Synthesis of C-3 branched allyl and pentadienyl glucosamines via radical coupling of sugar-thionocarbonates

Article abstract of DOI:10.1081/CAR-120030469

The intermolecular AIBN-promoted free radical reaction of glucosamine thionocarbonates as radical donors, and allyl or pentadienyl-tributyltin reagents gave the expected C-3 branched sugar derivatives in good yield and with total equatorial selectivity. Copyright

Full text of DOI:10.1081/CAR-120030469

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Synthesis of C‐3 Branched Allyl and Pentadienyl
Glucosamines via Radical Coupling of
Sugar‐Thionocarbonates
Qian Wan a , André Lubineau a & Marie‐Christine Scherrmann a
a Laboratoire de Chimie Organique Multifonctionnelle , Université de Paris‐Sud , UMR
8614, ICMMO, Bâtiment 420, 91405, Orsay, Cedex, France
Published online: 18 Aug 2006.
To cite this article: Qian Wan , André Lubineau & Marie‐Christine Scherrmann (2004) Synthesis of C‐3 Branched Allyl and
Pentadienyl Glucosamines via Radical Coupling of Sugar‐Thionocarbonates, Journal of Carbohydrate Chemistry, 23:2-3,
83-93, DOI: 10.1081/CAR-120030469
To link to this article: http://dx.doi.org/10.1081/CAR-120030469
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 23, Nos. 2 & 3, pp. 83–93, 2004
Synthesis of C-3 Branched Allyl and Pentadienyl
Glucosamines via Radical Coupling of
Sugar-Thionocarbonates
*
´
Qian Wan, Andre Lubineau, and Marie-Christine Scherrmann
´
Laboratoire de Chimie Organique Multifonctionnelle, Universite de Paris-Sud,
Orsay, France
ABSTRACT
The intermolecular AIBN-promoted free radical reaction of glucosamine thionocarbo-
nates as radical donors, and allyl or pentadienyl-tributyltin reagents gave the expected
C-3 branched sugar derivatives in good yield and with total equatorial selectivity.
Key Words: C-Branched alkenyl sugars; Radical reaction; Pentadienyltributyltin;
Allyltributyltin; Thionocarbonates.
INTRODUCTION
C-Branched alkenyl sugars are useful precursors for the synthesis of more complex
C-glycosides.[1–6] For instance, benzyl 2-acetamido-3-C-allyl-2,3-dideoxy-4,6-O-isopro-
pylidene-a-D-glucopyranoside 2 has been used for the synthesis of C-trisaccharides
related to the H-type I blood group determinant.[7,8] More recently, Liu and Postema
reported the preparation and use of various C-allyl branched sugars as starting materials
*
Correspondence: Marie-Christine Scherrmann, Laboratoire de Chimie Organique Multifonction-
´ ˆ
nelle, Universite de Paris-Sud, UMR 8614, ICMMO, Batiment 420, 91405 Orsay, Cedex, France;
Fax: þ(0)1-69-15-47-15; E-mail: mcscherr@icmo.u-psud.fr.
83
DOI: 10.1081/CAR-120030469
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Wan, Lubineau, and Scherrmann
for the synthesis of C-disaccharides via metathesis.[9,10] Alternatively, we have shown that
C-dienyl glycosides are useful precursors for the synthesis of C-disaccharide analogs by
hetero Diels–Alder reaction.[11] These de novo strategies are highly attractive since
they should allow stereostructural variation leading to molecular diversity. Since import-
ant naturally occurring oligosaccharides feature a N-acetyl glucosamine (GlcNAc) moiety
substituted at the 3 position by a galactose (Gal) unit (H-type blood determinant or Lewis
A) or a fucose (Fuc) residue (Lewis X), we have investigated the synthesis of C-allyl and
penta-20,40-dienyl glucosamines via radical coupling using tributyltin derivatives.
RESULTS AND DISCUSSION
Preparation of the 3-C-allyl derivative 2 in 46% yield was reported by Sutherlin and
Armstrong,[7,8] by an AIBN-initiated radical reaction of methyl dithiocarbonate (xanthate)
1 and allyltributyltin. However in our hands, isolation of pure 2 was rather troublesome.
The radical coupling was therefore reinvestigated in order to improve both the yield of the
reaction and the purification step. Paying careful attention to the known protocol,[7,8] we
were able to isolate the pure target 2 (45%) as well as the 3-deoxysaccharide 3[12] (30%)
and the rearranged derivative 4 (ꢀ15%) (Sch. 1). Despite the fact that the latter compound
was slightly contaminated by 2, its structure was established by NMR analysis and mass
spectrometry. The mass spectrum indicated the same molecular peak as that of starting
xanthate 1 but a signal at 169.7 ppm in the 13C NMR spectra indicated the presence of
a carbonyl group, whereas the thiocarbonyl group in compound 1 had a chemical shift
of 217.6 ppm. Furthermore, because of the C–S linkage, the signal of C-3 in 4 was
shielded by more than 30 ppm (d ¼ 46.6 ppm) in respect to that of C-3 in xanthate 1
(d ¼ 78.8 ppm).
Although 4 was a minor product relative to 2 and 3, it was important to limit its for-
mation since when present, the rearrangement product interfered with the monitoring of
the reaction. Besides, it was difficult to separate the latter from allylic derivative 2.
The Schonberg rearrangement[13–15] leading to 4, i.e., the thermal O to S transposition
¨
of the dithiocarbonate, has been observed when xanthates were subjected to the Barton–
McCombie reaction.[16–18] It arose, as explained by Quiclet-Sire and Zard,[16] when a
sugar radical 5 adds to the thiocarbonyl group of another molecule of starting dithio-
carbonate 1, instead of reacting with allyltributyltin (Sch. 2).
Scheme 1. AIBN-mediated radical coupling of xanthate 1 with allyl-tributyltin.

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85
Scheme 2. Mechanism of the radical reaction involving 1.
The heterolytic cleavage of intermediate 6 gives thiocarbonate 4 and radical 5. Thus,
it should be possible to diminish the amount of rearranged product 4 if the radical 5 is
formed in a medium containing a large excess of allyltributyltin. In fact, suppression of
the unwanted rearranged product 4 was achieved when the dithiocarbonate 1 was slowly
added (syringe pump) to a refluxing toluene solution of allyltributyltin (5 equiv.) and
AIBN (0.3 equiv.). As a result, the yield of the desired compound 2 was improved to
60%, the only by-product being the 3-deoxy sugar 3. However, because of the somewhat
tedious nature of this procedure, especially for large-scale syntheses, we investigated the
use of other 3-substituted precursors to GlcNAc-derivatives. We turned to the use of thio-
nocarbonates, known to react slower than xanthates in radical deoxygenation reactions,[19]
which should lower the radical concentration and so disfavor the unwanted rearrangement.
Hence, thionocarbonates 8a–c were prepared in quantitative yields by reaction of 7 with
phenyl, tolyl, and p-fluorophenyl chlorothioformate in pyridine (Sch. 3).
The thionocarbonate sugars were subjected to radical coupling with allyltributyltin
(5 equiv.) and AIBN (0.3 equiv.) in toluene at 808C and 1208C (Table 1). Rearrangement
of the thionocarbonate to thiocarbonate was never observed. (Furthermore, the stereo-
chemistry of the allylation was again exclusively equatorial. The exclusive equatorial
4
formation of the C–C bond is related to the C1 chair conformation of the radical 5, see
Ref.[20]). At 1208C, compounds 8a and 8b gave similar yields of 2 (50%) with a slight
improvement observed upon using 8c (60%). The use of a lower temperature (808C)
resulted in an improved isolated yield of 2 (60%) when starting from 8a and 8b, but 8c
surprisingly gave a poorer result (30%). The by-product 3 derived from the reduction of
Scheme 3. Preparation of thionocarbonates 8a–c.

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Wan, Lubineau, and Scherrmann
Table 1. Isolated yields of 2 upon AIBN-mediated radical
coupling of 8a–c and allyltributyltin in toluene.
Radical precursor
808C (%)
1208C (%)
8a
8b
8c
60 (72a)
60
30
50
50
60
aRefluxing benzene.
Scheme 4. AIBN-mediated radical coupling of xanthate 1 with allyltributyltin.
the radical intermediates could be limited by using benzene as the solvent instead of tolu-
ene (e.g., 72% yield of 2 from 8a). However, formation of the reduced product 3 is not
totally suppressed under these conditions (yield ,10%), suggesting the possibility of
hydrogen abstraction from the acetamido groupa or from the anomeric benzyl protecting
group[10] by sugar radical 5.
When applied to the b-derivative 10, prepared from 9[22] the above conditions lead to
the allylic compound 11 in 60% yield. Again, total equatorial selectivity was observed
(Sch. 4) as established by 1H NMR spectroscopy. The 1H NMR spectrum notably exhib-
ited a large coupling constant for the H-2 signal (J2,3 ¼ 12.5 Hz), indicating a trans-diaxial
orientation of the C-2 and C-3 hydrogen atoms as expected for D-glucose adopting a 4C1
conformation.
Having optimized the yield of the radical allylation, the route towards diene 13 was
carried on by ozonolysis of 2 as described[7,8] (Sch. 5). Aldehyde 12 was then condensed
aHydrogen abstraction from NH group by radical has already been hypothesized, see Ref.[21]
.

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87
Scheme 5. Synthesis of diene 13 via a Wittig reaction.
with allylidenetriphenylphosphorane in a Wittig reaction affording, in 60% isolated yield,
an inseparable 1 : 1 mixture of E and Z diene 13.
Due to the poor selectivity of the Wittig reaction, we took advantage of the results
obtained for the radical allylation and turned to the direct preparation of diene 13 using
2,4-pentadienyltributyltin.[23–25] Thus, dithiocarbonate 2 and thionocarbonates 8a–c
were reacted with 2,4-pentadienyltributyltin (5 equiv.) in toluene at 808C in the presence
of 0.3 equiv. of AIBN (Sch. 6, Table 2).
As in the case of allylation, the stereochemistry of the radical pentadienylation was
exclusively equatorial (J2,3 ¼ 12.0 Hz). Xanthate 1 afforded the dienyl derivatives as a
5 : 1 mixture of E/Z isomers in 50% yield. The thionocarbonates 8a and 8c afforded 13
in 70% yield, whereas the yield obtained with 8b was lower (50%). In all cases, the
only isolated by-product was the readily separable deoxy compound 3. Once again, the
yield was slightly enhanced when benzene was used as the solvent (75% from 8a). More-
over, under these conditions, the three thionocarbonate derivatives afforded diene 13 in a
0
0
9 : 1 ratio of two isomers. The J3 ,4 value of the major one was 15.5 Hz, thus establishing
that it was the E-isomer. Using 8a as the radical donor, we found that running the reaction
at 958C gave the best yield (81%) of 13 but lowered the E/Z selectivity to 6.5 : 1. As can be
seen from Table 2, the faster the radical is formed (from very reactive xanthate 1 or by
increasing the temperature in the reaction involving 8a), the poorer is the E/Z selectivity
of the addition. This is the first example of diene synthesis from dithiocarbonate or thio-
nocarbonate. While diene 13 seemed to be very pure by NMR analysis, we were unable to
obtain good elemental analysis presumably because of traces of tin derivatives. The con-
densation product was thus characterized as its diacetate analog 15. The latter was
obtained in 97% yield by acid removal of the isopropylidene group in 13 affording 14,
which was acetylated with pyridine and acetic anhydride (Sch. 7).
Scheme 6. Synthesis of diene 13 via AIBN-mediated radical coupling of 1 or 8a–c with penta-
dienyltributyltin.

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Wan, Lubineau, and Scherrmann
Table 2. Isolated yields of 13 upon the AIBN-mediated radical
coupling of 1, 8a–c, and pentadienyltributyltin in toluene at
808C (if not otherwise specified).
Radical precursor
Isolated yield (%)
Z/E
1 (R ¼ CH3S)
8a (R ¼ PhO)
50
1 : 5
1 : 9
1 : 6.5
1 : 9
1 : 9
70 (75a)
81b
50
8b (R ¼ pCH3PhO)
8c (R ¼ pFPhO)
70
aRefluxing benzene.
bToluene, 958C.
Scheme 7. Synthesis of acetylated diene 15.
CONCLUSION
We have shown that the radical alkenylation at position 3 of GlcNAc derivatives can
be improved using thiocarbonates rather than dithiocarbonate as radical donors. The
allylic compounds 2 and 11 were isolated as pure compounds in 60% yield since formation
of the rearranged product derived from xanthate 1 could be suppressed. The diene 13 was
obtained in multigram quantities with good E/Z selectivity and good yield using this
straightforward method. These C-branched alkenyl derivatives will be used for the syn-
thesis of more complex C-glycosides.
EXPERIMENTAL
General
Melting points were determined with a capillary apparatus and are uncorrected.
Optical rotations were measured at 288C + 28C. IR spectra were recorded as KBr pellets.
NMR spectra were recorded at r.t. with Bruker AC 200 or AC 250 spectrometers. Mass
spectrometry was recorded on a MAT 95S instrument. Elemental analyses were performed
at the CNRS Microanalytical Laboratory (Gif sur Yvette, France). All moisture-sensitive
reactions were performed under an argon atmosphere using oven-dried glassware. All
solvents were dried over standard drying agents and freshly distilled prior to use. Flash
column chromatography was performed with Silica Gel 60A C.C. (6–35 mm, SDS).
The reactions were monitored by TLC using Silica Gel 60 F254 with detection by UV
light (254 nm) and by charring with sulfuric acid.

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89
General Procedure for the Preparation of Thionocarbonates 8a–c
To a solution of 7 (1.06 g, 5.7 mmol) in dry pyridine (10 mL) was added phenyl, tolyl,
or p-fluorophenyl chlorothioformate (6.8 mmol, 1.2 equiv.). The reaction was kept at r.t.
for 12 hr. After evaporation of the solvent under reduced pressure (bath temperature not
exceeding 408C), the residue was partitioned into CH2Cl2–water. The organic phase
was concentrated and the residue was purified by flash chromatography to give the target
products in quantitative yields. Solvents for chromatography, and analytical data are
shown below.
Benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-(phenylthioformate)-a-
1
D-glucopyranoside (8a).[12] Flash chromatography (EtOAc–toluene, 1 : 2). H and 13C
NMR spectra were identical to those described.[12] [a]D þ42 (c 1, CH2Cl2); lit.[12] [a]D
þ31 (c 0.4, CHCl3); m.p. 1648C (EtOAc, petroleum ether), lit.[12] m.p. 158–1628C.
Benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-(p-tolylthioformate)-a-D-
glucopyranoside (8b). Flash chromatography (EtOAc–toluene 1 : 4!2 : 1). [a]D þ 30 (c
1, CH2Cl2); m.p. 588C (EtOAc, petroleum ether), IR: 3437, 3065, 3039, 2995, 2938,
1
2912, 2882, 2868, 1756, 1667, 1503, 1454, 1382, 1263, 1105, 1079, 860 cm21. H NMR
(CDCl3, 250 MHz) d: 7.42–7.27 (m, 5H, Ar), 7.22–7.10 (m, 2H, Ar), 7.00–6.92 (m, 2H,
Ar), 5.85 (d, 1H, J ¼ 10.0Hz, NH), 5.77 (dd, 1H, J ¼ 10.5, 11.0Hz, H-3), 4.89 (d, 1H,
J ¼ 4.0 Hz, H-1), 4.72 (d, 1H, J ¼ 13.0Hz, CH2), 4.48 (d, 1H, J ¼ 13.0Hz, CH2), 4.46
(ddd, 1H J ¼ 4.0, 10.0, 10.5Hz, H-2), 3.91 (ddd, 1H, J ¼ 3.5, 5.5, 10.0Hz, H-5), 3.75–
3.87 (m, 3H, H-4, H-6a, and H-6b), 2.34 (s, 3H, PhCH3), 1.90 (s, 3H, NHCOCH3), 1.48
and 1.41 (2s, 6H, 2CH3). 13C NMR (CDCl3, 63MHz) d: 196.1, 169.8, 151.1, 136.5,
136.2, 129.9, 129.8, 128.5, 128.2, 128.0, 127.9, 121.2, 120.5, 99.9, 97.1, 80.4, 71.7,
69.8, 63.8, 62.1, 60.3, 52.7, 28.9, 23.2, 20.8, 18.9, 14.0. HRMS (ESI): m/z calcd for
[C26H31NO7S þ Na]þ: 524.1719. Found 524.1719.
Anal. Calcd for C26H31NO7S: C, 62.26; H, 6.23; N, 2.79. Found: C, 62.25; H, 6.48;
N, 2.84.
Benzyl 2-acetamido-2-deoxy-3-O-(p-fluorophenylthioformate)-4,6-O-isopropyli-
dene-a-D-glucopyranoside (8c). Flash chromatography (EtOAc–toluene 1 : 3); [a]D þ 28
(c 1, CH2Cl2); m.p. 1518C (EtOAc, petroleum ether); IR: 3435, 3283, 3075, 2996, 2937,
1
2915, 2883, 2869, 1676, 1500, 1382, 1260, 1192, 1080, 1052, 1009cm21. H NMR
(CDCl3, 250 MHz) d: 7.45–7.30 (m, 5H, Ar), 7.15–7.00 (m, 4H, Ar), 5.83 (d, 1H,
J ¼ 9.0 Hz, NH), 5.77 (dd, 1H, J ¼ 9.0, 10.5Hz, H-3), 4.91 (d, 1H, J ¼ 4.0 Hz, H-1),
4.76 (d, 1H, J ¼ 12.0Hz, CH2), 4.53 (d, 1H, J ¼ 12.0Hz, CH2), 4.48 (ddd, 1H, J ¼ 4.0,
10.0, 10.5Hz, H-2), 3.91 (ddd, 1H, J ¼ 3.5, 5.5, 10.0Hz, H-5), 3.75–3.87 (m, 3H, H-4,
H-6a, and H-6b), 1.92 (s, 3H, NHCOCH3), 1.50 and 1.43 (2s, 6H, 2CH3). 13C NMR
1
(CDCl3, 63 MHz) d: 195.8, 169.8, 160.6 (d, JC–F ¼ 246 Hz), 149.1, 136.5, 128.6, 128.3,
3
2
128.1, 123.1 (d, JC–F ¼ 8 Hz), 117.6 (d, JC–F ¼ 23Hz), 100.0, 97.6, 80.9, 71.7, 69.9,
63.9, 62.2, 52.7, 29.0, 23.3, 18.9. HRMS (ESI): m/z calcd for [C25H28FNO7S þ Na]þ:
528.1468. Found 528.1468.
Anal. Calcd for C25H28FNO7S: C, 59.39; H, 5.58; N, 2.77. Found: C, 59.35; H, 5.53;
N, 3.06.
Benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-(p-tolylthioformate)-b-
D-glucopyranoside (10). Treatment of 9 (0.4 g, 1.13 mmol) in dry pyridine (2.4 mL)
with p-tolylchlorothioformate (176 mL, 1.3 equiv.) as described for 8a–c gave, after
flash chromatography (EtOAc–toluene 1 : 4), compound 10 (477 mg, 85%). [a]D 2123

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Wan, Lubineau, and Scherrmann
(c 1, CH2Cl2); m.p. 1588C (EtOAc, petroleum ether), IR: 3290, 3089, 3031, 2994, 2945,
1
2880, 1654, 1560, 1506, 1374, 1290, 1221, 1198, 1091, 1039, 855, 698 cm21. H NMR
(CDCl3, 250 MHz) d: 7.26–7.40 (m, 5H, Ar), 7.14–7.25 (m, 2H, Ar), 6.92–7.00
(m, 2H, Ar), 5.72 (dd, 1H, J ¼ 10.5, 10.0 Hz, H-3), 5.57 (d, 1H, J ¼ 10.0 Hz,
NHCOCH3), 4.91 (d, 1H, J ¼ 13.0 Hz, PhCH2), 4.67 (d, 1H, J ¼ 9.0 Hz, H-1), 4.61
(d, 1H, J ¼ 13.0 Hz, PhCH2), 4.19 (dt, 1H, J ¼ 10.0, 9.0 Hz, H-2), 4.15 (dd, 1H,
J ¼ 11.5, 6.0 Hz, H-6a), 3.92 (t, 1H, J ¼ 10.5, H-4), 3.86 (dd, 1H, J ¼ 10.5, 11.5 Hz,
H-6b), 3.39 (dt, 1H, J ¼ 10.5, 6.0 Hz, H-5), 2.37 (s, 3H, PhCH3), 1.94 (s, 3H, NHCOCH3),
1.52 and 1.43 (2s, 6H, 2CH3). 13C NMR (CDCl3, 63 MHz) d: 196.1, 170.0, 151.2, 136.9,
136.4, 129.9, 128.4, 127.9, 127.9, 121.2, 100.2, 99.8, 81.6, 71.6, 70.7, 67.0, 62.0, 55.2,
30.8, 28.9, 23.4, 20.9, 18.9. HRMS (ESI): m/z calcd for [C26H31NO7S þ Na]þ:
524.1719. Found 524.1720.
Anal. Calcd for C26H31NO7S: C, 62.26; H, 6.23; N, 2.79. Found: C, 62.39; H, 6.35;
N, 2.81.
Benzyl 2-acetamido-3-C-allyl-2,3-dideoxy-4,6-O-isopropylidene-a-D-glucopyra-
noside (2). A solution of 8c (200 mg, 0.39 mmol), allyltributyltin (580 mL, 2 mmol),
and AIBN (19.5 mg, 0.12 mmol) in 1.6 mL of anhyd. degassed toluene was heated at
1208C under argon for 6 hr (complete disappearance of the starting material by TLC
analysis CH2Cl2–MeOH 9 : 1). The solution was concentrated and the residue purified
by flash chromatography (EtOAc–toluene 2 : 3). Eluted first was 2[7,8] (90 mg, 60%).
Eluted second was compound 3 (39 mg, 30%).[12] This compound proved spectrosco-
pically identical to the one described[12] but the optical rotation differed considerably. [a]D
þ113 (c 0.3, CHCl3), lit.[12] [a]D þ42 (c 0.3, CHCl3).
When the reaction was conducted with xanthate 1, eluted first was compound 4 (15%)
(this compound was contaminated by ꢀ10% of 2). 1H NMR (CDCl3, 250 MHz) d: 7.44–
7.27 (m, 5H, Ar), 5.87 (d, 1H, J ¼ 10.0 Hz, NH), 4.86 (d, 1H, J ¼ 3.5 Hz, H-1), 4.74
(d, 1H, J ¼ 12.5 Hz, PhCH2), 4.44 (d, 1H, J ¼ 12.5 Hz, PhCH2), 4.27 (ddd, J ¼ 3.8,
10.0, 12.0 Hz, H-5), 3.99 (t, 1H, J ¼ 11.5 Hz, H-3), 3.88–3.54 (m, 4H, H-2, H-4, H-6a,
H-6b), 2.42 (s, 3H, SCH3), 1.89 (s, 3H, COCH3), 1.46 (s, 3H, CH3), 1.41 (s, 3H, CH3).
13C NMR (CDCl3, 63 MHz) d: 169.7, 169.5, 136.7, 128.15, 128.1, 128.0, 99.4, 96.8,
70.6, 69.7, 65.9, 64.9, 62.5, 53.0, 46.6, 28.9, 22.9, 18.9, 13.29. MS (ESI): m/z 464.2
(M þ Naþ). HRMS (ESI): m/z calcd for [C20H27NO6S2 þ Na]þ: 464.1177. Found
464.1178.
Benzyl 2-acetamido-3-C-allyl-2,3-dideoxy-4,6-O-isopropylidene-b-D-glucopyra-
noside (11). A solution of 10 (200 mg, 0.4 mmol), allyltributyltin (620 mL, 2 mmol),
and AIBN (19.5 mg, 0.3 equiv.) in 1.6 mL of anhyd. degassed toluene was treated as
described for the preparation of 2. Flash chromatography (EtOAc–toluene 1 : 2) gave
11 (91 mg, 60%). [a]D 269 (c 1, CH2Cl2); m.p. 1778C (EtOAc, petroleum ether); IR:
3343, 3060, 3031, 3001, 2945, 2896, 1677, 1535, 1373, 1263, 1209, 1198, 1167, 1080,
1
1023, 918, 852, 753, 703, 589 cm21. H NMR (CDCl3, 250 MHz) d: 7.38–7.27 (m, 5H,
Ar), 5.92–5.68 (m, 1H, CH ¼ CH2), 5.16 (d, 1H, J ¼ 10.0 Hz, NHCOCH3), 5.04 (t, 2H,
CH ¼ CH2), 4.87 (d, 1H, J ¼ 13.0 Hz, PhCH2), 4.57 (d, 1H, J ¼ 13.0 Hz, PhCH2), 4.50
(d, 1H, J ¼ 9.0 Hz, H-1), 3.93 (dd, 1H, J ¼ 11.5, 5.5 Hz, H-6a), 3.80 (ddd, 1H,
J ¼ 12.5, 10.0, 9.0 Hz, H-2), 3.77 (t, 1H, J ¼ 11.5, H-6b), 3.45 (dd, 1H, J ¼ 10.5,
10.0 Hz, H-4), 3.30 (ddd, 1H, J ¼ 11.5, 10.5, 5.5 Hz, H-5), 2.12–2.39 (m, 2H, CH2CH ¼
CH2), 1.95 (s, 3H, NHCOCH3), 1.94–1.80 (m, 1H, H-3), 1.40 and 1.46 (2s, 6H, 2CH3).
13C NMR (CDCl3, 63 MHz) d: 169.7, 137.4, 134.1, 128.5, 128.4, 127.9, 127.8, 117.8,

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Synthesis of C-3 Branched Allyl and Pentadienyl Glucosamines
91
101.3, 99.4, 70.3, 62.6, 52.6, 43.03, 30.3, 29.1, 23.4, 18.9. HRMS (ESI): m/z calcd for
[C21H29NO5 þ Na]þ: 398.1943. Found 398.1942.
Anal. Calcd for C21H29NO5: C, 67.18; H, 7.79; N, 3.73; O, 21.31. Found: C, 67.23;
H, 7.83; N, 3.67; O, 21.53.
Benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-3-C-(10-penta-20,40-dienyl)-
a-D-glucopyranoside (13). A solution of 8a (18 g, 37mmol), pentadienyltributyltin
(66.2 g, 185.3 mmol), and AIBN (1.8g, 11.1mmol) in 200 mL of anhyd. degassed toluene
was heated at 958C for 3 hr (complete disappearance of the starting material by TLC
analysis CH2Cl2–MeOH 9 : 1). The solution was concentrated and the residue purified by
flash chromatography (CH2Cl2/acetone 100 : 3) to afford a 6.5 : 1 E/Z mixture of diene
1
13 (12 g, 81%). Spectroscopic data for E-13: H NMR (CDCl3, 250 MHz) d: 7.42–7.27
(m, 5H, Ar), 6.33 (dt, 1H, J ¼ 10.5, 17.5Hz, H-40), 6.04 (dd, 1H, J ¼ 10.5, 15.5Hz,
H-30), 5.73 (ddd, 1H, J ¼ 7.0, 8.5, 15.5Hz, H-20), 5.58 (d, 1H, J ¼ 10.0Hz, NH), 5.10
(dd, 1H, J ¼ 17.5, 1.5 Hz, H-5a0), 4.97 (dd, 1H, J ¼ 1.5, 10.0Hz, H-5b0), 4.74 (d, 1H,
J ¼ 12.0Hz, PhCH2), 4.73 (d, 1H, J ¼ 3.5 Hz, H-1), 4.44 (d, 1H, PhCH2), 4.18 (ddd, 1H,
J ¼ 3.5, 10.0, 12.0Hz, H-2), 3.90–3.63 (m, 3H, H-5, H-6a, H-6b), 3.50–3.38 (m, 1H,
H-4), 2.40–2.20 (m, 2H, H-1a0, H-1b0), 1.93 (s, 3H, COCH3), 2.03–1.87 (m, 1H, H-3),
1.44 and 1.42 (2s, 6H, 2CH3). 13C NMR (CDCl3, 63 MHz) d: 169.5, 137.1, 136.9, 133.8,
130.7, 128.5, 128.0, 115.2, 99.4, 96.6, 70.9, 69.4, 64.9, 62.8, 50.0, 40.01, 29.2, 29.0, 23.2,
19.0. HRMS (ESI): m/z calcd for [C23H31O5N þ Na]þ: 424.2100. Found 424.2092.
Benzyl 2-acetamido-2,3-dideoxy-3-C-(10-penta-20,40-dienyl)-a-D-glucopyranoside
(14). To a solution of 13 (E/Z 9 : 1, 406 mg, 1.01 mmol) in methanol (5 mL) Dowex
50X8-200 Hþ (400 mg) was added. The mixture was heated at 608C for 4 hr and then
diluted with CH2Cl2/MeOH (1 : 1, 5 mL) and filtered. The solution was concentrated to
afford a white powder which was washed with petroleum ether to afford 14 (E/Z 9 : 1,
357 mg, 98%). Spectroscopic data for E-14: 1H NMR (CDCl3 þ 1 drop CD3OD,
250 MHz) d: 7.41–7.26 (m, 5H, Ar), 7.01 (d, 1H, J ¼ 9.5 Hz, NH), 6.30 (dt, 1H,
J ¼ 10.5, 17.0 Hz, H-40), 6.08 (dd, 1H, J ¼ 10.5, 15.5 Hz, H-30), 5.70 (dt, 1H, J ¼ 7.0,
15.5 Hz, H-20), 5.07 (dd, 1H, J ¼ 17.0, 1.5 Hz, H-5a0), 4.95 (dd, 1H, J ¼ 1.5, 10.5 Hz,
H-5b0), 4.75 (d, 1H, J ¼ 12.0 Hz, PhCH2), 4.75 (d, 1H, J ¼ 3.5 Hz, H-1), 4.47 (d, 1H,
J ¼ 12.0 Hz, PhCH2), 3.97 (ddd, 1H, J ¼ 12.0, 9.5, 3.5 Hz, H-2), 3.79 (dd, 1H, J ¼ 12.0,
3.5 Hz, H-6a), 3.73 (dd, 1H, J ¼ 12.0, 4.0 Hz, H-6b), 3.63 (ddd, 1H, J ¼ 10.0, 4.0, 3.5 Hz,
H-5), 3.40 (t, 1H, J ¼ 10.0 Hz, H-4), 2.31–2.40 (m, 2H, H-1a0, H-1b0), 1.93 (s, 3H,
COCH3), 2.05–1.87 (m, 1H, H-3), 1.93 (s, 3H, COCH3). 13C NMR (d6-DMSO, 63 MHz),
d: 168.9, 138.0, 137.2, 133.0, 131.4, 128.1, 127.6, 127.4, 115.1, 95.2, 73.7, 67.6, 66.0,
60.9, 49.3, 49.3, 29.1, 22.3.
.
Anal. Calcd for C20H27NO5 0.3H2O: C, 65.48; H, 7.58; N, 3.82; O, 23.12. Found: C,
65.61; H, 7.45; N, 3.73; O, 23.11.
Benzyl 2-acetamido-4,6 di-O-acetyl-2,3-dideoxy-3-C-(10-penta-20,40-dienyl)-a-D-
glucopyranoside (15). To a solution of 14 (300 mg, 0.83 mmol) in pyridine (5 mL)
390 mL of acetic anhydride was added. After one night, the mixture was concentrated
and the residue was purified by flash chromatography (toluene/acetone 3 : 1) to afford a
1
9 : 1 E/Z mixture of diene 15 (366 mg, 99%). Spectroscopic data for E-15: H NMR
(CDCl3, 250 MHz) d: 7.41–7.26 (m, 5H, Ar), 6.23 (dt, 1H, J ¼ 10.5, 17.0 Hz, H-40),
5.93 (dd, 1H, J ¼ 10.5, 15.5 Hz, H-30), 5.55 (dt, 1H, J ¼ 7.0, 15.5 Hz, H-20), 5.53
(d, 1H, J ¼ 10.0 Hz, NH), 5.06 (dd, 1H, J ¼ 17.0, 1.5 Hz, H-5a0), 4.94 (dd, 1H, J ¼ 1.5,
10.5 Hz, H-5b0), 4.86 (t, 1H, J ¼ 10.0 Hz, H-4), 4.76 (d, 1H, J ¼ 3.5 Hz, H-1), 4.70

ORDER
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92
Wan, Lubineau, and Scherrmann
(d, 1H, J ¼ 12.0 Hz, PhCH2), 4.46 (d, 1H, J ¼ 12.0 Hz, PhCH2), 4.14 (dd, 1H, J ¼ 12.0,
5.0 Hz, H-6a), 4.13 (ddd, 1H, J ¼ 12.0, 10.0, 3.5 Hz, H-2), 4.96 (dd, 1H, J ¼ 12.0, 2.0 Hz,
H-6b), 4.88 (ddd, 1H, J ¼ 10.0, 5.0, 2.0 Hz, H-5), 2.33–2.10 (m, 3H, H-3, H-10a, H-10b),
2.03 (s, 3H, NHCOCH3), 1.96 (s, 3H, COCH3), 1.89 (s, 3H, COCH3). 13C NMR (CDCl3,
63 MHz) d: 170.7, 169.7, 169.6, 136.9, 136.7, 132.5, 131.5, 131.4, 128.6, 128.2, 128.1,
115.8, 96.1, 69.7, 69.2, 68.7, 62.5, 50.3, 40.4, 31.7, 23.2, 20.8, 20.7. HRMS (ESI): m/z
calcd for [C24H31NO7 þ Na]þ: 468.1998. Found 468.2007.
Anal. Calcd for C24H31NO7: C, 64.70; H, 7.01; N, 3.14; O, 25.14. Found: C, 64.48;
H, 7.03; N, 3.03; O, 25.33.
ACKNOWLEDGMENTS
`
This work was supported by the CNRS and the Ministere de l’Education Nationale, de
´ `
l’Enseignement Superieur et de la Recherche. Q.W. thanks the Ministere des Affaires
´
Etrangeres for an Eiffel fellowship.
`
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Received June 2, 2003
Accepted December 8, 2003

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