Stereocontrolled synthesis of enantiopure polyhydroxylated azetidines via 1,2-oxazines

Article abstract of DOI:10.1055/S-0029-1218531

A set of new enantiopure polyhydroxylated azetidine derivatives has been prepared. The key starting materials, 3,6-dihydro-2H-1,2-oxazines, were subjected to a hydroboration-oxidation sequence to introduce the required 5-hydroxy group. Subsequent cleavage of the N-O bond with samarium diiodide, selective protection of the primary hydroxy! group, and ring closure after activation of the secondary hydroxyl group provided the protected azetidine derivatives. The efficacy of each individual step of this sequence depends on the configuration of the starting material. Three representative azetidine derivatives were converted into the deprotected polyhydroxylated azetidines which are interesting candidates as glycosidase inhibitors. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1218531

42
LETTER
Stereocontrolled Synthesis of Enantiopure Polyhydroxylated Azetidines via
1,2-Oxazines
S
ynthese
s
of Enan
j
tiopure
e
Polyhydr
o
k
xylated Azet
o
idines via 1,2
s
-Oxazine
l
s
av Dekaris, Hans-Ulrich Reissig*
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany
Fax +49(30)83855367; E-mail: hans.reissig@chemie.fu-berlin.de
Received 24 September 2009
Hydroboration of 3,6-dihydro-2H-1,2-oxazines with sub-
Abstract: A set of new enantiopure polyhydroxylated azetidine de-
rivatives has been prepared. The key starting materials, 3,6-dihy-
dro-2H-1,2-oxazines, were subjected to a hydroboration–oxidation
sequence to introduce the required 5-hydroxy group. Subsequent
sequent oxidation and hydrolysis constitutes an approved
method for the introduction of a hydroxyl group at 5-po-
sition of the heterocycle (Equation 1).6b It allows the con-
cleavage of the N–O bond with samarium diiodide, selective protec- trol of the relative configuration of the newly formed
tion of the primary hydroxyl group, and ring closure after activation
of the secondary hydroxyl group provided the protected azetidine
derivatives. The efficacy of each individual step of this sequence
borane reagent. Certainly, the overall stereoselectivity
depends on the configuration of the starting material. Three repre-
sentative azetidine derivatives were converted into the deprotected
adjacent stereogenic centres at C-4 and C-5 since their
configuration results from cis addition of the employed
will be dependent on the inducing power of the existing
chiral units.
polyhydroxylated azetidines which are interesting candidates as
glycosidase inhibitors.
OR2 OR1
*
OR2 OR1
*
Key words: 1,2-oxazine, hydroboration, samarium diiodide, azeti-
dine, intramolecular substitution
HO
*
*
*
1) BH3⋅THF
n
n
H
H
*
2) NaOH, H2O2
NBn
O
NBn
O
1
2
Enantiopure 3,6-dihydro-2H-1,2-oxazines are versatile
precursors for the construction of a variety of important
heterocyclic compounds. They are smoothly accessible
with excellent stereocontrol in a [3+3] cyclization by the
addition of lithiated alkoxyallenes to carbohydrate-
derived nitrones and subsequent spontaneous ring clo-
sure.1 We already demonstrated their utilisation for the
syntheses of oxepane and pyran derivatives2 as well as oli-
gosaccharide mimetics derived thereof.3 Alternatively,
various enantiopure furan derivatives could be
synthesised4 and recently we reported the preparation of
N-acetyl neuraminic acid and analogues.5 In addition, di-
hydropyrroles or polyhydroxylated pyrrolidine deriva-
tives were prepared by hydroboration of the enol ether
double bond of 3,6-dihydro-2H-1,2-oxazines followed by
samarium diiodide induced N–O bond cleavage and sub-
sequent ring closure.6,7 This led to compounds being
known or having the potential as glycosidase inhibitors.8
We envisioned that a modified sequence should allow the
synthesis of enantiopure azetidine derivatives. Although a
range of old or new methods exists for the efficient con-
struction of this interesting class of four-membered het-
erocycles,9 their synthesis in an enantio- and
stereoselective fashion with a high degree of substitution
is still a challenging task. Herein we report the stereocon-
trolled synthesis of different highly substituted azetidine
stereoisomers and their deprotection to the respective
polyhydroxylated compounds starting from enantiopure
3,6-dihydro-2H-1,2-oxazines.
Equation 1 Hydroboration of 3,6-dihydro-2H-1,2-oxazines
In case of syn-1,2-oxazines the hydroboration employing
the borane–THF complex followed by oxidative workup
is highly chemo-, regio-, and stereoselective.6b As expect-
ed 5-hydroxy-1,2-oxazines 2a and ent-2a were obtained
in good yields (Table 1). Earlier published results on the
hydroboration of an anti-configured 1,2-oxazine contain-
ing a 4-methoxy group already revealed problems to de-
liver the corresponding 5-hydroxy compound. It was
isolated only in 30% yield and major byproducts were
identified as acyclic compounds, probably resulting from
a borane mediated N–O bond cleavage.6b This approach
was now extended to two additional 1,2-oxazines anti-1a
and anti-1b. Unfortunately, hydroboration of anti-1a re-
sulted in only 13% isolated yield of 2b. Numerous at-
tempts were conducted to overcome the difficulties,
including variations of hydroboration agents, hydrobora-
tions in the presence of additives, or with different N-pro-
tective groups. None of these experiments proved to be
successful.
Interestingly, arabinose-derived 1,2-oxazine anti-1b with
an extended side chain allowed the isolation of the desired
hydroboration product 2c in 50% yield (Table 1). Since
N–O bond cleavage seems to be the major side reaction
for anti-1a we assume that the different pattern of func-
tional groups in anti-1b results in a preferred conforma-
tion, which shields the nucleophilic nitrogen lone pair
suppressing reductive N–O bond cleavage.10
SYNLETT 2010, No. 1, pp 0042–0046
x
x.
x
x.
2
0
1
0
Advanced online publication: 02.12.2009
DOI: 10.1055/s-0029-1218531; Art ID: G33009ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Enantiopure Polyhydroxylated Azetidines via 1,2-Oxazines
43
Table 1 Hydroboration of 3,6-Dihydro-2H-1,2-oxazines 1a
1,2-Oxazine
Conditions
ref. 6b
Hydroboration product
Yield (%)
78
OBn
OBn
O
O
O
O
O
O
O
O
O
O
HO
NBn
NBn
O
O
syn-1a
2a
OBn
O
OBn
HO
a
a
69
13
NBn
NBn
O
O
ent-syn-1a
ent-2a
OBn
OBn
O
HO
NBn
NBn
O
O
anti-1a
2b
OBn
OBn
O
O
O
O
O
O
b
50
HO
O
NBn
NBn O
O
O
anti-1b
2c
a Reagents and conditions: a) BH3·THF (1 M in THF, 4 equiv), THF, –30 °C to r.t., 4 h, then 2 N NaOH, 30% H2O2, –10 °C to r.t., overnight;
b) BH3·THF (1 M in THF, 4 equiv), THF, –30 °C to r.t., 1 d, then 2 N NaOH, 30% H2O2, –10 °C to r.t., overnight.
For the preparation of an additional 5-hydroxy-1,2- the corresponding azetidine derivatives. The sequence
oxazine stereoisomer the relative configuration at C-5 starts with a samarium diiodide induced reductive ring
should be inverted. Certainly, the Mitsunobu reaction opening of the 1,2-oxazines.6b,7 Cyclisation should occur
would be an obvious choice for this transformation.11 Re- after protection of the primary alcohol as a TBS ether fol-
markably, neither under classical or modified Mitsunobu lowed by activation of the secondary alcohol via sulfony-
conditions nor with other SN-type procedures we could lation. After an intramolecular SN2 reaction protected
achieve this goal. Therefore we decided to employ an 1,2,3,4-tetrasubstituted azetidines should become accessi-
oxidation–reduction sequence in order to invert the ste- ble (Scheme 1).
reogenic centre at C-5. Oxidation of 2a with three equiv-
alents of Dess–Martin periodinane12 gave a clean reaction
OR2
OR1
*
n
OR2 OR1
*
within six hours affording the desired ketone intermediate
in 80% yield after recrystallisation (Equation 2). Stereo-
selective reduction was performed with 1.5 equivalents of
L-Selectride at –78 °C yielding alcohol 2d in 75%.
HO
HO
*
HO
*
*
*
SmI2
*
H
n
H
*
NHBn
NBn
O
2
3
TBSCl
OBn
O
OBn
O
O
O
HO
HO
a, b
OR1
*
n
OR1
*
n
NBn
NBn
60%
(over 2 steps)
OR2
R2O
O
O
H
*
HO
*
MsCl or Tf2
O
*
*
*
H
2a
2d
NBn
*
base
NHBn
TBSO
Equation 2 Inversion of configuration of 2a by an oxidation–reduc-
tion sequence leading to 2d. Reagents and conditions: a) Dess–Martin
periodinane (3 equiv), CH2Cl2, r.t., 6 h; b) L-Selectride (1 M in THF,
1.5 equiv), THF, –78 °C, 3 h.
OTBS
5
4
Scheme 1 Synthesis of polyhydroxylated azetidines 5 starting from
5-hydroxy-1,2-oxazines 2
With five different 5-hydroxy-1,2-oxazine derivatives in
hand we were in the position to study the preparation of
Synlett 2010, No. 1, 42–46 © Thieme Stuttgart · New York

44
V. Dekaris, H.-U. Reissig
LETTER
With regard to N–O bond cleavage stereoisomers 2a, ent- Again yields for stereoisomers 3a–c exceeded that for 3d.
2a, 2b, and 2d could be converted within four hours at Selective protection of 3b could neither be achieved at
room temperature into the acyclic amino alcohols in mod- room temperature nor with slight excess of TBSCl. A sig-
erate to good yields (Table 2).13 Only compound 2c gave nificant amount of the bis-O-silylated byproduct was al-
a rather low yield of the desired product 3d.14 Regioselec- ways formed. Using one equivalent of TBSCl and stirring
tive protection of the primary hydroxyl group was con- at –10 °C to 0 °C for three days essentially suppressed
ducted in the presence of a slight excess of TBSCl, byproduct formation and allowed isolation of amino alco-
triethylamine, and catalytic amounts of DMAP at room hol 4b in 51% yield.
temperature. To assure completion of the protection, the
reaction times were extended for 4c even to eleven days.
Key step of the depicted reaction sequence (Scheme 1)
was the cyclisation to tetrasubstituted azetidine deriva-
Table 2 Synthesis of Different Protected Polyhydroxylated Azetidine Stereoisomers 5a
1,2-Oxazine
N–O bond cleavage
Protection with TBS
Azetidine formation
O
O
OBn
HO
BnO
O
O
O
O
O
O
O
O
ref. 6b, 78%
3a
b, 7 d, 78%
4a
NBn
NBn
O
OTBS
2a
d, 84%
5a
O
O
OBn
BnO
a, 73%
ent-3a
b, 3 d, 77%
ent-4a
HO
NBn
NBn
O
OTBS
ent-2a
d, 81%
ent-5a
O
O
OBn
BnO
a, 85%
3b
c, 3 d, 51%
4b
HO
NBn
NBn
O
OTBS
2d
e, 64%
5b
O
O
OBn
BnO
a, 68%
b, 11 d, 71%
HO
3c
4c
NBn
NBn
O
OTBS
2b
f, 71%
5c
O
O
O
MeO
OMe
O
O
a, 32%
3d
b, 6 d, 45%
4d
O
HO
O
NBn
O
NBn
O
OTBS
2c
d, 91%
5d
a Reagents and conditions: a) SmI2 (3.5 equiv), THF, r.t., 4 h; b) TBSCl (1.1 equiv), Et3N (1.1 equiv), DMAP (0.05 equiv), CH2Cl2, r.t.;
c) TBSCl (1.0 equiv), Et3N (1.0 equiv), DMAP (0.05 equiv), CH2Cl2, –10 °C to 0 °C; d) MsCl (1.4 equiv), pyridine, r.t., 1 d, then 50 °C, 3 d;
e) MsCl (1.4 equiv), pyridine, r.t., 3 d; f) Tf2O (1.4 equiv), pyridine (2.5 equiv), CH2Cl2, r.t., 5 h.
Synlett 2010, No. 1, 42–46 © Thieme Stuttgart · New York

LETTER
Synthesis of Enantiopure Polyhydroxylated Azetidines via 1,2-Oxazines
45
tives 5a–d (Table 2). Best conditions found for this pro-
cess were activation of the secondary alcohol by
mesylation at room temperature for one day utilising py-
ridine as base as well as solvent and subsequent stirring at
55 °C for three days.15 Alternatively, we could achieve
complete conversion within a few hours at room tempera-
ture in the presence of triflic acid anhydride and pyridine
in dichloromethane.
Table 3 Two-Step Deprotection of Selected Azetidine Stereoiso-
mers 5 Leading to 7a
Azetidine
Conditions
Deprotected azetidine Yield (%)
HO
OH
O
O
O
O
HO
BnO
a, 1 d
b, DOWEX 50
85
NH
NBn
OTBS
With the exception of 4b both methods were successfully
applied to all compounds. Table 2 summarises yields and
conditions for the method found to be superior for the in-
dividual substrate. In general, yields were good to excel-
lent with perfect stereoselectivity as expected for an
intramolecular SN2-type substitution reaction. Only one
stereoisomer was detected in the crude cyclisation prod-
uct. Heating and rather long reaction times in case of acti-
vation with mesyl chloride reflect the leaving-group
ability and kinetic difficulties in forming a four-mem-
bered ring. Cyclisation to 5b had to be conducted at room
temperature only. Heating to 55 °C resulted in consider-
able side reactions and lower yields.
OH
7a
5a
HO
OH
O
HO
BnO
a, 1 d
b, DOWEX 50
48
NH
NBn
OH
OTBS
ent-7a
ent-5a
HO
OH
O
HO
a, 2 d
BnO
Finally, deprotection of these highly functionalised het-
erocycles gives entry to the polyhydroxylated azetidines
which are interesting candidates as glycosidase inhibi-
tors.8a A mild two-step deprotection sequence was chosen
including reductive debenzylation and subsequent cleav-
age of acid-labile protective groups with DOWEX ion-
exchange resin (Scheme 2).
b, DOWEX 100,
5 d
71
NH
NBn
OH
OTBS
7b
5b
a Reagents and conditions: a) H2, Pd/C (0.2 equiv), MeOH, r.t.; b)
DOWEX, EtOH, 55 °C, 3 d.
sion of the 1,2-oxazine side chain. The configuration at C-
5 of one derivative was efficiently inverted by an oxida-
tion–reduction sequence. The key step, cyclisation to the
respective azetidines, proved to be a reliable reaction un-
der the described conditions. Finally, three azetidine de-
rivatives were deprotected to the respective amino
polyols. The biological activity of the deprotected aze-
tidines is currently under investigation.
O
*
HO
O
*
O
OH
O
HO
HO
BnO
*
*
*
*
H2, Pd/C
DOWEX
*
*
*
NH
NH
NBn
*
*
*
OTBS
OH
OTBS
5
6
7
Scheme 2 Stepwise deprotection of polyhydroxylated azetidines 5
Acknowledgment
Deprotection under these conditions worked well for aze-
tidine 5a furnishing polyhydroxylated compound 7a with
85% yield over both steps (Table 3).16 Purification was
achieved by crystallisation in methanol. For ent-7a the
overall yield dropped below 50%, mainly because of dif-
ficulties during the reaction with DOWEX. The crude
mixture contained side products; therefore it was not pos-
sible to crystallise as efficiently as in the case of 7a. At
last, azetidine 5b was completely deprotected to 7b which
contained approximately 5–10% of a byproduct, possibly
an acyclic compound resulting from the prolonged reac-
tion time. Purification via chromatography or crystallisa-
tion was not possible so far.
The authors thank the Deutsche Forschungsgemeinschaft, the
Fonds der Chemischen Industrie, and Bayer Schering Pharma AG
for financial support. We are grateful to Karol Nowosinski, Paul
Hommes, Michael Wilsdorf, and Luise Schefzig for experimental
help. We thankfully acknowledge the help of Dr. R. Zimmer during
preparation of this manuscript.
References and Notes
(1) (a) Schade, W.; Reissig, H.-U. Synlett 1999, 632.
(b) Helms, M.; Schade, W.; Pulz, R.; Watanabe, T.; Al-
Harrasi, A.; Fišera, L.; Hlobilová, I.; Zahn, G.; Reissig,
H.-U. Eur. J. Org. Chem. 2005, 1003.
(2) (a) Al-Harrasi, A.; Reissig, H.-U. Angew. Chem. Int. Ed.
2005, 44, 6227; Angew. Chem. 2005, 117, 6383. (b) Al-
Harrasi, A.; Pfrengle, F.; Prisyazhnyuk, V.; Yekta, S.; Koóš,
P.; Reissig, H.-U. Chem. Eur. J. 2009, 15, 11632.
(3) Pfrengle, F.; Lentz, D.; Reissig, H.-U. Angew. Chem. Int. Ed.
2009, 48, 3165; Angew. Chem. 2009, 121, 3211.
In conclusion, starting from 3,6-dihydro-2H-1,2-oxazines
we have accomplished a stereoselective synthesis of five
tetrasubstituted azetidines thus demonstrating the general-
ity of the chosen route. Difficulties in hydroboration of
anti-1,2-oxazines could be partially overcome by exten-
Synlett 2010, No. 1, 42–46 © Thieme Stuttgart · New York

46
V. Dekaris, H.-U. Reissig
LETTER
(4) Bressel, B.; Egart, B.; Al-Harrasi, A.; Pulz, R.; Reissig,
H.-U.; Brüdgam, I. Eur. J. Org. Chem. 2008, 467.
(5) Bressel, B.; Reissig, H.-U. Org. Lett. 2009, 11, 527.
(6) (a) Pulz, R.; Watanabe, T.; Schade, W.; Reissig, H.-U.
Synlett 2000, 983. (b) Pulz, R.; Al-Harrasi, A.; Reissig,
H.-U. Org. Lett. 2002, 4, 2353.
(7) (a) Keck, G. E.; McHardy, S. F.; Wager, T. T. Tetrahedron
Lett. 1995, 36, 7419. (b) Chiara, J. L.; Destabel, C.; Gallego,
P.; Marco-Contelles, J. J. Org. Chem. 1996, 61, 359.
(c) Revuelta, J.; Cicchi, S.; Brandi, A. Tetrahedron Lett.
2004, 45, 8375. (d) Young, I. S.; Williams, J. L.; Kerr, M. A.
Org. Lett. 2005, 7, 953.
(8) (a) Krämer, B.; Franz, T.; Picasso, S.; Pruschek, P.; Jäger, V.
Synlett 1997, 295. For selected review articles on glyco-
sidase inhibition in general, see: (b) Iminosugars as
Glycosidase Inhibitors; Stütz, A. E., Ed.; Wiley-VCH:
Weinheim, 1999. (c) Zechel, D. L.; Withers, S. G. Acc.
Chem. Res. 2000, 33, 11. (d) Lillelund, V. H.; Jensen, H. H.;
Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515.
(e) Winchester, B. G. Tetrahedron: Asymmetry 2009, 20,
645. (f) Davis, B. G. Tetrahedron: Asymmetry 2009, 20,
652.
d = 1.34 (s, 6 H, Me), 2.97 (dd, J = 3.2, 8.1 Hz, 1 H, 4-H),
3.66–3.74 (m, 5 H, 1-H, 3-H, 5¢-HA, NCH2), 3.88 (mc, 1 H,
2-H), 3.93 (d, J = 13.1 Hz, 1 H, NCH2), 3.98–4.03 (m, 1 H,
5¢-HB), 4.35 (mc, 1 H, 4¢-H), AB-system (dA = 4.49,
dB = 4.55, J = 11.5 Hz, 2 H, OCH2Ph), 7.22–7.36 (m, 10 H,
Ph) ppm. OH and NH could not be assigned. 13C NMR (126
MHz, CDCl3): d = 25.6, 26.7 (2 q, Me), 51.9 (t, NCH2), 60.7
(d, C-4), 63.5 (t, C-1), 67.7 (t, C-5¢), 72.6 (d, C-2), 72.8 (d,
C-3), 73.1 (t, OCH2Ph), 75.3 (d, C-4¢), 108.5 (s, C-2¢), 127.5,
128.0, 128.1, 128.2, 137.5, 138.7 (4 d, 2 s, Ph) ppm. IR
(KBr): 3420, 3310 (OH, NH), 3085–3030 (=CH), 2985–
2855 (CH) cm–1. HRMS (ESI-TOF-MS): m/z calcd for
C23H31NO5 [M + H]+: 402.2275; found: 402.2280.
(14) This result may be improved since the reaction was only
performed once and samarium(II) was consumed mostly
before completion of the reaction probably by traces of air
indicated by the greenish colour of the solution.
(15) Typical Procedure for Ring Closure of 4a to 5a
To a solution of 4a (697 mg, 1.35 mmol) in pyridine (50 mL)
under argon at r.t. MsCl (0.15 mL, 1.94 mmol) was added.
The mixture was stirred 1 d at r.t. and 3 d at 50 °C. After
quenching with 5% CuSO4 solution (50 mL) the mixture was
extracted three times with Et2O, the combined organic layers
were washed twice with H2O, and dried with MgSO4. After
filtration and removal of the solvents, purification via silica
gel column chromatography (hexane–EtOAc) afforded 5a
(565 mg, 84%) as a colourless oil.
(9) For review articles, see: (a) Cromwell, N. H.; Phillips, B.
Chem. Rev. 1979, 79, 331. (b) Brandi, A.; Cicchi, S.;
Cordero, F. M. Chem. Rev. 2008, 108, 3988.
(10) So far we do not know at which stage of the hydroboration
process the N–O bond cleavage occurs.
(11) (a) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn. 1967,
40, 2380. (b) Mitsunobu, O. Synthesis 1981, 1. (c) Yuen,
T.; But, S.; Toy, P. H. Chem. Asian J. 2007, 2, 1340.
(d) For a recent review, see: Kumara Swamy, K. C.;
Bhuvan Kumar, N. N.; Balaraman, E.; Pavan Kumar,
K. V. P. Chem. Rev. 2009, 109, 2551.
(12) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
(13) Typical Procedure for Ring Cleavage of 2d to 3b
To a suspension of samarium (1.98 g, 13.2 mmol) in THF
(20 mL) under argon at r.t. 1,2-diiodoethane (2.65 g, 9.40
mmol) was added. The mixture was stirred for 2 h at r.t. and
turned to a dark blue colour. Afterwards 1,2-oxazine 2d
(1.50 g, 3.75 mmol) was dissolved in THF (20 mL) and
added slowly to the SmI2 solution. The mixture was stirred
for 4 h at r.t., then quenched with sat. NaHCO3 solution,
extracted three times with Et2O, and the combined organic
layers were dried with MgSO4. After filtration and removal
of the solvent recrystallization with a mixture of hexane and
EtOAc afforded 3b (1.27 g, 84%) as a colourless solid (mp
94–96 °C).
Analytical Data of (2S,3S,4R,4¢S)-1-Benzyl-3-benzyloxy-
2-(tert-butyldimethylsiloxymethyl)-4-(2¢,2¢-dimethyl-
1¢,3¢-dioxolan-4¢-yl)azetidine (5a)
[a]D20 +12.3 (c 0.9, CHCl3). 1H NMR (500 MHz, CDCl3):
d = 0.00 (s, 6 H, SiMe2), 0.83 (s, 9 H, Sit-Bu), 1.32, 1.35 (2
s, 6 H, Me), 2.95–3.35 (m, 2 H, 4-CH2), 3.49 (mc, 1 H, 4-H),
3.85 (mc, 1 H, 2-H), 4.03 (dd, J = 4.6, 7.3 Hz, 1 H, 3-H),
3.75, 4.18 (2 d, J = 12.7 Hz, 2 H, NCH2), 4.34, 4.60 (2 d,
J = 11.9 Hz, 2 H, OCH2Ph), 4.23 (mc, 2 H, 5¢-H), 4.81 (mc,
1 H, 4¢-H), 7.20–7.36 (m, 10 H, Ph) ppm. 13C NMR (126
MHz, CDCl3): d = –5.54, –5.52 (2 q, SiMe2), 18.2, 25.9 (s,
q, Sit-Bu), 25.5, 26.7 (2 q, Me), 55.7 (t, NCH2), 64.2 (t, 4-
CH2), 67.9 (t, C-5¢), 69.1 (d, C-2), 71.1 (t, OCH2Ph), 72.3 (d,
C-4), 73.9 (d, C-4¢), 74.2 (d, C-3), 108.6 (s, C-2¢), 127.3,
127.5, 128.0, 128.3, 128.5, 128.7 (6 d, Ph), 138.2, 140.1 (2
s, Ph) ppm. IR (film): 3085-3030 (=CH), 2985–2855 (CH)
cm–1. MS (EI, 80 eV, 90 °C): m/z (%) = 497 (2) [M+], 482 (4)
[M – CH3]+, 406 (26) [M – C7H7]+, 396 (54) [M – C5H9O2]+,
91 (100) [C7H7]+. Anal. Calcd for C29H43NO4Si (497.7): C,
69.98; H, 8.71; N, 2.81. Found: C, 69.72; H, 8.61; N, 2.62.
(16) The constitution and configuration of compound 7a was
unequivocally proven by an X-ray analysis: Brüdgam, I.;
Institut für Chemie und Biochemie, Freie Universität Berlin,
unpublished results.
Analytical Data of (2S,3R,4S,4¢S)-4-Benzylamino-3-
benzyloxy-4-(2¢,2¢-dimethyl-1¢,3¢-dioxolan-4¢-yl)butane-
1,2-diol (3b)
[a]D20 –25.6 (c 0.40, CHCl3). 1H NMR (500 MHz, CDCl3):
Synlett 2010, No. 1, 42–46 © Thieme Stuttgart · New York

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