Asymmetric synthesis of 2-amino-1,3-diols and D-erythro-sphinganine

Article abstract of DOI:10.1002/ejoc.200300788

The asymmetric synthesis of protected 2-amino-1,3-diols (S,R)-5 starting from 2,2-dimethyl-1,3-dioxan-5-one is described. The stereogenic centres are generated by α-alkylation using the SAMP/RAMP hydrazone methodology and diastereoselective reduction of t

Full text of DOI:10.1002/ejoc.200300788

FULL PAPER
Asymmetric Synthesis of 2-Amino-1,3-diols and -erythro-Sphinganine
D
Dieter Enders*[a] and Anke Müller-Hüwen[a]
Keywords: Asymmetric synthesis / Hydrazones / Alkylation / Amino alcohols / Natural products
The asymmetric synthesis of protected 2-amino-1,3-diols
(S,R)-5 starting from 2,2-dimethyl-1,3-dioxan-5-one is de-
dride. The products are obtained in high diastereomeric and
enantiomeric excesses (de Ն 96%, ee = 90−94%). By em-
-erythro-
sphinganine (R,S)-11 was synthesised starting from RAMP-
hydrazone (R)-1 in 47% overall yield and with excellent dia-
stereomeric and enantiomeric excess (de, ee Ն 96%).
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
scribed. The stereogenic centres are generated by α-al- ploying this methodology, the ammonium salt of
kylation using the SAMP/RAMP hydrazone methodology
and diastereoselective reduction of the ketones (S)-2 with
D
L-
selectride. The resulting alcohols (S,S)-3 are converted into
the amines (S,R)-4 by nucleophilic substitution with sodium
azide and subsequent reduction with lithium aluminium hy- Germany, 2004)
Introduction
Results and Discussion
The vicinal amino alcohol functionality is a common
structural feature in many natural products and biologically
active molecules.[1] A broad class of naturally occurring
molecules containing the vicinal amino alcohol moiety are
the sphingolipids, such as ceramides, cerebrosides and gang-
liosides. Structurally, these molecules contain a 2-amino-
1,3-diol subunit. They are important components of the cell
membrane and take part in many physiological processes
like cell recognition, signal transduction and cell-growth
modulation.[2] Additionally, members of the sphinganine
family have been found to be potent inhibitors of the pro-
tein kinase C.[3] The key step in the preparation of the
sphinganines is the stereoselective synthesis of the amino-
diol functionality. In the last few years various methods for
the synthesis of sphinganine and its derivatives have been
developed.[4]
As shown in Scheme 1, our synthesis starts from the
SAMP-hydrazone (S)-1, which was readily prepared on a
multigram scale by condensation of (S)-1-amino-2-meth-
oxymethylpyrrolidine (SAMP) with 2,2-dimethyl-1,3-di-
oxan-5-one.[6] In the first step the SAMP-hydrazone (S)-1
was alkylated in the α-position.[7] Subsequently, the chiral
auxiliary was removed by treatment with a saturated aque-
ous solution of oxalic acid[8] to afford the acetal-protected
Our synthetic strategy, employing the SAMP/RAMP-hy-
drazone methodology[5] starting from the easily available di-
hydroxy acetone equivalent 1,3-dioxan-5-one, provides a
flexible route to 2-amino-1,3-diols and allows a broad range
of modifications in the side chain of the sphinganines. In
addition, both anti-configured enantiomers are accessible
by this method.
[a]
Institut für Organische Chemie, Rheinisch-Westfälische
Technische Hochschule,
Scheme 1. a) tBuLi, THF, Ϫ78 °C, then RX, Ϫ100 °C; b) aq. oxalic
acid; c) -Selectride, THF, Ϫ78 °C; d) MsCl, CH2Cl2, Et3N, 0 °C
Ǟ room temp.; e) NaN3, 18-crown-6, DMF, 100 °C; f) LAH, THF,
room temp.
Professor-Pirlet-Strasse 1, 52074 Aachen, Germany
Fax: (internat.) ϩ 49-(0)241-8092127
E-mail: enders@rwth-aachen.de
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300788
Eur. J. Org. Chem. 2004, 1732Ϫ1739

Asymmetric Synthesis of 2-Amino-1,3-diols and D-erythro-Sphinganine
FULL PAPER
ketodiols (S)-2 (Scheme 1). After the racemisation-free re-
moval of the auxiliary a variety of α-substituted ketones
(S)-2aϪe could be obtained in good overall yields
(56Ϫ76%) and very good enantiomeric excess (ee ϭ
90Ϫ94%; Table 1).
Table 3. Synthesis of the azides (S,R)-4aϪe
Table 1. Synthesis of α-substituted ketones (S)-2aϪe
[a]
[b]
Overall yield starting from (S,S)-3 after flash chromatography.
[c]
Determined by 13C NMR spectroscopy. All optical rotations
were measured in Uvasol grade CHCl3 at T ϭ 26 Ϯ 3 °C.
Table 4. Synthesis of the amines (S,R)-5aϪe
[a]
[b]
Overall yield starting from (S)-1.
Determined by GC on a
chiral stationary phase by comparison with racemic samples. [c] All
optical rotations were measured in Uvasol grade CHCl3 at T ϭ 26
Ϯ 3 °C.
The alcohols (S,S)-3aϪe were prepared by diastereoselec-
tive reduction of the ketones (S)-2aϪe with -selectride.
The results are shown in Table 2. All compounds could be
obtained in very good yields (88Ϫ95%) and excellent dia-
stereomeric excess (de Ն 96%).
[a]
[b]
Determined by 13C NMR spectroscopy. All optical rotations
were measured in Uvasol grade CHCl3 at T ϭ 26 Ϯ 3 °C.
The relative configuration of the amines (S,R)-5aϪe was
determined to be anti by H NMR spectroscopy. For all
Table 2. Synthesis of the alcohols (S,S)-3aϪe
1
synthesised amines (S,R)-5aϪe the coupling constant for
the corresponding H atoms is 9.6 Hz. Due to the known
(S)-configuration of the stereogenic centre generated by α-
alkylation, the absolute configuration could be assigned as
(S,R).[7]
Finally, the acetal group of the amine (S,R)-5c was re-
moved by hydrolysis with trifluoroacetic acid (TFA) in a
mixture of THF and water at room temperature to afford
the ammonium salt (S,R)-6c in excellent yield (Scheme 2).
The enantiomeric excess of the final products was based on
the diastereomeric excess, as all further reaction steps pro-
ceed without racemisation.
[a] Based on isolated material after flash chromatography. [b] Deter-
[c]
mined by 13C NMR spectroscopy.
All optical rotations were
[d]
measured in Uvasol grade CHCl3 at T ϭ 26 Ϯ 3 °C.
Numbers
[e]
in parenthesis indicate the value after column chromatography.
Rotations were measured in Uvasol grade C6H6 at T ϭ 26 Ϯ 3 °C.
The azides (S,R)-4aϪe were synthesised by conversion of
the hydroxy group into a mesylate and subsequent nucleo-
philic substitution with sodium azide.[9] The reaction oc-
curred with complete inversion of configuration at the stere-
ogenic centre. The results are summarised in Table 3.
The synthesis of the amines (S,R)-5 was carried out by
reduction of the azides (S,R)-4 with lithium aluminium hy-
Scheme 2. Cleavage of the acetal group by trifluoroacetic acid
We then employed our protocol in the synthesis of the
dride in THF. The amines (S,R)-5aϪe could be obtained ammonium salt -erythro-sphinganine (R,S)-11 (Scheme 3).
in very good yields (65Ϫ99%) and excellent diastereomeric In this case the RAMP-hydrazone (R)-1 was used instead
excess (de Ն 96%) without further purification (Table 4).
of the SAMP-hydrazone to afford the correct absolute con-
Eur. J. Org. Chem. 2004, 1732Ϫ1739
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. Enders, A. Müller-Hüwen
FULL PAPER
mercial quality were used from freshly opened containers. Analyti-
cal TLC: Silica gel 60 F254 plates Merck, Darmstadt. Preparative
column chromatography: Silica gel 60, particle size
0.040Ϫ0.063 mm, Merck, Darmstadt. Optical rotation values were
measured on a PerkinϪElmer P241 (589 nm), solvents used were of
Merck Uvasol quality. Microanalyses were obtained with Heraeus,
CHN-O-Rapid. All melting points (Büchi 510) are uncorrected. IR:
PerkinϪElmer FT/IR 1750. NMR spectra: Varian VXR 300,
Varian Gemini 300, Varian Inova 400, TMS as internal standard.
MS: Finnigan MAT 212 and Finnigan SSQ 7000 (EI, 70 eV, CI
100 eV). High resolution MS: Finnigan MAT 95. The hydrazones
(S)-1 and (R)-1 were prepared according to a published procedure[7]
from SAMP or RAMP[10] and 2,2-dimethyl-1,3-dioxan-5-one.[7m,11]
General Procedure for the Preparation of the Ketones (S)-2 (GP 1):
SAMP-hydrazone (S)-1, (1.0 equiv.) was dissolved in anhydrous
THF (2 mL/mmol hydrazone) and tBuLi (15% in n-pentane) (1.1
equiv.) was added dropwise at Ϫ78 °C. After stirring for 2 h at this
temperature, the lithiated hydrazone was cooled to Ϫ100 °C and
the electrophile (1.1 equiv.) slowly added. After 2 h the mixture was
warmed to room temp. over 15 h. The mixture was quenched with
pH 7 buffer solution and diluted with diethyl ether. The organic
layer was washed with pH 7 buffer solution and brine. The com-
bined organic layers were dried (MgSO4) and concentrated under
reduced pressure. The obtained monoalkylated SAMP-hydrazone
Scheme 3. a) tBuLi, THF, Ϫ78 °C, then pentadecyl bromide, Ϫ100
°C; b) aq. oxalic acid; c) -Selectride, THF, Ϫ78 °C; d) MsCl,
CH2Cl2, Et3N, 0 °C Ǟ room temp.; e) NaN3, 18-crown-6, DMF,
100 °C; f) LAH, THF, room temp.; g) TFA, THF/H2O, room temp.
figuration. In the first step the hydrazone (R)-1 was alkyl-
ated with pentadecyl bromide. Subsequently the hydrazone was dissolved in diethyl ether (10 mL/mmol) and then a saturated
aqueous solution of oxalic acid (2 mL/mmol) was added. After
three hours the aqueous layer was extracted with diethyl ether and
the combined organic layers were washed with pH 7 buffer solution
and brine. After drying (MgSO4) and concentration under reduced
pressure, the crude product was purified by flash chromatography
to afford the ketones (S)-2.
was cleaved with a saturated aqueous solution of oxalic acid
(Scheme 3). As a result the ketone (R)-7 could be obtained
in excellent yield (96%) and enantiomeric excess (ee Ն
96%). As described in the former cases the ketone (R)-7
was reduced with -Selectride to give the alcohol (R,R)-8 in
practically quantitative yield (98%) and very high dia-
stereomeric excess (de Ն 96%). Treatment of the alcohol
with methanesulfonyl chloride yielded the corresponding
mesylate, which was then converted into the azide (R,S)-9
by nucleophilic substitution with sodium azide in DMF in
the presence of 18-crown-6. Reduction of the azide (R,S)-
9 with lithium aluminium hydride followed by hydrolytic
cleavage of the acetonide group with trifluoroacetic acid in
THF and water afforded the ammonium salt (R,S)-11 with
an overall yield of 47%, a diastereomeric excess of greater
than 96% and an enantiomeric excess of greater than 96%.
General Procedure for the Preparation of the Alcohols (S)-3 by Re-
duction with l
-Selectride (GP 2): -Selectride (1  in THF) (1.2
equiv.) was added dropwise to a stirred solution of the ketone (S)-
2 (1.0 equiv.) in anhydrous THF (6 mL/mmol ketone) at Ϫ78 °C.
After stirring for 2 h at this temperature the mixture was warmed to
room temp. over 15 h. The reaction was quenched with a saturated
solution of aqueous ammonium chloride (2 mL/mmol) followed by
a dropwise addition of a H2O2 solution (30%, 0.5 mL/mmol) and
sodium hydroxide (c ϭ 0.1 mol/L, 0.5 mL/mmol). After stirring at
room temp. for 15 min the mixture was extracted with diethyl ether
and the combined organic layers dried (MgSO4). Concentration
under reduced pressure and flash chromatography afforded the de-
sired product.
General Procedure for the Preparation of the Azides (S,R)-4 (GP 3):
Triethylamine (10.0 equiv.), followed by methanesulfonyl chloride
(5.0 equiv.), were added dropwise to a stirred solution of the al-
cohol (S,S)-3 (1.0 equiv.) in CH2Cl2 (10 mL/mmol) at 0 °C under
argon. The resulting red solution was stirred at room temperature
for 10 min then poured into water and extracted with CH2Cl2. The
combined organic layers were washed with water, brine, dried
(MgSO4) and concentrated in vacuo. Sodium azide (10.0 equiv.)
and 18-crown-6 ether (1.0 equiv.) were added to a stirred solution
of the crude mesylate (1.0 equiv.) in DMF (10 mL/mmol) at room
temp. This reaction mixture was heated to 100 °C under argon for
12Ϫ48 h. Upon cooling the reaction mixture was poured into water
and extracted with diethyl ether. The combined organic extracts
were washed with brine (3 x) and dried (MgSO4). Concentration
under reduced pressure and flash chromatography afforded the de-
sired azide 4.
Conclusion
In summary, a practical method for the diastereo- and
enantioselective synthesis of 2-amino-1,3-diols, using the
SAMP/RAMP-hydrazone methodology as stereoselective
key step, has been developed. This methodology was ap-
plied to generate the 2-amino-1,3-diol functionality in the
efficient asymmetric synthesis of the -erythro-sphinganine
ammonium salt.
Experimental Section
General Remarks: All solvents were dried and purified prior to use.
All reactions were carried out under dry argon, using standard
Schlenk techniques. THF was freshly distilled under argon from
Na/Pb alloy in the presence of benzophenone. Reagents of com-
General Procedure for the Preparation of the Amines (S,R)-5 (GP
4): A solution of the azide (S,R)-4 (1.0 equiv.) in THF (3 mL/mmol)
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Eur. J. Org. Chem. 2004, 1732Ϫ1739

Asymmetric Synthesis of 2-Amino-1,3-diols and D-erythro-Sphinganine
FULL PAPER
was added dropwise to a stirred suspension of lithium aluminium
hydride (2.0 equiv.) in THF (3 mL/mmol) at room temp. under ar-
gon. The reaction mixture was stirred for 20 min and then a 10%
aq. NaOH solution (3.6 equiv.) was added dropwise, and diluted
ee ϭ 90%. IR (film): ν˜ ϭ 2988 (s), 2937 (m), 2881 (m), 1748 (vs,
CϭO), 1489 (s), 1378 (s), 1224 (s), 1173 (m), 1102 (s), 1069 (s),1014
1
(s), 901 (m), 806 (m), 634 (w), 536 (m), 519 (m) cmϪ1. H NMR
(400 MHz, CDCl3): δ ϭ 1.33 (s, 3 H, CCH3), 1.41 (s, 3 H, CCH3),
with CH2Cl2. This biphasic system was stirred for 5 min and then 2.75 (dd, J ϭ 9.0/14.8 Hz, 1 H, CHCHH), 3.16 (dd, J ϭ 3.3/
separated. The aqueous phase was further extracted with CH2Cl2
and the combined organic phases were washed with brine and dried
(MgSO4). Concentration under reduced pressure afforded the ex-
pected amine 5 without need for further purification.
14.8 Hz, 1 H, CHCHH), 3.99 (d, J ϭ 17.0 Hz, 1 H, OCHH), 4.23
(dd, J ϭ 1.4/17.0 Hz, 1 H, OCHH), 4.40 (m, 1 H, CH), 7.13 [d,
J ϭ 8.8 Hz, 2 H, CHmeta), 7.39 (d, J ϭ 8.5 Hz, 2 H, CHortho) ppm.
13C NMR (100 MHz, CDCl3): δ ϭ 23.5, 23.8, 33.1, 66.5, 75.1,
100.8, 120.2, 130.8, 131.1, 136.4, 208.1 ppm. MS (EI): m/z (%) ϭ
300 (17) [Mϩ ϩ 1], 298 (16), 201 (7), 200 (80), 199 (9), 198 (85),
184 (6), 182 (5), 171 (46), 171 (20), 169 (39), 161 (5), 131 (12), 130
(5), 129 (67), 103 (12), 102 (10), 101 (5), 100 (5), 91 (11), 90 (18),
89 (14), 77 (11), 73 (10), 72 (100), 59 (20), 58 (6), 55 (7), 51 (5).
C13H15BrO3 (299.16): calcd. C 52.19, H 5.05; found C 52.63, H
5.38.
(4S)-4-(2-Bromoallyl)-2,2-dimethyl-1,3-dioxane-5-one [(S)-2a]: Ac-
cording to GP 1, (S)-2a was obtained as a yellow oil after purifi-
cation by column chromatography (SiO2, diethyl ether/pentane,
1:5). Yield: 0.70 g (56%). Rt ϭ 8.32 min (CP-Sil-8, 60Ϫ10Ϫ300).
Rf ϭ 0.53 (pentane/Et2O, 5:1). [α]2D4 ϭ Ϫ216.0 (c ϭ 1.07, CHCl3).
ee ϭ 94%. IR (film): ν˜ ϭ 2988 (s), 2939 (m), 2883 (m), 1750 (vs,
CϭO), 1634 (s), 1423 (m), 1378 (s), 1273 (m), 1244 (s), 1222 (s),
1176 (m), 1162 (m), 1109 (s), 1069 (m), 1030 (m), 965 (m), 898 (s),
(4S)-Benzyloxymethyl-2,2-dimethyl-1,3-dioxan-5-one [(S)-2e]: Ac-
cording to GP 1, (S)-2e was obtained as a colourless oil after purifi-
cation by column chromatography (SiO2, diethyl ether/pentane,
1:3). Yield: 1.48 g (59%). Rt ϭ 9.93 min (CP-Sil-8, 100Ϫ10Ϫ300).
Rf ϭ 0.48 (pentane/Et2O, 3:1). [α]2D4 ϭ Ϫ171.8 (c ϭ 1.08, CHCl3).
1
837 (m), 526 (m) cmϪ1. H NMR (400 MHz, CDCl3): δ ϭ 1.43 (s,
3 H, CCH3), 1.50 (s, 3 H, CCH3), 2.57 (m, 1 H, CHH), 3.03 (m, 1
H, CHH), 4.04 (dd, J ϭ 1.4/17.3 Hz, 1 H, OCHH), 4.29 (dd, J ϭ
1.4/17.3 Hz, 1 H, OCHH), 4.60 (m, 1 H, CH), 5.51 (m, 1 H, CBrϭ
CHH), 5.71 (m, 1 H, CBrϭCHH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 23.6, 23.7, 40.0, 66.3, 72.2, 101.1, 119.5, 128.7,
207.8 ppm. MS (EI): m/z (%) ϭ 250 (1) [Mϩ ϩ 1], 169 (9), 129
(10), 111 (99), 100 (13), 83 (13), 81 (11), 73 (10), 72 (100), 59 (39),
58 (11), 55 (13), 53 (31), 51 (9). C9H13BrO3 (249.10): calcd. C 43.40,
H 5.26; found C 43.53, H 5.54.
1
ee ϭ 94%. H NMR (400 MHz, CDCl3): δ ϭ 1.47 (s, 3 H, CH3),
1.48 (s, 3 H, CH3), 3.73 (dd, J ϭ 6.3/11.0 Hz, 1 H, CHHCHO),
3.88 (dd, J ϭ 2.8/11.0 Hz, 1 H, CHHCHO), 3.98 (d, J ϭ 16.8 Hz,
1 H, OHCH), 4.28 (dd, J ϭ 1.7/16.8 Hz, 1 H, OHCH), 4.46 (m, 1
H, CH), 4.57 (d, J ϭ 5.5 Hz, 2 H, OCH2C6H5), 7.32 (s, 5 H, C6H5)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 23.5, 24.1, 66.6, 67.8,
73.5, 75.1, 100.7, 127.5, 128.2, 137.7, 207.1 pm. For further analyti-
cal data see ref.[7]
(4S)-4-Decyl-2,2-dimethyl-1,3-dioxan-5-one [(S)-2b]: According to
GP 1, (S)-2b was obtained as a colourless oil after purification by
column chromatography (SiO2, diethyl ether/pentane, 1:10). Yield:
2.04 g (76%). Rt ϭ 8.45 min (CP-Sil-8, 120Ϫ10Ϫ300). Rf ϭ 0.62
(pentane/Et2O, 10:1). [α]2D4 ϭ Ϫ181.5 (c ϭ 1.03, CHCl3). ee ϭ 93%.
IR (film): ν˜ ϭ 2987 (s), 2925 (vs), 2855 (vs), 1750 (vs, CϭO), 1466
(m), 1375 (s), 1251 (m), 1225 (s), 1103 (s), 870 (m) cmϪ1. 1H NMR
(400 MHz, CDCl3): δ ϭ 0.88 (t, J ϭ 6.9 Hz, 3 H, CH2CH3), 1.26
[m, 16 H, CH2(CH2)8CH3], 1.43 (s, 3 H, CCH3), 1.45 (s, 3 H,
CCH3), 1.53 (m, 1 H, CHCHH), 1.86 (m, 1 H, CHCHH), 3.97 (d,
J ϭ 16.8 Hz, 1 H, OCHH), 4.20 (m, 1 H, CH), 4.25 (dd, J ϭ 1.4/
16.8 Hz, 1 H, OCHH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
14.1, 22.7, 23.5, 24.0, 25.1, 28.4, 29.3, 29.4, 29.4, 29.6, 31.9, 66.5,
74.6, 100.5, 209.5 ppm. MS (EI): m/z (%) ϭ 255 (1) [Mϩ Ϫ CH3],
101 (14), 100 (31), 96 (7), 86 (13), 82 (7), 72 (100), 69 (6), 59 (26),
58 (10), 55 (17). C16H30O3 (270.41): calcd. C 71.07, H 11.18; found
C 71.18, H 11.05.
(4R)-2,2-Dimethyl-4-pentadecyl-1,3-dioxan-5-one [(R)-7]: Accord-
ing to GP 1 [starting with (R)-1], (R)-7 was obtained as a colourless
oil after purification by column chromatography (SiO2, diethyl
ether/pentane, 1:10). Yield: 3.26 g (96%). Rt ϭ 7.48 min (CP-Sil-8,
180Ϫ10Ϫ300). Rf ϭ 0.62 (pentane/Et2O, 10:1). [α]2D5 ϭ ϩ127.9 (c ϭ
1.21, CHCl3). ee ϭ 96%. IR (film): ν˜ ϭ 2987 (m), 2925 (vs), 2854
(s), 1750 (s, CϭO), 1464 (m), 1377 (m), 1224 (s), 1172 (w), 1104
(m), 864 (w), 722 (ww) cmϪ1 1H NMR (400 MHz, CDCl3): δ ϭ
.
0.88 [t, J ϭ 6.9 Hz, 3 H, (CH2)14CH3], 1.26 [m, 26 H, (CH2)13CH3],
1.41 (s, 3 H, CCH3), 1.43 (s, 3 H, CCH3), 1.53 (m, 1 H, OCHCHH),
1.85 (m, 1 H, OCHCHH), 3.94 (d, J ϭ 16.8 Hz, 1 H, OCHH), 4.18
(m, 1 H, OCH), 4.22 (dd, J ϭ 1.7/16.8 Hz, 1 H, OCHH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 14.2, 22.8, 23.6, 24.0, 25.2, 28.5,
29.49, 29.6, 29.8, 29.8, 29.8, 32.0, 66.5, 74.6, 100.5, 209.0 ppm. MS
(EI): m/z (%) ϭ 325 (2) [Mϩ Ϫ CH3], 170 (6), 156 (6), 142 (7), 128
(7), 114 (10), 101 (28), 100 (34), 98 (5), 97 (7), 96 (10), 95 (7), 86
(12), 85 (5), 83 (9), 82 (9), 81 (6), 73 (6), 72 (100), 71 (7), 69 (9), 67
(6), 59 (31), 58 (9), 57 (18), 55 (24). C21H40O3 (340.54): calcd. C
74.07, H 11.84; found C 73.87, H 11.63.
(4S)-Benzyl-2,2-dimethyl-1,3-dioxan-5-one [(S)-2c]: According to
GP 1, (S)-2c was obtained as a colourless oil after purification by
column chromatography (SiO2, diethyl ether/pentane, 1:20). Yield:
1.59 g (72%). Rt ϭ 7.23 min (CP-Sil-8, 100Ϫ10Ϫ300). Rf ϭ 0.31
(pentane/Et2O, 20:1). [α]2D4 ϭ Ϫ212.6 (c ϭ 1.06, CHCl3). ee ϭ 94%.
1H NMR (400 MHz, CDCl3): δ ϭ 1.34 (s, 3 H, CH3), 1.42 (s, 3 H,
CH3), 2.79 (dd, J ϭ 9.1/14.8 Hz, 1 H, HCHC6H5), 3.24 (dd, J ϭ
3.3/14.8 Hz, 1 H, HCHC6H5), 4.01 (d, J ϭ 17.0 Hz, 1 H, OHCH),
4.26 (dd, J ϭ 1.7/17.0 Hz, 1 H, OHCH), 4.46 (m, 1 H, CH), 7.27
(s, 5 H, C6H5) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 23.5, 23.9,
34.4, 66.5, 75.5, 100.8, 126.2, 128.0, 129.0, 137.5, 208.6 ppm. For
further analytical data see ref.[7]
(4S,5S)-(2-Bromoallyl)-2,2-dimethyl-1,3-dioxan-5-ol [(S,S)-3a]: Ac-
cording to GP 2, (S,S)-3a was obtained as a red oil after purifi-
cation by column chromatography (SiO2, diethyl ether/pentane,
1:2). Yield: 0.46 g (88%). Rt ϭ 7.07 min (CP-Sil-8, 80Ϫ10Ϫ300).
Rf ϭ 0.24 (pentane/Et2O, 2:1). [α]2D4 ϭ Ϫ2.4 (c ϭ 0.99, CHCl3).
de ϭ 96%. IR (film): ν˜ ϭ 3449 (vs, OH), 2992 (vs), 2939 (s), 1795
(w), 1633 (vs), 1456 (s), 1382 (vs), 1271 (s), 1246 (s), 1201 (s), 1166
(s), 1128 (s), 1052 (vs), 979 (s), 941 (m), 898 (vs), 847 (s), 817 (s),
776 (w), 749 (m), 626 (m), 560 (m), 537 (s) cmϪ1 1H NMR
.
(4S)-(4-Bromobenzyl)-2,2-dimethyl-1,3-dioxan-5-one [(S)-2d]: Ac-
cording to GP 1, (S)-2d was obtained as a green oil after purifi-
(400 MHz, CDCl3): δ ϭ 1.43 (s, 3 H, CH3), 1.50 (s, 3 H, CH3),
2.70 (m, 2 H, CHCH2), 3.18 (s, 1 H, OH), 3.40 (s, 1 H, CHOH),
cation by column chromatography (SiO2, diethyl ether/pentane, 3.87 (dd, J ϭ 1.9/12.4 Hz, 1 H, OCHH), 4.10 (d, J ϭ 12.4 Hz, 1
1:5). Yield: 1.08 g (71%). Rt ϭ 10.64 min (CP-Sil-8, 100Ϫ10Ϫ300). H, OCHH), 4.22 (m, 1 H, OCH), 5.50 (m, 1 H, CBrCHH), 5.73
Rf ϭ 0.38 (pentane/Et2O, 5:1). [α]2D5 ϭ Ϫ166.6 (c ϭ 1.08, CHCl3).
(m, 1 H, CBrCHH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 18.4,
Eur. J. Org. Chem. 2004, 1732Ϫ1739
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1735

D. Enders, A. Müller-Hüwen
(4S,5S)-Benzyloxymethyl-2,2-dimethyl-1,3-dioxan-5-ol [(S,S)-3e]:
FULL PAPER
29.3, 43.0, 64.2, 65.9, 69.8, 99.3, 119.8, 129.6 ppm. MS (EI): m/z
(%) ϭ 236 (Mϩ Ϫ CH3, 1), 235 (9), 131 (8), 102 (10), 74 (12), 59 According to GP 2, (S,S)-3e was obtained as a colourless oil after
(100), 45 (18). C9H15BrO3 (251.12): calcd. C 43.05, H 6.02; found
C 43.29, H 6.18.
purification by column chromatography (SiO2, diethyl ether/pen-
tane, 1:1). Yield: 1.49 g (95%). Rt 10.75 min (CP-Sil-8,
ϭ
100Ϫ10Ϫ300). Rf ϭ 0.24 (pentane/Et2O, 1:1). [α]2D4 ϭ ϩ8.9 (c ϭ
1.15, C6H6). de ϭ 96%. IR (film): ν˜ ϭ 3382 (vs, OH), 3063 (m),
3030 (m), 2992 (vs), 2939 (vs), 2874 (vs), 1497 (m), 1455 (vs), 1382
(vs), 1278 (s), 1236 (m), 1200 (vs), 1171 (s), 1143 (s), 1070 (vs),
(4S,5S)-Decyl-2,2-dimethyl-1,3-dioxan-5-ol [(S,S)-3b]: According to
GP 2, (S,S)-3b was obtained as a colourless oil after purification by
column chromatography (SiO2, diethyl ether/pentane, 1:1). Yield:
1.68 g (89%). Rt ϭ 5.57 min (CP-Sil-8, 160Ϫ10Ϫ300). Rf ϭ 0.47
(pentane/Et2O, 1:1). [α]2D7 ϭ ϩ5.6 (c ϭ 1.00, CHCl3). de ϭ 96%. IR
(film): ν˜ ϭ 3435 (m, OH), 2992 (s), 2925 (vs), 2855 (vs), 1463 (m),
1378 (s), 1270 (m), 1227 (m), 1201 (s), 1167 (m), 1140 (w), 1112
(w), 1072 (s), 977 (m), 898 (w), 853 (m), 752 (w), 722 (w), 521 (w)
1028 (w), 976 (s), 904 (s), 849 (vs), 747 (vs), 700 (vs) cmϪ1 1H
.
NMR (300 MHz, C6D6): δ ϭ 1.17 (s, 3 H, CH3), 1.41 (s, 3 H, CH3),
3.25 (m, 1 H, CHOH), 3.55Ϫ3.74 (m, 4 H, OCH2; CH2O), 3.88
(m, 1 H, OCH), 4.41 (s, 2 H, OCH2), 7.10Ϫ7.31 (m, 5 H, C6H5)
ppm. 13C NMR (75 MHz, C6D6): δ ϭ 18.4, 29.5, 63.9, 65.7, 70.3,
71.5, 73.5, 98.9, 127.6, 127.8, 128.1, 138.6 ppm. MS (EI): m/z (%) ϭ
252 (1) [Mϩ], 237 (4) [Mϩ Ϫ CH3], 194 (10), 176 (8), 149 (5), 133
(8), 131 (9), 107 (14), 105 (6), 92 (12), 91 (100), 65 (6), 59 (42).
C14H20O4 (252.31): calcd. C 66.65, H 7.99; found C 66.64, H 8.24.
1
cmϪ1. H NMR (400 MHz, CDCl3): δ ϭ 0.88 (t, J ϭ 6.5 Hz, 3 H/
7.1; (CH2)9CH3], 1.25 (m, 16 H, CH2(CH2)8CH3], 1.42 (s, 3 H,
CH3), 1.45 (s, 3 H, CH3), 1.56 (m, 2 H, OCHCH2), 2.58 (s, 1 H,
OH), 3.31 (s, 1 H, CHOH), 3.82 (m, 2 H, COCH; COCHH), 4.03
(dd, J ϭ 1.4/12.1, 1 H, OCHH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 14.1, 18.4, 22.7, 24.8, 29.29, 29.5, 29.6, 29.7, 31.3,
(4R,5R)-2,2-Dimethyl-4-pentadecyl-1,3-dioxan-5-ol [(R,R)-8]: Ac-
cording to GP 2, (RR)-8 was obtained as a colourless oil after
purification by column chromatography (SiO2, diethyl ether/pen-
31.8, 65.0, 66.2, 72.1, 98.7 ppm. MS (EI): m/z (%) ϭ 257 (Mϩ
Ϫ
CH3, 9), 229 (8), 102 (13), 83 (5), 69 (5), 59 (100), 57 (6), 55 (7).
C16H32O3 (272.43): calcd. C 70.54, H 11.84; found C 70.35, H
11.66.
tane, 1:2). Yield: 1.68 g (98%). Rt
ϭ 8.05 min (CP-Sil-8,
180Ϫ10Ϫ300). Rf ϭ 0.34 (pentane/Et2O, 2:1). [α]2D4 ϭ Ϫ3.32 (c ϭ
0.91, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 3420 (m, OH), 2991 (m),
2921 (vs), 2852 (vs), 1471 (s), 1381 (m), 1274 (m), 1247 (m), 1199
(s), 1170 (m), 1139 (m), 1076 (m), 1025 (w), 976 (m), 948 (w), 904
(m), 850 (m), 802 (w), 720 (m), 622 (w), 561 (w), 519 (w) cmϪ1. 1H
NMR (400 MHz, CDCl3): δ ϭ 0.89 [t, 3 H, (CH2)14CH3], 1.26 [m,
28 H, (CH2)14CH3], 1.42 (s, 3 H, CH3), 1.46 (s, 3 H, CH3), 2.57 (d,
J ϭ 11.5 Hz, 1 H, OH), 3.32 (dd, J ϭ 0.8/11.5 Hz, 1 H, CHOH),
3.82 (m, 1 H, OCH), 3.84 (dd, J ϭ 1.9/12.0 Hz, 1 H, OCHH), 4.04
(dd, J ϭ 1.1/12.0 Hz, 1 H, OCHH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 14.1, 18.4, 22.7, 24.9, 29.3, 29.5, 29.6, 29.6, 29.7, 31.3,
31.9, 65.0, 66.2, 72.0, 98.7 ppm. MS (EI): m/z (%) ϭ 327 (100) [Mϩ
Ϫ CH3], 311 (12), 123 (6), 111 (8), 109 (11), 101 (34), 97 (19), 95
(17), 85 (9), 83 (18), 82 (5), 81 (12), 73 (6), 71 (12), 70 (5), 69 (15),
67 (9), 60 (5), 59 (82), 57 (33), 56 (6), 55 (26), 45 (7). C21H42O3
(342.56): calcd. C 73.63, H 12.36; found C 73.49, H 12.66.
(4S,5S)-Benzyl-2,2-dimethyl-1,3-dioxan-5-ol [(S,S)-3c]: According
to GP 2, (S,S)-3c was obtained as a colourless oil after purification
by column chromatography (SiO2, diethyl ether/pentane, 1:1).
Yield: 1.31 g (90%). Rt ϭ 8.16 min (CP-Sil-8, 100Ϫ10Ϫ300). Rf ϭ
0.36 (pentane/Et2O, 1:1). [α]2D4 ϭ ϩ4.7 (c ϭ 1.28, C6H6). de ϭ 96%.
IR (film): ν˜ ϭ 3437 (s, OH), 3085 (vw), 3062 (w), 3028 (w), 2992
(s), 2939 (s), 2873 (s), 1604 (w), 1496 (s), 1455 (s), 1380 (vs), 1270
(s), 1227 (w), 1202 (s), 1162 (s), 1127 (s), 1073 (vs), 963 (s), 895 (s),
867 (w), 829 (s), 778 (vw), 751 (s), 701 (vs), 593 (w), 552 (w), 522
(s) cmϪ1 1H NMR (300 MHz, CDCl3): δ ϭ 1.44 (s, 3 H, CH3),
.
1.47 (s, 3 H, CH3), 2.82 (m, 1 H, CHHC6H5), 2.96 (m, 1 H,
CHHC6H5), 3.22 (s, 1 H, CHOH), 3.82 (d, J ϭ 12.3 Hz, 1 H,
OCHH), 3.95 (d, J ϭ 12.3 Hz, 1 H, OCHH), 4.02 (m, 1 H, CH),
7.23 (s, 5 H, C6H5) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 18.4,
29.4, 37.5, 63.6, 66.0, 73.3, 99.1, 126.2, 128.2, 129.3, 137.0 ppm.
MS (EI): m/z (%) ϭ 222 (M, 1), 207(7), 179 (28), 147 (5), 131 (38),
129 (10), 121 (5), 105 (5), 103 (6), 102 (8), 92 (9), 91 (20), 59 (100).
C13H18O3 (222.28): calcd. C 70.24, H 8.16; found C 70.02, H 8.17.
(4S,5R)-5-Azido-4-(2-bromoallyl)-2,2-dimethyl-1,3-dioxane [(S,R)-
4a]: According to GP 3, (S,R)-4a was obtained as a colourless oil
after purification by column chromatography (SiO2, diethyl ether/
pentane, 1:10). Yield: 167 mg (30%). Rt ϭ 8.23 min (CP-Sil-8,
80Ϫ10Ϫ300). Rf ϭ 0.49 (pentane/Et2O, 10:1). [α]2D7 ϭ Ϫ40.7 (c ϭ
1.08, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 2994 (m), 2943 (m), 2874
(m), 2108 (vs, N3), 1633 (m), 1459 (w), 1382 (s), 1329 (w), 1295 (s),
1266 (s), 1240 (m), 1200 (s), 1165 (s), 1123 (s), 1070 (m), 1030 (m),
975 (w), 962 (w), 900 (m), 844 (w), 829 (m), 749 (w), 645 (w), 554
(w), 521 (w) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 1.38 (s, 3 H,
CH3), 1.46 (s, 3 H, CH3), 2.59 (m, 1 H, CHCHH), 2.87 (m, 1 H,
CHCHH), 3.28 (dt, J ϭ 5.5/9.6 Hz, 1 H, CHN3), 3.74 (dd, J ϭ 9.6/
11.5 Hz, 1 H, OCHH), 3.93 (m, 1 H, OCH), 4.00 (dd, J ϭ 5.5/
11.5 Hz, 1 H, OCHH), 5.52 (m, 1 H, CBrCHH), 5.69 (m, 1 H,
CBrCHH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 19.1, 28.3,
44.6, 58.1, 62.3, 69.9, 99.1, 119.3, 128.5 ppm. MS (EI): m/z (%) ϭ
261 (27) [Mϩ Ϫ CH3], 260 (27), 234 (5), 110 (15), 84 (17), 82 (11),
80 (16), 73 (5), 72 (28), 70 (7), 69 (28), 65 (5), 59 (100), 56 (8), 55
(7), 54 (8), 53 (28), 45 (15). C9H14BrN3O2 (276.13): calcd. C 39.15,
H 5.11, N 15.23; found C 39.34, H 5.38, N 15.64.
(4S,5S)-(4-Bromobenzyl)-2,2-dimethyl-1,3-dioxan-5-ol
[(S,S)-3d]:
According to GP 2, (S,S)-3d was obtained as a colourless solid
after purification by column chromatography (SiO2, diethyl ether/
pentane, 1:2). Yield: 0.67 g (85%). Rt ϭ 11.83 min (CP-Sil-8,
100Ϫ10Ϫ300). Rf ϭ 0.22 (pentane/Et2O, 2:1). [α]2D4 ϭ Ϫ6.2 (c ϭ
0.98, CHCl3). m.p. 75 °C. de ϭ 96%. IR (film): ν˜ ϭ 3431 (vs, OH),
2992 (vs), 2938 (s), 2873 (s), 1899 (w), 1642 (w), 1592 (w), 1488
(vs), 1402 (m), 1380 (vs), 1270 (s), 1227 (s), 1201 (vs), 1161 (s), 1126
(s), 1071 (vs), 1013 (s), 964 (s), 901 (s), 869 (s), 830 (vs), 805 (s),
736 (s), 635 (m), 559 (m), 536 (m), 521 (s), cmϪ1 1H NMR
.
(400 MHz, CDCl3): δ ϭ 1.43 (s, 3 H, CH3), 1.44 (s, 3 H, CH3),
2.77 (dd, J ϭ 6.4/13.4 Hz, 2 H, HCHC6H4Br, OH), 2.89 (dd, J ϭ
7.9/13.4 Hz, 1 H, HCHC6H4Br), 3.20 (s, 1 H, CHOH), 3.80 (dd,
J ϭ 2.0/12.4 Hz, 1 H, OHCH), 3.96 (m, 2 H, OHCH; OCH), 7.12
(d, J ϭ 8.4 Hz, 2 H, C6HmetaBr), 7.40 (d, J ϭ 8.4 Hz, 2 H,
C6HorthoBr) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 18.3, 29.6,
37.1, 63.6, 66.0, 73.0, 98.9, 120.1, 131.1, 131.2, 136.2 ppm. MS (EI): (4S,5R)-5-Azido-4-decyl-2,2-dimethyl-1,3-dioxane [(S,R)-4b]: Ac-
m/z (%) ϭ 301 (4) [Mϩ], 286 (Mϩ Ϫ CH3, 9), 285 (8), 171 (9), 169
cording to GP 3, (S,R)-4b was obtained as a colourless oil after
(8), 131 (45), 128 (10), 103 (7), 102 (16), 90 (5), 59 (100). purification by column chromatography (SiO2, diethyl ether/pen-
C13H17BrO3 (301.18): calcd. C 51.99, H 5.87; found C 51.84, H
5.69.
tane, 1:40). Yield: 192 mg (32%). Rt
ϭ 7.72 min (CP-Sil-8,
140Ϫ10Ϫ300). Rf ϭ 0.40 (pentane/Et2O, 40:1). [α]2D7 ϭ Ϫ31.0 (c ϭ
1736
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1732Ϫ1739

Asymmetric Synthesis of 2-Amino-1,3-diols and D-erythro-Sphinganine
FULL PAPER
1.12, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 2994 (m), 2926 (vs), 2855 (7), 104 (10), 103 (19), 102 (13), 99 (14), 98 (6), 91 (12), 90 (23), 89
(s), 2107 (vs, N3), 1684 (w), 1465 (m), 1381 (m), 1370 (m), 1266 (s), (20), 86 (8), 84 (35), 77 (16), 72 (49), 69 (33), 63 (10), 59 (100), 58
1227 (m), 1201 (s), 1166 (w), 1140 (w), 1111 (w), 1079 (w), 982 (m), (25). C13H16BrN3O2 (326.19): calcd. C 47.87, H 4.94, N 12.88;
866 (w), 699 (w) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 0.88 [m, found C 47.95, H 5.11, N 12.88.
3 H, (CH2)9CH3], 1.27 [m, 16 H, CHCH2(CH2)8CH3], 1.37 (s, 3 H,
(4S,5R)-5-Azido-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxane
CCH3), 1.42 (s, 3 H, CCH3), 1.69 [m, 1 H, CHCHH(CH2)8CH3],
[(S,R)-4e]: According to GP 3, (S,R)-4e was obtained as a colour-
1.73 [m, 1 H, CHCHH(CH2)8CH3], 3.21 (ddd, J ϭ 5.5/9.6/15.5 Hz,
less oil after purification by column chromatography (SiO2, diethyl
1 H, CHN3), 3.57 (m, 1 H, COCH), 3.67 (dd, J ϭ 9.6/15.5 Hz, 1
ether/pentane, 1:10). Yield: 177 mg (32%). Rt ϭ 11.24 min (CP-Sil-
H, COCHH), 3.95 (dd, J ϭ 5.5/15.5 Hz, 1 H, COCHH) ppm. 13C
8, 100Ϫ10Ϫ300). Rf ϭ 0.30 (pentane/Et2O, 10:1). [α]2D5 ϭ Ϫ21.8
NMR (100 MHz, CDCl3): δ ϭ 14.1, 19.4, 22.7, 24.8, 28.5, 29.3,
(c ϭ 0.99, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 3030 (w), 2993 (m),
2941 (M), 2870 (m), 2109 (vs, N3), 1497 (w), 1454 (m), 1381 (m),
1308 (w), 1270 (s), 1224 (m), 1201 (s), 1168 (m), 1131 (m), 1098 (s),
29.4, 29.5, 29.6, 31.9, 32.9, 59.0, 62.4, 72.0, 98.8 ppm. MS (EI):
m/z (%) ϭ 282 (27 ) [Mϩ Ϫ CH3], 169 (14), 156 (5), 98 (6), 97 (12),
95 (11), 85 (6), 84 (69), 83 (9), 82 (6), 81 (7), 72 (43), 70 (10), 69
1061 (m), 1028 (w), 986 (m), 913 (w), 845 (m), 738 (m), 689 (s),
(100), 68 (6), 67 (8), 59 (95), 57 (15), 56 (25), 55 (28), 54 (6). HRMS:
521 (w) cmϪ1 1H NMR (500 MHz, CDCl3): δ ϭ 1.41 (s, 3 H,
.
[C16H31N3O2 Ϫ CH3] calcd. 282.2182; found 282.2183.
CH3), 1.43 (s, 3 H, CH3), 3.60Ϫ3.70 (kB, 4 H, CHN3, OCHH,
CHCH2O), 3.76 (m, 1 H, OCH), 3.96 (dd, J ϭ 5.0/11.ϭ Hz, 1 H,
OCHH), 4.57 (d, J ϭ 12.0 Hz, 1 H, OCHHC6H5), 4.64 (d, J ϭ
12.0 Hz, 1 H, OCHHC6H5), 7.34 (m, 5 H, C6H5) ppm. 13C NMR
(125 MHz, CDCl3): δ ϭ 19.3, 28.4, 54.9, 62.2, 70.0, 72.2, 73.6, 99.1,
127.7, 127.8, 128.3, 138.0 ppm. MS (EI): m/z (%) ϭ 262 (6) [Mϩ
Ϫ CH3], 234 (11), 149 (11), 132 (8), 131 (22), 130 (7), 107 (28), 106
(5), 105 (6), 104 (18), 100 (19), 92 (8), 91 (100), 84 (8), 77 (6),
72 (14), 69 (9), 65 (11), 59 (22), 58 (7), 56 (7), 51 (5). HRMS:
[C14H19N3O3ϪCH3] calcd. 262.1192; found 262.1193.
(4S,5R)-5-Azido-4-benzyl-2,2-dimethyl-1,3-dioxane [(S,R)-4c]: Ac-
cording to GP 3, (S,R)-4c was obtained as a yellow oil after purifi-
cation by column chromatography (SiO2, diethyl ether/pentane,
1:20). Yield: 229 mg (48%). Rt
ϭ
8.70 min (CP-Sil-8,
100Ϫ10Ϫ300). Rf ϭ 0.41 (pentane/Et2O, 20:1). [α]2D6 ϭ Ϫ39.1 (c ϭ
1.03, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 3086 (w), 3063 (w), 3029
(w), 2994 (m), 2942 (m), 2873 (m), 2234 (w), 2107 (vs, N3), 1604
(w), 1496 (m), 1455 (m), 1435 (w), 1379 (s), 1265 (s), 1225 (m),
1202 (s), 1162 (m), 1126 (m), 1105 (m), 1082 (m), 1031 (w), 981
(m), 955 (w), 894 (w), 829 (m), 797 (w), 751 (m), 700 (s), 544 (w),
(4R,5S)-5-Azido-2,2-dimethyl-4-pentadecyl-1,3-dioxane [(R,S)-9]:
According to GP 3, (R,S)-9 was obtained as a colourless solid after
purification by column chromatography (SiO2, diethyl ether/pen-
tane, 1:40). Yield: 0.70 g (63%). GC: decomposition. Rf ϭ 0.37
(pentane/Et2O, 40:1). [α]2D5 ϭ ϩ32.5 (c ϭ 0.80, CHCl3). M.p. 35 °C.
de ϭ 96%. IR (KBr): ν˜ ϭ 2920 (vs), 2852 (s), 2229 (m), 2105 (N3,
vs), 1469 (m), 1379 (m), 1316 (m), 1266 (s), 1200 (s), 1166 (m), 1116
(m), 1091 (m), 1060 (m), 984 (m), 942 (w), 890 (m), 864 (m), 836
(w), 805 (w), 722 (w), 700 (m), 524 (w) cmϪ1. 1H NMR (300 MHz,
CDCl3): δ ϭ 0.88 [t, J ϭ 6.7 Hz, 3 H, (CH2)14CH3], 1.26 [m, 26 H,
(CH2)13CH3], 1.38 (s, 3 H, CH3), 1.43 (s, 3 H, CH3), 1.49 (m, 1 H,
CHCHH), 1.71 (m, 1 H, CHCHH), 3.21 (ddd, J ϭ 5.4/9.4/9.7 Hz,
1 H, CHN3), 3.57 (m, 1 H, OCH), 3.67 (dd, J ϭ 9.4/11.4 Hz, 1 H,
OCHH), 3.95 (dd, J ϭ 5.4/11.4 Hz, 1 H, OCHH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 14.1, 19.4, 22.7, 24.8, 28.5, 29.4, 29.5, 29.6,
29.6, 29.7, 32.0, 33.0, 59.1, 62.5, 72.1, 98.9 ppm. MS (EI): m/z
(%) ϭ 352 (53) [Mϩ Ϫ CH3], 282 (8), 239 (14), 113 (5), 111 (6),
109 (6), 99 (6), 98 (5), 97 (15), 96 (5), 95 (12), 91 (7), 85 (15), 84
(90), 83 (19), 82 (6), 81 (9), 74 (21), 73 (11), 72 (37), 71 (12), 70
(11), 69 (99), 68 (5), 67 (10), 60 (5), 59 (100), 58 (5), 57 (36), 56
(32), 55 (33), 54 (6). C21H41N3O3 (367.57): calcd. C 68.62, H 11.24,
N 11.43; found C 68.45, H 11.02, N 11.31.
1
521 (w), 494 (w) cmϪ1. H NMR (300 MHz, CDCl3): δ ϭ 1.35 (s,
3 H, CH3), 1.36 (s, 3 H, CH3), 2.80 (dd, J ϭ 7.4/14.3 Hz, 1 H,
CHHC6H5), 3.02 (dd, J ϭ 3.0/14.3 Hz, 1 H, CHHC6H5), 3.22 (ddd,
J ϭ 5.7/9.6 Hz, 1 H, CHN3), 3.69 (dd, J ϭ 9.6/11.6, 1 H, OCHH),
3.82 (ddd, J ϭ 3.0/7.4/9.6 Hz, 1 H, OCH), (3.93 (dd, J ϭ 5.7/
11.6 Hz, 1 H, COCHH), 7.25 (m, 5 H, C6H5) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 19.1, 28.4, 38.8, 57.7, 62.2, 72.5, 98.7, 126.2,
127.9, 129.4, 137.1 ppm. MS (EI): m/z (%) ϭ 247 (1) [Mϩ], 233 (5),
232 (41) [Mϩ Ϫ CH3], 190 (6), 189 (48), 162 (5), 156 (20), 146 (8),
144 (9), 133 (8), 132 (6), 131 (6), 130 (29), 129 (17), 121 (32), 120
(23), 119 (30), 118 (7), 117 (16), 115 (8), 105 (20), 104 (35), 103
(29), 99 (12), 92 (38), 91 (97), 84 (34), 78 (15), 77 (15), 74 (17), 73
(8), 72 (47), 70 (7), 69 (37), 65 (16), 61 (5), 59 (100), 58 (40), 57 (7),
56 (17), 55 (13), 51 (7), 46 (8), 45 (36). HRMS: [C13H17N3O2
CH3] calcd. 232.1086; found 232.1087.
Ϫ
(4S,5R)-5-Azido-4-(4-bromobenzyl)-2,2-dimethyl-1,3-dioxane
[(S,R)-4d]: According to GP 3, (S,R)-4d was obtained as a colour-
less solid after purification by column chromatography (SiO2, di-
ethyl ether/pentane, 1:5). Yield: 419 mg (76%). Rt ϭ 10.07 min (CP-
Sil-8, 120Ϫ10Ϫ300). Rf ϭ 0.49 (pentane/Et2O, 5:1). [α]2D5 ϭ Ϫ31.0
(c ϭ 1.06, CHCl3). M.p. 53 °C. de ϭ 96%. IR (KBr): ν˜ ϭ 2998
(m), 2945 (m), 2920 (m), 2878 (m), 2226 (w), 2106 (vs, N3), 1488 (4S,5R)-4-(2-Bromoallyl)-2,2-dimethyl-1,3-dioxan-5-amine [(S,R)-
(m), 1440 (w), 1404 (w), 1379 (s), 1303 (w), 1271 (s), 1204 (m), 1165 5a]: According to GP 4, (S,R)-5a was obtained as a colourless oil.
(m), 1125 (m), 1104 (m), 1062 (s), 1010 (m), 978 (m), 955 (w), 922 A further purification by column chromatography was not neces-
(w), 901 (m), 831 (s), 800 (m), 747 (w), 714 (w), 695 (w), 647 (w), sary. Yield: 70 mg (65%). Rt ϭ 7.58 min (CP-Sil-8, 80Ϫ10Ϫ300).
548 (m), 523 (m), 498 (w) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ
1.35 [s, 6 H, (CH3)2], 2.75 (dd, J ϭ 7.7/14.3 Hz, 1 H, CHCHH),
[α]2D2 ϭ Ϫ33.4 (c ϭ 1.08, CHCl3). de ϭ 96%. IR (CHCl3): ν˜ ϭ 3375
(m, NH), 3298 (m), 2991 (vs), 2938 (s), 2864 (s), 1632 (s), 1460 (m),
2.98 (dd, J ϭ 3.0/14.3 Hz, 1 H, CHCHH), 3.70 (dd, J ϭ 9.6/ 1422 (w), 1379 (vs), 1316 (w), 1265 (s), 1200 (vs), 1164 (vs), 1070
11.5 Hz, 1 H, OCHH), 3.77 (ddd, J ϭ 3.0/7.7/9.9 Hz, 1 H, OCH), (vs), 964 (m), 899 (s), 831 (s), 748 (w), 673 (w), 643 (w), 565 (m),
1
3.95 (dd, J ϭ 5.5/11.5 Hz, 1 H, OCHH), 3.22 (ddd, J ϭ 5.5/9.6/ 521 (m) cm Ϫ1. H NMR (400 MHz, CDCl3): δ ϭ 1.26 (br. s, 2 H,
9.9 Hz, 1 H, CHN3), 7.13 (d, J ϭ 8.5 Hz, 2 H, C6HorthoBr), 7.40 NH2), 1.38 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 2.54 (dd, J ϭ 8.8/
(d, J ϭ 8.5 Hz, 2 H, C6HmetaBr) ppm. 13C NMR (100 MHz, 15.11 Hz, 1 H, CHCHH), 2.69 (dt, J ϭ 5.5/9.6 Hz, 1 H, CHNH2),
CDCl3): δ ϭ 19.1, 28.5, 38.2, 57.6, 62.2, 72.4, 99.0, 120.4, 131.22, 2.92 (dd, J ϭ 2.8/11.5 Hz, 1 H, CHCHH), 3.48 (dd, J ϭ 9.9/
131.4, 136.3 ppm. MS (EI): m/z (%) ϭ 327 (3) [Mϩ ϩ 1], 312 (29),
11.5 Hz, 1 H, OCHH), 3.77 (dt, J ϭ 2.8/9.6 Hz, 1 H, OCH), 3.84
310 (27), 269 (14), 267 (15), 201 (10), 200 (51), 199 (12), 198 (53), (dd, J ϭ 5.5/11.5 Hz, 1 H, OCHH), 5.50 (m, 1 H, CBrCHH), 5.70
185 (5), 184 (13), 183 (7), 182 (13), 172 (6), 171 (44), 170 (7), 169 (m, 1 H, CBrCHH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 19.0,
(46), 156 (19), 143 (9), 130 (17), 129 (10), 128 (13), 116 (11), 115 28.9, 44.4, 49.3, 66.2, 73.8, 98.5, 118.8, 130.0 ppm. MS (EI): m/z
Eur. J. Org. Chem. 2004, 1732Ϫ1739
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1737

D. Enders, A. Müller-Hüwen
FULL PAPER
(%) ϭ 234 (30) [Mϩ Ϫ CH3], 193 (11), 191 (10), 176 (19), 174 (22), C(CH3)2], 2.64 (dt, J ϭ 5.5/9.6 Hz, 1 H, CHNH2), 2.71 (dd, J ϭ
171 (8), 170 (83), 161 (5), 112 (27), 101 (33), 100 (6), 95 (18), 94 8.0/14.3 Hz, 1 H, CHCHH), 3.01 (dd, J ϭ 2.8/14.3 Hz, 1 H,
(20), 83 (9), 82 (100), 81 (6), 80 (20), 73 (6), 72 (26), 67 (12), 65 (7), CHCHH), 3.44 (m, 1 H, OCHH), 3.62 (dt, J ϭ 2.8/9.6 Hz, 1 H,
60 (15), 59 (38), 58 (8), 56 (31), 55 (17), 54 (14), 53 (17), 51 (7).
HRMS: C9H16NO2Br Ϫ CH3: calcd. 234.0130; found 234.0130.
OCH), 3.78 (dd, J ϭ 5.5/11.5 Hz, 1 H, OCHH), 7.14 (m, 2 H,
C6HorthoBr), 7.38 (m, 2 H, C6HmetaBr) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 19.1, 28.9, 37.9, 49.0, 66.1, 76.0, 98.2, 119.8, 130.9,
131.1, 137.4 ppm. MS (EI): m/z (%) ϭ 301 (2) [Mϩ ϩ1], 286 (32),
284 (32), 243 (27), 241 (19), 241 (16), 226 (6), 226 (16), 223 (22),
213 (9), 212 (19), 211 (7), 210 (17), 184 (9), 182 (9), 170 (28), 168
(28), 163 (6), 156 (11), 145 (14), 133 (8), 132 (48), 130 (34), 130 (6),
129 (7), 128 (19), 116 (12), 115 (20), 104 (9), 103 (6), 102 (21), 101
(100), 91 (18), 90 (24), 89 (19), 83 (6), 77 (10), 73 (10), 72 (60), 71
(5), 70 (6), 69 (41), 65 (11), 64 (5), 63 (9), 61 (13), 60 (29), 59
(23), 58 (13), 57 (10), 56 (29), 55 (14), 54 (16), 51 (10), 45 (12).
C13H18BrNO2 (300.19): calcd. C 52.01, H 6.04, N 4.67; found C
52.01, H 5.91, N 4.67.
(4S,5R)-4-Decyl-2,2-dimethyl-1,3-dioxan-5-amine [(S,R)-5b]: Ac-
cording to GP 4, (S,R)-5b was obtained as a colourless oil. A
further purification by column chromatography was not necessary.
Yield: 110 mg (99%). Rt ϭ 7.21 min (CP-Sil-8, 140Ϫ10Ϫ300).
[α]2D3 ϭ Ϫ30.8 (c ϭ 1.02, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 3375
(w, NH), 2992 (m), 2925 (vs), 2864 (vs), 1610 (w), 1463 (m), 1378
(s), 1268 (m), 1201 (s), 1166 (m), 1140 (w), 1075 (m), 1013 (w), 976
(w), 872 (w), 621 (w) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 0.88
[t, J ϭ 6.9 Hz, 3 H, (CH2)9CH3], 1.13 (br. s, 2 H, NH2), 1.27 [m,
16 H, (CH2)8CH3], 1.38 (s, 3 H, CH3), 1.43 (s, 3 H, CH3), 1.50 (m,
1 H, CHCHH), 1.73 (m, 1 H, OCHCHH), 2.63 (dt, J ϭ 5.5/9.6 Hz,
1 H, CHNH2), 3.40 (dt, J ϭ 2.5/9.0 Hz, 1 H, OCH), 3.45 (dd, J ϭ (4S,5R)-4-Benzyloxymethyl-2,2-dimethyl-1,3-dioxan-5-amine [(S,R)-
9.6/11.5 Hz, 1 H, OCHH), 3.80 (dd, J ϭ 5.5/11.5 Hz, 1 H, OCHH) 5e]: According to GP 4, (S,R)-5e was obtained as a colourless oil. A
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 14.1, 19.3, 22.7, 25.1,
further purification by column chromatography was not necessary.
29.1, 29.3, 29.6, 31.9, 32.3, 49.7, 66.14, 75.5, 98.2 ppm. MS (EI):
Yield: 160 mg (97%). Rt ϭ 6.99 min (CP-Sil-8, 140Ϫ10Ϫ300).
m/z (%) ϭ 257 (14) [M ϩϪ CH3 ϩ 1], 256 (97) [Mϩ Ϫ CH3], 213 [α]D27 ϭ Ϫ12.4 (c ϭ 0.93, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 3374 (m,
(8), 197 (9), 196 (59), 182 (7), 138 (6), 126 (5), 112 (8), 109 (6), 102
(17), 101 (100), 98 (5), 97 (6), 95 (13), 85 (5), 83 (14), 82 (9), 81
(12), 73 (7), 72 (14), 71 (7), 70 (24), 69 (84), 868 (6), 67 (14), 61
(23), 60 (24), 59 (36), 58 (15), 57 (26), 56 (97), 55 (45), 54 (9), 45
NH), 3302 (m), 3063 (m), 3030 (m), 2992 (s), 2938 (s), 2863 (vs),
1603 (m, NH), 1496 (m), 1455 (s), 1376 (vs), 1271 (s), 1225 (s),
1200 (vs), 1167 (s), 1088 (vs), 1057 (s), 1028 (m), 975 (m), 909 (s),
844 (s), 741 (s), 700 (s), 614 (w), 521 (m) cmϪ1 1H NMR
.
(10). HRMS: [C16H33NO2
256.2275.
Ϫ
CH3] calcd. 256.2277; found (400 MHz, CDCl3): δ ϭ 1.28 (br. s, 2 H, NH2), 1.40 (s, 3 H, CH3),
1.45 (s, 3 H, CH3), 2.87 (m, 1 H, CHNH2), 3.47 (dd, J ϭ 10.1/
10.4 Hz, 1 H, OCHH), 3.64 (m, 3 H, CHCH2, OCH), 3.80 (dd,
(4S,5R)-4-Benzyl-2,2-dimethyl-1,3-dioxan-5-amine [(S,R)-5c]: Ac-
cording to GP 4, (S,R)-5c was obtained as a colourless oil. A
further purification by column chromatography was not necessary.
Yield: 160 mg (99%). Rt ϭ 8.21 min (CP-Sil-8, 100Ϫ10Ϫ300).
[α]2D7 ϭ Ϫ46.9 (c ϭ 0.98, CHCl3). de ϭ 96%. IR (film): ν˜ ϭ 3377
(m, NH), 3320 (m), 3085 (m), 3062 (m), 3028 (s), 2993 (vs), 2938
(s), 2857 (s), 1605 (s, NH), 1496 (s), 1455 (s), 1378 (vs), 1267 (s),
1202 (vs), 1161 (vs), 1131 (s), 1079 (vs), 1030 (s), 961 (s), 898 (s),
J ϭ 5.5/11.5 Hz, 1 H, OCHH), 4.58 (m, 2 H, OCH2C6H5), 7.34
(m, 5 H, C6H5) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 19.1, 28.9,
47.3, 65.6, 71.4, 73.4, 74.7, 98.2, 127.5, 127.5, 128.2, 137.9 ppm.
MS (EI): m/z (%) ϭ 236 (19) [Mϩ Ϫ CH3], 194 (5), 193 (37), 160
(5), 145 (6), 101 (8), 100 (16), 92 (11), 91 (100), 87 (6), 83 (6), 72
(23), 65 (11), 60 (5), 59 (13), 58 (11), 57 (23), 56 (23), 45 (5). HRMS:
[C14H21NO3 Ϫ CH3] calcd. 236.1286; found 236.1285.
830 (s), 797 (m), 750 (s), 701 (vs), 676 (w), 636 (w), 592 (w), 550 (4R,5S)-2,2-Dimethyl-4-pentadecyl-1,3-dioxan-5-amine [(R,S)-10]:
(w), 522 (s), 501 (m) cmϪ1. 1H NMR (400 MHz, CDCl3): δ ϭ 0.98 According to GP 4, (S,R)-10 was obtained as a colourless solid. A
(br.s, 2 H, NH2), 1.37 [m, 6 H, C(CH3)2], 2.66 (ddd, J ϭ 5.5/9.6/ further purification by column chromatography was not necessary.
10.0 Hz, 1 H, CHNH2), 2.78 (dd, J ϭ 7.7/14.3 Hz, 1 H, CHCHH), Yield: 110.0 mg (91%). Rt ϭ 11.92 min (CP-Sil-8, 140Ϫ10Ϫ300).
3.02 (dd, J ϭ 3.3/14.3 Hz, 1 H, CHCHH), 3.43 (dd, J ϭ 10.0/
11.5 Hz, 1 H, OCHH), 3.67 (ddd, J ϭ 3.3/7.7/9.6 Hz, 1 H, OCH),
[α]2D3 ϭ ϩ27.6 (c ϭ 1.06, CHCl3). M.p. 36 °C. de ϭ 96%. IR (KBr):
ν˜ ϭ 2995 (m), 2919 (vs), 2852 (vs), 1624 (w), 1469 (m), 1379 (m),
3.77 (dd, J ϭ 5.5/11.5 Hz, 1 H, OCHH), 7.26 (m, 5 H, C6H5) ppm. 1267 (w), 1203 (m), 1167 (m), 1113 (m), 1095 (m), 1074 (m), 1000
1
13C NMR (100 MHz, CDCl3): δ ϭ 19.1, 29.0, 38.8, 49.2, 66.0, 76.3,
(w), 916 (w), 892 (m), 864 (w), 835 (w), 721 (w), 524 (w) cmϪ1. H
98.2, 125.9, 127.9, 129.2, 138.4 ppm. MS (EI): m/z (%) ϭ 206 (42) NMR (400 MHz, CDCl3): δ ϭ 0.88 [m, 3 H, (CH2)14CH3], 1.26
[Mϩ Ϫ CH3], 164 (7), 163 (53), 156 (10), 147 (6), 146 (45), 144 (7), [m, 26 H, (CH2)13CH3], 1.38 (s, 3 H, CH3), 1.44 (s, 3 H, CH3), 1.50
135 (6), 134 (6), 133 (44), 132 (71), 131 (6), 130 (23), 129 (38), 128
[m, 1 H, CHH(CH2)13CH3], 1.72 [m, 1 H, CHH(CH2)13CH3], 2.64
(6), 127 (10), 117 (17), 116 (17), 115 (26), 106 (7), 105 (29), 104 (9), (ddd, J ϭ 5.5/9.6/9.6 Hz, 1 H, CHNH2), 3.40 (m, 1 H, OCH), 3.45
103 (17), 102 (20), 101 (88), 92 (11), 91 (100), 89 (6), 79 (6), 78 (8), (dd, J ϭ 9.6/11.3 Hz, 1 H, OCHH), 3.81 (dd, J ϭ 5.5/11.3 Hz, 1
77 (18), 73 (8), 72 (47), 70 (7), 69 (65), 65 (30), 63 (8), 61 (62), 60 H, OCHH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 14.3, 19.4,
(35), 59 (33), 58 (15), 56 (42), 55 (19), 54 (26), 51 (17), 45 (34).
HRMS: [C13H19NO2 Ϫ CH3] calcd. 206.1181; found 206.1182.
22.8, 25.2, 29.2, 29.5, 29.8, 29.8, 32.1, 32.4, 49.9, 66.3, 75.7,
98.4 ppm. MS (EI): m/z (%) ϭ 342 (3) [Mϩ ϩ 1], 327 (16), 326 (72)
[Mϩ Ϫ CH3], 283 (7), 267 (8), 266 (36), 252 (6), 102 (10), 101 (100),
95 (8), 83 (11), 82 88), 81 (8), 72 (9), 71 88), 70 (9), 69 (12), 67 (11),
60 (14), 59 (19), 58 (9), 57 (25), 56 (54), 55 (39). C21H43NO2
(341.58): calcd. C 73.84, H 12.69, N 4.10; found C 74.27, H 12.20,
N 3.80.
(4S,5R)-4-(4-Bromobenzyl)-2,2-dimethyl-1,3-dioxane-5-amine
[(S,R)-5d]: According to GP 4, (S,R)-5d was obtained as a colour-
less oil. A further purification by column chromatography was not
necessary. Yield: 210 mg (99%). Rt
ϭ 11.62 min (CP-Sil-8,
100Ϫ10Ϫ300). [α]2D7 ϭ Ϫ36.4 (c ϭ 0.99, CHCl3). de ϭ 96%. IR
(CHCl3): ν˜ ϭ 3376 (m, NH), 3319 (m), 2991 (vs), 2926 (vs), 2856 2-Hydroxy-1-hydroxymethyl-3-phenylpropylammonium Trifluoro-
(vs), 1594 (m, NH), 1488 (vs), 1458 (m), 1436 (m), 1404 (m), 1378 acetate [(S,R)-6c]: 1.5 Equivalents of trifluoroacetic acid was added
(vs), 1267 (s), 1202 (vs), 1160 (s), 1131 (m), 1072 (vs), 1032 (m), dropwise to a stirred solution of amine (S,R)-5c (0.10 g) in THF
1012 (s), 962 (s), 901 (s), 831 (vs), 802 (s), 748 (m), 702 (w), 676
(w), 634 (w), 555 (w), 522 (s), 504 (m), 474 (w) cmϪ1 1H NMR 20 min at room temp. the solvent was removed in vacuo to give the
(400 MHz, CDCl3): δ ϭ 1.09 (br. s, 2 H, NH2), 1.36 [s, 6 H, product as a colourless solid. Yield: 130 mg (95%). [α]2D3 ϭ ϩ10.7
(15.0 mL/mmol) and water (7.5 mL/mmol). After stirring for
.
1738
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1732Ϫ1739

Asymmetric Synthesis of 2-Amino-1,3-diols and D-erythro-Sphinganine
(c ϭ 1.02, acetone). M.p. 132 °C. de ϭ 96%. IR (KBr): ν˜ ϭ 3220
FULL PAPER
Acknowledgments
(m), 3092 (m), 3036 (m), 2948 (m), 2901 (m), 2397 (s), 2268 (s),
1666 (vs), 1499 (w), 1454 (m), 1437 (m), 1376 (w), 1338 (w), 1308
(w), 1186 (vs), 1134 (vs), 1091 (m), 1054 (m), 998 (w), 964 (w), 903
(w), 840 (m), 801 (m), 762 (m), 725 (m), 700 (m), 634 (w), 532 (w),
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 380) and the Fonds der Chemischen Industrie. We thank De-
gussa AG, BASF AG, and Bayer AG for the donation of chemicals.
1
488 (w) cmϪ1. H NMR (300 MHz, CD3OD): δ ϭ 2.86 (dd, J ϭ
[1]
S. C. Bergmeier, Tetrahedron 2000, 56, 2561.
[2] [2a]
[2b]
1.7/6.2 Hz, 2 H, CH2C6H5), 3.25 (ddd, J ϭ 4.0/7.9/8.2 Hz, 1 H,
CHNH3ϩ), 3.86 (dd, J ϭ 8.5/11.9 Hz, 1 H, HCHOH), 4.02 (dd,
J ϭ 4.0/11.9 Hz, 1 H, HCHOH), 4.14 (ddd, J ϭ 1.7/6.2/7.9 Hz, 1
H, CHOH), 7.34 (m, 5 H, C6H5) ppm. 13C NMR (75 MHz,
CD3OD): δ ϭ 39.3, 56.3, 57.4, 70.5, 126.3, 128.2, 128.9, 137.7 ppm.
MS (FAB) [DTE/DTT/Sul]: Cation: m/z (%) ϭ 183 (11) [Mϩ ϩ 1],
182 (100) [Mϩ], 91 (7), 60 (8), anion: m/z (%) ϭ 113 (100) [Mϩ], 69
(5). C12H16F3NO4 (295.26): calcd. C 48.82, H 5.46, N 4.74; found C
48.92, H 5.68, N 4.76.
Y. A. Hannun, R. M. Bell, Science 1989, 243, 500.
Y.
A. Hannun, Sphingolipid-Mediated Signal Transduction, Chap-
man & Hall; New York, 1997. [2c]T. Kolter, K. Sandhoff, An-
gew. Chem. 1999, 111, 1633; Angew. Chem. Int. Ed. 1999, 38,
1532.
[3]
G. K. Schwartz, J. Jiang, D. Kelsen, A. P. Albino, J. Nat. Can-
cer Inst. 1993, 85, 402.
[4] [4a]
G. R. Cook, K. Pararajasingham, Tetrahedron Lett. 2002,
43, 9027. [4b] A. J. Ndakala, M. Hashemzadeh, R. C. So, A. R.
Howell, Org. Lett. 2002, 4, 1719. [4c] C. Hertweck, P. Sebek, A.
[4d]
Svatos, Synlett 2001, 1965.
J. Org. Chem. 2000, 65, 7618.
Eur. J. Org. Chem. 2000, 3447.
L. He, H.-S. Byun, R. Bittman,
[4e]
R. A. Fernandes, P. Kumar,
H. Azuma, S. Tamagaki, K.
[4f]
[4g]
2-Hydroxy-1-(hydroxymethyl)heptadecylammonium Trifluoroacetate
[(R,S)-11]: 1.5 Equivalents of trifluoroacetic acid was added drop-
wise to a stirred solution of amine (R,S)-10 (80.0 mg) in THF
(15.0 mL/mmol) and water (7.5 mL/mmol),. After stirring for
20 min at room temp. the solvent was removed in vacuo to give the
product as a colourless solid. Yield: 90 mg (87%). [α]2D3 ϭ Ϫ7.9 (c ϭ
0.96, acetone). M.p. 100 °C. de ϭ 96%. IR (KBr): ν˜ ϭ 3345 (m),
3075 (s), 2922 (vs), 2851 (s), 2298 (w), 1656 (s), 1526 (w), 1469 (m),
1445 (w), 1346 (w), 1212 (s), 1185 (s), 1157 (s), 1053 (m), 844 (m),
Ogino, J. Org. Chem. 2000, 65, 3538.
R. A. Fernandes, P.
Kumar, Tetrahedron: Asymmetry 1999, 10, 4797. [4h] R. Villard,
F. Fotiadu, G. Buono, Tetrahedron: Asymmetry 1998, 9, 607.
[4i]
R. V. Hoffman, J. Tao, J. Org. Chem. 1998, 63, 3979.
[5]
[6]
[5a] A. Job, C. F. Janeck, W. Bettray, R. Peters, D. Enders, Tetra-
[5b]
hedron 2002, 58, 2253.
D. Enders, in Asymmetric Synthesis
(Ed.: J. D. Morrison), Academic Press: Orlando, 1984, vol. 3B;
[5c]
275.
D. Enders, M. Klatt, in Encyclopedia of Reagents for
Organic Synthesis (Ed.: L. A. Paquette), John Wiley & Sons,
New York, 1995, 3368.
D. Enders, B. Bockstiegel, W. Gatzweiler, U. Jegelka, B.
Dücker, L. Wortmann, Chimica Oggi/Chemistry Today 1997,
15, 20.
D. Enders, B. Bockstiegel, Synthesis 1989, 493.
D. Enders, T. Hundertmark, R. Lazny, Synlett 1998, 721.
D. Enders, D. L. Whitehouse, J. Runsink, Chem. Eur. J. 1995,
1, 382.
1
806 (m), 726 (m) cmϪ1. H NMR (300 MHz, CD3OD): δ ϭ 0.93
[t, J ϭ 6.7 Hz, 3 H, (CH2)13CH3], 1.32 [m, 26 H, (CH2)13CH3], 1.52
[m, 2 H, CH2(CH2)13CH3], 3.23 (m, 1 H, CHNH3ϩ), 3.74 (dd, J ϭ
8.4/11.6 Hz, 1 H, HCHOH), 3.82 (m, 1 H, CHOH), 3.87 (dd, J ϭ
4.2/11.8 Hz, 1 H, HCHOH) ppm. 13C NMR (75 MHz, CD3OD):
δ ϭ 13.1, 22.4, 25.6, 29.1, 29.2, 29.3, 29.4, 31.7, 32.8, 57.0, 57.5,
68.5 ppm. MS (FAB) [DTE/DTT/Sul]: cation: m/z (%) ϭ 303 (14)
[Mϩ ϩ 1], 302 (100) [Mϩ], 300 (11), 284 (15), 67 (6), 60 (45), 56
(6), 55 (12), anion: m/z (%) ϭ 113 (100) [Mϩ], 69 (5). C20H40F3NO4
(415.53): calcd. C 57.81, H 9.70, N 3.37; found C 58.04, H 9.92,
N 3.13.
[7]
[8]
[9]
[10]
[11]
D. Enders, P. Fey, H. Kipphardt, Org. Synth. 1987, 65, 173,
183.
D. Hoppe, H. Schminke, H. W. Kleemann, Tetrahedron 1989,
45, 687.
Received December 18, 2003
Eur. J. Org. Chem. 2004, 1732Ϫ1739
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1739