Synthesis of C-2 methylene O- and C-glycosides and sugar derived α-methylene-δ-valerolactones from C-2-acetoxymethyl glycals

Article abstract of DOI:10.1016/S0040-4020(00)00775-4

C-2-Methylene O- and C-glycosides are readily synthesized from C-2-acetoxymethyl glycals using Nafion-H, montmorillonite K-10, LiClO₄ (0.07 M) in dichloromethane and Pd(PPh₃)₄ as catalysts. Exclusive α or β selectivities have been observed with various primary, secondary and tertiary alcohols, phenols and diethyl malonate. Further, C-2-acetoxymethyl glycals are also converted into corresponding α-methylene-δ-valerolactones in good yields in one step using m-CPBA in the presence of BF₃·Et₂O. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00775-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 8525±8531
Synthesis of C-2 Methylene O- and C-Glycosides and
Sugar Derived a-Methylene-d-valerolactones from
C-2-Acetoxymethyl Glycalsq
*
Anuradha Gupta and Yashwant D. Vankar
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 12 April 2000; revised 9 August 2000; accepted 23 August 2000
AbstractÐC-2-Methylene O- and C-glycosides are readily synthesized from C-2-acetoxymethyl glycals using Na®on-Hw, montmorillonite
K-10, LiClO4 (0.07 M) in dichloromethane and Pd(PPh3)4 as catalysts. Exclusive a or b selectivities have been observed with various
primary, secondary and tertiary alcohols, phenols and diethyl malonate. Further, C-2-acetoxymethyl glycals are also converted into corre-
sponding a-methylene-d-valerolactones in good yields in one step using m-CPBA in the presence of BF3´Et2O. q 2000 Elsevier Science Ltd.
All rights reserved.
Synthesis of branched chain sugars has gained importance
in recent years mainly because of the occurrence of such
type of structural units in nature.1 As a result, efforts have
been made to prepare analogs of such branched chain sugars
for biological evaluation. Besides this, branched sugars also
serve as useful intermediates for the synthesis of other
non-sugar chiral molecules. Likewise, sugar derived
a-methylene-d-valerolactones are useful in the synthesis
of C-glycosides using radical chemistry2 and a-methylene
unit in such lactones also serves as an appendage for
branched chain sugar synthesis. In this paper, we present
our results pertaining to the synthesis of C-2 methylene O-
and C-glycosides and a-methylene-d-valerolactones from
C-2-acetoxymethy glycals.
Recently,9 Na®on-H has been employed as a catalyst to
effect the Ferrier reaction. In the present study 2-acetoxy-
methyl glycals 1 and 2 (Scheme 1) and Na®on-H (wt.
equiv.) in CH2Cl2 gave the corresponding O-glycosides 3
in good yields (Table 1) leading to predominantly a-isomers
as the corresponding b-isomers, if formed, could not be
isolated. Reactions were cleaner in CH2Cl2 than in
1
CH3CN, CHCl3 or Et2O. The H NMR as well as 13C
NMR spectra were in complete agreement with the a-glyco-
sides and nOe experiments10 further con®rmed the
structures assigned. Except t-BuOH, other alcohols such
as benzyl alcohol, cyclohexanol and allyl alcohol reacted
smoothly to give the corresponding C-2-methylene-O-
glycosides 3a, 3b, 3c and 3d in fair to good yields
(Table 1). A sugar derived alcohol 4 also reacted with 1 to
yield the corresponding disaccharide 5 in 65% yield
possessing a-con®guration.
Conversion of glycals3 into C-2 formyl glycals followed by
their conversion to C-2-methylene-O-glycosides has been
reported by Balasubramanian et al.4 by applying the Ferrier
reaction protocol using BF3´Et2O as a catalyst. In all the
cases studied by Balasubramanian et al., a-glycosides
were formed as the major products. In an effort to improve
the selectivity in such reactions, and possibly reverse the
anomeric selectivity, and synthesize C-glycosides, we have
screened several different types of catalysts. These include
two solid acidic catalysts, viz. Na®on-H5 and montmorillo-
nite K-106 and soluble catalysts LiClO47 and Pd(PPh3)4.8
Because of the importance11 of O-aryl glycosides we reacted
phenols (phenol, p-cresol, b-naphthol) with 1 and 2 in the
presence of Na®on-H as a catalyst. Although the parent
phenol did not react to give any clean product, p-cresol
and b-naphthol reacted smoothly with 2 to give the corre-
sponding O-glycosylated products 6 and 7 in 60 and 65%
yields, respectively, but interestingly having b-con®gura-
tions. It is noteworthy that O-aryl glycosides were not
formed when phenols were reacted with 1 and 2 using
BF3´Et2O as a catalyst as reported by Ramesh and
Balasubramanian.12 Instead, glycosylation was found to
take place using phenols and under Mitsunobu activation
conditions to give a mixture of a and b-O-aryl glycosides
and a small amount of aryl ether, via allylic substitution. In
this regard the use of Na®on-H in the present study to form
only b-O-aryl glycoside is useful.
q
To be considered as Part 1 in the series: `Transformations in Carbohy-
drate Chemistry'.
Keywords: montmorillonite K-10; Na®on-H; O- and C-glycosides.
* Corresponding author. Tel.: 191-512-597169; fax: 191-512-590007;
e-mail: vankar@iitk.ac.in
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00775-4

8526
A. Gupta, Y. D. Vankar / Tetrahedron 56 (2000) 8525±8531
Scheme 1.
Since no glycosylation occurred with t-BuOH in the
presence of Na®on-H as a catalyst, probably due to its
strong acidic nature, we utilized a yet another solid catalyst
viz. montmorillonite K-106 for this purpose which has, in
recent times, gained importance in organic synthesis due to
its stability, ease of handling, lack of corrosion and ease of
regeneration. It has also been employed in carbohydrate
chemistry, for example, in O-glycosylation13 involving
trichloroacetimidate donors, C-glycosylation of glycals14
and unprotected sugars.15 In the present study, gratifyingly,
t-BuOH reacted smoothly with 2, in the presence of
montmorillonite K-10 (1 wt. equiv.) to form the correspond-
ing O-glycoside 3e in 70% yield. Interestingly and surpris-
ingly this O-glycoside also possessed a-con®guration as
con®rmed by nOe experiments. Likewise, several other
glycosyl acceptors viz. benzyl alcohol, cyclohexanol, allyl
alcohol, and sugar derived alcohol 4 reacted smoothly to
form the corresponding O-glycosides in good yields
(Table 1), having a-con®gurations. Results with p-cresol
and b-naphthol, however, were rather unexpectedly
different. Thus, with p-cresol, a C-glycoside 8 was formed
possessing b-con®guration whereas with b-naphthol, on the
other hand, a b-O-glycoside 7 was obtained. Formation of
C-glycoside 8 is not surprising as Toshima et al.15 have
Table 1.
Entry
Allyl acetate
Nucleophile
Catalyst
Na®on H
Montmorillonite
LiClO4
Na®on H
Montmorillonite
LiClO4
Na®on-H
Montmorillonite
LiClO4
Na®on H
Montmorillonite
LiClO4
Na®on-H
Montmorillonite
LiClO4
Na®on-H
Montmorillonite
LiClO4
Montmorillonite
LiClO4
Na®on-H
Time (h)
Product
Yield (%)
Rotation [a]D in CH2Cl2, Cl
1
2
3
4
5
6
7
8
1
2
2
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
BnOH
BnOH
BnOH
4
4
4
Cyclohexanol
Cyclohexanol
Cyclohexanol
Allyl alcohol
Allyl alcohol
Allyl alcohol
t-BuOH
t-BuOH
t-BuOH
p-cresol
p-cresol
p-cresol
20
15
1
15
12
2
10
8
1.5
6
4
1
±
5
1
4
5
4
3a
3b
3b
5
5
5
3c
3c
3c
3d
3d
3d
±
3e
3e
6
80
70
75
65
65
75
70
65
65
65
70
75
±
70
75
60
62
65
60
70
65
1116.4
1122.6
1100.5
198.1
190.1
1100.2
180.0
182.0
175.4
174.6
178.0
180.9
9
10
11
12
13
14
15
16
17
18
19
20
21
170.0
164.0
2294.0
260.2
2270
2288.0
2280.9
2288.0
8
6
7
7
b-naphthol
b-naphthol
b-naphthol
5
1
7
7

A. Gupta, Y. D. Vankar / Tetrahedron 56 (2000) 8525±8531
8527
Scheme 2.
reported b-aryl-C-glycosylations with unprotected sugars
with phenols in the presence of montmorillonite K-10.
However, formation of 7 is not clear.
Initial experiments with allyl acetate 1 with benzyl alcohol
as a nucleophile in the presence of Pd(Ph3)4 led to no reac-
tion. However, use of the allylic carbonate 9 (Scheme 2) in
such a reaction led to the formation of the a-glycoside 3a in
65% yield in re¯uxing THF with Pd(PPh3)4. Likewise, 4
also readily reacted with 9 to form 5. Since these glycosides
were `a' in nature, it is clear that the formation of the p-allyl
complex 10 (Scheme 2) occurs from b-face followed by the
attack of nucleophiles from `a' side. This became even
more clear when p-cresol and b-naphthol were found to
give the corresponding a and not b-glycosides 3f and 3g.
Clearly, these results with phenols are complementary to the
ones obtained using Na®on-H, montmorillonite K-10 and
LiClO4 where b-glycosides were formed. The geometry of
the a-glycoside bond was con®rmed by nOe experiments. In
an effort to study the scope of these palladium catalyzed
reactions some carbon nucleophiles were also utilized to
form C-glycosides. Towards this effect nitromethane and
diethyl malonate were reacted with 1. Unfortunately, reac-
tion of nitromethane with 9 in the presence of Pd(PPh3)4
gave the corresponding allylated product 11 (Scheme 2)
and not the expected glycosylated product. On the other
hand, diethyl malonate did not react at all under these
Ever since the introduction of LiClO4 in organic solvents by
Grieco et al.7a it has gained enormous importance organic
synthesis. In carbohydrate chemistry, Waldman et al.16 have
made use of LiClO4 for glycosylation under neutral con-
ditions. In our case, we have found that 2 underwent smooth
glycosylation with a variety of alcohols, including t-BuOH
using a 0.07 M solution of LiClO4 in CH2Cl2 and the corre-
sponding a-O-glycosides were obtained in good yields in
1±1.5 h at 08C to room temperature (Table 1). On the other
hand, phenols such as p-cresol and b-naphthol gave the
corresponding b-O-glycosides as observed in Na®on-H
mediated reactions (vide supra). In general, it was noted
that reactions with LiClO4 were more clean than with
Na®on-H or montmorillonite K-10. Since the use of acid
catalysts led to the formation of a-glycosides in all the
cases using aliphatic alcohols as glycosyl acceptors, we
decided to explore palladium catalyzed reactions for
O-glycosylations hoping to exploit the orientation of
p-allyl palladium complex to direct the stereoselectivity.
Scheme 3.

8528
A. Gupta, Y. D. Vankar / Tetrahedron 56 (2000) 8525±8531
conditions. However, use of dppe as a ligand, in place of
Ph3P, led to the formation of the expected C-glycoside 12
having a-con®guration.
Preparation of allyl actates 1 and 2
To a solution of a C-2-formyl glycal (1.96 g, 9.1 mmol) and
dry MeOH (60 mL) at 08C, sodium borohydride (504 mg,
13.6 mmol) was added portionwise over a period of 15 min.
The reaction mixture was brought to room temperature and
stirred for 5±10 min before quenching with a saturated solu-
tion of NH4Cl (1±2 mL). Methanol was evaporated under
reduced pressure and the product extracted with CH2Cl2
(3£40 mL) and washed with water (2£25 mL) followed
by brine (25 mL). The dried (anhydrous Na2SO4) organic
phase was concentrated on rotary evaporator and the crude
product puri®ed by column chromatography.
In continuation to explore the potential of compounds 1 and
2, we have found that they can be easily converted into a
a-methylene d-valerolactones such as 15 (Scheme 3).
Importance of these kinds of lactones has been demon-
strated by Giese and Schmidt2 in their studies pertaining
to C-disaccharide synthesis via radical mediated conjugate
addition of an anomeric pyranosyl radical. There have been
three reports on the synthesis of such lactones, by (i)
Schmidt et al.17 using sulfur chemistry, (ii) by Ramana
and Nagarajan18 using cyclopropane based chemistry and
more recently, (iii) by Chmielewski et al.19 using
compounds of type 1 and 2 (Scheme 3) in three steps in
moderate yields. We have, however, found that compounds
1 and 2 (and their benzyl derivatives) react with m-chloro-
perbenzoic acid20 in the presence of BF3´Et2O to directly
give the corresponding a-methylene-d-valerolactones in
good yields (cf. Experimental). In view of the importance
of such lactones in C-disaccharide synthesis2 and their being
potentially useful synthons, due to a,b-unsaturated lactone
moiety and the fact that compounds of type 1 and 2 are
readily available from the corresponding glycals, we believe
that the synthesis described here will ®nd application.
1,5-Anhydro-3,4,6-tri-O-methyl-1,2-di-deoxy-2-acetoxy-
d-arabino-hex-1-enitol (1). Yield: 90%. [a]Dˆ1102 (c 1,
CH2Cl2). IR (CCl4): n 1720 cm21 1H NMR (CDCl3,
.
80 MHz): d 2.0 (s, 3H, ±OCOCH3), 3.46 (s, 3H,
0
±CH2OCH3), 3.46±3.75 (m, 9H, 2£±OCH3, H6,6 , H4),
3.83±3.85 (d, 1H, Jˆ5 Hz, H3), 4.08±4.15 (m, 1H, H5),
4.44±4.66 (q, 2H, Jˆ12.8 Hz, ±CH2OAc), 6.52 (s, 1H,
H1). 13C NMR (CDCl3, 100 MHz): d 20.92, 57.52, 58.55,
58.97, 62.19, 70.17, 74.94, 75.09, 75.66, 108.02, 145.13,
170.86. Mass spectrum (m/z): 283 [(M1123), 100], 201
[(M1260), 32], 171(9). Anal. Calcd for C12H20O6 C,
55.37; H, 7.74. Found: C, 55.62; H, 8.17.
In summary, our study related to the employment of
substrates like 1 and 2 (or their derivatives) has led to the
formation of O- and C-glycosides (including aryl glyco-
sides) in highly stereoselective manner. Further these
substrates are also useful in the synthesis of a-methylene-
d-valerolactones, which are useful intermediates.
1,5-Anhydro-3,4,6-tri-O-methyl-1,2-di-deoxy-2-acetoxy-
methyl-d-lyxo-hex-1-enitol (2). Yield: 84%. [a]Dˆ184 (c
1
1, CH2Cl2). IR (CCl4): n 1720 cm21. H NMR (CDCl3,
80 MHz): d 2.0 (s, 3H, ±OCOCH3), 3.41 (s, 3H, ±OCH3),
3.51±3.58 (s, 6H, 2£±OCH3), 3.63 (dd, 2H, Jˆ7.2 Hz,
0
5.4 Hz, H6,6 ), 3.76 (m, 1H, H4), 3.97 (d, 1H, Jˆ3.6 Hz,
H3), 4.17±4.19 (m, 1H, H5), 4.41±4.73 (q, 2H,
Jˆ12.7 Hz, ±CH2OAc), 6.47 (s, 1H, H1). 13C NMR
(CDCl3, 100 MHz): d 20.97, 57.44, 59.09, 59.89, 62.33,
70.23, 73.24, 75.30, 75.46, 108.26, 144.67, 170.84. Mass
spectrum (m/z): 283 [(M1123), 100], 201 [(M1223), 20],
171(9). Anal. Calcd for: C12H20O6: C, 55.37; H, 7.74.
Found: C, 55.10; H, 8.00.
Experimental
Optical rotations were recorded on Autopol II automatic
polarimeter at the wavelength of the sodium D-line
(589 nm) and at an ambient temperature. Infrared spectra
were recorded on Perkin±Elmer 1320 or Bruker FT/IR
1
General procedure for the glycosylation of allyl acetates
1 and 2 using Na®on-H
Vector 22 spectrometers. H NMR spectra were recorded
on Jeol-PMX 60, Bruker WP-80, Bruker WM-300 (or 400)
or Jeol LA-400 NMR spectrometers using tetramethylsilane
as the internal standard. 13C NMR spectra were recorded on
Bruker WM-300 and 400 or Jeol LA-400 NMR spectro-
meters. FAB mass spectra were obtained using Jeol SX
102/DA-6000 spectrometer. Elemental analyses were
carried out in Coleman automatic C,H,N,O or Carlo±Erba
EA 1110 analyzer.
To a solution of allyl acetates 1 or 2 (1 mmol) at 08C, in dry
CH2Cl2 (2 mL), Na®on-H (wt. equiv.) and glycosyl acceptor
(1.1 mmol) were added. After stirring for 12 h at room
temperature, it was ®ltered over a sintered funnel. The
reaction was monitored by TLC (H2SO4 charring). The
®ltrate was evaporated to dryness and was puri®ed by
column chromatography.
Na®onw resin (Dupont) was obtained as a gift from Prof.
George Olah and Prof. G. K. Surya Prakash, University of
Southern California, USA. The Na®on resin, obtained in the
form of Na®on-K, was converted to Na®on-H as per the
reported procedure.5a Montmorillonite (K-10) was obtained
from Fluka Chemical Company, Switzerland. Lithium
perchlorate was prepared7a by acidfying an aqueous solution
of LiOH with perchloric acid (70%).7b The resulting solid
was dried at 1508C under vacuum for 10 h to obtain
anhydrous LiClO4. 3,4,6-Tri-O-methyl-C-2-formyl-glycals
and 3,4,6-tri-O-benzyl-C-2-formyl glycals were prepared
according to the literature report.3
General procedure for the glycosylation of allyl acetates
1 and 2 using montmorillonite K-10
To a solution of allylic acetate 1 and 2 (1 mmol) at 08C, in
dry CH2Cl2 (2 mL) and montmorillonite (1 wt. equiv.) and a
glycosyl acceptor (1.1 mmol) was added and stirred under
nitrogen atmosphere for the time speci®ed in Table 1. After
the completion of the reaction, (tlc monitoring) the reaction
mixture was ®ltered through a sintered funnel and the
solvent evaporated at reduced pressure to give a crude
product, which was puri®ed by column chromatography.

A. Gupta, Y. D. Vankar / Tetrahedron 56 (2000) 8525±8531
8529
0
General procedure for glycosylation of allyl acetate 1
and 2 using 0.07 M LiClO4 in dichloromethane
3H, ±OCH3), 3.54±3.62 (m, 2H, H6,6 ), 3.72 (br d, 1H,
H4), 4.11±4.13 (m, 2H, H3, H5), 5.14 (s, 1H, ole®nic-H),
5.22 (s, 1H, ole®nic-H), 5.27 (s, 1H, H1). 13C NMR (CDCl3,
300 MHz): d 26.0, 25.5, 29.0, 31.5, 33.4, 57.3, 59.1, 60.9,
69.9, 70.3, 70.8, 78.6, 79.3, 100.8, 110.8, 141.2. Mass spec-
trum (m/z): No M11 peak, 201 [M1299], 169, 170, 139.
Anal. Calcd for C16H28O5: C, 64.00; 9.40. Found: C, 63.90;
H, 9.46.
Anhydrous LiClO4 (40 mg, 0.38 mmol) was dissolved in
4 mL of dry CH2Cl2 under N2 atmosphere and to this was
added a mixture of allyl acetate 1 or 2 (50 mg, 0.19 mmol)
and a glycosyl acceptor (0.19 mmol) in 1.4 mL of CH2Cl2,
dropwise at 08C. The reaction was stirred at room tempera-
ture for the speci®ed time. After the reaction was complete,
reaction mixture was washed with H2O (2£10 mL) and
subsequently with CH2Cl2 (2£10 mL). The organic layer
was dried over anhydrous Na2SO4 and evaporated under
reduced pressure. The crude product was puri®ed by column
chromatography.
Allyl-3,4,6-tri-O-methyl-2-deoxy-2-methylene-a-d-lyxo-
hexopyranoside (3d). [a]Dˆ174.6 (c 1.5, CHCl3); IR
(CH2Cl2): n 1615 cm21. H NMR (CDCl3, 300 MHz): d
3.40 (s, 3H, CH2OCH3), 3.50 (s, 3H, OCH3), 3.54 (s, 3H,
1
0
OCH3), 3.52±3.71 (m, 2H, H6,6 ), 3.72 (br d, 1H, Jˆ3.5 Hz,
H4). 4.00±4.21 (m, 4H, H5, H3, allylic-CH2), 5.18±5.21
(3£s, 3H, 2£ole®nic-H, H1), 5.27 (s, 1H, Hole®nic), 5.33 (s,
1H, Hole®nic), 5.86±5.99 (m, 1H, vinylic-H). 13C NMR
(CDCl3, 100 MHz): d 59.1, 59.2, 60.4, 71.2, 76.4, 79.6,
81.6, 82.6, 100.4, 110.3, 117.3, 133.8, 142.0. Mass spectrum
(m/z): No M1 or [M11]1 peak; 201 [M1245], 170, 139.
Anal. Calcd for C13H22O5: C, 60.46; H, 8.59. Found: C,
60.45; H, 8.56.
Benzyl-3,4,6-tri-O-methyl-2-deoxy-C-2-methylene-a-d-
xylo-hexopyranoside (3a). [a]Dˆ1116.4 (c 1, CH2Cl2). IR
1
(CCl4): n 1605 cm21. H NMR (CDCl3, 300 MHz): d 3.19
(t, 1H, Jˆ9.8 Hz, H4), 3.41 (s, 3H, OCH3), 3.53±3.79 (m,
0
8H, 2£OCH3, H6,6 ), 3.21±3.86 (m, 1H, H5), 4.04±4.08 (m,
1H, H3), 4.5±4.74 (ABQ, 2H, Jˆ11.4 Hz, CH2OPh), 5.07 (s,
1H, ole®nic-H), 5.18 (s, 1H, ole®nic-H), 5.19 (s, 1H, H1).
7.31 (s, 5H, Ph-H); 13C NMR (CDCl3, 75 MHz): d 59.2,
59.3, 60.4, 68.8, 71.3, 71.5, 81.7, 82.7, 100.7, 110.5,
127.6, 127.9, 128.3, 137.5, 142.1. Mass spectrum (m/z):
200 (M12108), 142, 91. Anal. Calcd for C17H24O5: C,
66.21; H, 7.84. Found: C, 66.17; H, 7.58.
t-Butyl-1,5-anhydro-3,4,6-tri-O-methyl-2-methylene-a-
d-lyxo-hexopyranoside (3e). [a]Dˆ164 (c 0.5, CHCl3); IR
(CH2Cl2): n 1615 cm21. H NMR (CDCl3, 300 MHz): d
1.25 (s, 9H, t-butyl-H), 3.39 (s, 3H, ±CH2OCH3), 3.49 (s,
1
0
3H, OCH3), 3.54 (s, 3H, OCH3), 3.54±3.60 (m, 2H, H6,6 ),
3.73 (br d, 1H, J3,4ˆ2.5 Hz H4), 4.13 (d, 1H, J5,6ˆ2.5 Hz,
Benzyl-3,4,6-tri-O-methyl-2-deoxy-C-2-methylene-a-d-
lyxo-hexopyranoside (3b). [a]Dˆ1122.6 (c 1.3, CHCl3).
0
H3), 4.18 (t, 1H, J5, 6,6 ˆ7.3 Hz H5), 5.05 (s, 1H, ole®nic-H),
5.19 (s, 1H, ole®nic-H), 5.40 (s, 1H, H1). 13C NMR (CDCl3,
100 MHz): d 33.8, 56.6, 59.7, 60.2, 60.6, 65.8, 71.8, 71.9,
72.5, 82.5, 82.9, 100.3, 110.9, 141.3. Mass spectrum
(m/z): No M11/M1 peak, 201 [M1273], 169, 156. Anal.
Calcd for C14H26O5: C, 61.31; H, 9.56,. Found: C, 61.30; H,
9.60.
1
IR (CCl4): n 1610 cm21. H NMR (CDCl3, 300 MHz): d
3.40 (s, 3H, ±CH2OCH3), 3.49 (s, 3H, ±OCH3), 3.54 (s,
0
3H, ±OCH3), 3.49±3.61 (m, 2H, H6,6 ), 3.72 (br s, 1H,
0
H4), 4.10±4.16 (br s and t, 2H, H3, H5, J5,6 ˆ8 Hz),
6
4.52±4.79 (ABQ, 2H, CH2OPh, Jgemˆ14.7 Hz), 5.18 (s,
1H, ole®nic-H), 5.28 (s, 1H, ole®nic-H), 5.23 (s, 1H, H1),
7.31 (s, 5H, Ph-H); 13C NMR (CDCl3, 75 MHz): d 59.8,
60.1, 60.7, 69.9, 71.8, 71.9, 82.0, 82.9, 101.0, 111.2,
127.8, 127.9, 128.3, 137.6, 142.3. Anal. Calcd for
C17H24O5: C, 66.21; H, 7.84. Found: C, 66.52; H, 7.58.
4-Methyl-2-O-(3,4,6-tri-O-methyl-2-methylene-b-d-lyxo-
hexopyranosyl)-phenol (6). [a]Dˆ2294.0 (c 1, CHCl3), IR
1
(CH2Cl2): n 1610 cm21. H NMR (CDCl3, 300 MHz): d
2.48 (s, 3H, CH3), 3.43 (s, 3H, OCH3), 3.44 (s, 6H,
2£OCH3), 3.61±3.64 (m, 1H, H4), 3.69±3.71 (m, 3H,
Methyl-6-O-(3,4,6-tri-O-methyl-C-2-methylene-a-d-xylo-
hexopyranosyl)-2,3,4,tri-O-benzyl-a-d-glucopyranoside
0
H6,6 , H3), 4.18 (m, 1H, H5), 5.58 (s, 1H, H1), 6.18 (s, 1H,
(5). [a]Dˆ176.7 (c 1.7, CH2Cl2); IR (CCl4): n 1608 cm21
.
ole®nic-H), 6.19 (s, 1H, ole®nic-H), 6.90 (d, 2H, Ph-H),
7.00 (d, 2H, Ph-H). 13C NMR (CDCl3, 100 MHz): d 20.1,
56.8, 59.8, 69.6, 71.4, 71.4, 80.8, 81.0, 93.3, 111.0, 117.0,
119.2, 120.5, 129.3, 128.91, 135.1, 151.3. Mass spectrum
(m/z): no (M11)1, 201 (M12107), 156. Anal. Calcd for
C17H24O5: C, 66.23; H, 7.85. Found: C, 66.30; H, 7.88.
1H NMR (CDCl3, 300 MHz): d 3.16±3.5 (t, 1H, Jˆ10.4 Hz,
H4), 3.34 (s, 3H, ±OCH3), 3.37 (s, 3H, ±OCH3), 3.45±3.52
0
0
0
0
(m, 2H, H3 , H5 , H6,6 ), 3.52±3.56 (s, 8H, 2£±OCH3, H6,6 ),
0
3.67±3.85 (m, 4H, H2 , H5, H6,6 ), 3.9±4.04 (m, 2H, H3, H4 ),
0
0
4.59±5.0 (dd, 6H, 3£OCH2Ph), 4.6 (d, 1H, J1±2ˆ3.5 Hz,
0
H1 ), 5.05 (s, 1H, ole®nic-H), 5.14 (s, 1H, ole®nic-H),
5.15 (s, 1H, H1), 7.29 (s, 15H, 3£Ph-H). 13C NMR
(CDCl3, 75 MHz) d 49.9, 54.0, 54.1, 55.2, 60.6, 64.7,
66.1, 66.2, 68.2, 69.7, 70.6, 71.5, 71.9, 72.3, 72.7, 74.9,
92.7, 96.3, 105.4, 122.5, 122.7, 122.9, 123.2, 123.3, 133.0,
133.2, 133.5, 136.8. Mass spectrum (m/z): No M11 peak,
201, 171. Anal. Calcd for C38H48O10: C, 68.67; H, 7.28.
Found: C, 68.79; H, 7.24.
1-O-(3,4,6-Tri-O-methyl-2-methylene-b-d-lyxo-hexo-
pyranosyl)-naphthol (7). [a]Dˆ2288.0 (c 1.5, CHCl3). IR
1
(CH2Cl2): n 1615 cm21. H NMR (CDCl3, 400 MHz): d
3.47 (s, 9H, 3£OCH3), 3.68 (d, 1H, Jˆ4.2 Hz, H4), 3.76±
0
3.79 (m, 2H, H6,6 ) 3.96 (br s, 1H, H3), 4.22±4.26 (m, 1H,
H5), 5.69 (s, 1H, H1), 6.30 (s, 1H, ole®nic-H), 6.31 (s, 1H,
ole®nic-H), 7.15±7.84 (m, 7H, naphthyl-H). 13C NMR
(CDCl3, 100 MHz): d 56.87, 59.32, 59.54, 69.68, 71.54,
71.75, 80.85, 80.92, 93.47, 112.68, 119.02, 121.77,
123.73, 126.66, 128.39, 128.50, 129.20, 132.15, 135.04,
151.19. Mass spectrum (m/z): 345 [M11]1, 330, 300.
Anal. Calcd for C20H24O5: C, 69.76; H, 7.03. Found: C,
69.75; H, 7.00.
Cyclohexanyl-3,4,6-tri-O-methyl-2-deoxy-C-2-methylene-
a-d-lyxo hexopyranoside (3c). [a]Dˆ198.18 (c 1.1,
CHCl3); IR (CCl4): n 1610 cm21 1H NMR (CDCl3,
.
300 MHz): d 1.26±1.91 (m, 11H, cyclohexyl protons),
3.40 (s, 3H, CH2OCH3), 3.49 (s, 3H, 2£OCH3), 3.54 (s,

8530
A. Gupta, Y. D. Vankar / Tetrahedron 56 (2000) 8525±8531
4-Methyl-2-(3,4,6-tri-O-methyl-2-methylene-b-d-lyxo-
hexopyranosyl)-phenol (8). [a]Dˆ260.2 [c 0.8, CHCl3],
(m/z): 309 (M11)1, 201, (M12108), 171. Anal. Calcd for
C17H24O5: C, 66.23; H, 7.85. Found: C, 66.20; H, 7.86.
1
IR (CDCl3): n 3600 cm21, H NMR (CDCl3, 300 MHz): d
2.24 (s, 3H, CH3), 3.34 (s, 3H, ±OCH3), 3.31±3.43 (s, 6H,
1-O-(3,4,6-tri-O-methyl-2-methylene-a-d-arabino-hexo-
pyranoside)-2-naphthol (3g). [a]Dˆ176.8 (c 1.6, CHCl3).
IR (CH2Cl2): n 1615 cm21. 1H NMR (CDCl3, 300 MHz): d
3.39 (s, 3H, OCH3), 3.37±3.43 (m, 1H, H4), 3.52±3.64 (m,
0
2£±OCH3), 3.52 (dd, Jˆ8 Hz, 2H, H6,6 ), 3.79 (br s, 1H,
H4), 4.05 (t, 1H, Jˆ6 Hz, H5), 4.11 (d, 1H, Jˆ21 Hz, H3),
5.04 (s, 1H, H1), 5.21 (s, 1H, ole®nic-H), 5.28 (s, 1H,
ole®nic-H), 6.29 (s, 1H, OH), 6.82±7.01, (m, 3H, Ar-H).
13C NMR (CDCl3, 100 MHz): d 20.9, 57.9, 59.10, 61.0,
69.5, 71.5, 73.2, 74.5, 78.3, 110.7, 117.0, 124.2, 125.9,
127.7, 129.9, 140.9, 150.9. Mass spectrum (m/z): 308
(M1), 201, 156. Anal. Calcd for C17H24O6: C, 66.23; H,
7.85, Found: C, 66.39; H, 7.75.
0
2H, H6,6 ), 3.61 (s, 3H, OCH3), 3.67 (s, 3H, OCH3), 3.90±
3.95 (m, 1H, H5), 4.28 (d, J3,4ˆ10.4 Hz, 1H, H3), 5.34 (s,
1H, ole®nic-H), 5.35 (s, 1H, ole®nic-H), 6.00 (s, 1H, H1),
7.16±7.80 (m, 7H, naphthyl-H). 13C NMR (CDCl3,
300 MHz): d 59.09, 60.48, 70.72, 71.98, 81.10, 82.06,
99.85, 110.62, 118.97, 124.117, 126.232, 127.103, 127.10,
127.53, 127.57, 129.31, 129.50, 134.31, 141.19, 154.05.
Mass spectrum (m/z): 345 (M11)1, 201, 170, 139. Anal.
Calcd for C20H24O5: C, 69.76; H, 7.03. Found: C, 69.70; H,
7.00.
Preparation21 of methyl-1,5-anhydro-3,4,6-tri-O-methyl-
1,2-di-deoxy-d-arabino-hex-1-enitolyl-ethyl carbonate
(9). To a stirred solution of allylic alcohol (100 mg,
0.45 mmol) in THF (2 mL), pyridine (181 mg,
2.26 mmol), ethyl chloroformate (245 mg, 2.20 mL) and
catalytic amount of DMAP were added. The progress of
the reaction was monitored by TLC. After completion of
the reaction, (12 h) THF was evaporated under reduced
pressure and the usual work up gave a crude product
which was puri®ed by ¯ash column chromatography.
1,5-Anhydro-3,4,6-tri-O-methyl-1,2-di-deoxy-2-nitro-
ethane-d-arabino-hex-1-enitol (11). Reaction time: 8 h.
1
[a]Dˆ1120 [c 0.7, CHCl3). IR (CDCl3): n 1560 cm21. H
NMR (CDCl3, 300 MHz): d 2.53±2.78 (m, 2H, CH2±
CH2NO2), 3.39 (s, 3H, OCH3), 3.45 (s, 3H, OCH3), 3.51
(s, 3H, OCH3), 3.57±3.62 (m, 2H, CH2OCH3), 3.62±3.67
(m, 1H, H4), 3.76 (d, 1H, Jˆ8 Hz, H3), 4.02±4.07 (m, 1H,
H5), 4.42±4.52 (m, 2H, CH2NO2), 6.29 (s, 1H, H1). 13C
NMR (CDCl3, 100 MHz): d 28.05, 56.99, 58.65, 59.15,
70.07, 71.30, 71.5, 81.22, 82.60, 106.67, 142.87. Mass spec-
trum (m/z): 261 (M1), 230, 201, 170. Anal. Calcd for
C11H19NO6: C, 50.57; H, 7.33; N, 5.36. Found: C, 50.56;
H, 7.32; N, 5.35.
Yield: 65%. [a]Dˆ1100.9 (c 1.5, CHCl3). IR (CDCl3): n
1750 cm21 1H NMR (CDCl3, 300 MHz): d 1.30 (t, 3H,
Jˆ7.35 Hz, OCH2CH3), 3.4 (s, 3H, OCH3), 3.49 (s, 3H,
0
OCH3), 3.52 (s, 3H, OCH3), 3.59±3.68 (m, 3H, H4, H6,6 ),
3.89 (d, Jˆ6 Hz, 1H, H3), 4.07±4.12 (m, 1H, H5), 4.20 (q,
Jˆ4.2 Hz, 2H, OCH2CH3), 4.5±4.7 (ABQ; 2H, Jˆ8.2 Hz,
CH2±), 6.64 (s, 1H, H1). 13C NMR (CDCl3, 100 MHz); d
15.0, 59.18, 59.4, 60.4, 60.5, 62.5, 71.3, 71.7, 82.0, 82.7,
110.1, 142.3, 165.5. Mass spectrum (m/z): No M1 or
(M11)1 peak, 201, 170.9, 138.9, 108.9. Anal. Calcd for
C13H22O7: C, 53.79; H, 7.64. Found: C, 54.01; H, 7.64.
Ethyl-2-(1,5-anhydro-3,4,6-tri-O-methyl-1,2-di-deoxy-
C-2-a-d-arabino-hexopyranosyl)-2-(ethoxy
acetate (12). Reaction time: 5 h, [a]Dˆ152.2 [c 1,
CHCl3]. IR (CDCl3): n 1750 cm21 1H NMR (CDCl3,
carbonyl)
.
300 MHz); d 1.23±1.3 (m, 3H, Jˆ6 Hz, OCH2CH3), 3.17±
3.21 (d, Jˆ10 Hz, 1H, H4), 3.35 (s, 3H, OCH3), 3.52 (s, 3H,
General procedure for the Pd(0) catalyzed O- and C-
glycosylations
0
OCH3), 3.53 (s, 3H, OCH3), 3.52±3.62 (m, 2H, H6,6 ), 3.66±
3.69 (m, 1H, H5), 3.86, 3.96 (m, 1H, H3), 3.96±3.98 (d, 1H,
Jˆ12 Hz, CH(CO2Et)2), 4.11±4.26 (m, 4H, 2£OCH2), 4.99
(d, 1H, Jˆ12 Hz, H1), 5.13 (s, 1H, ole®nic-H), 5.23 (s,
1H,ole®nic-H). 13C NMR (CDCl3, 100 MHz): d 13.98,
53.58, 59.13, 59.21, 60.25, 61.56, 61.66, 71.22, 74.09,
81.23, 81.69, 86.07, 107.80, 140.80, 165.30. Mass spectrum
(m/z): 329 [M1231], 201 [M12159], 171, 139. Anal. Calcd
for C17H28O8: C, 56.66; H, 7.83. Found: C, 56.66; H, 7.84.
To a solution of the carbonate 9 (1 mmol) in THF (2 mL), an
alcohol or diethyl malonate or nitromethane (1 mmol) under
N2 atm, triphenylphosphine or dppe (10 mol%) and freshly
prepared Pd(0) (2 mol%) were successively added. After
re¯uxing for the given time, (for compounds 3a and 5 the
reaction time were, 8 and 10 h, respectively) the THF was
evaporated, mixture was ®ltered over a sintered funnel and
washed thoroughly with ethyl acetate (2£25 mL). The
solvent was evaporated under reduced pressure and the
crude product so obtained was puri®ed by column chroma-
tography.
Conversion of allyl acetates 1, 2, 1312, and 1412 to lactones
15a±15d respectively
General procedure. To a stirred solution of an allyl acetate,
(1 mmol) in dry CH2Cl2 (5 mL), cooled to 2658C, was
added m-CPBA (50%, 344 mg, 2 mmol) followed by drop-
wise addition of freshly distilled (from CaH2) BF3´Et2O
(0.12 mL, 1 mmol) under N2 atmosphere. The reaction
was stirred for about 1 h until it was complete (TLC moni-
toring) and then quenched with 2 mL of 10% aq. Na2S2O4
solution and brought it to room temperature. Usual work up
thereafter followed by column chromatography puri®cation
gave the desired lactones. Lactones 15c and 15d gave satis-
factory spectral and analytical data which were comparable
with the literature17 values.
p-Methyl phenyl-3,4,6-tri-O-methyl-C-2-methylene-a-d-
arabino-hexo-pyranoside (3f). [a]Dˆ1119.2 (c 1.3,
CHCl3). IR (CH2Cl2): n 1608 cm21 1H NMR (CDCl3,
.
300 MHz): d 2.28 (s, 3H, CH3), 3.36 (s, 3H, OCH3), 3.39
(t, 1H, Jˆ10 Hz, H4), 3.57±3.62 (2s, 6H, 2£OCH3), 3.47±
0
3.62 (m, 2H, H6,6 ), 3.85±3.89 (m, 1H, H5), 4.20 (d, 1H,
Jˆ12 Hz, H3), 5.17 (s, 1H, ole®nic-H), 5.26 (s, 1H, ole®-
nic-H), 5.77 (s, 1H, H1), 7.05 (q, Jˆ9.3 Hz, Ph-H). 13C
NMR (CDCl3, 100 MHz): d 20.2, 59.05, 59.8, 60.56,
70.71, 71.5, 77.8, 80.1, 100.1, 110.91, 117.09, 119.20,
120.57, 128.31, 130.47, 140.92, 151.33. Mass spectrum

A. Gupta, Y. D. Vankar / Tetrahedron 56 (2000) 8525±8531
8531
513. (b) Olah, G. A.; Prakash, G. K. S. Encyclopedia of Reagents
for Organic Synthesis; Paquette, L. A., Ed.; 1995, 6, 3697.
6. Kawai, M.; Onaka, M.; Izumi, Y. Bull. Chem. Soc. J. 1988, 61,
1237.
3,4,6-Tri-O-methyl-2-deoxy-2-methylene-d-arabino-
hexono-1,5-lactone 3 (15a). Yield: 65%. [a]Dˆ265 [c 2,
CHCl3). IR (CCl4): n 1730 cm21 1H NMR (300 MHz,
.
CDCl3): d 3.19 (t, 1H, Jˆ8 Hz, H4), 3.39, 3.52, 3.59 (3S,
0
7. (a) Collins, J. L.; Grieco, P. A.; Walker, J. K. Tetrahedron Lett.
1997, 38, 1321. (b) Saraswathy, V. G.; Sankararaman, S. J. Org.
Chem. 1994, 59, 4665.
3H each, 3£±OCH3), 3.64±3.69, (m, 2H, 2£H6,6 ), 3.99 (br
d, Jˆ8.8 Hz, 1H, H3), 4.26 (m, 1H, H5), 5.96 (br s, 1H,
ole®nic-H), 6.6 (br s, 1H, ole®nic-H). 13C NMR (75 MHz,
CDCl3): d 57.7, 58.8, 59.3, 71.0, 77.2 78.6, 80.7, 130.1,
134.1, 164.8. Mass spectrum (m/z): 217 [(M11)1, 2.3],
216 [(M1), 5.3], 201 (14.30), 139 (17), 46 (100). Anal.
Calcd for C, 55.55; H, 7.46. Found: C, 55.50 H, 7.69.
8. Trost, B. M. Angew. Chem., Int. Ed. Engl. 1989, 28, 1173.
9. Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M. Synlett 1995,
306.
10. Irradiation of b-anomeric hydrogen of the a-glycosides
resulted in enhancement of one of the exo methylene hydrogens
and vice versa in the nOe difference spectra. From the molecular
model it is clear that one of the exo methylene hydrogens is closer
to the b than to the a anomeric hydrogen. As expected, indeed
enhancements were not observed in the nOe experiments done on
compounds 6, 7, and 8 which are b glycosides and possess
a-anomeric hydrogens. Additionally, no enhancements were
found in the nOe experiments between C-1 and C-5 methine
signals analogous to the literature reports.4
3,4,6-Tri-O-methyl-2-deoxy-2-methylene-d-lyxo-hexono-
1,5-lactone (15b). Yield: 62%. [a]Dˆ180 [c 1, CHCl3). IR
(CCl4): 1730 cm21. 1H NMR (300 MHz, CDCl3): d 3.42 (s,
3H, ±OCH3), 3.55, 3.57 (2s, 3H each, 2£±OCH3), 3.59±
0
3.71 (m, 2H, H6,6 ), 3.99 (br s, 1H, H4), 4.11 (d, 1H,
Jˆ3.3 Hz, H3), 4.4 (t, 1H, Jˆ9.9 Hz, H5), 6.11 (br s, 1H,
ole®nic-H), 6.64 (br s, 1H, ole®nic-H). 13C NMR (75 MHz,
CDCl3): d 57.4, 59.2, 60.4, 70.2, 71.7, 76.6, 80.0, 129.2,
133.8, 163.6. Mass spectrum (m/z): 216 [(M1), 5], 201(3),
171 (10), 46 (100). Anal. Calcd for C, 55.55; H, 7.46.
Found: C, 55.41; H, 7.42.
11. Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114,
3471.
12. Ramesh, N. G.; Balasubramanian, K. K. Tetrahedron 1995,
51, 255.
13. Fukase, K.; Winamo, H.; Kusumoto, S. Chem. Express 1993,
8, 409.
Acknowledgements
14. Toshima, K.; Miyamoto, N.; Matsuo, G.; Nakata, M.;
Matsumura, S. J. Chem. Soc., Chem. Commun. 1996, 1379.
15. Toshima, K.; Ushiki, Y.; Matsuo, G.; Matsumura, S.
Tetrahedron Lett. 1997, 38, 7375.
We are grateful to the Department of Science and Tech-
nology, New Delhi for ®nancial support (through grant #
SP/S1/G-07/1997). A. G. thanks UGC, New Delhi, for a
Senior Research Fellowship.
16. (a) Waldman, H.; Bohm, G.; Schmid, K.; Roltele, H. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1994. (b) Schene, H.; Waldmann,
H. J. Chem. Soc., Chem. Commun. 1998, 2759 and references cited
therein.
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