Intramolecular carbene and nitrene insertions at C-2 of diacetone-D-glucose

Article abstract of DOI:10.1016/S0040-4039(02)00698-6

Decomposition of a diazoester and an azidoformate attached at O-3 of 1,2;5,6-di-O-isopropylidene-D-glucofuranose ('diacetone-D-glucose') leads to intramolecular insertion into the C-2-H bond as the major process in both cases.

Full text of DOI:10.1016/S0040-4039(02)00698-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3961–3962
Intramolecular carbene and nitrene insertions at C-2 of
diacetone- -glucose
D
Daniel F. Berndt and Peter Norris*
Department of Chemistry Youngstown State University, Youngstown, OH 44555, USA
Received 20 February 2002; accepted 20 March 2002
Abstract—Decomposition of a diazoester and an azidoformate attached at O-3 of 1,2;5,6-di-O-isopropylidene-
(‘diacetone-
Science Ltd. All rights reserved.
D-glucofuranose
D
-glucose’) leads to intramolecular insertion into the C-2ꢀH bond as the major process in both cases. © 2002 Elsevier
The functionalization of carbohydrates by the direct
insertion of carbenes (or carbenoids) to produce
branched sugars, and nitrene species to produce
aminosugars, has received little attention considering
the potential for such chemistry to provide rapid access
to products that might otherwise be difficult to pre-
pare.1 Despite recent progress in metal-catalyzed diazo
decomposition chemistry,2 the use of carbenic methods
for branched-chain sugar synthesis has been limited to
the cyclopropanation of various glycals.3 Similarly,
insertion of nitrenes into glycals produces aziridines,
which are subsequently opened by alcohols to provide
an interesting glycosylation strategy.4 Nitrene insertion
into CꢀH bonds on sugars has produced enantiomeri-
cally pure 1,3-oxazin-2-ones that have then been
employed as auxiliaries in asymmetric synthesis;5 how-
ever, intramolecular nitrene insertions as applied to
aminosugar synthesis have been rare.6
Thus, conversion of 1 to phenacyl ester 2 (Scheme 1)
was effected in 90% yield using conventional DCC–
DMAP coupling conditions and conversion of 2 to the
diazoester 3 was accomplished using p-acetamidoben-
Our interest lies in developing both carbenic and
nitrenic insertions on simple carbohydrates as a poten-
tial method for producing branched-chain sugars and
aminosugars, respectively, and herein we disclose
results using diazoester and azidoformate derivatives of
readily available diacetone- -glucose (1). The fairly
D
rigid furanose structure of 1 was expected to limit the
possible reaction pathways open to a carbene or nitrene
species attached at O-3, with insertion into either the
C-1ꢀH or C-2ꢀH bonds being the most likely events.
The former pathway would provide a novel route to
ketose derivatives, whereas the latter process would
afford C-2 branched-chain analogues of
D-glucose.
* Corresponding author. Tel.: +1 330 742 1553; fax: +1 330 742 1579;
e-mail: pnorris@cc.ysu.edu
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00698-6

3962
D. F. Berndt, P. Norris / Tetrahedron Letters 43 (2002) 3961–3962
presently expanding the scope of these reactions to other
carbohydrates.
zenesulfonyl azide (p-ABSA) and DBU to furnish 3 as
a yellow syrup in 93% yield after flash column chro-
matography. Decomposition of the diazoester using
Rh2(OAc)4 as catalyst was then studied with the cleanest
reaction mixtures resulting from slow addition of a
CH2Cl2 solution of 3 to a suspension of the catalyst in
CH2Cl2. After resolution of the reaction mixture by
MPLC, the major product proved to be compound 4,7
the result of insertion of an intermediate carbenoid into
the C-2ꢀH bond. Branched-chain sugar 4, isolated in 47%
yield as a colorless syrup, was identified primarily from
its mass and NMR spectra; however, the configuration
of the new stereogenic carbon a- to the ester is as yet
unknown.
Acknowledgements
We thank the YSU PACER initiative as well as the
donors of the Petroleum Research Fund of the American
Chemical Society for financial support.
References
1. Bluchel, C.; Linden, A.; Vasella, A. Helv. Chim. Acta
2001, 84, 3495–3502 and references cited therein.
2. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds:
From Cyclopropanes to Ylides; Wiley: New York, 1998.
3. (a) Henry, K. J., Jr.; Fraser-Reid, B. Tetrahedron Lett.
1995, 36, 8901; (b) Lakhrissi, M.; Chaouch, A.; Chapleur,
Y. Bull. Soc. Chim. Fr. 1996, 133, 531.
4. (a) Kozlowska-Gramsz, E.; Descotes, G. Tetrahedron
Lett. 1981, 22, 563; (b) Egli, M.; Dreiding, S. A. Helv.
Chim. Acta 1986, 69, 1442.
5. Banks, M. R.; Cadogan, J. I. G.; Gosney, I.; Gaur, S.;
Hodgson, P. K. G. Tetrahedron: Asymmetry 1994, 5,
2447.
In addition to the appearance of M+ (+H2O) in the mass
1
spectrum, the H NMR spectrum if 4 revealed a 1H
singlet at 5.83 ppm that was assigned to H-1 of the
furanose ring. In the precursors 1–3 the signal for H-1
appears as a doublet between 5.80 and 5.92 ppm, with
JH1ꢀH2 typically 3.7 Hz, indicating a coupling with H-2.8
Additionally the 13C NMR spectrum of 4 shows signals
for three acetal carbons, two of which have no protons
attached with the carbon at 110.9 ppm (C-1) having one
H attached as seen from an APT experiment. The
observation that the major insertion process occurred to
form a five-membered ring rather than to form a six-
membered ring mirrors the studies of Adams and co-
6. (a) Wright, J. J. K.; Albarella, J. A.; Lee, P. J. Org.
Chem. 1982, 47, 523; (b) Williams, D. R.; Rojas, C. M.;
Bogen, S. L. J. Org. Chem. 1999, 64, 736.
workers who showed
a
similar preference in
non-carbohydrate systems9 and used C–H insertion
chemistry as the key step in the synthesis of several
natural products.10 It is of interest here to note that
insertion into the C-1ꢀH bond at the anomeric carbon,
which is activated by two oxygen atoms, is not the major
process and that five-membered ring formation is
favored.
7. Characterization data for compound 4 (syrup): [h]D20
−80.5° (c 3.3, CH2Cl2); 1H NMR (400 MHz, CDCl3) l
1.29 (s, 3H), 1.41 (s, 3H), 1.46 (s, 3H), 1.49 (s, 3H), 3.99
(s, 1H), 4.07 (dd, 1H, J=4.4, 8.8 Hz), 4.17 (dd, 1H,
J=6.0, 8.7 Hz), 4.28 (dd, 1H, J=2.7, 8.4 Hz), 4.42 (ddd,
1H, J=4.6, 6.0, 10.1 Hz), 4.91 (d, 1H, J=2.7 Hz), 5.83
(s, 1H); 7.21–7.62 (m, 5H); 13C NMR (100 MHz, CDCl3)
l 25.1, 26.7, 27.0, 27.7, 52.9, 67.1, 72.4, 81.1, 85.1, 109.7,
110.9, 113.3, 128.1, 128.6 (double intensity), 128.9 (dou-
ble intensity), 129.9, 132.2, 173.2; MS (EI pos) calcd for
C20H24O7 (M+H++H2O) 393.15, found 393.16.
To study the insertion preferences of a nitrene attached
at O-3 of diacetone- -glucose, 1 was treated with triphos-
D
gene to afford the chloroformate 5 in 79% yield (Scheme
1), which was then reacted with NaN3 to provide the
azidoformate 6, isolated as a colorless syrup in 78% yield.
Decomposition of 6 in refluxing 1,1,2,2-tetrachloro-
ethane gave a major product in 44% yield that
was identified as 7,11 the result of nitrene insertion into
the C-2ꢀH bond of the furanose ring. In 2addition to the
8. Due to their essentially orthogonal relationship, the sig-
nal for H-3 in compound 4 at 4.91 ppm would likely not
be affected by the loss of H-2 if carbene insertion had
indeed occurred at that position.
9. (a) Spero, D. M.; Adams, J. Tetrahedron Lett. 1992, 33,
1143; (b) Wang, P.; Adams, J. J. Am. Chem. Soc. 1994,
116, 3296.
1
mass spectrum of 7 (M++H+=302.16), the H spectrum
of this material showed a 1H singlet at 5.63 ppm
corresponding to H-1 of the furanose ring, as well as a
broad N–H signal at 7.73 ppm. The 13C spectrum of 7
showed four signals between 101–112 ppm (C-1, C-2 and
2×CMe2) of which three had no hydrogens attached and
one (C-1) with one H attached as seen from an APT
experiment.
10. (a) Adams, J.; Poupart, M.-A.; Grenier, L. Tetrahedron
Lett. 1989, 30, 1753; (b) Adams, J.; Frenette, R. Tetra-
hedron Lett. 1987, 28, 4773.
11. Characterization data for compound 7 (syrup): [h]D20
−16.0° (c 2.2, CH2Cl2); 1H NMR (400 MHz, CDCl3) l
1.36 (s, 3H), 1.45 (s, 6H), 1.52 (s, 3H), 4.02 (dd, 1H,
J=4.2, 8.8 Hz), 4.13 (dd, 1H, J=5.5, 8.6 Hz), 4.31 (m,
1H), 4.36 (d, 1H, J=3.3 Hz), 4.75 (d, 1H, J=3.5 Hz),
5.63 (s, 1H), 7.73 (s, 1H, N-H); 13C NMR (100 MHz) l
25.1, 26.9, 27.0, 27.1, 66.7, 72.0, 81.1, 84.7, 101.6, 106.9,
109.7, 112.3, 156.9; MS (APCI pos) calcd for C13H19NO7
(M+H+) 302.12, found 302.16.
In conclusion, decomposition of a diazoester and an
azido-formate linked at O-3 of diacetone-D-glucose both
result in the insertion of the thus generated intermediate
into the C-2ꢀH bond of the furanose ring. We are