Bromination of alkenyl glycosides with copper(II) bromide and lithium bromide: Synthesis, mechanism, and DFT calculations

Full text of DOI:10.1021/jo9718509

1758
J . Org. Chem. 1999, 64, 1758-1761
Sch em e 1
Br om in a tion of Alk en yl Glycosid es w ith
Cop p er (II) Br om id e a n d Lith iu m Br om id e:
Syn th esis, Mech a n ism , a n d DF T
Ca lcu la tion s
Robert Rodebaugh,† J ohn S. Debenham,†
Bert Fraser-Reid,*,‡ and J ames P. Snyder*,§
Paul M. Gross Chemical Laboratory, Duke University,
Durham, North Carolina 27708, Natural Products and
Glycotechnology Research Institute, 4118 Swarthmore Road,
Durham, North Carolina 27707, and Department of
Chemistry, Emory University, Atlanta, Georgia 30322
Received February 26, 1998
Since their discovery in our laboratories in 1988,
n-pentenyl glycosides (NPGs),1 e.g., 1, have been explored
as mechanistic probes for anomeric activation,2a as donors
or acceptors in oligosaccharide synthesis,2b and as models
for preparing novel protecting groups.2c A valuable at-
tribute of NPGs is their ability to serve both as an
activating moiety on glycosyl donors for oligosaccharide
couplings and as a protecting group for the anomeric
center during other synthetic manipulations including
glycosidation reactions. However, in order for an NPG
to serve as a glycosyl acceptor during halonium-promoted
couplings, the sugar must either be “disarmed”, by
electron-withdrawing groups such as esters3 (i.e., 1, X )
OCOR), or the terminal double bond must be dibromi-
nated (e.g., 3).4 Indeed, dibromination of the n-pentenyl
double bond offers the capability of using even “armed”
substrates as glycosyl acceptors. Dibromides can be
considered latent NPGs, since the n-pentenyl group can
be regenerated by reductive debromination.5 In this
paper, we report the reagent combination CuBr2/LiBr as
a new method for the dibromination of NPGs. We also
propose a mechanism to account for the transformation
based on density functional theory (DFT) calculations.
The standard conditions (Br2/Et4NBr in CH2Cl2, at 0
°C) previously developed4 and successfully used with
pentenyl mannosides (80-90% yields)6 give erratic re-
sults when applied to protected 2-amino-2-deoxy sugars.
Normally, with the excess bromide ion from Et4NBr, the
bimolecular reaction leading to the dibromide 3 is able
to overwhelm the intramolecular process, 2 f 4 f 5 f 6
(Scheme 1). However, in the case of phthaloyl-protected
glucosamines, the C-1 hydrolysis product usually pre-
dominated. For our recent synthesis of the nodulation
factor, NodRf-III (C18:1, MeFuc),7 which required large
Ta ble 1. Br om in a tion w ith Va r iou s Rea gen ts
amounts of dibromide 7b, an alternative method of
dibromination was needed.
On the assumption that these results were associated
with the phthalimide residue, we investigated different
dibromination protocols using the perbenzylated NPG 9
as a model (Table 1). Treatment of 9 with Br2 in CH2Cl2
at 0 °C produced the desired dibromide 10 in only 10%
yield. Addition of excess bromide ion by way of Et4NBr
increased the yield of 10 to only 20%. Again, the major
product of both reactions was the known hemiacetal8
produced from oxidative hydrolysis of the n-pentenyl
† Duke University.
‡ Natural Products and Glycotechnology Research Institute.
§ Emory University.
(1) (a) Fraser-Reid, B.; Udodong, U. E.; Wu, Z.; Ottosson, H.; Merritt,
J . R.; Rao, C. S.; Roberts, C.; Madsen, R. Synlett 1992, 927-942. (b)
Madsen, R.; Fraser-Reid, B. In Modern Methods in Carbohydrate
Synthesis; Khan, S. H., O’Neill, R. A., Eds.; Harwood Academic
Publishers: Amsterdam, 1996; Chapter 4.
(5) Merritt, J . R.; Debenham, J . S.; Fraser-Reid, B. J . Carbohydr.
Chem. 1996, 15, 65-72.
(6) Merritt, J . R.; Naisang, E.; Fraser-Reid, B. J . Org. Chem. 1994,
59, 443-4449.
(7) (a) Debenham, J . S.; Rodebaugh, R.; Fraser-Reid, B. J . Org.
Chem. 1996, 61, 6478-6479. (b) Debenham, J . S.; Rodebaugh, R.;
Fraser-Reid, B. J . Org. Chem. 1997, 62, 4591-4600.
(8) Yamazaki, F.; Kitajima, T.; Nukada, T.; Ito, Y.; Ogawa, T.
Carbohydr. Res. 1990, 201, 15-30.
(2) See, for example: (a) Andrews, C. W.; Rodebaugh, R.; Fraser-
Reid, B. J . Org. Chem. 1996, 61, 5280-5289. (b) Arasappan, A.; Fraser-
Reid, B. J . Org. Chem. 1996, 61, 2401-2406. (c) Madsen, R.; Fraser-
Reid, B. J . Chem. Soc., Chem. Commun. 1994, 749.
(3) Mootoo, D. R.; Knoradsson, P.; Udodong, U.; Fraser-Reid, B. J .
Am. Chem. Soc. 1988, 110, 5583-5584.
(4) Fraser-Reid, B.; Wu, Z.; Udodong, U. E.; Ottosson, H. J . Org.
Chem. 1990, 55, 6068-6070.
10.1021/jo9718509 CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/18/1999

Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1759
Ta ble 2. Cu Br 2/LiBr Br om in a tion of Su ga r sa
Sch em e 2
Of special interest to us was the N-pentenoyl glu-
cosaminide derivative 16a . Previous work in our labora-
tories11 had shown that the N-pentenoyl group underwent
halonium activation and subsequent cleavage more readily
than the n-pentenyl moiety. For 16a , dibromination was
therefore expected to be more difficult than for the
pentenyl glycosides in Table 2. However, 16a was suc-
cessfully dibrominated for the first time, yielding dibro-
mide 16b in 85% yield.12
To account mechanistically for the surprisingly smooth
and quantitative bromination of alkenyl sugars, the
success of CuBr2/LiBr needs to be measured against the
failure of Br2, which suggests that the process is not an
ordinary electrophilic addition. A mechanism that ac-
commodates the difference and accounts for other factors
is outlined in Scheme 2. In the first step, a paramagnetic
π-complex, 17, is formed from cupric(II) bromide and the
olefin. X-ray crystal structures of many such complexes
are known.13 Bromide ion displaces the metal on carbon
as a molecule of solvent coordinates at the metal to give
the square planar CuII-anion 18. The latter transfers an
electron to CuIIBr2 to yield the neutral copper species 19,
CuIBr, and 1 equiv of bromide ion. Reductive elimination
through the neutral transition state 20 provides the
trans-dibromide and a second equivalent of CuIBr coor-
dinated to solvent.
group. Yields of 10 increased dramatically to 85% by use
of a mixture of N-bromosuccinimide and Et4NBr; how-
ever, even more impressive was the near-quantitative
result received upon treatment of 9 with CuBr2 and LiBr
at room temperature.
It is important to note that LiBr is necessary for this
reaction to proceed in a near-quantitative fashion. Thus,
although CuBr2 alone has been used previously as a
reagent for the dibromination of simple alkenes,9 exclu-
sion of LiBr resulted in substantial hemiacetal production
(45% yield). To our knowledge, the CuBr2/LiBr reagent
combination has not been previously used for the specific
purpose of dibromination of olefins.10
An issue that influences the energetics of Scheme 2
concerns our use of 5 and 10 equiv of CuBr2 and LiBr in
acetonitrile-THF, respectively, relative to a given con-
centration of alkenyl glycoside. Although it might be
assumed that a large excess of CuBr2 and Br- is present
in solution, the situation is more complex. Copper
bromide is known to couple with halide ions both in
With CuBr2 and LiBr as our preferred dibromination
method, we examined the halogenation of additional
alkenyl glycosides (Table 2). In general, the dibromides
were produced virtually quantitatively. Phthalimide
derivatives 7a and 11a as well as tetrachlorophthalimide
(TCP)7 substrates 12a , 13a , and 14a gave the desired
products (7b, 11b-14b) in high yields. Similarly, dibro-
mination of n-pentenyl mannoside 15a gave 15b.6 It is
noteworthy that protecting groups such as O-benzyl, O-p-
methoxybenzyl, O-acetyl, N-phthaloyl, and TCP are not
affected by these mild reaction conditions.
water14,15 and acetonitrile15,16 to produce CuBr4 and
2-
2-
perhaps CuBr3-. The existence of CuBr4 in the solid
(11) Madsen, R.; Roberts, C.; Fraser-Reid, B. J . Org. Chem. 1995,
60, 7920-7926.
(12) A significant improvement in the yield of the desired dibromide
was obtained by using only THF as the solvent in this case.
(13) Cambridge Structural Database; http://www.ccdc.cam.ac.uk/
prods/csd.html.
(14) Matsuo, S. J . Chem. Soc. J pn. (Nippon Kagaku Zasshi) 1961,
82, 1330-1334, 1334-1337.
(15) Barnes, J . C.; Hume, D. N. Inorg. Chem. 1963, 2, 444-448.
(16) Furlani, C.; Morpurgo, G. Theor. Chim. Acta (Berlin) 1963, 1,
102-115.
(9) (a) Castro, C. E.; Gaughan, E. J .; Owsley, D. C. J . Org. Chem.
1965, 30, 587-592. (b) Baird, W. C., J r.; Surridge, J . H.; Buza, M. J .
Org. Chem. 1971, 36, 3324-3330.
(10) For aromatization of cyclohexenones using CuBr2/LiBr, see: (a)
Kosower, E. M.; Wu, G.-S. J . Org. Chem. 1963, 28, 633-638. (b)
Bondon, D.; Pietrasanta, Y.; Pucci, B. Tetrahedron Lett. 1977, 821-
824. (c) Bennetau, B.; Rajarison, F.; Dunogues, J . Tetrahedron 1994,
50, 1179-1188.

1760 J . Org. Chem., Vol. 64, No. 5, 1999
Notes
state is amply underscored by numerous single-crystal
X-ray structures.17 The salts are usually prepared by
treating cupric bromide with excess HBr in various
solvents in the presence of a suitable cation. Structures
of a variety of higher Cu/Br aggregates have been derived
in a similar manner.18 In acetonitrile, electronic spectra
suggest that solvent can compete with bromide, leading
to the presence of dihalide species such as CuBr2-
(MeCN)2.16 Lithium bromide likewise exhibits its own
propensity for clustering. In THF near room temperature,
the salt is a mixture of both monomeric contact ion pairs
and higher aggregates.19 Finally, it is well-known that
the cupric ion is capable of forming complexes with
glycosides.20 An additional complication in assessing the
composition of the glycoside bromination medium is the
autoxidation-reduction of cupric bromide at room tem-
perature. In acetonitrile about 50% is reduced in 24 h.15
Clearly, under the present reaction conditions, copper
and halide reagents as well as glycosides can interact and
participate in a web of equilibria that depletes the
effective concentration of CuBr2/LiBr in the brominating
mixture. With the exception of the relatively slow reduc-
tion of CuBr2, however, we presume the equilibria to be
reversible and to furnish the required entities in a facile
and controlled fashion during the course of the reaction.
Each of the species in Scheme 2 has been subjected to
geometry optimization with the Becke3LYP/LANL2DZ
DFT protocol21 and, except for 20, found to be a local
minimum. Formation of complex 17 is calculated to be
10.7 kcal/mol exothermic as compared to 6.0 kcal/mol for
the corresponding Br2/CH2dCH2 complex. Optimized
CuBr42- is calculated to be 22.0 kcal/mol more stable than
CuBr2 and a pair of bromide ions (not shown in Scheme
2).22 If formation of CuBr42- is taken as a rough measure
of the diversion of CuBr2/LiBr from the first step in
Scheme 2, then the latter is endothermic by ca. 11 kcal/
mol. The implication is that the production of 17 may
well correspond to the rate-determining step along the
bromination pathway.23 Despite the various equilibria in
the reaction mixture, we believe the large available pool
of CuBr2 and LiBr used in Table 2 not only promotes the
rapid second-order generation of 17 but also ensures its
equally rapid conversion to 18.24,25 Any other soluble
bromide source, such as Et4Br, should work as well as
LiBr in the reaction. Using a methyl model (i.e., BrCH2-
CH2dCH3), the formation of 19 by electron transfer from
18 to CuBr2 has been estimated to release 39.4 kcal/mol.
Finally, the calculated reductive elimination of 19 through
transition state 2026 is a close analogue of the process
modeled for the rate determining step of cuprate conju-
gate addition.27 The resulting activation barrier of 7.5
kcal/mol is likewise very similar to that derived for the
latter reaction.
In conclusion, the CuBr2/LiBr procedure provides
quantitative access to the dibromides from alkenyl sugars
that are resistant to straightforward reaction with mo-
lecular bromine. The combined mechanistic and DFT
analysis accounts for the side-product-free result in the
presence of excess CuBr2/LiBr by sketching an overall
exothermic reaction pathway. In addition, the mechanism
predicts that the dibromide is created with trans stere-
ochemistry. The latter results from inversion in 17 and
retention in 19/20. Previous exposures of alkenes to
CuBr2 or CuCl2 alone result in stereospecific trans
addition.28
Exp er im en ta l Section
Gen er a l Meth od s. General experimental procedures and
information concerning the calculations can be found in refs 5
and 21, respectively.
Gen er a l P r oced u r es for Dibr om in a tion . N-Br om osu c-
cin im id e/Et4NBr . To N-bromosuccinimide (177.0 mg, 1.00
mmol, 5 equiv) and Et4NBr (210.0 mg, 1.00 mmol, 5 equiv) in
CH2Cl2 (1.4 mL) was added freshly activated, powdered 4 Å
molecular sieves. The mixture was cooled to 0 °C. A solution of
the pentenyl glycoside 9 (115.0 mg, 0.178 mmol) (azeotropically
dried with toluene and vacuum-dried) in CH2Cl2 (1 mL) was
added dropwise. The mixture was stirred for 18 h at room
temperature, was diluted with CH2Cl2 (30 mL), was filtered
through Celite, and was washed with 10% aqueous Na2S2O3 (15
mL), H2O (15 mL), and brine (15 mL). The organic phase was
concentrated. The residue subjected to flash chromatography.
Elution with 4:1 petroleum ether/ethyl acetate gave 10 (121.0
mg, 85%).
Cu Br 2/LiBr . To CuBr2 (5 equiv) and LiBr (10 equiv) in CH3-
CN/THF (3:1) was cannulated the pentenyl glycoside in CH3-
CN/THF (2:1) to make a 35 mM solution in terms of the alkene.
The mixture was stirred for 16 h, was concentrated to 20% of
its original volume, was diluted with EtOAc, and was washed
with H2O and brine. The aqueous portions were reextracted with
EtOAc. The residue from the combined and evaporated organic
phases was purified via flash chromatography by elution with
petroleum ether/EtOAc (4:1) to afford the dibromide.
(17) (a) Roman, P.; Sertucha, J .; Luque, A.; Lezama, L.; Rojo, T.
Polyhedron 1996, 15, 1253-1262. (b) Chen, L.; Thompson, L. K.;
Bridson, J . N. Inorg. Chim. Acta 1996, 244, 87-93. (c) Willett, R.; Place,
H.; Middleton, M. J . Am. Chem. Soc. 1988, 110, 8639-8650. (d)
Massabni, A. C.; Nascimento, O. R.; Halvorson, K.; Willett, R. D. Inorg.
Chem. 1992, 31, 1779-1784. (e) Mori, T.; Sakai, F.; Saito, G.; Inokuchi,
K. Acta Crystallogr., Sect. C 1990, 46, 1603-1609. (f) Place, Willett,
R. D. Acta Crystallogr., Sect. C 1988, 44, 34-38; 1987, 43, 1050-1053.
(g) Fernandez, V.; Moran, M.; Gutierrez-Rios, M. T.; Foces-Foces, C.;
Cano, F. H. Inorg. Chim. Acta 1987, 128, 239-243. (h) Trouelan, P.;
Lefebvre, J .; Derollez, P. Acta Crystallogr., Sect. C 1984, 40, 386-389.
(18) (a) Savel’eva, Z. A.; Romanenko, G. V.; Podberezskaya, N. V.;
Larionov, S. V. Polyhedron 1996, 15, 3581-3584. (b) Subramanian,
L.; Hoffmann, R. Inorg. Chem. 1992, 31, 1021-1029. (c) Willett, R. D.
Coord. Chem. Rev. 1991, 109, 181-205.
(19) (a) Reich, H. J .; Borst, J . P.; Dykstra, R. R.; Green, D. P. J .
Am. Chem. Soc. 1993, 115, 8728-8741. (b) Menard, D.; Chabanel, M.
J . Phys. Chem. 1975, 79, 1081-1085. (c) Turner, W. E. S.; Bissett, C.
C. J . Chem. Soc. 1915, 105, 1777-1786.
(20) Piarulli, U.; Floriani, C. Prog. Inorg. Chem. 1997, 45, 400-403.
(21) For basis set details, see: Huang, H.; Alvarez, K.; Cui, Q.;
Barnhart, T. M.; Snyder, J . P.; Penner-Hahn, J . E. J . Am. Chem. Soc.
4,5-Dibr om op en ta n yl 3-O-a cetyl-6-O-ben zyl-2-d eoxy-2-
p h t h a lim id o-â-D-glu cop yr a n osid e (7b ): 99% yield; Rf 0.36
(45:55 EtOAc/petroleum ether); [R]20 13.0° (c ) 1.36, CHCl3);
D
1H NMR (300 MHz, CDCl3) δ 7.71-7.87 (m, 4H), 7.31-7.37 (m,
5H), 5.64 (dd, J ) 8.6, 10.4 Hz, 1H), 5.37 (d, J ) 8.4 Hz, 1H),
(24) Although CH3CN solvent was utilized to coordinate the metal
in the reaction pathway calculations, THF and other ethers can clearly
serve the same purpose (ref 25); cf. 16 in Table 2.
(25) (a) Kingsbury, C. L.; Smith, R. A. J . J . Org. Chem. 1997, 62,
4629-4634. (b) Kingsbury, C. L.; Smith, R. A. J . J . Org. Chem. 1997,
76377-7643.
(26) Verification that 20 is indeed a stationary point, located at the
calculated saddle point between 19 and products, follows from the
presence of a single imaginary frequency in the force constant matrix.
The frequency in question corresponds to the formation of a bond
between Br and CH2 as shown in Scheme 2.
(27) (a) Snyder, J . P. J . Am. Chem. Soc. 1995, 117, 11025-11026.
(b) Frantz, D. E.; Singleton, D. A.; Snyder, J . P. J . Am. Chem. Soc.
1997, 119, 3383-3384.
(28) Arganbright, R. P.; Yates, W. F. J . Org. Chem. 1962, 27, 1205-
1208.
1996, 118, 8808-8816.
(22) The predicted geometry of CuBr4
2-
is that of a flattened
tetrahedron with Br-Cu-Br bond angles of 100.7, 101.3, 127.7, and
128.8°. The result is in accord with angular deformation of the carefully
2-
studied CuCl4 anion, which exhibits many examples of Cl-Cu-Cl
angles from 125 to 160°.18c
(23) We appreciate the insights of a reviewer who drew our attention
2-
to the facile formation of CuBr4 and the possibility that step one in
Scheme 2 may be rate determining.

Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1761
4.63 (dd, J ) 12.1, 18.1 Hz, 2H), 4.23 (dd, J ) 8.5, 10.8 Hz, 1H),
3.72-4.00 (m, 6H), 3.59-3.65 (m, 1H), 3.45-3.58 (m, 1H), 3.29-
3.38 (m, 1H), 3.01 (d, J ) 2.9 Hz, 1H), 1.93 (s, 3H), 1.92-1.22
(m, 1H), 1.56-1.66 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 171.16,
168.88 (bs), 137.67, 134.18, 131.31, 128.37, 127.71, 127.60,
123.51, 97.91, 97.83, 74.38, 73.60, 73.43, 71.05, 69.94, 68.56,
68.51, 54.54, 52.36, 52.27, 36.10, 36.06, 32.71, 32.63, 26.94, 26.82,
20.60; MS (FAB) m/e 670.09 (MH+).
4,5-Dibr om open tan yl 3,4,6-tr i-O-ben zyl-2-deoxy-2-ph th al-
im id o-â-D-glu cop yr a n osid e (10): 99% yield; Rf 0.68 (75:25
petroleum ether/ethyl acetate); 1H NMR (300 MHz) δ 7.61-7.82
(m, 4H), 7.18-7.41 (m, 10H), 6.80-7.14 (m, 5 H), 5.14 (d, J )
8.4 Hz, 1H), 4.83 (t, J ) 12.5, 1H), 4.55-4.72 (m, 3H), 4.45 (d,
J ) 12.1 Hz, 1H), 4.32 (m, 1H), 4.15 (m, 1H), 3.71-3.97 (m, 4H),
3.52-3.66 (m, 3H), 3.23-3.47 (m, 2H), 1.87-2.03 (m, 1H), 1.41-
1.76 (m, 3H); 13C NMR (75 MHz) δ 168.12 (bs), 138.16, 138.00,
133.79, 128.47, 128.42, 128.08, 127.98, 127.90, 127.82, 127.67,
127.35, 123.35, 98.36, 98.28, 79.74, 79.34, 75.11, 75.01, 74.83,
73.56, 68.77, 68.41, 68.36, 55.91, 52.59, 52.48, 36.27, 32.93, 32.85,
27.08, 26.97; MS (FAB) m/e 814.14 (M + Li)+.
4,5 Dibr om op en ta n yl 3,4,6-tr i-O-a cetyl-2-d eoxy-2-tetr a -
ch lor op h th a lim id o-â-D-glu cop yr a n osid e (12b): 98% yield;
Rf 0.59 (70:30 petroleum ether/ethyl acetate); 1H NMR (400
MHz) δ 5.66-5.70 (m, 1H), 5.34 (d, J ) 8.3 Hz, 1H), 5.19 (t, J )
10.2 Hz, 1H), 4.82-4.90 (m, 2H), 4.14-4.36 (m, 3H), 3.79-3.85
(m, 2H), 3.42-3.55 (m, 2H), 2.11 (s, 3H), 2.04 (s, 3H), 1.90 (s,
3H), 1.90-2.01 (m, 1H), 1.50-1.72 (m, 3H); 13C NMR (100 MHz)
δ 170.46, 170.39, 169.10, 163.30, 162.46, 140.37, 137.42, 129.78,
126.75, 71.66, 70.76, 69.18, 68.50, 61.89, 55.45, 36.17, 36.15,
32.78, 32.72, 26.89, 26.76, 20.61, 20.45, 20.36; MS (FAB) m/e
800.92 (M-).
(125 MHz) δ 171.36, 140.50, 137.47, 129.91, 128.47, 127.99,
127.73, 126.99, 97.65, 97.62, 74.01, 73.75, 73.53, 71.11, 69.90,
68.62, 68.59, 55.32, 52.21, 36.21, 36.11, 32.76, 32,72, 26.98, 26.86,
20.70; MS (FAB) m/e 806.7 (M-).
Anal. Calcd for C28H27NO8Br2Cl4: C, 41.67; H, 3.37. Found:
C, 41.75; H, 3.41.
4,5 Dibr om op en ta n yl 3,6-d i-O-ben zyl-2-d eoxy-2-tetr a -
ch lor op h th a lim id o-â-D-glu cop yr a n osid e (14b): 99% yield;
Rf 0.51 (70:30 petroleum ether/ethyl acetate); 1H NMR (400
MHz) δ 7.30-7.40 (m, 5H), 6.75-7.07 (m, 5H), 5.09 (d, J ) 8.2
Hz, 1H), 4.85 (d, J ) 13 Hz, 1H), 4.61 (dd, J ) 12.0 Hz, 27.3 Hz,
2H), 4.42 (d, J ) 13 Hz, 1H), 3.96-4.14 (m, 3H), 3.76-3.86 (m,
6H), 3.36-3.45 (m, 2H), 3.04 (bs, 1H), 1.97-2.04 (m, 1H), 1.51-
1.72 (m, 3H); 13C NMR (100 MHz) δ 163.38, 162.46, 139.68,
138.63, 137.42, 128.56, 128.04, 128.00, 127.95, 127.84, 126,92,
97.89, 79.37, 75.00, 74.72, 73.83, 70.61, 68.37, 68.30, 55.95, 55.94,
52.29, 36.25, 36.17, 32.78, 32.72, 26.97, 26.85; MS (FAB) m/e
854.9 (M-).
p-Meth oxyben zyl 3,4,6-tr i-O-a cetyl-2-d eoxy-(4,5-d ibr o-
m op en ta n oyla m in o)-â-D-glu cop yr a n osid e (16b): 85%; Rf
1
0.52 (3:1 ethyl acetate/petroleum ether); H NMR (300 MHz) δ
7.20-7.25 (m, 2H), 6.85-6.90 (m, 2H), 5.40 (dd, J ) 8.7, 19.5
Hz, 1H), 5.22 (dd, J ) 10.6, 21.6 Hz, 1H), 5.08 (t, J ) 9.4 Hz,
1H), 4.82 (dd, J ) 3.5, 11.5 Hz, 1H), 4.63 (dd, J ) 8.4, 21.6 Hz,
1H), 4.28 (dd, J ) 3.5, 11.8, 1H), 4.10-4.31 (m, 3H), 3.89-3.94
(m, 1H), 3.79 (s, 3H), 3.50-3.71 (m, 3H), 2.43-2.55 (m, 1H),
2.20-2.35 (m, 2H), 2.11 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H), 1.82-
1.97 (m, 1H); 13C NMR (75 MHz) δ 172.31, 170.65, 170.60,
169.21, 159.4, 129.76, 128.71, 99.50, 72.60, 71.91, 70.25, 68.61,
62.20, 55.25, 54.35, 54.60, 36.78, 36.64, 30.62, 30.21, 20.80, 20.72,
20.61; MS (FAB) m/e 668.05 (M + H)+.
Anal. Calcd for C25H25NO10Br2Cl4: C, 37.48; H, 3.15; N, 1.75.
Found: C, 37.19; H, 3.20; N 1.79.
Ack n ow led gm en t. This work was supported by
4,5-Dibr om op en ta n yl 3-O-a cetyl-6-O-ben zyl-2-d eoxy-2-
tetr a ch lor op h th a lim id o-â-D-glu cop yr a n osid e (13b): 99%
yield; Rf 0.69 (65:35 petroleum ether/ethyl acetate); [R]21D -4.4°
(c ) 1.00, CHCl3); 1H NMR (500 MHz) δ 7.30-7.39 (m, 5H), 5.53
(dt, J ) 8.9, 10.6 Hz, 1H), 5.33 (d, J ) 8.4 Hz, 1H), 4.65 (dd, J
) 11.9, 31.1 Hz, 2H), 4.19-4.24 (m, 1H), 4.02-4.05 (m, 1H),
3.66-3.88 (m, 6H), 3.44-3.50 (m, 2H), 2.94 (d, J ) 3.4 Hz, 1H),
2.05-2.09 (m, 1H), 1.97 (s, 3H), 1.60-1.77 (m, 3H); 13C NMR
NIH grant GM-40171.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR for compounds 7b, 10, 14b, and 16b. Copies of the 13C
NMR for compounds 7b, 10, and 14b. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O9718509