Synthesis of C-glycosyl lactones and protected C-glycosyl amino acids: Use of radical cyclization

Article abstract of DOI:10.1021/jo981435w

Protected carbohydrates 6a-13a, having one free hydroxyl and a phenylseleno group or halogen on the adjacent carbon, were condensed with (2,2-diphenylhydrazono)acetic acid (2); the resulting esters undergo radical cyclization to afford carbohydrates fused to a 2,2-diphenylhydrazino lactone unit (6c,d-13c,d). In suitable cases (9c,d) such carbohydrate lactones can be elaborated into C-glycosyl amino acids.

Full text of DOI:10.1021/jo981435w

770
J . Org. Chem. 1999, 64, 770-779
Syn th esis of C-Glycosyl La cton es a n d P r otected C-Glycosyl Am in o
Acid s: Use of Ra d ica l Cycliza tion
J unhu Zhang and Derrick L. J . Clive*
Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Received J uly 22, 1998
Protected carbohydrates 6a -13a , having one free hydroxyl and a phenylseleno group or halogen
on the adjacent carbon, were condensed with (2,2-diphenylhydrazono)acetic acid (2); the resulting
esters undergo radical cyclization to afford carbohydrates fused to a 2,2-diphenylhydrazino lactone
unit (6c,d -13c,d ). In suitable cases (9c,d ) such carbohydrate lactones can be elaborated into
C-glycosyl amino acids.
Sch em e 1
In tr od u ction
Hydrazono esters of type 3 (X ) halogen or PhSe;
Scheme 1), which are easily available by esterification
of the crystalline reagent (2,2-diphenylhydrazono)acetic
acid (2),1 are converted into hydrazino lactones 5, on
treatment with a stannane and initiator (3 f 4 f 5).2
We describe here the use of this sequence to make
carbohydrates fused to hydrazino lactones and show that,
in favorable cases, such lactones can be elaborated into
protected C-glycosyl amino acids.3 A number of antibiotics
belong to the class of C-glycosyl amino acids,4 and the
compounds are of value as components of carbon-linked
analogues of glycopeptides5 and as building blocks for
combinatorial synthesis.6
P r ep a r a tion of Sta r tin g Ma ter ia ls. The starting
materials for this work were modified carbohydrates,
some of which (6a ,b-13a ,b) are shown in Table 1. Each
of the hydrazono esters 6b-13b was made by DCC-
mediated coupling of the appropriate alcohol with reagent
2, using DMAP as a catalyst, and in every case the
reaction was efficient, the yields always being at least
90%. The alcohols required for the esterification were
prepared by conventional methods, as follows:
Treatment of commercial tetra-O-acetyl-â-D-ribofura-
nose with PhSeH in the presence of BF3‚Et2O7 gave (92%)
the â-phenyl selenide 148 (eq 1), from which 6a was
(1) Barber, H. J .; Lunt, E. J . Chem. Soc. 1965, 1468-1473.
(2) Clive, D. L. J .; Zhang, J . Chem. Commun. 1997, 549.
(3) For leading references to other preparations of C-glycosyl amino
acids, see, for example: (a) Dondoni, A.; J unquera, F.; Mercha´n, F. L.;
Merino, P.; Scherrmann, M.-C.; Tejero, T. J . Org. Chem. 1997, 62,
5484-5496. Recent examples of the synthesis of C-glycosyl amino acids
or peptides: (b) Czernecki, S.; Horns, S.; Valery, J .-M. J . Org. Chem.
1995, 60, 650-655. (c) Urban, D.; Skrydstrup, T.; Beau, J .-M. Chem.
Commun. 1998, 955-956. (d) Coutrot, P.; Grison, C.; Coutrot, F. Synlett
1998, 393-395. (e) Tedebark, U.; Meldal, M.; Panza, L.; Bock, K.
Tetrahedron Lett. 1998, 39, 1815-1818. (f) Hoffmann, M.; Burkhart,
F.; Hessler, G.; Kessler, H. Helv. Chim. Acta 1996, 79, 1519-1532. (g)
Rassu, G.; Zanardi, F.; Battistini, L.; Casiraghi, G. Tetrahedron:
Asymmetry 1995, 6, 371-374. (h) Petrusˇ, L.; BeMillar, J . N. Carbohydr.
Res. 1992, 230, 197-200. (i) Bertozzi, C. R.; Hoeprich, P. D., J r.;
Bednarski, M. D. J . Org. Chem. 1992, 57, 6092-6094. (j) Kessler, H.;
Wittmann, V.; Ko¨ck, M.; Kottenhahn, M. Angew. Chem., Int. Ed. Engl.
1992, 31, 902-904. (k) Colombo, L.; Casiraghi, G.; Pittalis, A. J . Org.
Chem. 1991, 56, 3897-3900. (l) Pochet, S.; Allard, P.; Huynh-Dinh,
T.; Igolen, J . J . Carbohydr. Chem. 1982-3, 1, 277-288. (m) Bischof-
berger, K.; Brink, A. J .; de Villiers, O. G.; Hall, R. H. J . Chem. Soc.,
Perkin Trans I 1977, 1472-1476. (n) Cf. Debenham, S. D.; Debenham,
J . S.; Burk, M. J .; Toone, E. J . J . Am. Chem. Soc. 1997, 119, 9897-
9898.
formed by base hydrolysis (K2CO3, THF-MeOH; 91%)
and silylation [i-Pr2Si(Cl)OSi(Cl)Pr2-i, pyridine; 80%].
L-Arabinose was converted (Scheme 2) by a known
procedure9 into its tetraacetate 15 (as a mixture of
anomers) which, on treatment with PhSeH/BF3‚Et2O,
gave R-selenide 16 (64%). Mild base hydrolysis (16 f 17,
K2CO3, THF-MeOH; 93%) and silylation [i-Pr2Si(Cl)OSi-
(Cl)Pr2-i, pyridine; 77%] afforded 7a .
A mixture of the anomeric diacetates 18 (Scheme 3),
made from diacetone glucose,10 afforded the â-selenide
19 on treatment with PhSeH/BF3‚Et2O (73%), and alcohol
(4) For examples of recent synthetic work related to such antibiotics,
see: (a) Zhang, D.; Miller, M. J . J . Org. Chem. 1998, 63, 755-759. (b)
Barrett, A. G. M.; Lebold, S. A. J . Org. Chem. 1990, 55, 3853-3857.
(c) Garner, P.; Park, J . M. J . Org. Chem. 1990, 55, 3772-3787.
(5) Review on glycobiology: Dwek, R. A. Chem. Rev. 1996, 96, 683-
720.
(7) Giese, B.; Gilges, S.; Gro¨ninger, K. S.; Lamberth, C.; Witzel, T.
J ustus Liebigs Ann. Chem. 1988, 615-617.
(8) A mixture of both anomers is formed by using PhSeSePh/Zn-
AcOH (Fourrey, J .-L.; Henry, G.; J ouin, P. Tetrahedron Lett. 1980,
455-458).
(9) Backinowsky, L. V.; Nepogod’ev, S. A.; Shashkov, A. S.; Kochet-
kov, N. K. Carbohydr. Res. 1985, 138, 41-54.
(6) Cf. McDevitt, J . P.; Lansbury, P. T., J r. J . Am. Chem. Soc. 1996,
118, 3818-3828.
(10) Du, Y.; Kong, F. J . Carbohydr. Chem. 1996, 15, 797-817.
10.1021/jo981435w CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/13/1999

Use of Radical Cyclization
Ta ble 1
J . Org. Chem., Vol. 64, No. 3, 1999 771
Sch em e 2a
a
(a) PhSeH, BF3‚Et2O, CH2Cl2; 64%. (b) K2CO3, 1:1 THF-
MeOH; 93%. (c) TIPSCl, pyridine, 77%.
Sch em e 3a
a
(a) PhSeH, BF3‚Et2O, CH2Cl2; 73%. (b) K2CO3, 1:1 THF-
MeOH; 96%.
Sch em e 4
8a was then obtained by base hydrolysis (19 f 8a , K2-
CO3, THF-MeOH; 96%).
Diacetone glucose was also used (Scheme 4) to syn-
thesize 9a . Selective deprotection of diacetone glucose at
C(5)-C(6) by acid hydrolysis,11 and tris-methylation12
(Me2SO4, DMSO, NaOH; 82% overall), gave 20 (Scheme
4).13 Mild hydrolysis (PhCO2H in water at reflux), fol-
lowed by acetylation took the route as far as 21 (82%).
This was treated with PhSeH/BF3‚Et2O (21 f 22, 85%),
and the required alcohol was again obtained by base
hydrolysis (22 f 9a , K2CO3, THF-MeOH; 96%).
Alcohol 10a was made by hydrolysis (K2CO3, THF-
MeOH; 92%) and ketalization (acetone, TsOH; 92%) of
selenide 14.
Diol 23 (eq 2) was prepared by the literature proce-
dure14 in two steps from diacetone glucose, and treatment
(11) Schmidt, O. Th. In Methods in Carbohydrate Chemistry; Whis-
tler, R. L., Wolfrom, M. L., Eds.; Academic Press: London, 1963; Vol.
2, p 322.
(12) Cf. Kuszmann, J .; Soha´r, P.; Kiss, L. Carbohydr. Res. 1978, 63,
115-125.
(13) de J ong, E. G.; Heerma, W.; Dujardin, B.; Haverkamp, J .;
Vliegenthart, J . F. G. Carbohydr. Res. 1978, 60, 229-239.
(14) Nayak, U. G.; Whistler, R. L. J . Org. Chem. 1969, 34, 97-100.
a
Isomer ratios are given in brackets, but we did not establish
which is the c or d isomer, except for 9c,d (9c:9d ) 42:40) and
b
12c,d (12c:12d ) 34:23). Structure of 11e is same as structure
c
of 11b, but with H instead of Br. Structure of 12e is the same as
the structure of 12b, but with H instead of I.

772 J . Org. Chem., Vol. 64, No. 3, 1999
Zhang and Clive
with Ph3P/CBr4 served to convert it into 11a (88%).
order of 107-108 s-1, while the corresponding value for
closure onto a carbon-carbon double bond (28, X ) CH2)
is only about 105 s-1 20
1,2-Acyl migrations have rate
.
constants that span the range18 (at 75 °C) of about 102-
106 s-1 and can be significantly faster than closure onto
a hydrazono unit.21 The fact that acyl migration does not
compete with the closures reported here shows that the
rotational barrier about the ester C(O)sO single bond is
sufficiently low22 to permit easy access to a conformation
in which the radical center is close to the CdN double
bond and that closure onto an R-acyl (as opposed to
R-alkyl) hydrazono unit is fast.
â-D-Galactose pentaacetate and D-mannose were con-
verted by literature procedures into 12a 15 and the
acetate16 corresponding to 13a , respectively. Simple
hydrolysis of the acetate gave 13a (90%).
A number of other modified carbohydrates (24-27)
were also prepared,17 but without full characterization,
as the critical radical closure proceeded poorly or not at
all (see below).
In exploratory experiments with hydrazono esters of
the six-membered sugars 24-26, and the furanose ex-
ample 27, the radical cyclization step gave complex
mixtures.23 With 13b (Table 1) the desired lactones are
formed inefficiently (ca. 48%) and, except for anhydro-
sugar 12b (Table 1), the six-membered series was not
examined further.
It is not clear whether the axial nature of the hydra-
zono pendant in the anhydrosugar 12b and the mannose
derivative 13b contributes to the relative efficiency of
closure, as compared with the galactose- (24) or glucose-
derived examples (25, 26), as efficient closures involving
both axial and equatorial pendants have been observed
experimentally.24
Mod ifica tion of th e Hyd r a zin o La cton es a n d
F or m a tion of C-Glycosyl Am in o Acid s. In principle,
opening of the lactone unit of the radical cyclization
products and hydrogenolysis of the N-N single bond
should afford a C-glycosyl amino acid, but in practice this
overall transformation had to be effected indirectly. Our
general experience25 is that hydrogenolysis of 2,2-diphen-
ylhydrazino lactones is unsuccessful, and lactone opening
with a base results in expulsion of diphenylamine.
Formation of C-glycosyl amino acids was therefore
achieved in the following way.
Hydride reduction (LiAlH4) of 9c (Scheme 5), selective
silylation of the resulting primary hydroxyl (t-BuPh2SiCl,
imidazole; 79% overall), hydrogenolysis (H2, Pd-C, cam-
phorsulfonic acid, MeOH), and benzoylation (PhCOCl,
Et3N, DMAP; 76% overall) gave 30a (9c f 29a f 30a ).
Desilylation, using Bu4NF, is complicated by benzoyl
migration, but this process could be suppressed by using
Bu4NF in the presence of 1.5 equiv of pyridinium
hydrochloride,26 and under these conditions the yield was
Ra d ica l Cycliza tion s. Our general procedure (see
Experimental Section) for radical cyclization involves
slow addition (ca. 10 h) of individual solutions of Bu3-
SnH (0.06-0.2 M, 1.5-3.0 equiv) and AIBN (0.003-0.020
M, 0.2-0.4 equiv) in PhMe to a stirred solution of the
hydrazono ester (0.015 M) in the same solvent at reflux.
With the exception of 13b, cyclization generally occurred
smoothly to give the product lactones 6c,d -12c,d in
yields of 57-82% (Table 1), and even a seven-membered
ring can be formed (10c,d ; 64%). A mixture of isomers
was always obtained, and in all but two cases (7c,d and
10c,d ) the isomers could be separated by flash chroma-
tography. In a few cases the simple reduction product
was also isolated [11e, 12% (as judged by 1H NMR
measurements); 12e, 25%], and trace amounts of Ph2NH
were sometimes detected. Use of an excess of stannane
(1.2-3.0 equiv, depending on the case) generally gives
better results. The structures of the lactones were clear
from their NMR spectra, and NOE measurements al-
lowed us to assign the stereochemistry at the position R
to the lactone carbonyl for compounds 9c,d and 12c,d .
In the former case, X-ray analysis of one of the isomers
(9d ) confirmed our assignment.
(18) Beckwith, A. L. J .; Crich, D.; Duggan, P. J .; Yao, Q. Chem. Rev.
1997, 97, 3273-3313.
(19) Giese, B.; Gro¨ninger, K. S. Org. Synth. 1990, 69, 66-71.
(20) Sturino, C. F.; Fallis, A. G. J . Org. Chem. 1994, 59, 6514-6516.
(21) For an example of rearrangement before closure, see ref 2.
(22) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
Wiley: New York, 1994; p 618.
A notable feature of the radical closure step is the
absence sat least to any major extent s of acyl migra-
tion.7,18,19 5-Exo-cyclization of a radical onto a CdNNPh2
group is extremely fast and, for an all-carbon chain, as
in 28 (X ) NNPh2), the rate constant at 80 °C is of the
(23) The 13C NMR spectrum of the crude reaction product from an
attempted radical cyclization of 26 showed signals at δ 172.9, 163.7,
and 101.0, suggesting the presence of a γ-lactone (δ 163.7) resulting
from acyl migration and cyclization [C(1) OCHO], as well as simple
reduction product or starting material (δ 172.9).
(24) (a) Beckwith, A. L. J .; Phillipou, G.; Serelis, A. K. Tetrahedron
Lett. 1981, 22, 2811-2814. (b) Clive, D. L. J .; J oussef, A. C. J . Chem.
Soc., Perkin Trans. 1 1991, 2797-2799 and references therein.
(25) J . Zhang, unpublished observations.
(26) Cf.: Verdegaal, C. H. M.; J ansse, P. L.; de Rooij, J . F. M.; van
Boom, J . H. Tetrahedron Lett. 1980, 1571-1574.
(15) Knapp, S.; Naughton, A. B. J .; J aramillo, C.; Pipik, B. J . Org.
Chem. 1992, 57, 7328-7334.
(16) Vauzeilles, B.; Cravo, D.; Mallet, J .-M.; Sinay¨, P. Synlett 1993,
522-524.
(17) The procedures are outlined in the Supporting Information.

Use of Radical Cyclization
Sch em e 5a
J . Org. Chem., Vol. 64, No. 3, 1999 773
the radical cyclization approach described here. The
stereochemistry R to the carboxyl is not controlled, but
the epimers are often separable, and the R or â stereo-
chemistry with respect to the carbohydrate subunit is
determined by the stereochemistry of the hydroxyl that
is initially acylated with reagent 2.
Exp er im en ta l Section
Gen er a l P r oced u r es. Unless stated to the contrary, the
general procedures used previously28 were followed. Optical
rotations were measured at room temperature.
The symbols s′, d′, t′, and q′ used for 13C NMR signals
indicate zero, one, two, or three attached hydrogens, respec-
tively.
(2,2-Dip h en ylh yd r a zon o)a cetic Acid (2). This procedure
differs from that reported1 in the literature. Glyoxylic acid
monohydrate (5.520 g, 60 mmol) was added to a stirred
solution of commercial Ph2NNH2‚HCl (13.248 g, 60 mmol) in
H2O (720 mL). Stirring was continued for 2 h, and the
precipitate was filtered off, washed with H2O (5 × 30 mL),
and dried under oil-pump vacuum to afford 2 (13.901 g, 96%)
as a gray power: mp 201-203 °C (lit.1 200-202 °C).
Gen er a l P r oced u r e for Cou p lin g of Alcoh ols w ith
Rea gen t 2. Glyoxylic acid diphenylhydrazone (1.2 equiv) was
added to a stirred mixture of the alcohol (1.0 equiv), DCC (1.32
equiv), and DMAP (0.12 equiv) in dry CH2Cl2. Stirring was
continued for 12 h, and the mixture was then filtered. The
insoluble material was washed with dry CH2Cl2 and the
combined filtrates were evaporated to give a residue, which
was processed as described for the individual experiments.
Gen er a l P r oced u r e for Ra d ica l Cycliza tion . The sub-
strate was placed in a round-bottomed flask equipped with a
Teflon-coated stirring bar and a reflux condenser sealed with
a rubber septum. The system was flushed with argon for 5-10
min, and dry PhMe was injected into the flask. The flask was
placed in an oil bath preheated to 110 °C, and solutions of Bu3-
SnH and AIBN in PhMe were injected simultaneously by
syringe pump over 10 h. Refluxing was continued for an
arbitrary period of 1-4 h after the addition, except in the
preparation of 12c,d , where a longer period (7 h) was used.
The reaction mixture was cooled, and the solvent was evapo-
rated to give a residue which was processed as described for
the individual experiments.
a
(a) LiAlH4, THF, 0 °C; t-BuPh2SiCl, imidazole; 79% overall
for 29a , 81% for 29b. (b) Camphorsulfonic acid, 10% Pd-C, H2
(50 psi); PhCOCl, Et3N; 76% overall for 30a , 75% for 30b. (c)
Bu4NF, pyridinium hydrochloride; 83% for 31a , 81% for 31b. (d)
J ones reagent; CH2N2; 76% overall for 32a , 77% for 32b. (e) (t-
BuOCO)2O, DMAP; MeOH, N2H4; 86%.
Sch em e 6
P h en yl 1-Selen o-3,5-O-(t et r a isop r op yld isiloxa n e-1,3-
d iyl)-â-D-r ibofu r a n osid e (6a ). (a ) P h en yl 1-Selen o-â-D-
r ibofu r a n osid e. K2CO3 (123.1 mg, 0.891 mmol) was added
to a stirred solution of 148 (370.0 mg, 0.891 mmol) in 1:1 THF-
MeOH (5 mL). Stirring was continued for 6 h, and the mixture
was filtered through a pad (1 cm × 2 mm) of silica gel and
evaporated. Flash chromatography of the residue over silica
gel (1.2 × 21 cm), using 2% MeOH-EtOAc, gave phenyl
1-seleno-â-D-ribofuranoside (235.8 mg, 91%) as a pale yellow
oil: FTIR (MeOH cast) 3374 cm-1; 1H NMR (CD3OD, 360 MHz)
δ 3.54-3.66 (m, 2 H), 3.92-3.97 (m, 1 H), 4.03 (dd, J ) 6.1,
5.0 Hz, 1 H), 4.13-4.15 (m, 1 H), 4.75-4.97 (br, 3 H), 5.48 (d,
83%. The resulting primary alcohol was oxidized and
esterified (31a f 32a ; 76%), and the N-benzoyl group
was replaced directly by a tert-butyloxycarbonyl group
[(t-BuOCO)2O, DMAP, NH2NH2; 86%],27 so as to afford
the protected C-glycosyl amino acid 33. The other iso-
meric hydrazone closure product (9d ) was subjected to
the same operations, except for the last step (Scheme 5),
and provided the protected C-glycosyl amino acid 32b.
In a slightly different set of reactions, alcohol 31a was
oxidized to the corresponding acid, and this was con-
verted into its benzyl ester (31a f 34; BnBr, NaHCO3,
NaI; 77%). Finally, the N-benzoyl group was replaced
directly by a tert-butyloxycarbonyl group [(t-BuOCO)2O,
DMAP, NH2NH2; 89%; 34 f 35].
J ) 3.3 Hz, 1 H), 7.25-7.36 (m, 3 H), 7.58-7.70 (m, 2 H); 13
C
NMR (CD3OD, 100.6 MHz) δ 63.72 (t′), 72.44 (d′), 77.64 (d′),
86.32 (d′), 88.17 (d′), 128.83 (d′), 130.12 (d′), 130.20 (s′), 135.63
(d′); exact mass m/z calcd for C11H14O4Se 290.0057, found
290.0062.
(b) P h en yl 1-Selen o-3,5-O-(tetr a isop r op yld isiloxa n e-
1,3-d iyl)-â-D-r ibofu r a n osid e (6a ). 1.3-Dichloro-1,1,3,3-tet-
raisopropyldisiloxane (470 µL, 1.4678 mmol) was added drop-
wise to a stirred and cooled (0 °C) solution of the above triol
(424.2 mg, 1.468 mmol) in dry pyridine (14 mL). Stirring was
continued for 30 min at 0 °C and then for 6 h after removal of
the ice bath. Pyridine was evaporated under vacuum, and flash
chromatography of the residue over silica gel (2.6 × 25 cm),
using 5% EtOAc-hexane, gave 6a (624.0 mg, 80%) as a
colorless oil: [R]D ) -112.3 (c 1.14, CHCl3); 1H NMR (CD2Cl2,
The formation of compounds 32a , 33, and 35 shows
that C-glycosyl amino acid derivatives are accessible by
(28) Clive, D. L. J .; Wickens, P. L.; Sgarbi, P. W. M. J . Org. Chem.
1996, 61, 7426-7437.
(27) Burke, M. J .; Allen, J . G. J . Org. Chem. 1997, 62, 7054-7057.

774 J . Org. Chem., Vol. 64, No. 3, 1999
Zhang and Clive
360 MHz) δ 0.93-1.17 (m, 28 H), 3.03 (d, J ) 1.6 Hz, 1 H),
3.88-4.02 (m, 3 H), 4.27 (dt, J ) 5.1, 1.4 Hz, 1 H), 4.37 (dd, J
) 6.2, 5.2 Hz, 1 H), 5.59 (d, J ) 1.2 Hz, 1 H), 7.26-7.35 (m, 3
H), 7.57-7.62 (m, 2 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 13.03
(d′), 13.22 (d′), 13.57 (d′), 13.64 (d′), 17.16 (q′), 17.19 (q′), 17.22
(q′), 17.40 (q′), 17.49 (q′), 17.60 (q′), 17.65 (q′), 64.44 (t′), 74.55
(d′), 77.96 (d′), 83.37 (d′), 86.10 (d′), 128.39 (d′), 128.81 (s′),
129.52 (d′), 135.25 (d′); exact mass (electrospray) m/z calcd for
CHCl3); FTIR (CH2Cl2 cast) 1747 cm-1; 1H NMR (CD2Cl2, 360
MHz) δ 2.06 (s, 3 H) 2.07 (s, 3 H), 2.12 (s, 3 H), 4.25 (dd, J )
12.0, 5.6 Hz, 1 H), 4.40 (dd, J ) 12.0, 3.7 Hz, 1 H), 4.46-4.50
(m, 1 H), 5.03-5.05 (m, 1 H), 5.34-5.38 (m, 1 H), 5.80-5.82
(m, 1 H), 7.29-7.34 (m, 3 H), 7.60-7.66 (m, 2 H); 13C NMR
(CD2Cl2, 75.5 MHz) δ 20.84 (q′), 62.90 (t′), 77.56 (d′), 81.54 (d′),
82.45 (d′), 87.31 (d′), 128.29 (d′), 129.49 (d′), 129.60 (s′), 134.60
(d′), 169.81 (s′), 170.17 (s′), 170.63 (s′); exact mass m/z calcd
for C17H20O7Se 416.0374, found 416.03774.
C
23H40NaO5SeSi2 (M + Na) 555.1477, found 555.1485.
P h en yl 2-O-(Dip h en ylh yd r a zon o)a cet yl-1-selen o-3,5-
P h en yl 1-Selen o-r-L-a r a bin ofu r a n osid e (17). K2CO3
(173.7 mg, 1.257 mmol) was added to a stirred solution of 16
(521.9 mg, 1.257 mmol) in 1:1 THF-MeOH (8 mL), and the
mixture was stirred for 1 h, filtered through a pad (1 cm × 2
mm) of silica gel, and evaporated. Flash chromatography of
the residue over silica gel (1.6 × 28 cm), using 2% MeOH-
EtOAc, gave 17 (337.8 mg, 93%) as a pale yellow oil: [R]D )
-267.9 (c 1.04, CHCl3); FTIR (CH2Cl2 cast) 3373 cm-1; 1H NMR
(CD2Cl2, 400 MHz) δ 3.71 (d, J ) 11.5 Hz, 1 H), 3.79 (d, J )
11.5 Hz, 1 H), 4.11 (br s, 2 H), 4.20-4.59 (br m, 4 H), 5.69 (d,
O-(t e t r a isop r op yld isiloxa n e -1,3-d iyl)-â-D-r ib ofu r a n o-
sid e (6b). The general procedure for coupling alcohols with
reagent 2 was followed, using 2 (341.4 mg, 1.423 mmol), 6a
(630.0 mg, 1.186 mmol), DCC (322.9 mg, 1.565 mmol), and
DMAP (20.0 mg, 0.164 mmol) in CH2Cl2 (10 mL). Flash
chromatography of the residue over silica gel (1.6 × 28 cm),
using 5% EtOAc-hexane, gave 6b (839.4 mg, 94%) as a pale
yellow oil: [R]D ) -57.7 (c 1.05, CHCl3); FTIR (CH2Cl2 cast)
1740, 1711 cm-1; 1H NMR (CD2Cl2, 360 MHz) δ 0.84-1.19 (m,
28 H), 3.90-4.06 (m, 3 H), 4.42-4.49 (m, 1 H), 5.62-5.68 (m,
2 H), 6.51 (d, J ) 2.2 Hz, 1 H), 7.14-7.69 (m, 15 H); 13C NMR
(CD2Cl2, 50.3 MHz) δ 13.19 (d′), 13.48 (d′), 13.63 (d′), 17.19
(q′), 17.25 (q′), 17.34 (q′), 17.49 (q′), 17.64 (q′), 63.36 (t′), 72.71
(d′), 79.16 (d′), 82.95 (d′), 83.68 (d′), 122.71 (d′), 123.97 (d′),
126.52 (d′), 128.52 (s′), 128.63 (d′), 129.59 (d′), 130.38 (d′),
135.58 (d′), 142.60 (s′), 163.49 (s′); exact mass (electrospray)
m/z calcd for C37H50N2NaO6SeSi2 (M + Na) 777.2270, found
777.2276.
3,6-An h yd r o-2-d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-5,7-O-
(t et r a isop r op yld isiloxa n e-1,3-d iyl)-D-glycer o-D-m a n n o-
h ep ton o-1,4-la cton e (6c) a n d 3,6-An h yd r o-2-d eoxy-2-(2,2-
d ip h en ylh yd r a zin o)-5,7-O-(tetr a isop r op yld isiloxa n e-1,3-
d iyl)-D-glycer o-D-glu co-h ep ton o-1,4-la cton e (6d ). The gen-
eral procedure for radical cyclization was followed, using 6b
(316.8 mg, 0.421 mmol) in PhMe (30 mL), Bu3SnH (340 µL,
1.261 mmol) in PhMe (10 mL), and AIBN (30 mg, 0.183 mmol)
in PhMe (10 mL). Flash chromatography of the residue over
silica gel (1.6 × 29 cm), using 3% EtOAc-hexane, gave the
chromatographically less polar product 6c (or 6d ) (117.2 mg,
46%), and the more polar product 6d (or 6c) (69.7 mg, 27%)
as colorless oils. The chromatographically less polar diastere-
omer: [R]D ) +27.6 (c 1.09, CHCl3); FTIR (CH2Cl2 cast) 1779
cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.01-1.17 (m, 28 H), 3.64
(dt, J ) 9.2, 2.3 Hz, 1 H), 3.77-3.79 (m, 1 H), 3.89-4.01 (m,
2 H), 4.28-4.35 (m, 2 H), 4.80 (dd, J ) 4.8, 0.6 Hz, 1 H), 5.13
(t, J ) 4.6 Hz, 1 H), 7.06-7.38 (m, 10 H); 13C NMR (CD2Cl2,
75.5 MHz) δ 12.95 (d′), 13.19 (d′), 13.37 (d′), 13.85 (d′), 17.02
(q′), 17.13 (q′), 17.29 (q′), 17.42 (q′), 17.48 (q′), 17.56 (q′), 60.08
(t′), 63.83 (d′), 71.75 (d′), 79.63 (d′), 79.76 (d′), 82.81 (d′), 121.22
(d′), 123.77 (d′), 129.81 (d′), 147.45 (s′), 174.87 (s′); exact mass
(electrospray) m/z calcd for C31H46N2NaO6Si2 (M + Na) 621.2792,
found 621.2792.
The chromatographically more polar diastereomer: [R]D )
+69.6 (c 1.09, CHCl3); FTIR (CH2Cl2 cast) 1786 cm-1; 1H NMR
(CD2Cl2, 400 MHz) δ 1.01-1.13 (m, 28 H), 3.76 (dt, J ) 9.2,
2.4 Hz, 1 H), 3.79 (dd, J ) 5.8, 3.5 Hz, 1 H), 3.94-4.10 (m, 2
H), 4.37 (dd, J ) 9.2, 4.1 Hz, 1 H), 4.56 (dd, J ) 5.8, 3.8 Hz,
1 H), 4.83 (t, J ) 3.9 Hz, 1 H), 4.86 (d, J ) 3.5 Hz, 1 H), 7.01-
7.35 (m, 10 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 13.08 (d′),
13.24 (d′), 13.44 (d′), 13.87 (d′), 17.07 (q′), 17.17 (q′), 17.31 (q′),
17.42 (q′), 17.46 (q′), 17.49 (q′), 17.60 (q′), 60.40 (d′), 60.53 (t′),
72.52 (d′), 75.67 (d′), 80.20 (d′), 81.21 (d′), 121.05 (d′), 123.22
(d′), 129.54 (d′), 147.56 (s′), 174.79 (s′); exact mass (electro-
spray) m/z calcd for C31H46N2NaO6Si2 (M + Na) 621.2792,
found 621.2791.
P h en yl 2,3,5-Tr i-O-a cetyl-1-selen o-r-L-a r a bin ofu r a n o-
sid e (16). BF3‚Et2O (232 µL, 1.88 mmol) was added dropwise
to a stirred and cooled (0 °C) solution of 159 (636.6 mg, 2.00
mmol) and PhSeH (314 µL, 2.96 mmol) in CH2Cl2 (20 mL).
Stirring was continued for 28 h at 0 °C, and then saturated
aqueous NaHCO3 (5 mL) was added. The organic phase was
washed with water (3 × 5 mL) and brine (5 mL), dried
(MgSO4), and evaporated. Flash chromatography of the residue
over silica gel (1.6 × 26 cm), using 20% EtOAc-hexane, gave
16 (533.4 mg, 64%) as a colorless oil: [R]D ) -161.4 (c 1.98,
J ) 2.6 Hz, 1 H), 7.22-7.30 (m, 3 H), 7.57-7.62 (m, 2 H); 13
C
NMR (CD2Cl2, 100.6 MHz) δ 61.34 (t′), 77.27 (d′), 83.11 (d′),
84.61 (d′), 89.21 (d′), 128.13 (d′), 129.57 (d′), 130.08 (s′), 134.32
(d′); exact mass m/z calcd for C11H14O4Se 290.0057, found
290.0056.
P h en yl 1-Selen o-3,5-O-(t et r a isop r op yld isiloxa n e-1,3-
d iyl)-r-L-a r a bin ofu r a n osid e (7a ). 1.3-Dichloro-1,1,3,3-tet-
raisopropyldisiloxane (304 µL, 0.9516 mmol) was added drop-
wise to a stirred and cooled (0 °C) solution of 17 (275.0 mg,
0.952 mmol) in dry pyridine (10 mL). Stirring was continued
for 30 min at 0 °C and then for 6 h after removal of the ice
bath. Pyridine was evaporated under vacuum, and flash
chromatography of the residue over silica gel (1.6 × 28 cm),
using 5% EtOAc-hexane, gave 7a (390.5 mg, 77%) as a
colorless oil: [R]D ) -141.2 (c 1.32, CHCl3); 1H NMR (CD2Cl2,
300 MHz) δ 0.96-1.15 (m, 28 H), 2.54 (d, J ) 5.1 Hz, 1 H),
3.91-4.04 (m, 3 H), 4.16-4.26 (m, 1 H), 3.33 (dd, J ) 10.4,
5.0 Hz, 1 H), 5.62 (d, J ) 4.6 Hz, 1 H) 7.27-7.33 (m, 3 H),
7.60-7.67 (m, 2 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 13.00 (d′),
13.32 (d′), 13.56 (d′), 13.93 (d′), 17.21 (q′), 17.27 (q′), 17.34 (q′),
17.55 (q′), 17.70 (q′), 61.88 (t′), 77.45 (d′), 82.05 (d′), 83.20 (d′),
88.55 (d′), 127.93 (d′), 129.45 (d′), 130.49 (s′), 134.03 (d′); exact
mass (electrospray) m/z calcd for C23H40NaO5SeSi2 (M + Na)
555.1477, found 555.1477.
P h en yl 2-O-(Dip h en ylh yd r a zon o)a cet yl-1-selen o-3,5-
O-(tetr a isop r op yld isiloxa n e-1,3-d iyl)-r-L-a r a bin ofu r a n o-
sid e (7b). The general procedure for coupling alcohols with
reagent 2 was followed, using 2 (162.6 mg, 0.677 mmol), 7a
(240.0 mg, 0.452 mmol), DCC (153.7 mg, 0.745 mmol), and
DMAP (10.0 mg, 0.082 mmol) in CH2Cl2 (4 mL). Flash
chromatography of the residue over silica gel (1.6 × 300 cm),
using 5% EtOAc-hexane, gave 7b (308.2 mg, 90%) as a pale
yellow oil: [R]D ) -56.9 (c 1.27, CHCl3); FTIR (CH2Cl2 cast)
1711 cm-1 1H NMR (CD2Cl2, 300 MHz) δ 0.98-1.17 (m, 28
;
H) 3.95 (dd, J ) 12.4, 5.4 Hz, 1 H), 4.07 (dd, J ) 12.4, 3.3 Hz,
1 H), 4.19-4.24 (m, 1 H), 4.46-4.50 (m, 1 H), 5.46-5.49 (m, 1
H), 5.72-5.76 (m, 1 H), 7.16-7.66 (m, 15 H); 13C NMR (CD2-
Cl2, 75.5 MHz) δ 12.89 (d′), 13.34 (d′), 13.63 (d′), 13.88 (d′),
17.17 (q′), 17.20 (q′), 17.59 (q′), 17.71 (q′), 62.04 (t′), 76.35 (d′),
82.52 (d′), 84.05 (d′), (86.08 (d′), 123.39 (d′), 127.96 (d′), 129.39
(d′), 130.40 (d′), 130.56 (s′), 134.22 (d′), 163.92 (s′), exact mass
(electrospray) m/z calcd for C37H50N2NaO6SeSi2 (M + Na)
777.2270, found 777.2279.
3,6-An h yd r o-2-d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-5,7-O-
(tetr a isop r op yld isiloxa n e-1,3-d iyl)-l-glycer o-L-gu lo-h ep -
t on o-1,4-la ct on e a n d 3,6-An h yd r o-2-d eoxy-2-(2,2-d i-
p h en ylh yd r a zin o)-5,7-O-(t et r a isop r op yld isiloxa n e-1,3-
d iyl)-L-glycer o-L-id o-h ep ton o-1,4-la cton e (7c,d ). The gen-
eral procedure for radical cyclization was followed, using 7b
(194.0 mg, 0.258 mmol) in PhMe (15 mL), Bu3SnH (208 µL,
0.773 mmol) in PhMe (5 mL), and AIBN (20 mg, 0.122 mmol)
in PhMe (5 mL). Flash chromatography of the residue over
silica gel (1.6 × 28 cm), using 2% EtOAc-hexane, gave 7c,d
(97.4 mg, 63%) as a colorless oil, which was a chromatographi-
cally inseparable mixture of two isomers in a 1.5:1 ratio (1H
NMR, 400 MHz): [R]D ) +70.5 (c 0.88, CHCl3); FTIR (CH2Cl2

Use of Radical Cyclization
J . Org. Chem., Vol. 64, No. 3, 1999 775
cast) 1791 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.02-1.17 (m,
28 H), 3.75-3.79 (m, 0.44 H), 3.84-4.03 (m, 2.54 H), 4.17 (dd,
J ) 10.8, 3.2 Hz, 0.61 H), 4.32 (d, J ) 2.0 Hz, 0.40 H), 4.37
(dd, J ) 7.5, 3.1 Hz, 0.37 H), 4.45-4.47 (m, 0.57 H), 4.53-
4.55 (m, 0.58 H), 4.73 (dd, J ) 3.6, 0.6 Hz, 0.58 H), 4.77 (dd,
J ) 5.9, 1.4 Hz, 0.39 H), 4.81 (d, J ) 3.7 Hz, 0.56 H), 5.14 (dd,
J ) 5.9, 3.1 Hz, 0.36 H), 7.02-7.38 (m, 10 H); 13C NMR (CD2-
Cl2, 100.6 MHz) δ 12.98 (d′), 13.20 (d′), 13.32 (d′), 13.57 (d′),
13.67 (d′), 13.73 (d′), 13.76 (d′), 17.08 (q′), 17.12 (q′), 17.17 (q′),
17.24 (q′), 17.33 (q′), 17.37 (q′), 17.51 (q′), 17.58 (q′), 17.66 (q′),
17.74 (q′), 61.34 (d′), 62.87 (t′), 63.27 (d′), 64.86 (t′), 77.46 (d′),
78.76 (d′), 80.47 (d′), 80.62 (d′), 84.86 (d′), 87.71 (d′), 88.65 (d′),
89.77 (d′), 120.97 (d′), 121.28 (d′), 123.21 (d′), 123.84 (d′), 129.56
(d′), 129.85 (d′), 147.46 (s′), 147.61 (s′), 173.41 (s′), 174.07 (s′);
exact mass (electrospray) m/z calcd for C31H46N2NaO6Si2 (M
+ Na) 621.2792, found, 621.2805.
(s, 1 H), 7.19-7.72 (m, 30 H); 13C NMR (CD2Cl2, 50.3 MHz) δ
70.53 (t′), 72.58 (t′), 72.66 (t′), 73.69 (t′), 76.36 (d′), 80.98 (d′),
81.20 (d′), 82.00 (d′), 87.51 (d′), 123.3 (d′), 126.69 (d′), 127.75
(d′), 127.81 (d′), 127.92 (d′), 128.15 (d′), 128.34 (d′), 128.53 (d′),
128.63 (d′), 128.71 (d′), 129.45 (d′), 130.39 (d′), 131.86 (s′),
133.93 (d′), 137.93 (s′), 139.11 (s′), 139.29 (s′), 142.38 (s′), 163.51
(s′); exact mass (electrospray) m/z calcd for C47H44N2NaO6Se
(M + Na) 835.2262, found 835.2264.
3,6-An h yd r o-5,7,8-t r i-O-b en zyl-2-d eoxy-2-(2,2-d ip h e-
n ylh yd r a zin o)-D-er yth r o-L-gu lo-oct on o-1,4-la ct on e (8c)
a n d 3,6-An h yd r o-5,7,8-tr i-O-ben zyl-2-d eoxy-2-(2,2-d ip h e-
n ylh ydr azin o)-D-er yth r o-L-ido-octon o-1,4-lacton e (8d). The
general procedure for radical cyclization was followed, using
8b (335.0 mg, 0.413 mmol) in PhMe (30 mL), Bu3SnH (334
µL, 1.239 mmol) in PhMe (10 mL), and AIBN (30 mg, 0.183
mmol) in PhMe (10 mL). Flash chromatography of the residue
over silica gel (1.6 × 27 cm), using 10% EtOAc-hexane, gave
the chromatographically less polar product 8c (or 8d ) (108.8
mg, 40%), and the more polar product 8d (or 8c) (105.5 mg,
38%) as a colorless oil. The chromatographically less polar
diastereomer: [R]D ) +1.9 (c 1.13, CHCl3); FTIR (CH2Cl2 cast)
3277, 1784 cm-1; 1H NMR (CD2Cl2, 300 MHz) δ 3.62 (dd, J )
10.7, 5.0 Hz, 1 H), 3.78-3.82 (m, 1 H), 3.88 (dd, J ) 10.7, 2.0
Hz, 1 H), 3.99 (ddd, J ) 8.6, 5.0, 2.0 Hz, 1 H), 4.09 (dd, J )
8.6, 3.3 Hz, 1 H), 4.32-4.38 (m, 2 H), 4.47-4.82 (m, 6 H), 4.93
(d, J ) 4.9 Hz, 1 H), 5.18 (d, J ) 4.9 Hz, 1 H), 7.07-7.40 (m,
25 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 62.96 (d′), 70.69 (t′),
72.51 (t′), 72.99 (t′), 73.68 (t′), 76.18 (d′), 80.10 (d′), 81.27 (d′),
81.38 (d′), 84.68 (d′), 121.19 (d′), 123.73 (d′), 127.77 (d′), 127.81
(d′), 127.93 (d′), 128.11 (d′), 128.33 (d′), 128.62 (d′), 128.83 (d′),
129.76 (d′), 137.79 (s′), 138.97 (s′), 139.17 (s′), 147.51 (s′), 174.24
(s′); exact mass (electrospray) m/z calcd for C41H40N2NaO6 (M
+ Na) 679.2784, found 679.2783.
P h en yl 2-O-Acetyl-3,5,6-tr i-O-ben zyl-1-selen o-â-D-glu -
cofu r a n osid e (19). BF3‚Et2O (476 µL, 3.8726 mmol) was
added dropwise to a stirred and cooled (0 °C) solution of 1810
(2.2001 g, 4.120 mmol) and PhSeH (648 µL, 6.0974 mmol) in
CH2Cl2 (40 mL). Stirring was continued for 2 h at 0 °C, and
then saturated aqueous NaHCO3 (5 mL) was added. The
organic phase was washed with water (2 × 10 mL) and brine
(10 mL), dried (MgSO4), and evaporated. Flash chromatogra-
phy of the residue over silica gel (2.6 × 28 cm), using 10%
EtOAc-hexane, gave 19 (1.9090 g, 73%) as a colorless oil:
[R]D ) -117.8 (c 1.27, CHCl3); FTIR (CH2Cl2 cast) 1747 cm-1
;
1H NMR (CD2Cl2, 300 MHz) δ 2.12 (s, 3 H), 3.80 (dd, J ) 10.8,
4.6 Hz, 1 H), 3.99 (dd, J ) 10.8, 2.0 Hz, 1 H), 4.21 (ddd, J )
9.4, 4.5, 1.9 Hz, 1 H), 4.26 (d, J ) 4.0 Hz, 1 H), 4.44 (dd, J )
9.4, 4.0 Hz, 1 H), 4.52 (d, J ) 11.3 Hz, 1 H), 4.61-4.65 (m, 3
H), 4.79 (d, J ) 11.3 Hz, 1 H), 4.95 (d, J ) 11.4 Hz, 1 H), 5.74
(s, 1 H), 7.29-7.51 (m, 18 H), 7.66-7.73 (m, 2 H); 13C NMR
(CD2Cl2, 75.5 MHz) δ 21.08 (q′), 70.48 (t′), 72.55 (t′), 72.64 (t′),
73.73 (t′), 76.37 (d′), 80.90 (d′), 81.12 (d′), 81.96 (d′), 87.51 (d′),
127.78 (d′), 127.86 (d′), 127.95 (d′), 128.16 (d′), 128.32 (d′),
128.56 (d′), 128.64 (d′), 128.73 (d′), 129.47 (d′), 131.92 (s′),
133.87 (d′), 137.90 (s′), 139.11 (s′), 139.30 (s′), 170.07 (s′); exact
mass (electrospray) m/z calcd for C35H36NaO6Se (M + Na)
655.1575, found 655.1577.
The chromatographically more polar diastereomer: [R]D )
1
+47 (c 1.19, CHCl3); FTIR (CH2Cl2 cast) 3289, 1791 cm-1; H
NMR (CD2Cl2, 300 MHz) δ 3.72 (dd, J ) 10.6, 5.2 Hz, 1 H),
3.78-3.83 (m, 1 H), 3.93 (dd, J ) 10.6, 1.8 Hz, 1 H), 3.98-
4.03 (m, 1 H), 4.16 (dd, J ) 9.0, 3.3 Hz, 1 H), 4.36 (d, J ) 3.1
Hz, 1 H), 4.41-4.66 (m, 6 H), 4.78-4.86 (m, 3 H), 7.00-7.41
(m, 25 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 60.76 (d′), 70.95
(t′), 72.48 (t′), 73.23 (t′), 73.86 (t′), 76.07 (d′), 77.49 (d′), 80.57
(d′), 81.53 (d′), 82.19 (d′), 120.90 (d′), 123.08 (d′), 127.74 (d′),
127.92 (d′), 128.03 (d′), 128.10 (d′), 128.38 (d′), 128.59 (d′),
128.74 (d′), 128.84 (d′), 129.46 (d′), 137.71 (s′), 139.00 (s′),
139.22 (s′), 147.53 (s′), 173.99 (s′); exact mass (electrospray)
m/z calcd for C41H40N2NaO6 (M + Na) 679.2784, found 679.2781.
1,2-Di-O-a ce t yl-3,5,6-t r i-O-m e t h yl-r,â-D -glu cofu r a -
n oses (21). PhCO2H (170.5 mg, 1.398 mmol) was added to a
stirred solution of 2013 (1.0970 g, 4.187 mmol) in water (8.5
mL) and the mixture was refluxed for 6 h, cooled in an ice
bath, and filtered. The insoluble material was washed with
cold H2O (2 × 1 mL), and the combined filtrates were
evaporated. Water (6 mL) was added, and the solution was
evaporated. The procedure was repeated with a further portion
of water (6 mL), and water (25 mL) was added to the residue.
The resulting solution was extracted with Et2O (2 × 4 mL).
Evaporation of the aqueous solution afforded a colorless syrup,
which was dried under vacuum. Pyridine (9 mL) and Ac2O (6
mL) were added to the dried residue, and the mixture was
stirred for 14 h. Excess of pyridine and Ac2O were evaporated
under vacuum, and flash chromatography of the residue over
silica gel (1.6 × 28 cm), using 30% EtOAc-hexane, gave 21
(1.0500 g, 82%) as a 67:33 mixture of R and â anomers [1H
NMR (300 MHz)]: [R]D ) +8.7 (c 1.47, CHCl3); FTIR (CH2Cl2
P h en yl 3,5,6-Tr i-O-b en zyl-1-selen o-â-D-glu cofu r a n o-
sid e (8a ). K2CO3 (177.8 mg, 1.287 mmol) was added to a
stirred solution of 19 (811.9 mg, 1.287 mmol) in 1:1 THF-
MeOH (10 mL), and the mixture was stirred vigorously for 15
min, filtered through a pad (2 cm × 1 mm) of silica gel, and
evaporated. Flash chromatography of the residue over silica
gel (1.6 × 28 cm), using 20% EtOAc-hexane, gave 8a (727.5
mg, 96%) as a colorless oil: [R]D ) -143.7 (c 1.47, CHCl3); FTIR
1
(CH2Cl2 cast) 3415 cm-1; H NMR (CD2Cl2, 300 MHz) δ 2.38
(br, 1 H), 3.74 (dd, J ) 10.8, 4.8 Hz, 1 H), 3.93 (dd, J ) 10.8,
2.0 Hz, 1 H), 4.07 (d, J ) 4.2 Hz, 1 H), 4.14 (ddd, J ) 9.2, 4.8,
2.0 Hz, 1 H), 4.43 (dd, J ) 9.2, 4.2 Hz, 1 H), 4.49 (dd, J )
11.4, 2.2 Hz, 1 H), 4.59 (s, 2 H), 4.67-4.77 (m, 3 H), 5.56 (br
s, 1 H), 7.22-7.41 (m, 18 H), 7.58-7.65 (m, 2 H); 13C NMR
(CD2Cl2, 75.5 MHz) δ 70.79 (t′), 72.61 (t′), 72.69 (t′), 73.70 (t′),
76.66 (d′), 80.09 (d′), 81.63 (d′), 83.20 (d′), 90.43 (d′), 127.56
(d′), 127.72 (d′), 127.76 (d′), 127.88 (d′), 127.96 (d′), 128.08 (d′),
128.12 (d′), 128.56 (d′), 128.61 (d′), 128.71 (d′), 129.44 (d′),
132.17 (s′), 133.59 (d′), 138.14 (s′), 139.08 (s′), 139.35 (s′); exact
mass (electrospray) m/z calcd for C33H34NaO5Se (M + Na)
613.1469, found 613.1480.
P h en yl 3,5,6-Tr i-O-ben zyl-2-O-(d ip h en ylh yd r a zon o)-
a cetyl-1-selen o-â-D-glu cofu r a n osid e (8b). The general pro-
cedure for coupling alcohols with reagent 2 was followed, using
2 (293.4 mg, 1.223 mmol), 8a (600.1 mg, 1.019 mmol), DCC
(277.4 mg, 1.345 mmol), and DMAP (15.0 mg, 0.123 mmol) in
CH2Cl2 (10 mL). Flash chromatography of the residue over
silica gel (1.6 × 28 cm), using 10% EtOAc-hexane, gave 8b
(804.7 mg, 97%) as a pale yellow oil: [R]D ) -81.7 (c 1.26,
1
cast) 1751 cm-1; H NMR (CD2Cl2, 300 MHz) δ 2.03 (s, 2 H),
2.05 (s, 1 H), 2.07 (br s, 3 H), 3.34-3.47 (m, 10 H), 3.52-3.69
(m, 2 H), 3.76 (d, J ) 4.5 Hz, 0.33 H), 3.91-3.93 (m, 0.67 H),
4.13-4.22 (m, 1 H), 5.14 (br s, 0.33 H), 5.19 (dd, J ) 4.5, 2.6
Hz, 0.67 H), 6.02 (s, 0.33 H), 6.29 (d, J ) 4.4 Hz, 0.67 H); 13C
NMR (CD2Cl2, 75.5 MHz) δ 20.68 (q′), 20.93 (q′), 21.03 (q′),
21.28 (q′), 58.07 (q′), 58.27 (q′), 59.39 (q′), 72.26 (t′), 75.69 (d′),
77.48 (d′), 77.53 (d′), 78.81 (d′), 78.97 (d′), 81.91 (d′), 82.34 (d′),
83.21 (d′), 95.03 (d′), 99.87 (d′), 169.68 (s′), 169.81 (s′), 169.93
(s′); exact mass (electrospray) m/z calcd for C13H22NaO8 (M +
Na) 329.1212, found 329.1211.
1
CHCl3); FTIR (CH2Cl2 cast) 1731, 1704 cm-1; H NMR (CD2-
Cl2, 300 MHz) δ 3.78 (dd, J ) 10.8, 4.6 Hz, 1 H), 3.98 (dd, J )
10.8, 1.9 Hz, 1 H), 4.21 (ddd, J ) 9.4, 4.6, 1.9 Hz, 1 H), 4.31
(d, J ) 4.0 Hz, 1 H), 4.43 (dd, J ) 9.3, 4.0 Hz, 1 H), 4.51 (d, J
) 11.3 Hz, 1 H), 4.61-4.68 (m, 3 H), 4.77 (d, J ) 11.3 Hz, 1
H), 4.99 (d, J ) 11.4 Hz, 1 H), 5.78 (s, 1 H), 5.87 (s, 1 H), 6.51

776 J . Org. Chem., Vol. 64, No. 3, 1999
Zhang and Clive
P h en yl 2-O-Acetyl-3,5,6-tr i-O-m eth yl-1-selen o-â-D-glu -
cofu r a n osid e (22). BF3‚Et2O (404 µL, 3.2869 mmol) was
added dropwise to a stirred and cooled (0 °C) solution of 21
(1.0701 g, 3.497 mmol) and PhSeH (557 µL, 5.2451 mmol) in
CH2Cl2 (35 mL). Stirring was continued for 1.5 h at 0 °C, and
then saturated aqueous NaHCO3 (5 mL) was added. The
organic phase was washed with water (2 × 10 mL) and brine
(10 mL), dried (MgSO4), and evaporated. Flash chromatogra-
phy of the residue over silica gel (1.6 × 28 cm), using 20%
EtOAc-hexane, gave 22 (1.2015 g, 85%) as a colorless oil:
3.47 (s, 3 H), 3.49-3.55 (m, 1 H), 3.65 (dd, J ) 10.7, 2.1 Hz, 1
H), 3.74-3.78 (m, 1 H), 3.85 (dd, J ) 8.8, 3.4 Hz, 1 H), 3.98 (d,
J ) 3.4 Hz, 1 H), 4.29 (d, J ) 2.0 Hz, 1 H), 4.84 (d, J ) 4.9 Hz,
1 H), 5.12 (d, J ) 4.9 Hz, 1 H), 7.05-7.37 (m, 10 H); 13C NMR
(CD2Cl2, 100.6 MHz) δ 58.13 (q′), 58.47 (q′), 59.4 (q′), 62.90
(d′), 72.36 (t′), 77.31 (d′), 79.74 (d′), 81.37 (d′), 83.04 (d′), 84.40
(d′), 121.23 (d′), 123.73 (d′), 129.74 (d′), 147.55 (s′), 174.36 (s′);
exact mass m/z calcd for C23H28N2O6 428.1947, found 428.1951.
Compound 9d : mp 141-142 °C; [R]D ) +59.7 (c 1.16, CHCl3);
FTIR (CH2Cl2 cast) 1790 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
3.39 (s, 3 H), 3.41 (s, 3 H), 3.44-3.49 [m, including s (3 H) at
δ 3.45, 4 H in all], 3.51-3.55 (m, 1 H), 3.70 (dd, J ) 10.5, 1.8
Hz, 1 H), 3.80 (t, J ) 4.9 Hz, 1 H), 3.92 (dd, J ) 9.0, 3.4 Hz,
1 H), 4.01 (d, J ) 3.4 Hz, 1 H), 4.52 (dd, J ) 5.2, 3.8 Hz, 1 H),
4.80-4.83 (m, 1 H), 7.00-7.34 (m, 10 H); 13C NMR (CD2Cl2,
100.6 MHz) δ 58.15 (q′), 58.70 (q′), 59.54 (q′), 60.78 (d′), 72.71
(t′), 77.23 (d′), 77.44 (d′), 80.37 (d′), 81.99 (d′), 83.26 (d′), 120.97
(d′), 123.14 (d′), 129.48 (d′). 147.61 (s′), 174.05 (s′); exact mass
m/z calcd for C23H28N2O 428.1947, found 428.1947. Irradiation
of the HCNHNPh2 1H NMR signal (for 9d ) caused an NOE of
13.3% in the signal for the C(1)H of the furanose ring, and
4.4% for the C(2)H; in the case of 9c, the corresponding values
were 4.9% and 1.2%, respectively. On this basis, we assigned
the stereochemistries as shown, and our assignment was
confirmed by an X-ray structure of 9d . Crystal data: mono-
clinic space group P21 with a ) 9.2836(5) Å, b ) 8.5947(4) Å,
c ) 13.8264(6) Å, â ) 91.089(5)°, V ) 1103.01(9) Å3, Z ) 2,
[R]D ) -147.7 (c 1.33, CHCl3); FTIR (CH2Cl2 cast) 1748 cm-1
;
1H NMR (CD2Cl2, 360 MHz) δ 2.04 (s, 3 H), 3.36 (s, 3 H), 3.42
(s, 3 H), 3.47-3.51 [m, including s (3 H) at δ 3.50, 4 H in all],
3.67-3.73 (m, 2 H), 3.83 (d, J ) 4.0 Hz, 1 H), 4.12 (dd, J )
9.5, 4.0 Hz, 1 H), 5.50 (s, 1 H), 5.57 (s, 1 H), 7.27-7.32 (m, 3
H), 7.57-7.63 (m, 2 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 21.04
(q′), 58.07 (q′), 58.20 (q′), 59.45 (q′), 72.14 (t′), 77.41 (d′), 80.88
(d′), 81.69 (d′), 82.72 (d′), 87.38 (d′), 127.75 (d′), 129.41 (d′),
131.78 (s′), 133.90 (d′), 170.02 (s′); exact mass (electrospray)
m/z calcd for C17H24NaO6Se (M + Na) 427.0636, found 427.0634.
P h en yl 3,5,6-Tr i-O-m et h yl-1-selen o-â-D-glu cofu r a n o-
sid e (9a ). K2CO3 (385.3 mg, 2.788 mmol) was added to a
stirred solution of 22 (1.1235 g, 2.788 mmol) in 1:1 THF-
MeOH (20 mL) and the mixture was stirred vigorously for 15
min, filtered through a pad (1 cm × 2 mm) of silica gel, and
evaporated. Flash chromatography of the residue over silica
gel (1.6 × 28 cm), using 40% EtOAc-hexane, gave 9a (0.9641
g, 96%) as a colorless oil: [R]D ) -196.0 (c 1.30, CHCl3); FTIR
dcalcd ) 1.290 g cm-3, µ (Cu KR [λ ) 1.541 78 Å]) ) 0.772 mm-1
;
1
2
(CH2Cl2 cast) 3410 cm-1; H NMR (CD2Cl2, 300 MHz) δ 2.88
3347 reflections measured (2913 unique; 2749 with Fo
g
2
(d, J ) 4.2 Hz, 1 H), 3.35 (s, 3 H), 3.42 (s, 3 H), 3.44 (s, 3 H),
3.47-3.53 (m, 1 H), 3.68-3.77 (m, 3 H), 4.19 (dd, J ) 9.2, 4.2
Hz, 1 H), 4.58-4.63 (m, 1 H), 5.50 (br s, 1 H), 7.25-7.32 (m,
3 H), 7.56-7.63 (m, 2 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 58.05
(q′), 58.09 (q′), 59.40 (q′), 72.31 (t′), 77.66 (d′), 79.74 (d′), 81.26
(d′), 84.91 (d′), 90.31 (d′), 127.53 (d′), 129.40 (d′), 132.09 (s′),
133.57 (d′); exact mass (electrospray) m/z calcd for C15H22NaO5-
Se (M + Na) 385.0530, found 385.0532.
2σ(Fo2)); R1(F) ) 0.0327 (Fo g 2σ(Fo2)), wR2(F2) ) 0.0868 (all
data), GOF ) 1.055 (all data).
P h en yl 2,3-O-Isop r op ylid en e-1-selen o-â-D-r ibofu r a n o-
sid e (10a ). p-MeC6H4SO3H‚H2O (9.2 mg, 0.048 mmol) was
added to a stirred solution of phenyl 1-seleno-â-D-ribofurano-
side (see above) (140.0 mg, 0.484 mmol) in acetone (5 mL).
Stirring was continued for 5 h, NaHCO3 (12.2 mg, 0.145 mmol)
was then added. Stirring was continued for another 0.5 h, and
the mixture was then evaporated. Flash chromatography of
the residue over silica gel (1.0 × 20 cm), using 30% EtOAc-
hexane, gave 10a (148.3 mg, 92%) as a colorless oil: FTIR
P h en yl 2-O-(Dip h en ylh yd r a zon o)a cet yl-3,5,6-t r i-O-
m eth yl-1-selen o-â-D-glu cofu r a n osid e (9b). The general
procedure for coupling alcohols with reagent 2 was followed,
using 2 (714.0 mg, 2.975 mmol), 9a (895.0 mg, 2.479 mmol),
DCC (675.2 mg, 3.273 mmol), and DMAP (36.3 mg, 0.298
mmol) in CH2Cl2 (25 mL). Flash chromatography of the residue
over silica gel (1.6 × 28 cm), using 30% EtOAc-hexane, gave
9b (1.5001 g, ca. 103%) as a partially crystalline light brown
mass which contained a small amount [<10 mol % by 1H NMR
(400 MHz)] of chromatographically inseparable impurities. An
analytical sample was prepared by swirling the material in
40% EtOAc-hexane (15 mL) and evaporating the clear su-
pernatant. The resulting 9b: [R]D ) -116.4 (c 1.12, CHCl3);
1
(CH2Cl2 cast) 3462 cm-1; H NMR (CD2Cl2, 360 MHz) δ 1.32
(s, 3 H), 1.48 (s, 3 H), 2.10 (dd, J ) 7.0, 6.3 Hz, 1 H), 3.69-
3.81 (m, 2 H), 4.30-4.33 (m, 1 H), 4.76 (dd, J ) 6.1, 1.8 Hz, 1
H), 4.88 (dd, J ) 6.1, 2.1 Hz, 1 H), 5.82 (d, J ) 2.1 Hz, 1 H),
7.28-7.40 (m, 3 H), 7.59-7.68 (m, 2 H); 13C NMR (CD2Cl2,
75.5 MHz) δ 25.43 (q′), 27.08 (q′), 63.10 (t′), 82.17 (d′), 87.13
(d′), 88.82 (d′), 88.94 (d′), 113.70 (s′), 128.34 (d′), 129.37 (s′),
129.65 (d′), 134.45 (d′); exact mass m/z calcd for C14H18O4Se
330.0370, found 330.0364.
P h en yl 5-O-(Dip h en ylh yd r a zon o)a cetyl-2,3-O-isop r o-
p ylid en e-1-selen o-â-D-r ibofu r a n osid e (10b). The general
procedure for coupling alcohols with reagent 2 was followed,
using 2 (121.0 mg, 0.504 mmol), alcohol 10a (148.3 mg, 0.449
mmol), DCC (114.0 mg, 0.550 mmol), and DMAP (6.1 mg, 0.050
mmol) in CH2Cl2 (2 mL). Flash chromatography of the residue
over silica gel (1.0 × 20 cm), using 20% EtOAc-hexane, gave
10b (230.0 mg, 92%) as a pale yellow oil: FTIR (CH2Cl2 cast)
FTIR (CH2Cl2 cast) 1734, 1708 cm-1 1H NMR (CD2Cl2, 400
;
MHz) δ 3.36 (s, 3 H), 3.42 (s, 3 H), 3.48-3.55 [m, including s
(3 H) at δ 3.54, 4 H in all], 3.68-3.75 (m, 2 H), 3.90 (d, J ) 4.0
Hz, 1 H) 4.14 (dd, J ) 9.1, 4.0 Hz, 1 H), 5.62 (s, 1 H), 5.65 (s,
1 H), 6.43 (s, 1 H), 7.15-7.65 (m, 15 H); 13C NMR (CD2Cl2,
100.6 MHz) δ 58.12 (q′), 58.27 (q′), 59.46 (q′), 72.23 (t′), 77.44
(d′), 81.02 (d′), 81.76 (d′), 82.83 (d′), 87.43 (d′), 123.38 (d′),
127.77 (d′), 129.43 (d′), 130.40 (d′), 131.79 (s′), 133.98 (d′),
163.48 (s′); exact mass (electrospray) m/z calcd for C29H32N2-
NaO6Se (M + Na) 607.1323, found 607.1323.
1
1731, 1706 cm-1; H NMR (CD2Cl2, 400 MHz) δ 1.37 (s, 3 H),
1.45 (s, 3 H), 4.39 (dd, J ) 10.0, 4.7 Hz, 1 H), 4.46-4.54 (m, 2
H), 4.81 (dd, J ) 6.0, 1.6 Hz, 1 H), 4.96 (dd, J ) 6.0, 1.8 Hz,
1 H), 5.82 (d, J ) 1.8 Hz, 1 H), 6.56 (s, 1 H), 7.20-7.64 (m, 15
H); 13C NMR (CD2Cl2, 100.6 MHz) δ 25.50 (q′), 27.04 (q′), 63.99
(t′), 82.67 (d′), 85.40 (d′), 87.16 (d′), 88.38 (d′), 113.86 (s′), 123.95
(d′), 126.59 (d′), 128.18 (d′), 129.45 (d′), 129.50 (d′), 130.37 (d′),
134.62 (d′), 164.17 (s′); exact mass m/z calcd for C28H28N2O5-
Se 552.1163, found 552.1157.
3,6-An h yd r o-2-d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-5,7,8-
tr i-O-m eth yl-D-er yth r o-L-id o-octon o-1,4-la cton e (9c) a n d
3,6-An h yd r o-2-d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-5,7,8-tr i-
O-m eth yl-D-er yth r o-L-gu lo-octon o-1,4-la cton e (9d ). The
general procedure for radical cyclization was followed, using
9b [containing 3% impurities (1H NMR, 400 MHz)] (392.6 mg,
0.651 mmol) in PhMe (45 mL), Bu3SnH (544 µL, 2.020 mmol)
in PhMe (10 mL), and AIBN (30 mg, 0.182 mmol) in PhMe
(10 mL). Flash chromatography of the residue over silica gel
(1.6 × 30 cm), using 15% EtOAc-hexane, gave 9c (117.2 mg,
42%) as a colorless oil, and further elution, using 30% EtOAc-
hexane, gave 9d (113.3 mg, 40%) as a crystalline solid.
Compound 9c: [R]D ) +14.7 (c 1.13, CHCl3); FTIR (CH2Cl2
3,6-An h yd r o-2-d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-4,5-O-
isop r op ylid en e-D-glycer o-D-a llo-h ep ton o-1,7-la cton e a n d
3,6-An h yd r o-2-d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-4,5-O-
isopropylidene-D-glycero-D-a ltro-heptono-1,7-lactone (10c,d).
The general procedure for radical cyclization was followed,
using 10b (160.0 mg, 0.290 mmol) in PhMe (20 mL), Bu3SnH
(120 µL, 0.4456 mmol) in PhMe (5 mL), and AIBN (10 mg,
0.061 mmol) in PhMe (5 mL). Flash chromatography of the
residue over silica gel (1.0 × 20 cm), using 20% EtOAc-
1
cast) 3265, 1783 cm-1; H NMR (CD2Cl2, 400 MHz) δ 3.31 (s,
3 H), 3.37-3.41 [m, including s (3 H) at δ 3.40, 4 H in all),

Use of Radical Cyclization
J . Org. Chem., Vol. 64, No. 3, 1999 777
hexane, gave 10c,d (73.9 mg, 64%) as a crystalline solid which
was a chromatographically inseparable mixture of two isomers
in a 1.5:1 ratio (1H NMR, 400 MHz): FTIR (CH2Cl2 cast) 3292,
1736 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.29 (s, 1.2 H), 1.37
(s, 1.8 H), 1.46 (s, 1.2 H), 1.48 (s, 1.8 H), 3.86 (d, J ) 2.4 Hz,
0.6 H), 3.98 (dd, J ) 4.9, 2.2 Hz, 0.4 H), 4.15-4.46 (m, 3.6 H),
4.60 (d, J ) 5.7 Hz, 0.4 H), 4.75-4.97 (m, 3 H), 7.03-7.37 (m,
10 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 24.45 (q′), 24.52 (q′),
26.09 (q′), 26.16 (q′), 64.22 (d′), 66.18 (d′), 70.64 (t′), 72.59 (t′),
80.75 (d′), 81.25 (d′), 81.55 (d′), 81.98 (d′), 82.61 (d′), 82.83 (d′),
83.49 (d′), 83.58 (d′), 112.79 (s′), 113.03 (s′), 121.05 (d′), 123.57
(d′), 129.73 (d′), 147.65 (s′), 170.83 (s′), 172.31 (s′); exact mass
m/z calcd for C22H24N2O5 396.1685, found 396.1686.
(d, J ) 6.3 Hz, 2 H), 1.49 (s, 3 H), 3.72-3.76 (m, 0.40 H), 3.92-
4.01 (m, 1.43 H), 4.18 (dd, J ) 8.4, 3.2 Hz, 0.65 H), 4.43-4.47
(m, 1.42 H), 4.59-4.65 (m, 2.12 H), 5.24-5.38 (m, 1 H), 5.90-
5.91 (m, 1 H), 6.42 (s, 0.65 H), 6.46 (s, 0.35 H), 7.15-7.52 (m,
15 H);
26.51 (q′), 26.90 (q′), 27.08 (q′), 34.33 (t′), 68.21 (d′), 69.23 (d′),
72.37 (t′), 72.51 (t′), 79.32 (d′), 81.18 (d′), 81.38 (d′), 82.34 (d′),
82.44 (d′), 105.56 (d′), 105.66 (d′), 111.99 (s′), 112.53 (s′), 122.81
(d′), 123.58 (d′), 124.77 (d′), 126.44 (d′), 128.18 (d′), 128.31 (d′),
128.40 (d′), 128.48 (d′), 128.75 (d′), 130.36 (d′), 137.58 (s′),
137.82 (s′), 142.61 (s′), 163.29 (s′), 163.47 (s′); exact mass
(electrospray) m/z calcd for C30H32N2NaO6 (M + Na) 539.2158,
found 539.2153.
13C NMR (CD2Cl2, 50.3 MHz) δ 17.90 (q′), 26.34 (q′),
3-O-Ben zyl-6-br om o-6-d eoxy-1,2-O-isop r op ylid en e-r-D-
glu cofu r a n ose (11a ). Ph3P (642.0 mg, 2.448 mmol) was added
to a stirred and cooled (0 °C) solution of 2314 (379.4 mg, 1.224
mmol), in pyridine (20 mL), and then CBr4 (405.9 mg, 1.224
mmol) was added in several portions at 0 °C. After the
addition, the mixture was heated to 60 °C for 10 min. MeOH
(5 mL) was added to destroy any excess of reagents, and the
mixture was evaporated. Flash chromatography of the residue
over silica gel (1.6 × 28 cm), using 20% EtOAc-hexane, gave
11a (402.8 mg, 88%) as a colorless oil: [R]D ) -41.8 (c 1.25,
CHCl3); FTIR (CH2Cl2 cast) 3482 cm-1; 1H NMR (CD2Cl2, 300
MHz) δ 1.31 (br s, 3 H), 1.46 (br s, 3 H), 2.38 (d, J ) 5.9, 1 H),
3.58 (dd, J ) 10.5, 5.7 Hz, 1 H), 3.71 (dd, J ) 10.5, 2.7 Hz, 1
H), 4.03-4.14 (m, 3 H), 4.58 (d, J ) 11.7 Hz, 1 H), 4.64 (d, J
) 3.7 Hz, 1 H), 4.72 (d, J ) 10.7 Hz, 1 H), 5.89 (d, J ) 3.7 Hz,
1 H), 7.32-7.40 (m, 5 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 26.46
(q′), 27.00 (q′), 38.83 (t′), 68.47 (d′), 72.56 (t′), 81.13 (d′), 81.98
(d′), 82.58 (d′), 105.62 (d′), 112.29 (s′), 128.24 (d′), 128.45 (d′),
128.92 (d′), 137.85 (s′); exact mass (electrospray) m/z calcd for
The chromatographically less polar lactone: [R]D ) -27.3
(c 1.19, CHCl3); FTIR (CH2Cl2 cast) 3278, 1782 cm-1; 1H NMR
(CD2Cl2, 400 MHz) δ 1.34 (s, 3 H), 1.51 (s, 3 H), 2.32-2.40 (m,
1 H), 2.65-2.71 (m, 1 H), 3.92-3.97 (m, 1 H), 4.11 (d, J ) 3.2
Hz, 1 H), 4.32 (dd, J ) 7.4, 3.2 Hz, 1 H), 4.56-4.73 (m, 5 H),
5.92 (d, J ) 3.7 Hz, 1 H), 7.02-7.39 (m, 15 H); 13C NMR (CD2-
Cl2, 100.6 MHz) δ 26.38 (q′), 27.03 (q′), 33.71 (t′), 56.54 (d′),
72.66 (t′), 74.50 (d′), 81.77 (d′), 82.03 (d′), 82.69 (d′), 105.68
(d′), 112.44 (s′), 120.83 (d′), 123.19 (d′), 128.10 (d′), 128.31 (d′),
128.81 (d′), 129.63 (d′), 137.86 (s′), 147.38 (s′), 175.09 (s′); exact
mass (electrospray) m/z calcd for C30H32N2NaO6 (M + Na)
539.2158, found 539.2160.
The chromatographically more polar lactone: [R]D ) -16.2
(c 1.25, CHCl3); FTIR (CH2Cl2 cast) 3282, 1779 cm-1; 1H NMR
(CD2Cl2, 400 MHz) δ 1.31 (s, 3 H), 1.45 (s, 3 H), 2.42-2.49 (m,
1 H), 2.59-2.65 (m, 1 H), 3.94-3.99 (m, 1 H), 4.05 (d, J ) 3.5
Hz, 1 H), 4.27 (dd, J ) 5.5, 3.4 Hz, 1 H), 4.53-4.56 (m, 2 H),
4.64-4.70 (m, 2 H), 4.93-4.99 (m, 1 H), 5.89 (d, J ) 3.7 Hz, 1
H), 7.02-7.39 (m, 15 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 26.36
(q′), 26.97 (q′), 31.12 (t′), 55.96 (d′), 72.62 (t′), 76.54 (d′), 81.20
(d′), 82.28 (d′), 82.67 (d′), 105.72 (d′), 112.39 (s′), 120.89 (d′),
123.27 (d′), 128.13 (d′), 128.36 (d′), 128.86 (d′), 129.63 (d′),
137.76 (s′), 147.72 (s′), 175.42 (s′); exact mass (electrospray)
C
16H21BrNaO5 (M + Na) 395.0470, found 395.0475.
3-O-Ben zyl-6-br om o-6-deoxy-5-O-(diph en ylh ydr azon o)-
a cetyl-1,2-O-isop r op ylid en e-r-D-glu cofu r a n ose (11b). The
general procedure for coupling alcohols with reagent 2 was
followed, using 2 (303.3 mg, 1.264 mmol), 11a (392.8 mg, 1.053
mmol), DCC (286.8 mg, 1.390 mmol), and DMAP (20.0 mg,
0.164 mmol) in CH2Cl2 (10 mL). Flash chromatography of the
residue over silica gel (1.6 × 28 cm), using 10% EtOAc-
hexane, gave 11b (601.4 mg, 96%) as a pale yellow oil: [R]D )
-38.1 (c 2.0, CHCl3); FTIR (CH2Cl2 cast) 1732, 1708 cm-1; 1H
NMR (CD2Cl2, 360 MHz) δ 1.33 (s, 3 H), 1.50 (s, 3 H), 3.75
(dd, J ) 11.5, 4.2 Hz, 1 H), 3.94 (dd, J ) 11.5, 2.7 Hz, 1 H),
4.01 (d, J ) 3.1 Hz, 1 H), 4.45-4.48 (m, 2 H), 4.60-4.66 (m, 2
H), 5.35-5.39 (m, 1 H), 5.90 (d, J ) 3.6 Hz, 1 H), 6.43 (s, 1 H),
7.16-7.52 (m, 15 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 26.54
(q′), 27.09 (q′), 34.33 (t′), 69.27 (d′), 72.53 (t′), 79.35 (d′), 81.21
(d′), 82.38 (d′), 105.68 (d′), 112.55 (s′), 123.60 (d′), 128.32 (d′),
128.49 (d′), 128.82 (d′), 130.40 (d′), 137.60 (s′), 163.30 (s′); exact
mass m/z calcd for C30H31N2O6Br 596.1345, found 596.1345.
3-O-Ben zyl-6-d eoxy-5-O-(d ip h en ylh yd r a zon o)a cet yl-
1,2-O-isop r op ylid en e-r-D-glu cofu r a n ose (11e), 3-O-Ben -
zyl-6,7-d id eoxy-7-(2,2-d ip h en ylh yd r a zin o)-1,2-O-isop r o-
pyliden e-L-glycer o-r-D-glu cofu r an u r on o-8,5-lacton e (11c),
a n d 3-O-Ben zyl-6,7-d id eoxy-7-(2,2-d ip h en ylh yd r a zin o)-
1,2-O-isop r op ylid en e-D-glycer o-r-D-glu cofu r a n u r on o-8,5-
la cton e (11d ). The general procedure for radical cyclization
was followed, using 11b (303.0 mg, 0.509 mmol) in PhMe (30
mL), Bu3SnH (274 µL, 1.0185 mmol) in PhMe (10 mL), and
AIBN (10 mg, 0.061 mmol) in PhMe (10 mL). Flash chroma-
tography of the residue over silica gel (1.6 × 29 cm), using
10% EtOAc-hexane, gave fractions 1, 2, and 3, which all
contained a small amount of tributyltin residues (1H NMR,
400 MHz). Each fraction was further purified by flash chro-
matography over silica gel (1.0 × 20 cm), using 10% EtOAc-
hexane. Fraction 1 gave a 1:1.7 mixture (51.4 mg) of the
starting material and the simple reduction product 11e (12%
as judged by 1H NMR measurements); fraction 2 gave the
chromatographically less polar lactone 11c (or 11d ) (71.0 mg,
27%) as a colorless oil; fraction 3 gave the chromatographically
more polar lactone 11d (or 11c) (81.3 mg, 31%) as a colorless
oil.
m/z calcd for
539.2153.
C30H32N2NaO6 (M + Na) 539.2158, found,
1,6-An h yd r o-2-O-ben zoyl-4-d eoxy-3-O-(d ip h en ylh yd r a -
zon o)a cetyl-4-iod o-â-D-glu cop yr a n ose (12b). The general
procedure for coupling alcohols with reagent 2 was followed,
using 2 (674.3 mg, 2.810 mmol), 12a 15 (880.3 mg, 2.341 mmol),
DCC (637.7 mg, 3.091 mmol), and DMAP (34.3 mg, 0.281
mmol) in CH2Cl2 (20 mL). Flash chromatography of the residue
over silica gel (2.6 × 28 cm), using first 10% EtOAc-hexane
(300 mL) and then 20% EtOAc-hexane, gave 12b (1.2769 g,
91%) as a pale yellow oil: [R]D ) -25.2 (c 1.0, CHCl3); FTIR
1
(CH2Cl2 cast) 1722 cm-1; H NMR (CD2Cl2, 300 MHz) δ 3.74
(dd, J ) 7.7, 5.6 Hz, 1 H), 4.29 (br s, 1 H), 4.33-4.36 (m, 1 H),
4.83 (d, J ) 5.1 Hz, 1 H), 4.92-4.96 (m, 1 H), 5.40-5.44 (m, 1
H), 5.64 (br s, 1 H), 6.49 (s, 1 H), 7.19-7.67 (m, 13 H), 8.18-
8.26 (m, 2 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 21.34 (d′), 67.63
(t′), 69.44 (d′), 73.69 (d′), 78.11 (d′), 99.53 (d′), 122.63 (d′),
128.83 (d′), 129.58 (s′), 130.44 (d′), 133.83 (d′), 162.99 (s′),
165.44 (s′); exact mass m/z calcd for C27H23N2O6I 598.0601,
found 598.0610.
1,6-An h yd r o-2-O-ben zyl-4-d eoxy-3-O-(d ip h en ylh yd r a -
zon o)a cetyl-â-D-xylo-h exop yr a n ose (12e), 1,6-An h yd r o-2-
O-ben zoyl-4-d eoxy-4-C-[(R)-(2,2-d ip h en ylh yd r a zin o)ca r -
boxym eth yl)]-â-D-galactopyr an ose 2′,3-Lacton e (12d), an d
1,6-An h yd r o-2-O-b en zoyl-4-d eoxy-4-C-[(S)-R-(2,2-d ip h e-
n ylh yd r a zin o)ca r boxym eth yl)]-â-D-ga la ctop yr a n ose 2′,3-
La cton e (12c). The general procedure for radical cyclization
was followed, using 12b (268.0 mg, 0.448 mmol) in PhMe (30
mL), Bu3SnH (181 µL, 0.6723 mmol) in PhMe (10 mL), and
AIBN (5 mg, 0.031 mmol) in PhMe (10 mL). Refluxing was
continued for 7 h after the addition. Flash chromatography of
the residue over silica gel (1.6 × 30 cm), using 10% EtOAc-
hexane, gave fractions 1, 2, and 3, which all contained a small
amount of tributyltin residues (1H NMR). Fraction 1 was
further purified by flash chromatography over silica gel (1.0
× 20 cm), using 10% EtOAc-hexane, and gave 12c (73.6 mg,
34%) as a colorless oil. Fraction 2 was purified similarly, using
20% EtOAc-hexane, and gave 12e (53.2 mg, 25%) as a
The fraction containing 11e: FTIR (CH2Cl2 cast) 1730, 1704
cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.29-1.34 (m, 3 H), 1.40

778 J . Org. Chem., Vol. 64, No. 3, 1999
Zhang and Clive
crystalline solid. Fraction 3 was purified similarly, using 20%
EtOAc-hexane, and gave 12d (48.6 mg, 23%) as a colorless
oil.
7.48 (m, 28 H), 7.61-7.65 (m, 2 H); 13C NMR (CD2Cl2, 100.6
MHz) δ 69.34 (t′), 71.51 (d′), 72.14 (t′), 73.59 (t′), 74.83 (d′),
75.01 (d′), 75.51 (t′), 79.28 (d′), 84.19 (d′), 123.48 (d′), 127.86
(d′), 127.96 (d′), 128.10 (d′), 128.18 (d′), 128.26 (d′), 128.62 (d′),
128.66 (d′), 128.75 (d′), 129.56 (d′), 129.64 (s′), 130.36 (d′),
134.43 (d′), 138.20 (s′), 138.75 (s′), 138.92 (s′), 163.85 (s′); exact
mass (electrospray) m/z calcd for C47H44N2NaO6Se (M + Na)
835.2262, found 835.2256.
Compound 12c: [R]D ) +87.8 (c 1.0, CHCl3); FTIR (CH2Cl2
1
cast) 1782, 1725 cm-1; H NMR (CD2Cl2, 400 MHz) δ 3.32-
3.37 (m, 1 H), 3.84 (dd, J ) 8.9, 5.4 Hz, 1 H), 4.01 (d, J ) 8.9
Hz, 1 H), 4.11 (dd, J ) 8.1, 1.4 Hz, 1 H), 4.42 (br s, 1 H), 4.47-
4.49 (m, 1 H), 4.58 (t, J ) 5.2 Hz, 1 H), 5.11-5.13 (m, 1 H),
5.56-5.58 (m, 1 H), 7.08-7.17 (m, 6 H), 7.32-7.66 (m, 7 H),
8.03-8.11 (m, 2 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 38.53 (d′),
57.89 (d′), 65.39 (t′), 67.59 (d′), 71.57 (d′), 75.04 (d′), 99.40 (d′),
121.22 (d′), 124.19 (d′), 128.92 (d′), 129.50 (s′), 129.95 (d′),
130.13 (d′), 134.02 (d′), 147.61 (s′), 165.35 (s′), 173.84 (s′); exact
mass m/z calcd for C27H24N2O6 472.1634, found 472.1629.
Irradiation of the CHNHNPh2 1H NMR signal caused an NOE
of 7% in the pyranose C(3)H signal; the corresponding value
for 12d was 0%.
3,6-An h yd r o-1-O-[(1,1-d im eth yleth yl)d ip h en ylsilyl]-2-
d eoxy-2-(2,2-d ip h en ylh yd r a zin o)-5,7,8-t r i-O-m et h yl-D-
er yth r o-L-id o-octitol (29a ). A solution of 9c (124.2 mg, 0.291
mmol) in THF (0.5 mL, plus 2 × 0.5 mL as a rinse) was added
to a stirred and cooled (0 °C) suspension of LiAlH4 (24.3 mg,
0.639 mmol) in THF (1.5 mL). Stirring was continued for 30
min at 0 °C, and then for 1 h after removal of the ice bath.
MeOH (0.2 mL) was added carefully to quench the reaction,
followed by saturated NaHCO3 (0.1 mL). The mixture was
stirred for 15 min, filtered through a pad (1 cm × 2 mm) of
Celite, using EtOAc, and evaporated, to give the expected diol.
t-BuPh2SiCl (77 µL, 0.2960 mmol) was added dropwise to a
stirred solution of the above diol and imidazole (37.0 mg, 0.543
mmol) in CH2Cl2 (3 mL). Stirring was continued for 3.5 h, and
the solvent was evaporated. Flash chromatography of the
residue over silica gel (1.6 × 28 cm), using 20% EtOAc-
Compound 12e: mp 169-171 °C; [R]D ) +126 (c 1.0, CHCl3);
FTIR (CH2Cl2 cast) 1722 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
1.85-1.89 (m, 1 H), 2.50-2.56 (m, 1 H), 3.79-3.82 (m, 1 H),
4.33 (d, J ) 6.9 Hz, 1 H), 4.62-4.64 (m, 1 H), 4.88 (d, J ) 1.2
Hz, 1 H), 5.15-5.17 (m, 1 H), 5.55 (br s, 1 H), 6.50 (s, 1 H),
7.18-7.64 (m, 13 H), 8.05-8.11 (m, 2 H); 13C NMR (CD2Cl2,
50.3 MHz) δ 31.57 (t′), 67.63 (t′), 67.84 (d′), 69.86 (d′), 71.66
(d′), 99.36 (d′), 123.82 (d′), 126.57 (d′), 128.82 (d′), 130.10 (d′),
130.39 (d′), 133.73 (d′), 163.70 (s′), 165.36 (s′); exact mass
(electrospray) m/z calcd for C27H24N2NaO6 (M + Na) 495.1532,
found 495.1537.
hexane, gave 29a (154.0 mg, 79%) as a colorless oil: [R]D
)
+3.5 (c 1.18, CHCl3); FTIR (CH2Cl2 cast) 3444 cm-1; 1H NMR
(CD2Cl2, 400 MHz) δ 1.08 (s, 9 H), 3.43 (s, 3 H), 3.45 (s, 3 H),
3.48 (s, 3 H), 3.52-3.67 (m, 5 H), 3.75-3.85 (m, 2 H), 3.94-
3.98 (m, 2 H), 4.12 (dd, J ) 9.1, 3.3 Hz, 1 H), 4.44 (br s, 1 H),
4.79 (s, 1 H), 6.95-7.05 (m, 6 H), 7.21-7.66 (m, 14 H); 13C
NMR (CD2Cl2, 100.6 MHz) δ 19.20 (s′), 26.97 (q′), 58.13 (q′),
58.20 (q′), 59.53 (q′), 59.71 (d′), 64.20 (t′), 73.17 (t′), 74.16 (d′),
77.57 (d′), 79.21 (d′), 83.70 (d′), 86.02 (d′), 120.49 (d′), 122.53
(d′), 128.27 (d′), 129.27 (d′), 130.41 (d′), 130.47 (d′), 132.45 (s′),
132.64 (s′), 135.87 (d′), 135.98 (d′), 148.20 (s′); exact mass m/z
calcd for C39H50N2O6Si 670.3438, found 670.3434.
Compound 12d : [R] ) +42.1 (c 0.73, CHCl3); FTIR (CH2Cl2
cast) 3280, 1783, 1725 cm-1 1H NMR (CD2Cl2, 400 MHz) δ
;
3.23-3.26 (m, 1 H), 3.58 (d, J ) 2.2 Hz, 1 H), 3.60-3.66 (m, 2
H), 4.38 (d, J ) 2.2 Hz, 1 H), 4.47-4.49 (m, 1 H), 4.88-4.94
(m, 1 H), 5.17 (br s, 1 H), 5.58-5.59 (m, 1 H), 7.05-7.68 (m,
13 H), 8.02-8.08 (m, 2 H); 13C NMR (CD2Cl2, 100.6 MHz) δ
38.94 (d′), 59.35 (d′), 64.88 (t′), 68.32 (d′), 71.96 (d′), 77.28 (d′),
99.56 (d′), 120.98 (d′), 123.86 (d′), 128.92 (d′), 129.00 (s′), 129.90
(d′), 130.17 (d′), 134.0 (d′), 147.30 (s′), 165.40 (s′), 172.79 (s′);
exact mass m/z calcd for C27H24N2O6 472.1634, found 472.1635.
P h en yl 3,4,6-Tr i-O-ben zyl-1-selen o-r-D-m a n n op yr a n o-
sid e (13a ). K2CO3 (153.0 mg, 1.107 mmol) was added to a
stirred solution of phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-se-
leno-R-d-mannopyranoside16 (350.0 mg, 0.555 mmol) in 1:1
THF-MeOH (10 mL), and the mixture was stirred vigorously
for 30 min, filtered through a pad (1 cm × 2 mm) of silica gel,
and evaporated. Flash chromatography of the residue over
silica gel (1.6 × 27 cm), using 20% EtOAc-hexane, gave 13a
(326.9 mg, 90%) as a colorless oil: [R]d ) +158.6 (c 1.2, CHCl3);
FTIR (CH2Cl2 cast) 3428 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ
2.87 (br, 1 H), 3.70 (dd, J ) 10.8, 1.9 Hz, 1 H); 3.82 (dd, J )
10.8, 4.5 Hz, 1 H), 3.89 (dd, J ) 9.1, 3.2 Hz, 1 H), 3.94-3.99
(m, 1 H), 4.19-4.23 (m, 1 H), 4.37 (dd, J ) 3.0, 1.5 Hz, 1 H),
4.50 (d, J ) 11.8, 1 H), 4.59-4.63 (m, 2 H), 4.73 (dd, J ) 17.1,
11.5 Hz, 1 H), 4.89 (d, J ) 10.9 Hz, 1 H), 5.90 (d, J ) 1.3 Hz,
1 H), 7.25-7.45 (m, 18 H), 7.62-7.66 (m, 2 H); 13C NMR (CD2-
Cl2, 100.6 MHz) δ 69.24 (t′), 70.68 (d′), 72.28 (t′), 73.63 (t′),
74.39 (d′), 74.71 (d′), 75.41 (t′), 80.94 (d′), 85.88 (d′), 127.93
(d′), 127.96 (d′), 128.11 (d′), 128.26 (d′), 128.33 (d′), 128.36 (d′),
128.63 (d′), 128.67 (d′), 128.87 (d′), 129.51 (d′), 129.66 (s′),
134.41 (d′), 138.25 (s′), 138.69 (s′), 138.94 (s′); exact mass
(electrospray) m/z calcd for C33H34NaO5Se (M + Na) 613.1469,
found 613.1477.
3,6-An h yd r o-2-b e n za m id o-4-O-b e n zoyl-1-O-[(1,1-d i-
methylethyl)diphenylsilyl]-2-deoxy-5,7,8-tri-O-methyl-D-erythro-L-
id o-octitol (30a ). Camphorsulfonic acid (72.4 mg, 0.312 mmol)
and then 10% Pd-C (30.0 mg) were added to a solution of 29a
(95.0 mg, 0.142 mmol) in a mixture of EtOAc (2.4 mL) and
MeOH (0.6 mL). The mixture was shaken under H2 (50 psi)
for 2 h (Parr shaker) and then filtered through a pad of Celite.
The pad was washed with EtOAc (3 × 5 mL), and the combined
filtrates were evaporated, and stored under oil-pump vacuum
for 4 h. CH2Cl2 (5 mL), Et3N (197 µL, 1.4170 mmol), PhCOCl
(131 µL, 1.1336 mmol), and DMAP (15.0 mg, 0.123 mmol) were
added in that order to a stirred solution of the resulting yellow
foam. Stirring was continued for 24 h, and the solvent was
evaporated. Flash chromatography of the residue over silica
gel (1.6 × 28 cm), using 30% EtOAc-hexane, gave 30a (77.0
mg, 76%) as a pale yellow oil: [R]D ) -7.5 (c 1.06, CHCl3);
1
FTIR (CH2Cl2 cast) 3438, 1723, 1667 cm-1; H NMR (CD2Cl2,
400 MHz) δ 1.07 (s, 9 H), 3.39 (s, 3 H), 3.43 (s, 3 H), 3.56 (dd,
J ) 10.5, 4.4 Hz, 1 H), 3.59 (s, 3 H), 3.63 (ddd, J ) 9.3, 4.4,
1.8 Hz, 1 H), 3.74-3.79 (m, 3 H), 3.93 (d, J ) 3.4 Hz, 1 H),
4.19 (dd, J ) 9.3, 3.4 Hz, 1 H), 4.52-4.60 (m, 1 H), 4.79-4.82
(m, 1 H), 5.64 (dd, J ) 4.0, 0.6 Hz, 1 H), 6.81 (d, J ) 8.3 Hz,
1 H), 7.15-7.54 (m, 12 H), 7.62-7.84 (m, 8 H); 13C NMR (CD2-
Cl2, 100.6 MHz) δ 19.52 (s′), 26.99 (q′), 50.21 (d′), 58.12 (q′),
58.32 (q′), 59.53 (q′), 64.63 (t′), 72.48 (t′), 77.08 (d′), 77.42 (d′),
77.46 (d′), 79.89 (d′), 84.36 (d′), 127.23 (d′), 128.07 (d′), 128.11
(d′), 128.58 (d′), 128.82 (d′), 129.72 (s′), 129.99 (d′), 130.08 (d′),
130.13 (d′), 131.67 (d′), 133.54 (d′), 133.66 (s′), 134.89 (s′),
135.91 (d′), 165.95 (s′), 166.08 (s′); exact mass (electrospray)
m/z calcd for C41H49NNaO8Si (M + Na) 734.3125, found
734.3130.
3,6-An h yd r o-2-b en za m id o-4-O-b en zoyl-2-d eoxy-5,7,8-
tr i-O-m eth yl-D-er yth r o-L-id o-octitol (31a ). Bu4NF (1.0 M
solution in THF, 388 µL, 0.3880 mmol) was added dropwise
to a stirred solution of 30a (92.0 mg, 0.129 mmol) and
anhydrous pyridinium hydrochloride (22.4 mg, 0.194 mmol)
in THF (1 mL). Stirring was continued for 12 h, and the
mixture was then evaporated. Flash chromatography of the
residue over silica gel (1.6 × 27 cm), using 80% EtOAc-
P h en yl 3,4,6-Tr i-O-ben zyl-2-O-(d ip h en ylh yd r a zon o)-
a cetyl-1-selen o-r-D-m a n n op yr a n osid e (13b). The general
procedure for coupling alcohols with reagent 2 was followed,
using 2 (156.5 mg, 0.652 mmol), alcohol 13a (310.0 mg, 0.526
mmol), DCC (148.0 mg, 0.717 mmol), and DMAP (15.0 mg,
0.123 mmol) in CH2Cl2 (10 mL). Flash chromatography of the
residue over silica gel (1.6 × 28 cm), using 10% EtOAc-
hexane, gave 13b (396.1 mg, 92%) as a pale yellow oil: [R]D )
+61.5 (c 0.96, CHCl3); FTIR (CH2Cl2 cast) 1728, 1705 cm-1
;
1H NMR (CD2Cl2, 400 MHz) δ 3.71 (dd, J ) 10.9, 1.9 Hz, 1 H),
3.81 (dd, J ) 10.9, 4.9 Hz, 1 H), 3.94-4.00 (m, 2 H), 4.18-
4.26 (m, 1 H), 4.49 (d, J ) 12.1 Hz, 1 H), 4.55-4.61 (m, 3 H),
4.77 (d, J ) 11.3 Hz, 1 H), 4.89 (d, J ) 10.9 Hz, 1 H), 5.8 (t, J
) 2.0 Hz, 1 H), 5.84 (d, J ) 1.3 Hz, 1 H), 6.56 (s, 1 H), 7.20-

Use of Radical Cyclization
J . Org. Chem., Vol. 64, No. 3, 1999 779
hexane, gave 31a (51.0 mg, 83%) as a pale yellow oil: [R]D )
-12.3 (c 1.4, CHCl3); FTIR (CH2Cl2 cast) 3427, 1722, 1651
cm-1; 1H NMR (CD2Cl2, 300 MHz) δ 3.25-3.35 (br, 1 H), 3.41
(br s, 6 H), 3.55-3.79 [m, including s (3 H) at δ 3.56, 8 H in
all], 3.93 (dd, J ) 3.4, 0.8 Hz, 1 H), 4.22 (dd, J ) 9.2, 3.4 Hz,
1 H), 4.38-4.47 (m, 1 H), 4.59 (t, J ) 3.9 Hz, 1 H), 5.64 (dd, J
) 3.9, 0.8 Hz, 1 H), 6.97 (d, J ) 7.5 Hz, 1 H), 7.15-7.55 (m, 6
H), 7.68-7.87 (m, 4 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 51.65
(d′), 58.01 (q′), 58.37 (q′), 59.56 (q′), 64.56 (t′), 72.25 (t′), 76.81
(d′), 77.24 (d′), 77.69 (d′), 79.95 (d′), 84.30 (d′), 127.29 (d′),
128.61 (d′), 128.84 (d′), 129.63 (s′), 129.95 (d′), 131.88 (d′),
133.60 (d′), 134.46 (s′), 165.90 (s′), 167.40 (s′); exact mass
(electrospray) m/z calcd for C25H31NNaO8 (M + Na) 496.1947,
found 496.1933.
(0 °C) solution of 31a (51.0 mg, 0.108 mmol) in acetone (0.9
mL). Stirring was continued for 1.5 h before the excess of J ones
reagent was quenched with i-PrOH (70 µL). Stirring was
continued for 2 h, the mixture was filtered, and the green
precipitate was washed with Et2O (3 × 5 mL). The combined
filtrates were washed with brine (2 × 2 mL), dried (MgSO4),
and evaporated. DMF (1 mL), NaHCO3 (27.2 mg, 0.323 mmol),
BnBr (64 µL, 0.539 mmol), and NaI (1.0 mg, 0.007 mmol) were
added to the resulting residue, and the mixture was stirred
for 22 h (TLC indicated complete reaction). The DMF was
evaporated under oil-pump vacuum. Flash chromatography of
the residue over silica gel (1.6 × 27 cm), using 40% EtOAc-
hexane, gave 34 (48.0 mg, 77%) as a colorless oil: [R]D ) -19.7
(c 0.98, CHCl3); FTIR (CH2Cl2 cast) 3350, 1725, 1668 cm-1
;
Meth yl 3,6-An h ydr o-2-ben zam ido-4-O-ben zoyl-2-deoxy-
5,7,8-tr i-O-m eth yl-D-er yth r o-L-id o-octon a te (32a ). J ones
reagent (125 µL, 8 N) was added dropwise to a stirred and
cooled (0 °C) solution of 31a (53.0 mg, 0.112 mmol) in acetone
(0.8 mL). Stirring was continued for 1.5 h before the excess of
J ones reagent was quenched with i-PrOH (70 µL). Stirring was
continued for 2 h, the mixture was filtered, and the green
precipitate was washed with Et2O (3 × 4 mL). The combined
filtrates were evaporated, dissolved in a little Et2O, and treated
with an ethereal solution of CH2N2 until a slight yellow color
persisted. The excess of CH2N2 was destroyed with a few drops
of AcOH, and the solvent was evaporated. Flash chromatog-
raphy of the residue over silica gel (1.6 × 27 cm), using 40%
EtOAc-hexane, gave 32a (43.0 mg, 76%) as a white foam:
[R]D ) -11.2 (c 0.86, CHCl3); FTIR (CH2Cl2 cast) 3344, 1725,
1H NMR (CD2Cl2, 400 MHz) δ 3.39 (s, 3 H), 3.41 (s, 3 H), 3.52
(dd, J ) 10.6, 4.3 Hz, 1 H), 3.55 (s, 3 H), 3.59 (ddd, J ) 9.2,
4.3, 1.8 Hz, 1 H), 3.73 (dd, J ) 10.6, 1.8 Hz, 1 H), 3.94 (dd, J
) 3.4, 0.6 Hz, 1 H), 4.24 (dd, J ) 9.2, 3.4 Hz, 1 H), 4.82 (t, J
) 3.9 Hz, 1 H), 5.09 (dd, J ) 8.2, 3.7 Hz, 1 H), 5.14 (d, J )
12.4 Hz, 1 H), 5.20 (d, J ) 12.4 Hz, 1 H), 5.69 (dd, J ) 4.1, 0.7
Hz, 1 H), 7.00 (d, J ) 8.2 Hz, 1 H), 7.19-7.56 (m, 11 H), 7.70-
7.87 (m, 4 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 52.50 (d′), 58.10
(q′), 58.42 (q′), 59.53 (q′), 67.68 (t′), 72.31 (t′), 76.56 (d′), 77.23
(d′), 78.51 (d′), 80.34 (d′), 84.22 (d′), 127.40 (d′), 128.35 (d′),
128.63 (d′), 128.86 (d′), 129.54 (s′), 130.00 (d′), 132.02 (d′),
133.65 (d′), 134.15 (s′), 135.88 (s′), 165.81 (s′), 166.87 (s′), 170.51
(s′); exact mass (electrospray) m/z calcd for C32H35NNaO9 (M
+ Na) 600.2209, found 600.2218.
Ben zyl 3,6-An h yd r o-4-O-ben zoyl-2-[[(1,1-d im eth yleth -
oxy)car bon yl]am in o]-2-deoxy-5,7,8-tr i-O-m eth yl-D-er yth r o-
L-id o-octon a te (35). (t-BuOCO)2O (56.0 mg, 0.257 mmol) was
added to a stirred solution of 34 (41.0 mg, 0.071 mmol) and
DMAP (2.2 mg, 0.018 mmol) in THF (1 mL), and the mixture
was refluxed for 4 h. The solution was cooled to room
temperature, MeOH (1 mL) and N2H4 (16 µL, 0.5097 mmol)
were added, and the mixture was stirred for 6 h (TLC indicated
complete reaction) and evaporated. Flash chromatography of
the residue over silica gel (1.6 × 25 cm), using 40% EtOAc-
hexane, gave 35 (36.5 mg, 89%) as a colorless oil: [R]D ) -2.7
(c 1.12, CHCl3); FTIR (CH2Cl2 cast) 3367, 1723, 1601, 1585
1667 cm-1 1H NMR (CD2Cl2, 300 MHz) δ 3.41 (br s, 6 H),
;
3.52-3.62 (m, 5 H), 3.70 (s, 3 H), 3.71-3.77 (m, 1 H), 3.92 (d,
J ) 3.4 Hz, 1 H), 4.24 (dd, J ) 9.0, 3.4 Hz, 1 H), 4.79 (t, J )
3.9 Hz, 1 H), 5.02 (dd, J ) 8.1, 3.6 Hz, 1 H), 5.71 (d, J ) 4.2
Hz, 1 H), 6.96 (d, J ) 8.1 Hz, 1 H), 7.19-7.57 (m, 6 H), 7.70-
7.88 (m, 4 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 52.20 (d′) or
(q′), 52.96 (d′) or (q′), 58.08 (q′), 58.42 (q′), 59.56 (q′), 72.23
(t′), 76.53 (d′), 77.23 (d′), 78.55 (d′), 80.37 (d′), 84.22 (d′), 127.40
(d′), 128.65 (d′), 128.88 (d′), 129.56 (s′), 130.00 (d′), 132.05 (d′),
133.68 (d′), 134.12 (s′), 165.85 (s′), 166.73 (s′), 171.11 (s′); exact
mass (electrospray) m/z calcd for C26H31NNaO9 (M + Na)
524.1896, found 524.1900.
1
cm-1; H NMR (CD2Cl2, 400 MHz) δ 1.29 (s, 9 H), 3.37 (s, 3
Meth yl 3,6-An h yd r o-4-O-ben zoyl-2-[[(1,1-d im eth yleth -
oxy)car bon yl]am in o]-2-deoxy-5,7,8-tr i-O-m eth yl-D-er yth r o-
L-id o-octon a te (33). (t-BuOCO)2O (56.0 mg, 0.257 mmol) was
added to a stirred solution of 32a (35.0 mg, 0.070 mmol) and
DMAP (2.1 mg, 0.017 mmol) in THF (1 mL), and the mixture
was refluxed for 4 h. The solution was cooled to room
temperature, MeOH (1 mL) and N2H4 (13 µL, 0.4194 mmol)
were added, and the mixture was stirred for 4 h (TLC indicated
complete reaction) and evaporated. Flash chromatography of
the residue over silica gel (1.6 × 24 cm), using first 30%
EtOAc-hexane (200 mL) and then 40% EtOAc-hexane, gave
33 (30.0 mg, 86%) as a colorless oil: [R]D ) -5.6 (c 1.02, CHCl3);
H), 3.40 (s, 3 H), 3.41-3.48 (m, 1 H), 3.51-3.58 [m, including
s (3 H) at δ 3.52, 4 H in all], 3.68 (dd, J ) 10.6, 1.9 Hz, 1 H),
3.92 (d, J ) 3.5 Hz, 1 H), 4.13 (dd, J ) 9.2, 3.7 Hz, 1 H), 4.55-
4.63 (m, 2 H), 5.12 (s, 2 H), 5.30 (d, J ) 8.1 Hz, 1 H), 5.58 (d,
J ) 3.3 Hz, 1 H), 7.25-7.62 (m, 8 H), 7.97-8.02 (m, 2 H); 13
C
NMR (CD2Cl2, 100.6 MHz) δ 28.23 (q′), 53.86 (d′), 58.30 (q′),
58.43 (q′), 59.43 (q′), 67.49 (t′), 72.94 (t′), 76.46 (d′), 77.39 (d′),
78.47 (d′), 79.91 (s′), 80.09 (d′), 84.26 (d′), 128.33 (d′), 128.56
(d′), 128.80 (d′), 129.79 (s′), 130.15 (d′), 133.70 (d′), 135.89 (s′),
155.57 (s′), 165.75 (s′), 170.87 (s′); exact mass (electrospray)
m/z calcd for C30H39NNaO10 (M + Na) 596.2472, found 596.2473.
FTIR (CH2Cl2 cast) 3365, 1723, 1601, 1585 cm-1 1H NMR
;
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada for finan-
cial support. J . Z. held an Alberta Province Graduate
Fellowship.
(CD2Cl2, 400 MHz) δ 1.30 (s, 9 H), 3.38 (s, 3 H), 3.40 (s, 3 H),
3.45-3.49 (m, 1 H), 3.52-3.58 [m, including s (3 H) at δ 3.54,
4 H in all], 3.66 (s, 3 H), 3.71 (dd, J ) 10.5, 1.9 Hz, 1 H), 3.91
(dd, J ) 3.6, 0.8 Hz, 1 H), 4.13 (dd, J ) 9.2, 3.6 Hz, 1 H), 4.48-
4.58 (m, 2 H), 5.26 (d, J ) 8.3 Hz, 1 H), 5.60 (d, J ) 3.4 Hz, 1
H), 7.42-7.62 (m, 3 H), 8.00-8.05 (m, 2 H); 13C NMR (CD2-
Cl2, 100.6 MHz) δ 28.25 (q′), 52.73 (d′) or (q′), 53.63 (d′) or (q′),
58.30 (q′), 58.44 (q′), 59.44 (q′), 72.96 (t′), 76.39 (d′), 77.41 (d′),
78.57 (d′), 79.92 (s′), 80.14 (d′), 84.32 (d′), 128.84 (d′), 129.83
(s′), 130.14 (d′), 133.75 (d′), 155.57 (s′), 165.80 (s′), 171.43 (s′);
exact mass (electrospray) m/z calcd for C24H35NNaO10 (M +
Na) 520.2159, found 520.2167.
Su p p or tin g In for m a tion Ava ila ble: An outline of the
procedure for making 24-27 and procedures for preparation
of 13c,d and 29b-32b, and copies of NMR spectra for
compounds not analyzed (59 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering informa-
tion. X-ray data on 9d has been submitted to the Cambridge
Crystallographic Data Centre.
Ben zyl 3,6-An h ydr o-2-ben zam ido-4-O-ben zoyl-2-deoxy-
5,7,8-tr i-O-m eth yl-D-er yth r o-L-id o-octon a te (34). J ones re-
agent (121 µL, 8 N) was added dropwise to a stirred and cooled
J O981435W