Control of diastereoselectivity in C=O/C=N reductive cyclizations using an intramolecularly tethered hydrazone

Article abstract of DOI:10.1055/s-2005-917083

Cyclic hydrazones are efficient ketyl radical acceptors in reductive coupling cyclizations mediated by samarium diiodide, affording cyclic amino alcohols with controlled stereochemistry at the new aminated stereocenter. This approach has been successfully

Full text of DOI:10.1055/s-2005-917083

LETTER
2607
Control of Diastereoselectivity in C=O/C=N Reductive Cyclizations Using an
Intramolecularly Tethered Hydrazone
S
tereosele
o
ctive
C
O/CN
s
Reductiv
e
e
Cyclization of
C
L
yclic
H
ydrazon
u
es is Chiara,* Ángela García
Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Fax +34915644853; E-mail: jl.chiara@iqog.csic.es
Received 5 July 2005
stituted, the cyclic product shows exclusively a trans
Abstract: Cyclic hydrazones are efficient ketyl radical acceptors in
reductive coupling cyclizations mediated by samarium diiodide,
affording cyclic amino alcohols with controlled stereochemistry at
the new aminated stereocenter. This approach has been successfully
relative stereochemistry between the amino function and
the a-substituent in all cases studied. The reasons under-
lying this stereocontrol can be understood in terms of the
applied to the stereoselective synthesis of a fully functionalized tre- lower activation energy associated with the cyclization
hazolin cyclitol starting from D-glucose, where the required cyclic
reaction of the imine conformer with a minimal allylic
hydrazone was directly obtained by partial hydrazynolysis of a 1,2-
1,3-strain, as shown in Scheme 1.
cyclic carbonate.
Key words: carbohydrates, electron transfer, hydrazones, ketones,
samarium
R1
HO R1
R1 OH
O
2e–, 2H+
XH
XH
+
X
Y
Y
Y
R2
R2
The ubiquitous presence of the vicinal amino alcohol sub-
unit among natural products and synthetic chiral ligands
has stimulated the development of a variety of methods
for its stereoselective preparation.1 Since the seminal re-
port of the first example of a pinacol-type radical cycliza-
tion of an oxime ether by Corey and Pyne,2 the ketyl
radical addition to an imino group has emerged as a valu-
able tool for the preparation of vicinal amino alcohols
with concurrent formation of a carbon–carbon bond.3,4
This reductive coupling reaction usually proceeds under
very mild conditions, with high stereoselectivity and is
compatible with a wide range of functional groups, offer-
ing many advantages over alternative ionic chemistry.
Zinc,2,5 electroreduction,6 SmI2,4,7 and n-Bu3SnH/AIBN8
have been shown to be efficient at promoting the reduc-
tive coupling of aldehydes or ketones with oxime
ethers,4,6,7a,7c–g,7i,p,8 hydrazones,4f,7b imines5,7h,j,k,7m–o or
nitrones7l,q in an inter- or intramolecular fashion. The
stereochemical features of the reaction have been well de-
lineated for the intramolecular case (Scheme 1). Cyclic
trans-amino alcohols are preferentially obtained in con-
formationally unrestricted systems under all conditions,
with the only exception of nitrones,7l,q which give exclu-
sively the cis-isomer. The preference for the trans-isomer
is probably a consequence of electrostatic repulsions be-
tween the ketyl radical anion and the reacting imino group
in a presumably highly polarized transition state. In the
case of nitrones, the reaction is proposed7l,q to involve sin-
gle electron transfer reduction of the C=N group followed
by radical addition to the carbonyl group in a chelated
transition state, thus leading to the different stereochemi-
cal outcome observed. When the C=N group is a-sub-
R2
R1 = H, alkyl
2 = OR, NR2
Y = CR2, O, NR
A
B
R
1,3A-strain
X
diastereoselectivity
N–OR
A > B
H
R1
X
N–NR2
A only
B only
X
R2
O
N(O)R
H
Scheme 1
In 1995, we described a simple entry to complex amino-
cycloalkanols via a highly efficient tandem carbonyl–
oxime ether reductive cyclization and subsequent N–O re-
ductive cleavage promoted by SmI2.7c This methodology
and related heteropinacol coupling approaches have been
successfully applied to the preparation of several natural
products,4 including the trehalase inhibitor trehazolin4c,d
and a series of analogues.7c–f,7i,p,q Depending on the pro-
tection pattern and the nature of the imino group, any of
the two diasteroisomeric trehazolin aminocyclopentitols
2a–c or 3a–c can be selectively obtained from glucose-
derived keto-oximes 1a–c (Scheme 2).
However, direct preparation of the fully functionalized
trehazolin cyclitol by a C=O/C=N reductive carbocycliza-
tion has not been described yet since it would require of a
strategy to overcome the 1,3A strain diastereocontrolling
factor mentioned above. We envisioned that intramolecu-
larly tethering the C=N group to the vicinal hydroxyl (A,
Scheme 2) could offer a possible solution to this problem
opening an entry to diastereoisomeric aminocyclitols not
directly accessible from substrates with the usual acyclic
imino groups. After initial unsuccessful attempts to imple-
ment this strategy using an oxime as imino group and an
SYNLETT 2005, No. 17, pp 2607–2610
1
7
.1
0
.2
0
0
5
Advanced online publication: 05.10.2005
DOI: 10.1055/s-2005-917083; Art ID: D18405ST
© Georg Thieme Verlag Stuttgart · New York

2608
J. L. Chiara, Á. García
LETTER
R1O
HO
R1O
R2O
BnO
OH
R1O
R2O
NHR3
OBn
NHR3
OBn
O
6 SmI2
R2O
+
X
THF, H2O
–30 °C to r.t.
BnO
2a
BnO
3a
OBn
1a (R1 = R2 = Bn)
1b (R1, R2 = PhCH)
1c (R1 = R2 = Bn)
88%7c–e
91%9
75%7k
(1:0)
(0:1)
(0:1)
X = NOBn
R3 = H
2b
2c
3b
3c
X = N(O)Bn
R
3 = Bn
OH
HO
O
OH
OH
O
OH
RO
RO
RO
RO
NH2
OR
O
NH
HO
N
A
N
HO
HO
trehazolin
RO
O
RO
OH
Scheme 2
isopropylidene acetal as tether, we arrived to the solution
shown in Scheme 3. Treatment of diol 4, readily available
from D-glucose,10 with Imid2CO gave the 1,2-cyclic car-
bonate 5.11 Reaction of 5 with hydrazine hydrochloride
and i-Pr2NEt in EtOH at reflux produced the target cyclic
hydrazone 612 via partial, regioselective hydrazinolysis of
the cyclic carbonate followed by intramolecular conden-
sation of the resultant hydrazide with the unmasked hemi-
acetal group. Optimization of this transformation required
much experimentation. The reaction conditions assayed
and the corresponding yields obtained are collected in part
in Table 1. Different combinations of hydrazine sources,
solvents and additives were tested. In most cases, highly
polar unidentified products were formed that did not
progress to 6 upon prolonged heating. Only the combina-
tion of an acidic hydrazine derivative (hydrazine hydro-
chloride) in the presence of a base afforded the expected
cyclic hydrazide product 6, EtOH being the best solvent
for this transformation.
Table 1 Different Reaction Conditions Tested for the Synthesis of 6
by Hydrazinolysis of Cyclic Carbonate 5a
Entry Hydrazine source Additive
Solvent
Yield of 6
(%)
b
1
2
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·HCl
NH2NH2·H2O
NH2NH2·AcOH
NH2NH2·AcOH
MeCN
EtOH
Toluene
DMF
–
c
–
3
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
DBU
8
4
28
5
MeCN
MeCN
MeCN
EtOH
EtOH
EtOH
DMF
30
6
17
7
Pyridine
i-Pr2NEt
NaOAc
19
8
40–68
14
9
c
10
11
12
–
Oxidation of the carbinol group in 6 to the ketone was
smoothly performed with the Dess–Martin periodinane to
give the target cyclization substrate 713 in moderate yield.
Treatment of 7 with a solution of SmI2 (3 equiv) in THF
b
–
Pyridine
EtOH
12
at –30 °C gave the expected cyclopentitol 814,15 in 65% a At 80 °C for 2–4 d.
b No reaction.
yield as a 7:1 mixture of isomers that could not be separat-
c Only unidentified, highly polar products were formed.
ed by chromatography. A complete assignment of the 1H
NMR and 13C NMR signals of both isomers was per-
formed by a combination of DQ-COSY, HSQC, and
HMBC spectra. The stereochemistry at the two new the stereochemistry at the quaternary center of both com-
stereocenters was deduced from the corresponding pounds as shown in Scheme 4. The major trans relative
NOESY spectrum of the mixture, which showed that the disposition between the newly formed stereocenters is in
products were epimers at the new quaternary carbinol ste- line with the general diastereoselectivity trends observed
reocenter. Thus, strong NOESY cross-peaks between H-1 for similar CO/CN reductive cyclizations, as explained
and H-2 are observed for both isomers indicating a cis above. Since a variety of methods are available for the
relative disposition between the amino function and the cleavage of the N–N bond to give the corresponding
vicinal acyloxi substituent, thus confirming the validity of amine,16 this approach could be considered a formal
our approach. The presence of cross-correlations between synthesis of trehazolamine, the aglycon of trehazolin (see
the hydroxyl proton and H-1 and H-4 in the major isomer, Scheme 2).
which are absent in the minor isomer, allowed us to assign
Synlett 2005, No. 17, 2607–2610 © Thieme Stuttgart · New York

LETTER
Stereoselective CO/CN Reductive Cyclization of Cyclic Hydrazones
Ortega, M. D.; Chiara, J. L. Org. Lett. 1999, 1, 1705.
2609
In conclusion, cyclic hydrazones are efficient ketyl radical
acceptors in reductive coupling cyclizations mediated by
samarium diiodide, affording cyclic amino alcohols with
controlled stereochemistry at the new aminated stereo-
center. This approach complements existing reductive
coupling methodologies allowing the preparation of dia-
stereoisomeric cyclic amino alcohols that are not directly
accessible via reductive cyclization of substrates with the
usual acyclic imino groups. We have successfully applied
this approach to the stereoselective synthesis of a fully
functionalized trehazolin cyclitol, using a substrate readi-
ly prepared from D-glucose.
(e) Miyabe, H.; Torieda, M.; Inoue, K.; Tajiri, K.; Kiguchi,
T.; Naito, T. J. Org. Chem. 1998, 63, 4397. (f) Riber, D.;
Hazell, R.; Skrydstrup, T. J. Org. Chem. 2000, 65, 5382.
(g) Nicolaou, K. C.; Snyder, S. A.; Giuseppone, N.; Huang,
X. H.; Bella, M.; Reddy, M. V.; Rao, P. B.; Koumbis, A. E.;
Giannakakou, P.; O’Brate, A. J. Am. Chem. Soc. 2004, 126,
10174.
(5) (a) Tsukinoki, T.; Nagashima, S.; Mitoma, Y.; Tashiro, M.
Green Chem. 2000, 2, 117. (b) Shimizu, M.; Iwata, A.;
Makino, H. Synlett 2002, 1538.
(6) (a) Shono, T.; Kise, N.; Fujimoto, T. Tetrahedron Lett. 1991,
32, 525. (b) Shono, T.; Kise, N.; Kunimi, N.; Nomura, R.
Chem. Lett. 1991, 2191. (c) Shono, T.; Kise, N.; Fujimoto,
T.; Yamanami, A.; Nomura, R. J. Org. Chem. 1994, 59,
1730.
BnO
BnO
BnO
BnO
O
O
Imid2CO, Et3N
CH2Cl2, r.t.
86%
(7) (a) Hanamoto, T.; Inanaga, J. Tetrahedron Lett. 1991, 32,
3555. (b) Sturino, C. F.; Fallis, A. G. J. Am. Chem. Soc.
1994, 116, 7447. (c) Chiara, J. L.; Marco-Contelles, J.;
Khiar, N.; Gallego, P.; Destabel, C.; Bernabe, M. J. Org.
Chem. 1995, 60, 6010. (d) Marco-Contelles, J.; Gallego, P.;
Rodriguez-Fernandez, M.; Khiar, N.; Destabel, C.; Bernabe,
M.; Martinez-Grau, A.; Chiara, J. L. J. Org. Chem. 1997, 62,
7397. (e) Storch de Garcia, I.; Dietrich, H.; Bobo, S.; Chiara,
J. L. J. Org. Chem. 1998, 63, 5883. (f) Chiara, J. L. In
Carbohydrate Mimics: Concepts and Methods; Chapleur,
Y., Ed.; Wiley-VCH: Weinheim, 1998, Chap. 7, 123–156.
(g) Miyabe, H.; Kanehira, S.; Kume, K.; Kandori, H.; Naito,
T. Tetrahedron 1998, 54, 5883. (h) Machrouhi, F.; Namy,
J.-L. Tetrahedron Lett. 1999, 40, 1315. (i) Bobo, S.; Storch
de Gracia, I.; Chiara, J. L. Synlett 1999, 1551.
OH
O
O
O
BnO
OH
BnO
4
5
NH2NH2·HCl,
i-Pr2NEt,
EtOH, 80 °C
40–68%
BnO
BnO
BnO
BnO
BnO
O
OH
DMP
N
N
CH2Cl2, r.t.
51%
NH
NH
O
BnO
O
O
O
7
6
(j) Taniguchi, N.; Uemura, M. J. Am. Chem. Soc. 2000, 122,
8301. (k) Ma, Y.; Zhang, Y.; Zhou, L. J. Chem. Res., Synop.
2000, 250. (l) Masson, G.; Py, S.; Vallee, Y. Angew. Chem.
Int. Ed. 2002, 41, 1772. (m) Tanaka, Y.; Taniguchi, N.;
Uemura, M. Org. Lett. 2002, 4, 835. (n) Tanaka, Y.;
Taniguchi, N.; Kimura, T.; Uemura, M. J. Org. Chem. 2002,
67, 9227. (o) Kimura, T.; Shoda, R.; Taniguchi, N.;
Kamikawa, K.; Uemura, M. Inorg. Chim. Acta 2004, 357,
1829. (p) Chiara, J. L.; de Gracia, I. S.; Garcia, A.; Bastida,
A.; Bobo, S.; Martin-Ortega, M. D. ChemBioChem 2005, 6,
186. (q) Masson, G.; Philouze, C.; Py, S. Org. Biomol.
Chem. 2005, 3, 2067.
Scheme 3
6
BnO
BnO
OH
HO
OBn
H
N
H
BnO
+
SmI2, t-BuOH
N
1
7
4
NH
O
NH
THF, –30 °C
65%
2
O
O
BnO
BnO
O
8a
8b
(7:1)
Scheme 4
(8) (a) Naito, T.; Tajiri, K.; Harimoto, T.; Ninomiya, I.; Kiguchi,
T. Tetrahedron Lett. 1994, 35, 2205. (b) Kiguchi, T.; Tajiri,
K.; Ninomiya, I.; Naito, T.; Hiramatsu, H. Tetrahedron Lett.
1995, 36, 253. (c) Tormo, J.; Hays, D. S.; Fu, G. C. J. Org.
Chem. 1998, 63, 201. (d) Egger, A.; Hunziker, J.; Rihs, G.;
Leumann, C. Helv. Chim. Acta 1998, 81, 734. (e) Naito, T.;
Nakagawa, K.; Nakamura, T.; Kasei, A.; Ninomiya, I.;
Kiguchi, T. J. Org. Chem. 1999, 64, 2003. (f) Naito, T.;
Nair, J. S.; Nishiki, A.; Yamashita, K.; Kiguchi, T.
Heterocycles 2000, 53, 2611.
(9) (a) Storch de Gracia, I. PhD Thesis; Universidad Autónoma
de Madrid: Spain, 2002. (b) See also ref. 4b (X = NOMe),
4c and 6h.
(10) (a) Lichtenthaler, F. W.; Schneider-Adams, T. J. Org. Chem.
1994, 59, 6728. (b) Fürstner, A.; Konetzki, I. J. Org. Chem.
1998, 63, 3072.
Acknowledgment
Financial support by the Ministry of Science and Technology of
Spain (project BQU2000-1501-C02-01) and Fundación Ramón
Areces (predoctoral fellowship to A. G.) are gratefully acknowled-
ged.
References
(1) Bergmeier, S. C. Tetrahedron 2000, 56, 2561.
(2) Corey, E. J.; Pyne, S. G. Tetrahedron Lett. 1983, 24, 2821.
(3) For recent reviews, see: (a) Fallis, A. G.; Brinza, I. M.
Tetrahedron 1997, 53, 17543. (b) Naito, T. Heterocycles
1999, 50, 505. (c) Friestad, G. K. Tetrahedron 2001, 57,
5461.
(11) Preparation of Compound 5.
To a solution of 4 (1.0 g, 2.22 mmol) in anhyd CH2Cl2 (30
mL) under argon was added carbonyldiimidazole (0.767 g,
4.73 mmol) and Et3N (0.9 ml, 2.8 mmol) and the mixture
was stirred at r.t. for 5 h. The reaction was concentrated
under reduced pressure, diluted with CH2Cl2 (10 mL) and
washed with aq HCl 2% (3 × 10 mL). The organic phase was
dried over Na2SO4, filtered and concentrated at reduced
(4) For selected applications in natural products synthesis, see:
(a) Miyabe, H.; Torieda, M.; Kiguchi, T.; Naito, T. Synlett
1997, 580. (b) Miyabe, H.; Torieda, M.; Inoue, K.; Tajiri,
K.; Kiguchi, T.; Naito, T. J. Org. Chem. 1998, 63, 4397.
(c) Boiron, A.; Zillig, P.; Faber, D.; Giese, B. J. Org. Chem.
1998, 63, 5877. (d) Storch de Garcia, I.; Bobo, S.; Martin-
Synlett 2005, No. 17, 2607–2610 © Thieme Stuttgart · New York

2610
J. L. Chiara, Á. García
LETTER
pressure. The crude was purified by flash chromatography
(silica gel, hexane–EtOAc 5:1) to give 5 (799 mg, 86%) as a
white solid. Mp 60–61 °C; [a]D20 +4.9 (c 4.8, CHCl3). IR
(KBr): 3435, 2862, 1813, 1453, 1367,1355, 1156,1050, 746,
696 cm–1. 1H NMR (300 MHz, CDCl3): d = 7.39–7.28 (m, 13
H), 7.26–7.17 (m, 2 H), 6.06 (d, 1 H, J = 6.3 Hz, H-1), 4.70–
4.42 (m, 7 H, H-2, 3 OCH2Ph), 3.93 (t, 1 H, J = 4.2 Hz),
3.84–3.81 (m, 2 H), 3.69–3.65 (m, 2 H). 13C NMR (75 MHz,
CDCl3): d = 152.4, 137.5, 137.3, 136.7, 128.5, 128.4, 128.2,
128.0, 127.9, 127.8, 127.8, 97.3, 77.2, 75.8, 73.4, 73.2, 73.1,
72.6, 71.6, 68.3. MS (ES+): m/z = 477.1 [M + H2O]+, 499.1
[M + Na]+. Anal. Calcd for C28H28O7: C, 70.57; H, 5.92.
Found: C, 69.97; H, 6.12.
1 H, J = 2.1, 5.4 Hz, H-2), 4.50 (s, 2 H OCH2Ph), 4.57 (d, 1
H, J = 11.4 Hz, H-6), 4.48 (s, 1 H), 4.39 (d, 1 H, J = 11.4 Hz,
H-6¢), 4.31 (d, 1 H, J = 3.9 Hz), 4.19 (m, 3 H). 13C NMR (75
MHz, CDCl3): d = 206.8, 148.2, 140.0, 136.9, 136.3, 135.9,
129.0, 129.0, 129.0, 128.9, 128.8, 128.4, 128.4, 80.5, 76.9,
74.7, 74.3, 74.3, 73.5, 73.4.
(14) Reductive Cyclization of Compound 7.
A solution of 7 (90 mg, 0.184 mmol) in THF (5 mL) was
added dropwise under argon to a 0.1 M THF solution of SmI2
(0.1 M, 5.5 mL, 0.552 mmol) and t-BuOH (88 mL, 0.92
mmol) at –30 °C. After stirring at –30 °C for 2 h, the flask
was opened to air to oxidize excess SmI2 and the crude
reaction mixture was filtered through Florisil®, rinsing with
CH2Cl2–MeOH 10:1. The filtrate was evaporated at reduced
pressure and the residue was purified by flash
chromatography (silica gel, hexane–EtOAc 1:2) to give 8 as
a 7:1 mixture of isomers (58 mg, 65%). IR (KBr): 3272,
2868, 1709, 1453, 1093, 1061, 924, 737, 697 cm–1. MS
(ES+): m/z = 491.1 [M + H]+, 513.3 [M + Na]+.
(12) Preparation of Compound 6.
To a solution of 5 (200 mg, 0.42 mmol) in EtOH (2 mL) was
added i-Pr2NEt (161 mL, 0.92 mmol) and hydrazine
hydrochloride (32 mg, 0.46 mmol) and the mixture was
heated at 80 °C for 4 d. The reaction was concentrated at
reduced pressure and the crude was purified by flash
chromatography (silica gel, hexane–EtOAc 3:1) to give 6
(140 mg, 68%) as a yellowish oil. [a]D20 –0.9 (c 1.7, CHCl3).
IR (KBr): 3306, 292, 1748, 1722, 1454, 1360, 1260, 1212,
1072, 1026, 751, 698 cm–1. 1H NMR (300 MHz, CDCl3): d
= 7.91 (br s, 1 H, NH), 7.49–7.27 (m, 13 H), 7.26–7.17 (m,
2 H), 7.02 (d, 1 H, J = 2.4 Hz, H-1), 4.91 (dd, 1 H, J = 1.8,
5.4 Hz, H-2), 4.75 (d, 1 H, J = 11.7 Hz, OCH2Ph), 4.64 (d, 1
H, J = 11.4 Hz, OCH2Ph), 4.54–4.48 (m, 4 H, 2 OCH2Ph),
4.11 (dd, 1 H, J = 4.2, 5.1 Hz), 4.01 (q, 1 H, H-5), 3.80 (dd,
1 H, J = 3.9, 7.5 Hz), 3.71–3.62 (m, 2 H), 2.56 (d, 1 H,
J = 6.6 Hz, OH). 13C NMR (75 MHz, CDCl3): d = 149.0,
140.8, 137.4, 137.2, 137.1, 128.5, 128.4, 128.3, 128.1,
128.0, 127.9, 76.9, 74.8, 74.3, 73.8, 73.5, 70.4, 70.1. MS
(ES+): m/z = 491.1 [M + H]+, 508.3 [M + Na]+.
Compound 8a: 1H NMR (400 MHz, CDCl3): d = 7.37–7.12
(m, 15 H), 6.92 (s, 1 H, NH), 5.04 (dd, 1 H, J = 3.5, 5.4 Hz,
H-2), 4.73 (d, 1 H, J = 12.0 Hz, OCH2Ph), 4.54 (d, 1 H,
J = 12.0 Hz, OCH2Ph), 4.55 (d, 2 H, J = 12.0 Hz, OCH2Ph),
4.47 (dd, 1 H, J = 1.5, 12.6 Hz, NH), 4.42 (d, 1 H, J = 11.7
Hz, OCH2Ph), 4.35 (d, 1 H, J = 11.7 Hz, OCH2Ph), 4.19 (d,
1 H, J = 3 Hz, H-3), 3.75 (s, 1 H, H-4), 3.72 (d, 1 H, J = 9.6
Hz, H-6), 3.62 (d, 1 H, J = 9.6 Hz, H-6¢), 3.51 (ddd, 1 H,
J = 1.5, 5.4, 12.6 Hz, H-1), 3.31 (s, OH). 13C NMR (75 MHz,
CDCl3): d = 153.5 (C=O), 137.3, 137.0, 136.5, 128.4, 128.4,
128.3, 128.1, 128.0 127.9, 127.9, 127.8, 127.7, 88.2 (C-3),
87.9 (C-2), 86.6 (C-4), 80.7 (C-5), 73.7 (OCH2Ph), 72.0
(OCH2Ph), 71.6 (OCH2Ph), 68.3 (C-6), 62.4 (C-1)
Compound 8b (partial spectrum): 1H NMR (400 MHz,
CDCl3): d = 6.81 (s, 1 H, NH), 4.58 (dd, 1 H, J = 3.4, 8.3 Hz,
H-2), 4.36 (m, 1 H, H-3), 3.93 (d, 1 H, J = 8.1 Hz), 3.75 (m,
1 H, H-1), 3.40 (d, 1 H, J = 9.2 Hz, H-6), 3.26 (d, 1 H, J = 9.2
Hz, H-6¢), 3.10 (s, OH). 13C NMR (75 MHz, CDCl3): d =
156.0 (C=O), 137.4, 87.2 (C-3), 83.2 (C-2), 80.1 (C-4), 73.4
(OCH2Ph), 73.3 (OCH2Ph), 72.6 (OCH2Ph), 69.4 (C-6), 55.3
(C-1).
(13) Preparation of Compound 7.
To a solution of 6 (50 mg, 0.101 mmol) in CH2Cl2 (1 mL)
under argon was added a suspension of Dess–Martin
periodinane (86.5 mg, 0.203 mmol) in CH2Cl2 (0.5 mL).
After stirring at r.t. for 1 h, the mixture was diluted with
CH2Cl2 (5 mL) and washed with aq sat. NaHCO3 (2 × 3 mL).
The organic phase was washed with aq 10% Na2S2O3 (2 × 3
mL), dried over Na2SO4, filtered and concentrated at
reduced pressure. The crude was purified by flash
chromatography (silica gel, hexane–EtOAc 2:1) to give 7
(25 mg, 51%) as a colorless oil. [a]D20 –6.6 (c 0.8, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.89 (s, 1 H, NH), 7.36–
7.20 (m, 15 H), 7.00–7.00 (d, 1 H, J = 2.1 Hz, H-1), 4.86 (dd,
(15) For clarity, the numbering of the carbons in the starting
glucose derivative 4 has been kept for all the compounds.
(16) Fernandez, R.; Ferrete, A.; Llera, J. M.; Magriz, A.; Martin-
Zamora, E.; Diez, E.; Lassaletta, J. M. Chem.–Eur. J. 2004,
10, 737; and references cited therein.
Synlett 2005, No. 17, 2607–2610 © Thieme Stuttgart · New York