature. The reaction mixture was diluted with CH2Cl2
(10 mL) and washed with brine. The aqueous layer was
extracted with CH2Cl2 (2 ×). The combined organic extracts
were dried over MgSO4 and filtered. Concentration of the
filtrate followed by flash chromatography (CHCl3-MeOH, 12:
1) gave the amine 20 (50 mg, 97%) as a white solid.
D
) 0.8, CHCl3) {lit.5 [R]23 +32.2 (CHCl3), lit.23 [R]21 +20 (c )
D
D
1.04, CHCl3)}; IR (film) 3366, 3281, 1746, 1658 cm-1; 1H NMR
δ 2.00-2.05 (15H, m), 4.37 and 4.63 (2H, ABq, J ) 13.2 Hz),
4.98-5.09 (2H, m), 5.36 (1H, br d, J ) 6.3 Hz), 5.43 (1H, dd,
J ) 9.3, 6.3 Hz), 5.80 (1H, br d, J ) 8.6 Hz), 5.87 (1H, dd, J )
5, 1.1 Hz); 13C NMR δ 20.6, 23.2, 44.9, 62.9, 68.5, 69.2, 71.2,
126.2, 134.3, 169.8, 170.0, 170.1, 170.2; MS (FAB) m/z (relative
intensity) 386 (MH+, 0.4). Anal. Calcd for C17H23NO9: C, 52.98;
H, 6.02; N, 3.63. Found: C, 52.60; H, 6.25; N, 3.47.
Ack n ow led gm en t. This work was supported by the
RGC Earmarked Grant (Ref. No. CUHK308/96P).
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR spectra for compounds 6, 10, 11, 12, 15, and 17. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Amine 20: mp 84-85 °C; Rf ) 0.43 (CHCl3-MeOH, 10:1);
[R]20 +18.7 (c ) 1.0, CHCl3); IR (film) 3365 cm-1; 1H NMR δ
D
2.19 (3H, br s), 3.54 (1H, br s), 3.80-3.82 (2H, m), 3.90 and
J O982024I