Stereoselective access to the versatile 4-aminohex-5-ene-1,2,3-triol pattern

Article abstract of DOI:10.1021/jo048766v

We developed a stereocontrolled route allowing potential access to the eight isomers of 4-benzyl-aminohex-5-ene-1,2,3-triol in two or four steps and ca. 50% yield from readily available chiral nonracemic cis- or trans-α,β-epoxyimine precursors. A new (NH<

Full text of DOI:10.1021/jo048766v

Stereoselective Access to the Versatile 4-Aminohex-5-ene-1,2,3-triol
Pattern
Tahar Ayad, Vanessa Faugeroux, Yves Ge´nisson,* Chantal Andre´, Michel Baltas, and
Liliane Gorrichon
Laboratoire Synthe`se et Physicochimie des Mole´cules d’Inte´ret Biologique, UMR 5068 CNRS,
Universite´ Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 04, France
genisson@chimie.ups-tlse.fr
Received July 20, 2004
We developed a stereocontrolled route allowing potential access to the eight isomers of 4-benzyl-
aminohex-5-ene-1,2,3-triol in two or four steps and ca. 50% yield from readily available chiral
nonracemic cis- or trans-R,â-epoxyimine precursors. A new (NH4)2CO3-based carboxylation/
intramolecular cyclization sequence allowed regio- and stereocontrolled C-3 epoxide opening while
neat C-2 hydrolysis was ensured by simple aqueous acidic treatment.
Introduction
Aliphatic intermediates presenting the 4-amino-1,2,3-
triol heading pattern have proven useful in the synthesis
of various natural compounds, such as the linear amino
acid portion of polyoxins1 1 and callipeltins2 2 (Figure
1).
This 4-amino-1,2,3-triol functional arrangement is also
commonly encountered in synthetic precursors of nitro-
genated heterocycles, accessible through 4- or 5-exo tet
cyclization upon an activated hydroxyl group. Prepara-
tion of several azetidine,3 pyrrolidine,4 and indolizidines
alkaloids5 relies, for instance, on the use of such deriva-
tives (Figure 2).
FIGURE 1. Amino acid moieties of polyoxines and callipeltins.
In the course of our ongoing research program directed
toward iminosugars,6 we developed a flexible and ste-
reoselective approach to the 4-benzylaminohex-5-ene-
1,2,3-triol intermediates in which the terminal vinyl
group allows further oxidative manipulation toward
various C1- or C2-oxygenated fragments and/or elongation
by means of olefin metathesis. We wish to describe herein
this work in details.
FIGURE 2. Alkaloids synthesized from a 4-amino-1,2,3-triol
pattern-containing intermediate.
amino group via Felkin-Anh type organometallic reagent
addition to an intermediate R,â-epoxyimine, and (3)
access to the four possible diastereoisomeric arrange-
ments through a stereochemical manifold based on the
combined choice of the C-2/C-3 epoxide opening site and
the cis/trans epoxide geometry (the cis series giving rise
to both 2,3-syn compounds and both 2,3-anti isomers
coming from the trans series).7
Preparation of the starting cis- or trans-R,â-epoxy-
aldehydes (3a or 3b) was readily accomplished from cis-
but-2-ene-1,4-diol (in three steps and 78% yield or five
steps and 67% yield, respectively) (not shown).8 Note-
worthy is the use of o-iodoxybenzoic acid (IBX) (1.5 equiv,
standard grade DMSO, rt, 5 h) to accomplish oxidation
Results and Discussion
Our approach, starting from R,â-epoxyaldehydes of
general structure 3, was based on three key features: (1)
optical series selection during the initial Sharpless ep-
oxidation, (2) diastereocontrolled establishment of the C-4
* To whom correspondence should be addressed. Fax: (33) (0)5 61
55 82 45.
(1) Palomo, C.; Oiarbide, M.; Esnal, A.; Landa, A.; Miranda, J. I.;
Linden, A. J. Org. Chem. 1998, 63, 5838-5846.
(2) Kumar, A. R.; Rao, B. V. Tetrahedron Lett. 2003, 44, 5645-5647.
(3) Yoda, H.; Uemura, T.; Takabe, K. Tetrahedron Lett. 2003, 44,
977-979.
(4) Hulme, A. N.; Rosser, E. M. Org. Lett. 2002, 4, 265-267.
(5) Razavi, H.; Polt, R. J. Org. Chem. 2000, 65, 5693-5706.
(6) (a) Ayad, T.; Ge´nisson, Y.; Baltas, M.; Gorrichon, L. Synlett 2001,
6, 866-868. (b) Ayad, T.; Ge´nisson, Y.; Broussy, S.; Baltas, M.;
Gorrichon, L. Eur J. Org. Chem. 2003, 2903-2910. (c) Ayad, T.;
Ge´nisson, Y.; Baltas, M.; Gorrichon, L. Chem. Commun. 2003, 582-
583.
(7) For matter of coherence the targeted aminotriol carbon number-
ing has been used throughout the article including for NMR peak
assignments.
10.1021/jo048766v CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/13/2004
J. Org. Chem. 2004, 69, 8775-8779
8775

Ayad et al.
SCHEME 1a
FIGURE 3. Proposed reaction intermediate for the carboxy-
lation/intramolecular cyclization process.
Central to our approach was the regio- and diastereo-
controlled opening of the oxirane moiety. Exclusive C-2
hydrolysis was accomplished by direct aqueous acidic
treatment of the C-1 silylated cis- and trans-R,â-ep-
oxyamines 4a and 4b. The resulting 2,3-syn-3,4-anti and
all-anti aminotriols 5a and 5b were isolated in good
yields (70 and 80%, respectively). No trace of other
diastereoisomers was detected in the crude reaction
mixtures (1H NMR). Such site-selective opening could
arise from the deactivation of the C-3 position by the
adjacent protonated amino group.12 Aminotriol 5a was
involved in a concise total synthesis of (-)-lentiginosine
and a pyrrolizidinic analogue thereof.6c
Regiocontrolled C-3 opening relied on a carboxylation/
intramolecular cyclization sequence using new conditions.
Treatment of epoxyamines 4a and 4b by (NH4)2CO3 in a
THF/H2O mixture at rt smoothly delivered oxazolidinones
6a and 6b respectively in excellent yields. From a
mechanistic point of view, this transformation is believed
to involve attack of the secondary amine onto the CO2
slowly released by decomposition of the carbonate salt
in the aqueous medium (Figure 3). Related formation of
oxazolidinones from R,â-epoxyamine under CO2 atmo-
sphere (MeOH, rt) has been described.13 The intermediate
carbamic acid salt would then spontaneously cyclize into
the oxazolidinone. Interestingly, the use of the am-
monium cation revealed determinant for reaction progress,
likely through electrophilic assistance of the oxirane
opening. A study conducted with the desilylated deriva-
tive 7a (vide infra) showed that, when NaHCO3 or K2-
CO3 were used, the presence of a catalytic amount of
pyridine was necessary to observe the desired carboxy-
lation/intramolecular cyclization process.14 It is worth
emphasizing the experimental simplicity of this efficient
and selective transformation.15 Moreover, the identity of
the trans-oxazolidinone in the cis-epoxide series was
unambiguously determined by X-ray diffraction analysis
of a single crystal of ent-6a and of the corresponding
benzyl ether ent-6c, both derived from R,â-epoxyaldehyde
ent-3a (see the Supporting Information). These X-ray
structures allowed confirmation of the previously as-
signed relative and absolute configuration. If one as-
sumes that this oxazolidinone arose from an SN2 invert-
a Reagents and conditions: (i) 1.0 equiv of BnNH2, 30% w/w 4
Å MS, Et2O, overnight, then 1.3 equiv of Et2O‚BF3, -78 to -40
°C, 5 min, then 1.7 equiv of CH2CHMgBr as a commercial 1.0 M
solution in THF, -78°C, 2 h; cis-epoxide 4a, 67% (dr >95:5); trans-
epoxide 4b (3,4-anti)/4c (3,4-syn), 70% (dr 94:6); (ii) 2.7 equiv of
H2SO4 as a 3 M aqueous solution, p-dioxane, reflux, 5 h; 2,3-syn
5a 70% from cis-epoxide; 2,3-anti 5b 80% from trans-epoxide; (iii)
8 equiv of (NH4)2CO3, THF/H2O (4:1), rt, 8-20 h, 2,3-syn 6a 94%
from cis-epoxide; 2,3-anti 6b 93% from trans-epoxide; (iv) 1.9 equiv
of TBAF on silica gel (1.25 mmol F-/g), THF, rt, overnight; 2,3-
syn 7a and 2,3-anti 7b 85%; (v) 6 equiv of LiOH.H2O, p-dioxane/
H2O (3:1), reflux, 8 h; 2,3-syn 8a and 2,3-anti 8b 95%. TBDPS )
tert-butyldiphenylsilyl.
steps in a very convenient and efficient manner (>90%
isolated yield in essentially pure material).9 Installation
of the allylic amine was then inspired from Procter’s
Grignard reagent addition to Et2O.BF3-chelated in situ
generated cis-R,â-epoxyimines.10 The adapted procedure
involving the simple benzylamine-derived imine allowed
production of the desired cis-epoxyamine 4a as a single
detectable isomer (67% yield from 3a) (Scheme 1). To our
satisfaction, this route was extended to the trans-R,â-
epoxyaldehyde 3b affording the corresponding adduct 4b/
4c with high selectivity (dr 94:6) and comparable effi-
ciency (66% yield in major diastereoisomer 4b to which
the 3,4-anti configuration was attributed by analogy with
the cis series). The main byproducts isolated were the
aziridines resulting from an aza-Payne type rearrange-
ment occurring under acidic catalysis during the course
of the reaction or the purification.11 The anti-epoxyamine
relationship, initially attributed on the basis of Procter’s
work, was further confirmed by means of chemical
filiation and X-ray crystallography in the trans-epoxide
series (vide infra).
(8) For previous report of these derivatives see: (a) Escudier, J.-
M.; Baltas, M.; Gorrichon, L. Tetrahedron 1993, 49, 5253-5266. For
reviews on formation and synthetic use of chiral epoxides, see: (b)
Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1-299. (c) Bonini, C.;
Righi, G. Tetrahedron 2002, 58, 4981-5021.
(12) Bordwell, F. G.; Brannen Jr, W. T. J. Am. Chem. Soc. 1964,
86, 4645-4650.
(13) Karikomi, M.; Yamazaki, T.; Toda, T. Chem. Lett. 1993, 1965-
1968.
(14) Participation of a pyridinium species in place of the ammonium
cation might explain this observation.
(9) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35, 8019-
8022.
(15) Similar reaction sequence has been achieved using the uncom-
mon carbonate form of Amberlyst A-26 resin. Although it involved a
reactive primary amine, this process was reported to be somewhat
slower than ours (48 h at room temperature): Wood, J. L.; Jones, D.
R.; Hirschmann, R.; Smith, A. M., III. Tetrahedron Lett. 1990, 31,
6329-6330.
(10) Beresford, K. J. M.; Howe, G. P.; Procter, G. Tetrahedron Lett.
1992, 33, 3355-3358.
(11) The proportion of rearranged product was found to depend on
the aging of the opened commercial vinyl Grignard solution. For the
same reason prolonged contact with silica gel should also be avoided.
8776 J. Org. Chem., Vol. 69, No. 25, 2004

Stereoselective Access to the 4-Aminohex-5-ene-1,2,3-triol Pattern
3JH3H2 ) 8.0 Hz, 1H, H-3), 3.00 (pseudot, 3JH2H1 ) 3JH2H3 ) 8.0
Hz, 1H, H-2), 1.07 (s, 9H, C(CH3)3); 13C NMR (100 MHz, CDCl3)
δ 140.00 (Cquat arom), 137.6 (C-5), 135.7, 135.6 (CH arom),
133.3, 133.1 (Cquat arom), 129.9, 128.4, 128.1, 127.9, 127.8,
127.0 (CH arom), 118.2 (C-6), 62.0 (C-1), 59.0 (C-4), 58.8 (C-
3), 56.9 (C-2), 50.9 (NCH2Ph), 26.9 (CH3), 19.2 (C(CH3)3); IR
(thin film) 3154 (N-H), 1633 (CdC), 1108 (C-O) cm-1 ; MS
(DCI/NH3) m/z 458 (MH+, 100); HRMS (DCI/NH3) m/z calcd
for C29H36NO2Si 458.2515, found 458.2512.
Compound 4b. trans-R,â-Epoxyamine 4b (2.22 g, 4.85
mmol, 66% yield) was prepared from R,â-trans-epoxyaldehyde
3b (2.5 g, 7.35 mmol) using the procedure described for the
preparation of compound 4a: Rf ) 0.24 (petroleum ether/
ing process, its trans arrangement is in agreement with
the proposed anti arrangement in the starting ep-
oxyamine. Both oxazolidinones 6a and 6b, presenting
three differentiated alcohol functions, constitute an
interesting platform for further synthetic developments.
The targeted aminotriols were finally prepared from
intermediates 6a and 6b by hydroxyl group desilylation,
delivering primary alcohols 7a and 7b in 85% yield,
followed by cyclic carbamate basic hydrolysis (95% yield).
That way, the all-syn derivative 8a and the 2,3-anti-3,4-
anti isomer 8b were readily obtained from the corre-
sponding oxazolidinones in good overall yield. Access to
derivative 6a already allowed a total synthesis of 1,4-
dideoxy-1,4-imino-glucitol.6a
EtOAc 90:10 under a saturated atmosphere of NH4OH); [R]25
D
1
-0.6 (c ) 1.94, CHCl3); H NMR (400 MHz, CDCl3) δ 7.80-
7.70 (m, 5H, Ph), 7.50-7.28 (m, 10H, Ph), 5.81 (ddd, 3JH5H4
)
7.8 Hz, 3JH5H6′ ) 10.2 Hz, and 3JH5H6 ) 17.3 Hz, 1H, H-5), 5.36
3
(brd, 3JH6H5 ) 17.3 Hz, 1H, H-6), 5.34 (brd, JH6′H5 ) 10.2 Hz,
Conclusion
2
1H, H-6′), 3.85 (ABq, Jgem ) 13.3 Hz, 2H, NCH2Ph, ∆δa-δb
3
3
In summary, we developed a stereocontrolled route
offering potential access to the eight isomers of the
4-benzylaminohex-5-ene-1,2,3-triol in two or four steps
(ca. 50% yield in both cases) from readily available chiral
nonracemic cis- or trans-R,â-epoxyimine precursors. Note-
worthy is the use of a practical and efficient carboxyla-
tion/intramolecular cyclization sequence involving the
trivial (NH4)2CO3 salt as reagent. Synthetic work further
exemplifying the versatility of these highly substituted
synthetic intermediates will be reported in due course.
) 57.0 Hz), 3.83 (AB of ABX, JH1H2 ) 3.5 Hz, JH1′H2 ) 4.6
Hz, and 2Jgem ) 11.8 Hz, 2H, 2 × H-1, ∆δa-δb ) 33.0 Hz), 3.30
(dd, 3JH4H3 ) 4.8 Hz and 3JH4H5 ) 7.8 Hz, 1H, H-4), 3.26-3.22
3
3
(m, 1H, H-2), 3.04 (dd, JH3H2 ) 2.2 Hz and JH3H4 ) 4.8 Hz,
1H, H-3), 1.85-1.77 (m, 1H, N-H), 1.14 (s, 9H, C(CH3)3); 13C
NMR (100 MHz, CDCl3) δ 140.4 (Cquat arom), 137.0 (C-5),
135.8 (CH arom), 133.5 (Cquat arom), 130.0, 128.7, 128.4,
128.0, 127.2 (CH arom), 118.7 (C-6), 64.0 (C-1), 60.7 (C-4), 58.0
(C-3), 56.4 (C-2), 51.3 (NCH2Ph), 27.1 (CH3), 19.5 (C(CH3)3);
IR (thin film) 2931 (N-H), 1588 (CdC), 1110 (C-O) cm-1; MS
(DCI/NH3) m/z 458 (MH+, 100); HRMS (DCI/NH3) m/z calcd
for C29H36NO2Si 458.2515, found 458.2514.
Compound 4c. In the course of the preparation of 4b the
3,4-syn minor diastereoisomer 4c was also isolated in 4%
yield: Rf ) 0.22 (petroleum ether/EtOAc 90:10 under a
Experimental Section
Compound 4a. Benzylamine (687 µL, 5.88 mmol) was
added dropwise to a solution of R,â-cis-epoxyaldehyde 3a (2.00
g, 5.88 mmol) in freshly distilled Et2O (40 mL) containing
powder activated 4 Å molecular sieves (30% w/w). The result-
ing mixture was vigorously stirred at room temperature until
no starting material could be detected by IR analysis (ca. 3 h,
disappearance of CdO bond 1729 cm-1 and appearance of Cd
N bond 1663 cm-1). The solution was then cooled to -78 °C,
and freshly distilled BF3‚Et2O (950 µL, 7.64 mmol) was added
dropwise at this temperature. The mixture was allowed to stir
at -40 °C for 5 min before being cooled again to -78 °C.
Vinylmagnesium bromide in THF (10.00 mL of a 1 M com-
mercial solution, 10.00 mmol) was then added dropwise over
5 min, and the mixture was vigorously stirred at -78 °C for 2
h. The reaction was quenched by portionwise addition of a
THF/saturated aqueous NH4Cl mixture (20:80, 20 mL) over 1
h 30 at -78 °C with vigorous stirring before being allowed to
warm to room temperature. The mixture was then filtered
through Celite, and the solvents were evaporated off under
reduced pressure. The resulting suspension was extracted with
Et2O (3 × 100 mL), and the combined extracts were succes-
sively washed with water and brine, dried over Na2SO4,
filtered, and concentrated under reduced pressure. The pale
yellow oil thus obtained was first filtered through a plug of
silica gel eluting with petroleum ether/EtOAc (90:10) to remove
magnesium salt. Concentration of the filtrate to dryness under
reduce pressure gave a crude product that was then purified
by medium-pressure column chromatography on silica gel
treated with 2.5% v/v Et3N eluting with petroleum ether/
EtOAc (gradient 95:5 to 80:20) to afford epoxyamine 4a (1.8
g, 3.94 mmol, 67% yield): Rf ) 0.21 (petroleum ether/EtOAc
saturated atmosphere of NH4OH); [R]25 -0.6 (c ) 1.94,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.80-7.65 (m, 5H, Ph),
7.30-6.80 (m, 10H, Ph), 5.89-5.79 (m, 1H, H-5), 5,34-5,28
2
(m, 2H, 2 × H-6), 3.86 (ABq, Jgem ) 13.3 Hz, 2H, NCH2Ph)
3
3
∆δa-δb ) 47.9 Hz, 3.82 (AB of ABX, JH1H2 ) 3.4 Hz, JH1′H2
2
) 4.6 Hz, Jgem ) 11.9 Hz, 2H, 2 × H-1) ∆δa-δb ) 38.5 Hz,
3.14 (m, 1H, H-2), 3.04-3.00 (m, 2H, H-3, H-4), 2.10-1.85 (m,
1H, N-H), 1.10 (s, 9H, C(CH3)3); 13C NMR (100 MHz, CDCl3) δ
140.3 (Cquat arom), 136.5 (C-5), 135.8 (CH arom), 133.5 (Cquat
arom), 130.0, 128.7, 128.4, 128.0, 127.2 (CH arom), 118.3 (C-
6), 63.1 (C-1), 62.6 (C-4), 58.8 (C-3), 56.7 (C-2), 51.3 (NCH2-
Ph), 27.0 (CH3), 19.5 (C(CH3)3); IR (thin film) 2931 (N-H),
1660 (CdC), 1110 (C-O) cm-1; MS (DCI/NH3) m/z 458 (MH+,
100); HRMS (DCI/NH3) m/z calcd for C29H36NO2 Si 458.2515,
found 458.2512.
Compound 5a. A 3 M aqueous H2SO4 solution (2.91 mL,
8.72 mmol) was added to a solution of cis-R,â-epoxyamine 4a
(500 mg, 1.09 mmol) in p-dioxane (10 mL). The mixture was
refluxed for 5 h and allowed to cool before neutralization with
a 3 M aqueous NaOH solution (6 mL, 18.00 mmol) followed
by solid NaHCO3. p-Dioxane was then evaporated off under
reduced pressure and the resulting aqueous phase extracted
with CH2Cl2 (3 × 100 mL) and with EtOAc (2 × 50 mL). The
combined organic phases were successively washed with water
and brine, dried over Na2SO4, filtered, and concentrated under
reduced pressure. The crude product was purified by flash
column chromatography on deactivated silica gel (treated with
2.5% v/v Et3N) eluting with EtOAc/Et2O/MeOH (gradient 85:
10:5 to 75:10:15) to afford aminotriol 5a (180 mg, 0.76 mmol,
70% yield): Rf ) 0.17 (EtOAc/Et2O/MeOH, 80:10:10 under a
saturated atmosphere of NH4OH); [R]25D +1.0 (c 6.00, CHCl3);
1H NMR (250 MHz, CDCl3) δ 7.38-7.25 (m, 5H, Ph), 5.87-
87:12 under a saturated atmosphere of NH4OH); [R]25 +6.5
D
1
(c 1.23, CHCl3); H NMR (400 MHz, CDCl3) δ 7.72-7.62 (m,
3
4H, Ph), 7.50-7.35 (m, 6H, Ph), 7.30-7.20 (m, 5H, Ph), 5.88
5.77 (m, 1H, H-5), 5.36 (brd, JH6H5 ) 11.9 Hz, 1H, H-6), 5.32
3
(ddd, 3JH5H4 ) 7.5 Hz, 3JH5H6 ) 10.3 Hz, and 3JH5H6′ ) 17.4 Hz,
(brd, JH6′H5 ) 18.1 Hz, 1H, H-6′), 3.85-3.82 (m, 1H, H-1),
3
1H, H-5), 5.31 (brd, JH6H5 ) 10.3 Hz, 1H, H-6), 5.27 (brd,
3.81-3.78 (m, 1H, H-1′), 3.76 (m, 1H, H-2), 3.75-3.72 (m, 1H,
H-3), 3.73 (ABq, 2Jgem ) 13.0 Hz, 2H, NCH2Ph, ∆δa-δb ) 112.2
Hz), 3.49 (brdd, 3JH4H3 ) 4.8 Hz and 3JH4H5 ) 8.4 Hz, 1H, H-4);
13C NMR (63 MHz, CDCl3) δ 139.5 (Cquat arom), 136.4 (C-5),
3JH6′H5 ) 17.2 Hz, 1H, H-6′), 3.83-3.80 (m, 2H, 2 × H-1), 3.76
(AB of an ABX, 2Jgem ) 13.4 Hz, ∆δa-δb ) 62.9 Hz, 2H, NCH2-
3
Ph), 3.24-3.19 (m, 1H, H-4), 3.07 (dd, JH3H4 ) 3.93 Hz and
J. Org. Chem, Vol. 69, No. 25, 2004 8777

Ayad et al.
128.7, 128.5, 127.4 (CH arom), 119.8 (C-6), 75.1 (C-3), 70.8 (C-
2), 65.4 (C-1), 64.3 (C-4), 51.2 (NCH2Ph); IR (thin film) 3421
(O-H), 1636 (CdC), 1060 (C-O) cm-1; MS (DCI/NH3) m/z 238
(MH+, 100); HRMS (DCI/NH3) m/z calcd for C13H20NO3
238.1443, found 238.1446.
(thin film) 3421 (O-H), 1741 (CdO), 1638 (CdC), 1109 (C-
O) cm-1; MS (DCI/NH3) m/z 519 (MNH4+, 100); HRMS (DCI/
NH3) m/z calcd for C30H37NO4Si 502.2414, found 502.2411
Compound 7a. TBAF on silica gel (0.89 g at ca. 1.25 mole
of fluoride/g, ca. 0.71 mmol) was added to a solution of silyl
ether 6a (300 mg, 0.59 mmol) in anhydrous THF (20 mL). The
reaction mixture was vigorously stirred until TLC analysis
showed no remaining starting material (ca. 20 h) and then
filtered. Silica gel was rinsed several times with ethyl acetate
(3 × 70 mL), and the combined filtrates were concentrated in
vacuo. The resulting crude product was purified by flash
column chromatography on silica gel eluting with CH2Cl2/
MeOH (gradient 100:0 to 95:5) to afford primary alcohol 7a
(133 mg, 0.51 mmol, 85% yield): Rf ) 0.20 (CH2Cl2/MeOH 95:
5); [R]25 D +71.6 (c 0.55, CHCl3); 1H NMR (400 MHz, CDCl3) δ
Compound 5b. By applying to trans-R,â-epoxyamine 4b
(400 mg, 0.87 mmol) the procedure described for the prepara-
tion of compound 5a, aminotriol 5b was obtained (165 mg, 0.70
mmol, 80% yield): Rf ) 0.18 (EtOAc/Et2O/MeOH, 80:10:10
under a saturated atmosphere of NH4OH); [R]25D -11.9 (c 0.80,
1
CH3OH); H NMR (400 MHz, CD3OD /D2O) δ 7.40-7.20 (m,
3
3
5H, Ph), 5.80 (ddd, JH5H4 ) 8.9 Hz, JH5H6 ) 10.3 Hz, and
3JH5H6′ ) 17.2 Hz, 1H, H-5), 5.38 (dd, 2Jgem ) 1.9 Hz and 3JH6H5
4
2
) 10.2 Hz, 1H, H-6), 5.28 (ddd, JH6′H4 ) 0.6 Hz, Jgem ) 1.9
3
2
Hz, and JH6′H5 ) 17.3 Hz, 1H, H-6′), 3.76 (ABq, Jgem ) 12.9
3
3
3
Hz, 2H, NCH2Ph, ∆δa-δb ) 86.6 Hz), 3.75 (dd, JH1H2 ) 3.6
7.27-7.18 (m, 5H, Ph), 5.61 (ddd, JH5H4 ) 8.9 Hz, JH5H6 )
2
3
Hz and Jgem ) 11.4 Hz, 1H, H-1), 3.61 (dd, JH3H2 ) 3.0 Hz
9.9 Hz, and 3JH5H6′ ) 16.9 Hz, 1H, H-5), 5.27 (d, 3JH6H5 ) 10.0
3
3
3
and JH3H4 ) 5.0 Hz, 1H, H-3), 3.60 (dd, JH1′H2 ) 5.2 Hz and
2Jgem ) 11.4 Hz, 1H, H-1′), 3.57-3.51 (m, 1H, H-2), 3.38 (brdd,
3JH4H3 ) 5.0 Hz and 3JH4H5 ) 8.9 Hz, 1H, H-4); 13C NMR (100
MHz, CD3OD /D2O) δ 139.1 (Cquat arom), 135.5 (C-5), 128.5,
128.4, 127.1 (CH arom), 118.9 (C-6), 73.5 (C-3), 72.3 (C-2), 63.6
(C-4), 63.4 (C-1), 50.3 (NCH2Ph); IR (thin film) 3365 (O-H),
1661 (CdC), 1025 (C-O); MS (DCI/NH3) m/z 238 (MH+, 100);
HRMS (DCI/NH3) m/z calcd for C13H19NO3 238.1443, found
238.1443.
Hz, 1H, H-6), 5.20 (d, JH6′H5 ) 17.0 Hz, 1H, H-6′), 4.32 (ABq,
2Jgem ) 15.3 Hz, 2H, NCH2Ph, ∆δa-δb ) 245.5 Hz), 4.17 (dd,
3JH3H2 ) 2.6 Hz and 3JH3H4 ) 7.1 Hz, 1H, H-3), 4.05 (dd, 3JH4H3
3
) 7.1 Hz and JH4H5 ) 8.9 Hz, 1H, H-4), 3.69-3.56 (m, 4H, 2
× H-1, H-2 and O-H); 13C NMR (100 MHz, CDCl3) δ 158.1
(CdO), 135.6 (Cquat arom), 134.5 (C-5), 128.8, 128.3, 127.9
(CH arom), 122.2 (C-6), 79.4 (C-3), 71.1 (C-2), 63.2 (C-1), 60.5
(C-4), 46.1 (NCH2Ph); IR (thin film) 3346 (O-H), 1729
(CdO), 1440 (CdC), 1079 (C-O) cm-1 ; MS (DCI/NH3) m/z 281
(MNH4+, 100); HRMS (DCI/NH3) m/z calcd for C14H18NO4
264.1236, found 264.1235
Compound 6a. To a solution of cis-R,â-epoxyamine 4a (400
mg, 0.87 mmol) in THF/water 4:1 (20 mL) was added (NH4)2-
CO3 (670 mg, 7.00 mmol), and the heterogeneous mixture was
vigorously stirred at room temperature until TLC analysis
showed no remaining starting material (ca. 20 h). The THF
was then evaporated off under reduced pressure and the
resulting aqueous phase extracted with Et2O (3 × 50 mL). The
combined organic phases were successively washed with water
and brine, dried over Na2SO4, filtered, and concentrated under
reduced pressure. The crude product was purified by flash
column chromatography on silica gel eluting with petroleum
ether/EtOAc (80:20) to afford oxazolidinone 6a (410 mg, 0.82
Compound 7b. By applying to silyl ether 6b (452 mg, 0.90
mmol) the procedure described for the preparation of com-
pound 7a, alcohol 7b (210 mg, 0.80 mmol, 85% yield) was
obtained: Rf ) 0.22 (CH2Cl2/MeOH 95:5); [R]25 D +82.0 (c 1.22,
CHCl3); 1H NMR (400 MHz, CDCl3/D2O) δ 7.40-7.20 (m, 5H,
Ph), 5.69 (ddd, 3JH5H4 ) 8.8 Hz, 3JH5H6 ) 10.0 Hz, and 3JH5H6′
)
17.0 Hz, 1H, H-5), 5.32 (d, 3JH6H5 ) 10.0 Hz, 1H, H-6), 5.26 (d,
2
3JH6′H5 ) 17.0 Hz, 1H, H-6′), 4.36 (ABq, Jgem ) 15.2 Hz, 2H,
NCH2Ph, ∆δa-δb ) 290.1 Hz), 4.19 (pseudot, 3JH3H2 ) 3JH3H4
) 5.6 Hz, 1H, H-3), 4.11 (dd, 3JH4H3 ) 5.9 Hz and 3JH4H5 ) 8.6
Hz, 1H, H-4), 3.84-3.78 (m, 1H, H-2), 3.63-3.52 (m, 2H, 2 ×
H-1); 13C NMR (100 MHz, CDCl3/D2O) δ 158.0 (CdO), 135.7
(Cquat arom), 135.0 (C-5), 129.0, 128.4, 128.1 (CH arom), 121.6
(C-6), 80.0 (C-3), 71.9 (C-2), 62.2 (C-1), 59.7 (C-4), 46.0 (NCH2-
Ph); IR (thin film) 3429 (O-H), 1723 (CdO), 1634 (CdC), 1060
(C-O) cm-1 ; MS (DCI/NH3) m/z 281 (MNH4+, 100); HRMS
(DCI/NH3) m/z calcd for C14H18NO4 264.1236, found 264.1239.
mmol, 94% yield): Rf ) 0.25 (petroleum ether/EtOAc 80:20);
[R]
+30.2 (c 1.06, CHCl3); 1H NMR (250 MHz, CDCl3) δ
25
D
7.63-7.59 (m, 5H, Ph), 7.43-7.26 (m, 10H, Ph), 5.67 (ddd,
3
3
3JH5H4 ) 8.9 Hz, JH5H6 ) 9.9 Hz, and JH5H6′ ) 16.8 Hz, 1H,
H-5), 5.33 (d, 3JH6H5 ) 9.3 Hz, 1H, H-6), 5.22 (d, 3JH6′H5 ) 16.8
Hz, 1H, H-6′), 4.39 (ABq, 2Jgem ) 15.1 Hz, 2H, NCH2Ph, ∆δa-
δb ) 181.0 Hz), 4.25 (dd, 3JH3H2 ) 2.3 Hz and 3JH3H4 ) 7.1 Hz,
3
3
1H, H-3), 4.05 (dd, JH4H3 ) 6.9 Hz and JH4H5 ) 9.1 Hz, 1H,
H-4), 3.82-3.55 (m, 3H, 2 × H-1 and H-2), 2.39-2.21 (m, 1H,
O-H), 1.04 (s, 9H, C(CH3)3); 13C NMR (63 MHz, CDCl3) δ 157.5
(CdO), 135.6 (Cquat arom), 135.6 (C-5), 135.5 (CH arom),
134.6 (Cquat arom), 132.9, 132.8 (Cquat arom), 130.0, 128.7,
128.3, 127.9 (CH arom), 122.9 (C-6), 78.0 (C-3), 70.8 (C-2), 64.1
(C-1), 60.0 (C-4), 46.0 (NCH2Ph), 27.0 (CH3), 19.2 (C(CH3)3);
IR (thin film) 3405 (O-H), 1726 (CdO), 1635 (CdC), 1064
(C-O) cm-1; MS (DCI/NH3) m/z 519 (MNH4+, 100); HRMS
(DCI/NH3) m/z calcd for C30H36NO4Si 502.2414, found 502.2415.
Compound 8a. LiOH‚H2O (485 mg, 11.4 mmol) was added
to a solution of oxazolidinone 7a (500 mg, 1.90 mmol) in
p-dioxane/water 3:1 (20 mL). The mixture was refluxed until
TLC showed no remaining starting material (ca. 8 h) and
allowed to cool before neutralization by solid NaHCO3. p-
Dioxane was then evaporated off under reduced pressure and
the resulting aqueous phase extracted with CH2Cl2 (3 × 70
mL) and with EtOAc (2 × 50 mL). The combined organic
phases were successively washed with water and brine, dried
over Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by flash column chro-
matography on deactivated silica gel (treated with 2.5% v/v
Et3N) eluting with EtOAc/Et2O/MeOH (90:10:0 to 75:10:15) to
afford aminotriol 8a (428 mg, 1.81 mmol, 95% yield): Rf )
0.22 (EtOAc/Et2O/MeOH, 85:10:5 under a saturated atmo-
sphere of NH4OH); [R]25D -20.0 (c 2.75, CHCl3); 1H NMR (400
Compound 6b. Oxazolidinone 6b (508 mg, 1.01 mmol, 93%
yield) was prepared from trans-R,â-epoxyamine 4b (500 mg,
1.09 mmol) using the procedure described for the preparation
25
of compound 6a: Rf ) 0.23 (petroleum ether/EtOAc 88:12); [R]
1
D +38.8 (c 1.19, CHCl3); H NMR (400 MHz, CDCl3) δ 7.70-
7.60 (m, 5H, Ph), 7.50-7.20 (m, 10H, Ph), 5.74 (ddd, 3JH5H4
)
8.8 Hz, 3JH5H6 ) 10.0 Hz, and 3JH5H6′ ) 17.1 Hz, 1H, H-5), 5.34
MHz, CDCl3/D2O) δ 7.40-7.24 (m, 5H, Ph), 5.79 (ddd, JH5H4
3
3
3
3
3
(1H, d, JH6H5 ) 10.0 Hz, H-6), 5.24 (d, JH6′H5 ) 17.0 Hz, 1H,
H-6′), 4.41 (ABq, Jgem ) 15.1 Hz, 2H, NCH2Ph, ∆δa-δb )
) 8.5 Hz, JH5H6 ) 10.3 Hz and JH5H6′ ) 17.2 Hz, 1H, H-5),
4 2 3
2
5.35 (ddd, JH6H4 ) 0.5 Hz, Jgem ) 1.5 Hz and JH6H5 ) 10.3
4 2
3
3
314.8 Hz), 4.27 (pseudot, JH3H2 ) JH3H4 ) 5.8 Hz, 1H, H-3),
4.12 (dd, 3JH4H3 ) 5.7 Hz and 3JH4H5 ) 8.6 Hz, 1H, H-4), 3.85-
3.69 (m, 3H, 2 × H-1 and H-2), 2.71 (d, 3JOH-H2 ) 4.7 Hz, 1H,
O-H), 1.08 (s, 9H, C(CH3)3); 13C NMR (100 MHz, CDCl3) δ 157.5
(CdO), 135.9 (Cquat arom), 135.7 (CH arom), 135.3 (C-5),
132.9, 132.8 (Cquat arom), 130.2, 128.9, 128.5, 128.2, 128.1,
128.0 (CH arom), 121.2 (C-6), 78.3 (C-3), 71.9 (C-2), 63.6 (C-
1), 59.7 (C-4), 45.9 (NCH2Ph), 27.1 (CH3), 19.5 (C(CH3)3); IR
Hz, 1H, H-6), 5.24 (ddd, JH6′H4 ) 0.8 Hz, Jgem ) 1.5 Hz, and
3JH6′H5 ) 17.2 Hz,1H, H-6′), 3.75 (ABq, Jgem ) 12.8 Hz, 2H,
2
NCH2Ph, ∆δa-δb ) 107.7 Hz), 3.75-3.73 (m, 2H, 2 × H-1),
3
3
3.72 (dd, JH2H3 ) 1.3 Hz and JH2H1 ) 3.3 Hz, 1H, H-2), 3.62
3
3
(dd, JH3H2 ) 1.3 Hz and JH3H4 ) 4.7 Hz, 1H, H-3), 3.22 (dd,
3JH4H3 ) 4.7 Hz and 3JH4H5 ) 8.5 Hz, 1H, H-4); 13C NMR (100
MHz, CDCl3/D2O) δ 139.2 (Cquat arom), 136.3 (C-5), 128.8,
128.6, 127.6 (CH arom), 118.9 (C-6), 74.1 (C-3), 72.4 (C-2), 65.4
8778 J. Org. Chem., Vol. 69, No. 25, 2004

Stereoselective Access to the 4-Aminohex-5-ene-1,2,3-triol Pattern
(C-1), 63.7 (C-4), 50.5 (NCH2Ph); IR (thin film) 3453 (O-H),
1638 (CdC), 1066 (C-O) cm-1 ; MS (DCI/NH3) m/z 238 (MH+,
100); HRMS (DCI/NH3) m/z calcd for C13H19NO3 238.1443,
found 238.1449.
(C-6), 73.7 (C-3), 73.5 (C-2), 62.8 (C-4), 62.7 (C-1), 50.6 (NCH2-
Ph); IR (thin film) 3426 (O-H), 2920 (N-H), 1637 (CdC), 1061
(C-O); (DCI/NH3) m/z 238 (MH+, 100); HRMS (DCI/NH3) m/z
calcd for C13H20NO3 238.1443, found 238.1444.
Compound 8b. Aminotriol 8b (214 mg, 0.90 mmol, 95%
yield) was prepared from oxazolidinone 7b (250 mg, 0.95 mmol)
using the procedure described for the preparation of compound
8a: Rf ) 0.22 (EtOAc/Et2O/MeOH 80:10:10 under a saturated
atmosphere of NH4OH); [R]25D -5.8 (c 1.38, CH3OH); 1H NMR
(400 MHz, CDCl3/D2O) δ 7.35-7.15 (m, 5H, Ph), 5.75 (ddd,
Acknowledgment. We are grateful to Heinz Gor-
nitzka for recording crystallographic data. Thanks are
due to the CNRS and the “Universite´ Paul Sabatier”
for financial support and to the “Ministe`re de la Re-
cheche et des Technologies” for grants (T.A. and V.F.).
3
3
3JH5H4 ) 8.7 Hz, JH5H6 ) 10.2 Hz, and JH5H6′ ) 17.2 Hz, 1H,
H-5), 5.27 (dd, 2Jgem ) 1.4 Hz and 3JH6H5 ) 10.3 Hz, 1H, H-6),
Supporting Information Available: General experimen-
tal methods. X-ray structure of the trans-oxazolidinone ent-
6a. CIFs for compounds ent-6a and ent-6c. This material is
available free of charge via the Internet at http://pubs.acs.org.
3
2
5.18 (d, JH6′H5 ) 17.2 Hz, 1H, H-6′), 3.65 (ABq, Jgem ) 12.7
Hz, 2H, NCH2Ph, ∆δa-δb ) 108.9 Hz), 3.68-3.50 (m, 4H, 2
3
3
× H-1, H-2 and H-3), 3.15 (dd, JH4H3 ) 4.9 Hz and JH4H5
)
8.7 Hz, 1H, H-4); 13C NMR (100 MHz, CDCl3/D2O) δ 139.1
(Cquat arom), 136.4 (C-5), 128.7, 128.6, 127.5 (CH arom), 119.2
JO048766V
J. Org. Chem, Vol. 69, No. 25, 2004 8779