Montmorillonite K-10 clay-catalyzed Ferrier rearrangement of 2-C-hydroxymethyl-D-glycals, 3,4,6-tri-O-alkyl-D-glycals, and 3,4-(dihydro-2H-pyran-5-yl)methanol: A few unexpected domino transformations

Article abstract of DOI:10.1016/j.carres.2011.03.027

Montmorillonite K-10 clay-catalyzed substitution reactions of 3,4,6-tri-O-alkyl-2-C-hydroxymethyl-Dglycals, 3,4,6-tri-O-acetyl-D-glycals, 3,4,6-tri-O-alkyl-D-glycals, and 3,4-(dihydro-2H-pyran-5-yl)methanol with a few alcohols and phenols are described. The reactions of 2-C-hydroxymethyl-D-glycals with phenols were similar to those of 2-C-acetoxymethyl-D-glycals and afforded pyrano[2,3-b]benzopyrans. This montmorillonite K-10 clay-catalyzed transformation is facile both under ambient (Method 1) and microwave conditions (Method 2). Ferrier rearrangement of 3,4-(dihydro-2H-pyran-5-yl)methanol with p-cresol, 2,6-xylenol, and ethanol led to totally unexpected transformations. Reaction of 2-C-hydroxymethyl- D-galactal with 2,6-dimethylphenol in the presence of montmorillonite K-10 led to a novel domino transformation affording 4-(5',6'-dihydro-4H-pyran-3'-ylmethyl)-2,6-dimethylphenol. In contrast, 3,4,6-tri-O-acetyl-D-glucal furnished the Ferrier rearrangement product, 2,6-dimethylphenyl 4,6-di-Oacetyl- 2,3-dideoxy-α-D-erythro-hex-2- enopyranoside. Also, isomerization of 3,4,6-tri-O-alkyl-D-glycals to products of allylic rearrangement, 2,3-unsaturated-O-glycosides in good yields is reported.

Full text of DOI:10.1016/j.carres.2011.03.027

Carbohydrate Research 346 (2011) 1654–1661
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Montmorillonite K-10 clay-catalyzed Ferrier rearrangement
of 2-C-hydroxymethyl-D-glycals, 3,4,6-tri-O-alkyl-D-glycals, and
3,4-(dihydro-2H-pyran-5-yl)methanol: a few unexpected domino
transformations
Elumalai Kumaran, Meenakshisundaram Santhi, Kalpattu K. Balasubramanian,
⇑
Shanmugasundaram Bhagavathy
Shasun Research Centre, No 27, Vandaloor-Kelambakkam Road, Keelakottaiyur village, Melakottaiyur post, Chennai 600 048, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 January 2011
Received in revised form 20 February 2011
Accepted 15 March 2011
Available online 21 March 2011
Montmorillonite K-10 clay-catalyzed substitution reactions of 3,4,6-tri-O-alkyl-2-C-hydroxymethyl-D-
glycals, 3,4,6-tri-O-acetyl-
anol with a few alcohols and phenols are described. The reactions of 2-C-hydroxymethyl-
phenols were similar to those of 2-C-acetoxymethyl- -glycals and afforded pyrano[2,3-b]benzopyrans.
D
-glycals, 3,4,6-tri-O-alkyl-
D
-glycals, and 3,4-(dihydro-2H-pyran-5-yl)meth-
D-glycals with
D
This montmorillonite K-10 clay-catalyzed transformation is facile both under ambient (Method 1) and
microwave conditions (Method 2). Ferrier rearrangement of 3,4-(dihydro-2H-pyran-5-yl)methanol with
p-cresol, 2,6-xylenol, and ethanol led to totally unexpected transformations. Reaction of 2-C-hydroxy-
Keywords:
Carbohydrates
methyl-
ino transformation affording 4-(50,60-dihydro-4H-pyran-30-ylmethyl)-2,6-dimethylphenol. In contrast,
3,4,6-tri-O-acetyl- -glucal furnished the Ferrier rearrangement product, 2,6-dimethylphenyl 4,6-di-O-
acetyl-2,3-dideoxy- -erythro-hex-2-enopyranoside. Also, isomerization of 3,4,6-tri-O-alkyl- -glycals
to products of allylic rearrangement, 2,3-unsaturated-O-glycosides in good yields is reported.
D-galactal with 2,6-dimethylphenol in the presence of montmorillonite K-10 led to a novel dom-
Microwave irradiation
Glycals
Allylic transposition
Ferrier rearrangement
Montmorillonite K-10
D
a-
D
D
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Balasubramanian.28 Since then a few reports have appeared on
this transformation using BF3ꢀEt2O,29 LiClO4
,
and InCl3.31,32
30
Glycosides are potential building blocks in synthetic organic
chemistry and have been widely used in synthesis of various
However, there are only scattered reports on the Ferrier rear-
rangement involving the 2-C-hydroxymethyl-D
-glycal.33–36 As
complex natural products,1–4 drugs, and drug intermediates.5–9
A
pyranobenzopyrans and their derivatives exhibit various biologi-
cal activities,37–39 an efficient and eco-friendly method is desir-
able for their synthesis. In line with the recent increasing
global interests to develop green chemical processes and envi-
ronmentally friendly catalysts, we chose montmorillonite K-10
clay as the catalyst for our present studies. Surprisingly we find
that the Ferrier rearrangement has not been studied on the par-
ent compound, 3,4-(dihydro-2H-pyran-5-yl)methanol (5) (Fig. 1).
But it is known that 3,4-dihydro-2H-pyran (6) behaves differ-
ently from glycals 7–8 during electrochemical oxidation.40
Herein we describe a mild and convenient method of glycosyl-
variety of reagents such as BF3ꢀEt2O,10 DDQ,11 SnCl4,12 FeCl3,13
NIS,14 Sc(OTf)3,15 InCl3,16 montmorillonite K-10,17 Fe2(SO4)3,18
AcClO4,19 and H3PO4,20 have been used as catalysts for the Ferrier
rearrangement. However, some are very expensive while others
are highly hygroscopic. There are a few reports on the micro-
wave-assisted Ferrier rearrangement of glycals.21,22 In a few cases
better stereoselectivity has been observed when the Ferrier rear-
rangements were performed under microwave irradiation.23 Ferri-
er rearrangements have been carried out mostly on allylic esters of
the glycals,24,25 although in a few cases, allylic ethers of gly-
cals18,26,27 have also been used as substrates.
ation of 2-C-hydroxymethyl-D-glycals 1–4 with few phenols using
A variant of the Ferrier rearrangement involving 2-C-ace-
toxymethyl-D-glycal was first reported by Booma and
the environmentally benign montmorillonite K-10 as catalyst and
without having to activate C-2 hydroxymethyl glycal as esters to-
wards the synthesis of pyranobenzopyrans. The reactions have
been compared under ambient conditions in the absence of micro-
waves (Method 1) and under microwave irradiation (Method 2).
We also report for the first time the Ferrier rearrangement on the
parent alcohol 5. We have extended this study to a few other
⇑
Corresponding author at present address: B.S. Abdur Rahman University,
Seethakathi Estate, Vandalur, Chennai 600 048, Tamil Nadu, India. Mobile: +91
9444936005.
E-mail address: bhagavathy@bsauniv.ac.in (S. Bhagavathy).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.03.027

E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
1655
lished by the reaction of the glycals 1–4 with p-cresol, p-methoxy-
phenol, (Scheme 1) and b-naphthol (Scheme 2). The reaction time,
yield, and anomeric ratio of the products are summarized in Table 1
OAc
OR
R1
O
O
O
O
R2
R2
R1
(Method 1). As expected, in all the cases
a anomer is the major prod-
OH
OH
OAc
uct. This montmorillonite K-10-catalyzed reaction offers a milder
and convenient method of synthesis of pyranobenzopyrans unlike
the other catalysts like BF3ꢀEt2O,28 TFA33, and InCl3.34
OR
1-4
5
6
7- 8
7 R1 = OAc, R2 = H
1 R1 = OMe, R2 = H, R = Me
R1 = H, R2 = OAc
We also investigated these reactions under microwave irradia-
tion (Method 2). As anticipated the reactions were very fast under
microwave irradiation conditions. Reaction of glucal 1 with p-cre-
sol (9) in the presence of montmorillonite K-10 under microwave
irradiation was complete in 3 min and afforded 11a as the major
product and 11b as the minor product. When this reaction was
performed under microwave irradiation in the absence of mont-
morillonite K-10 for 10 min., the products 11a and 11b were ob-
tained, but in very poor yields (4%). Thus, glycals 1–4 were
treated with p-cresol, p-methoxyphenol, and b-naphthol in the
presence of montmorillonite K-10 in DCE under the optimized
microwave conditions to afford the corresponding pyrano[2,3-
b]benzopyrans. The reaction time, yields, and anomeric ratios are
summarized in Table 1 (Method 2). The reactions were extremely
8
2
3
4
R
R
R
1 = H, R2 = OMe, R = Me
1 = OBn, R2 = H, R = Bn
1 = H, R2 = OBn, R = Bn
Figure 1. Glycals and dihydropyrans.
substrates, 3,4,6-tri-O-acetyl-D-glycal and 3,4,6-tri-O-alkyl-D-gly-
cals. We also disclose here the first report on the reaction of a Fer-
rier substrates 1 and 5 with 2,6-dimethylphenol, which furnished
the unexpected C-arylated products.
2. Results and discussion
2.1. Reaction of 2-C-hydroxymethyl-D-glycals with phenols
fast and showed higher
as compared to Method 1.
The
a selectivity under microwave irradiation
The key glycals 1–4 were synthesized as reported in the litera-
ture41 starting from tri-O-acetyl- -glycals, 7–8.42,43 Treatment of
2-C-hydroxymethyl- -glucal (1) (1.0 equiv) and p-cresol (9)
a
isomers (11a–18a and 20a–23a)31–33 and b isomers (11b,
20b, and 21b)31,32 have been isolated, and the spectral data are in
accord with those described in literature. Presently we could sep-
arate the new b isomers in few of the cases, 12b, 14b, 17b, 18b,
and 23b by repeated crystallization followed by column chroma-
tography. The data are reported in Table 1.
D
D
(2.0 equiv) with montmorillonite K-10 (100% w/w) in dichloroeth-
ane (DCE) at room temperature led to the formation of a mixture
of a-pyrano[2,3-b]benzopyran 11a and b-pyrano[2,3-b]benzopyran
11b in 68% yield with 11a as the major product (Method 1,
Scheme 1). The spectral data of 11a is in accord with those reported
in the literature.33 The generality of this transformation was estab-
The literature reveals that despite the numerous reports on the
Ferrier rearrangement of glycals with various phenols, this reaction
has not been investigated with 2,6-disubstituted phenols which
OR
H
H
OR
OR
OH
O
O
O
O
O
Mont. K10
+
R2
R1
R2
R1
R3
+
R2
R3
ClCH2CH2Cl
R1
R3
OH
OR
11b-18b
11a-18a
1 R1 = OMe, R2 = H, R = Me
2 R1 = H, R2 = OMe, R = Me
3 R1 = OBn, R2 = H, R = Bn
4 R1 = H, R2 = OBn, R = Bn
9
R3 = Me
11a, 11b R1 = OMe, R2 = H, R = Me, R3 = Me
10 R3 = OMe
12a, 12b R1 = OMe, R2 = H, R = Me, R3 = OMe
13a, 13b R1 = H, R2 = OMe, R = Me, R3 = Me
14a, 14b R1 = H, R2 = OMe, R = Me, R3 = OMe
15a, 15b R1 = OBn, R2 = H, R = Bn, R3 = Me
16a, 16b R1 = OBn, R2 = H, R = Bn, R3 = OMe
17a, 17b R1 = H, R2 = OBn, R = Bn, R3 = Me
18a, 18b R1 = H, R2 = OBn, R = Bn, R3 = OMe
Scheme 1. Synthesis of fused pyrano[2,3-b]benzopyrans.
OR
O
OR
OR
H
H
OH
Mont. K10
R2
O
O
O
O
+
+
R2
R1
R2
R1
R1
ClCH2CH2Cl
OH
OR
19
20b-23b
20a-23a
1 R1 = OMe, R2 = H, R = Me
2 R1 = H, R2 = OMe, R = Me
3 R1 = OBn, R2 = H, R = Bn
4 R1 = H, R2 = OBn, R = Bn
20a, 20b R1 = OMe, R2 = H, R = Me
21a, 21b R1 = H, R2 = OMe, R = Me
22a, 22b R1=OBn, R2 = H, R = Bn
23a, 23b R1 =H, R2 = OBn, R = Bn
Scheme 2. Synthesis of pyrano[2,3-b]naphthopyrans.

1656
E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
Table 1
Montmorillonite K-10-catalyzed reaction of 2-C-hydroxymethyl-D-glycals with phenols
Glycal
Nucleophile
Product
Method 1a
Yieldc (%)
Method 2b
Yieldc
Time (h)
a
:bd
Time (min)
a
:bd
1
1
1
2
2
2
3
3
3
4
4
4
p-Cresol
11a:11b
12a:12b
20a:20b
13a:13b
14a:14b
21a:21b
15a:15b
16a:16b
22a:22b
17a:17b
18a:18b
23a:23b
48
48
36
48
48
48
50
50
50
36
40
36
68
61
71
70
63
79
69
59
70
71
63
74
1:0.7
1:0.6
1:0.3
1:0.3
1:0.4
1:0.4
1:0.3
1:1.0
1:0.4
1:0.3
1:0.4
1:0.8
3
1
1
5
3
1
5
1
2
5
2
1
78
69
85
83
71
85
79
63
85
81
70
85
1:0.3
1:0.4
1:0.3
1:0.1
1:0.2
1:0.2
1:0.3
1:0.4
1:0.4
1:0.2
1:0.2
1:0.1
p-Methoxyphenol
b-Naphthol
p-Cresol
p-Methoxyphenol
b-Naphthol
p-Cresol
p-Methoxyphenol
b-Naphthol
p-Cresol
p-Methoxyphenol
b-Naphthol
a
b
c
Reaction performed at room temperature (25 °C).
Reaction performed under microwave irradiation at 80 °C, 300 W.
Isolated yield after column chromatography.
d
Ratio obtained from the 1H NMR spectrum of the crude product.
OBn
O
OBn
OBn
O
OBn
OBn
OH
BnO
+
O
Me
Me
Mont. K10
ClCH2CH2Cl
RT
Me
BnO
+
OBn
OR
BnO
Me
OR
BnO
28
25
26 R = H
Ac2O
Pyr.
4 R = H
24 R = Ac
27 R = Ac
Ac2O
Pyr.
Me
Me
OBn
O
OBn
OR
Me
O
O
BnO
BnO
Me
OBn
OBn
29
30
Scheme 3. Reaction of glycal 4 with 2,6-dimethylphenol.
Table 2
can lead to phenolic C-aryl glycosides by arylation of the glycal at
the anomeric position by C-4 of 2,6-dimethylphenol. In view of the
possibility for a carbon Ferrier rearrangement in the case of hin-
dered phenols, we investigated the reaction of 2-C-hydroxymeth-
ylglycal with 2,6-dimethylphenol (25).
Montmorillonite K-10-catalyzed reaction of 4, 5, 7, and 24 with various alcohols and
phenols
S. No
Substrate
Nucleophile
Product
Method 1a
Time (h)
Yieldb (%)
Exposure of 4 to 2,6-dimethylphenol in the presence of mont-
morillonite K-10 at ambient temperature for 6 h afforded 26 as a
colorless liquid in 51% yield along with a trace amount of 2828
(Scheme 3). Surprisingly, we did not observe the formation of
either 29 or 30. A cursory glance at the 1H NMR spectrum of 26
clearly indicated that it is not the simple Ferrier rearrangement
product, 2-C-exo-methylene galactoside 29 or the C-aryl galacto-
side 30. The structure of 26 was established by NMR and NOE spec-
tral data.
1
2
3
4
5
6
7
8
9
4
24
4
2,6-Dimethylphenol
2,6-Dimethylphenol
Ethanol
Benzylalcohol
Ethanol
Benzylalcohol
2,6-Dimethylphenol
Ethanol
Benzylalcohol
p-Cresol
26
26
33
28
33
28
34
36
38
40
41
6
6
4
51 (5)c
55 (9)c
60
72
65
76
11
68
58
4
4
24
24
7
5
5
20
12
4
6
2
10
11
5
5
3
2
60
40
2,6-Dimethylphenol
Further, 26 was readily converted to the acetate derivative 27
for confirming the structure (Scheme 3). When the reaction was
carried out under microwave irradiation, it did not lead to any trac-
table product. Likewise, the montmorillonite K-10-catalyzed reac-
tion of acetate 24 with 2,6-dimethylphenol by Method 1 also
yielded 26 as the major product (Table 2, entry 2) and the exo-
a
b
c
Reaction performed at room temperature (25 °C).
Yield after column chromatography.
In parenthesis yield of the side product 28.
to the other end (C-1). This type of allylic transposition of the ether
group from C-3 to C-1 has been reported as a minor side reaction in
a few cases of the Ferrier rearrangement of glycals.44 The prefer-
ence for a C-alkylation without allylic rearrangement exhibited
by 2,6-dimethylphenol is in contrast to the behavior of other phe-
nols which undergo O-alkylation with allylic rearrangement.
methylene a-benzyl glycoside 28 in minor amounts (9%).
The formation of the product 26 could probably be rationalized
by the acid-catalyzed substitution of 25 via its attack in the para
position with the glycal, followed by the attendant migration of
the benzyl ether group from one end of the allylic system (C-3)

E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
1657
2.2. Reaction of 2-C-hydroxymethylglycals with alcohols
in DCE furnished only the hitherto unknown Ferrier-rearranged
product 34, albeit in very low yield (Scheme 5, Table 2, entry 3).
In the light of these interesting transformations encountered in
the montmorillonite K-10-catalyzed reactions of 2-C-hydroxymeth-
ylglycals and phenols, we sought to investigate this reaction with a
few alcohols. Reaction of the glycal 4 with ethanol 31 and benzyl
alcohol 32 in the presence of montmorillonite K-10 under ambient
It is also important to note that the 3,4,6-tri-O-acetyl-
(8) failed to react with 25 under these conditions.
D-galactal
2.4. Reaction of 3,4-(dihydro-2H-pyran-5-yl)methanol (5) with
alcohols
conditions afforded the known
methylene- -galactoside (33) and
C-exo-methylene- -galactoside (28), respectively, in 60% yield
a
-ethyl 3,4,6-tri-O-benzyl-2-C-exo-
D
a
-benzyl 3,4,6-tri-O-benzyl-2-
Due to the basic structural similarity of 3,4-(dihydro-2H-pyran-
D
5-yl)methanol (5)45–47 with 2-C-hydroxymethyl-
D-glycal, we ex-
(Scheme 4, Table 2, entries 3 and 4). These results are similar to lit-
erature reports using BF3ꢀEt2O,28 except for the fact that the present
catalyst is eco-friendly and mild compared to BF3ꢀEt2O.
plored the above reactions using alcohol 5, which was synthesized
in two steps using our modified procedure. Dihydropyran was
formylated under Vilsmeier–Haack conditions to obtain 3,4-(dihy-
dro-2H-pyran-5-yl)methanal (35), which upon reduction with
NaBH4–methanol furnished the alcohol 5 in an overall 52% yield.
In remarkable contrast to the behavior of the glycals, the
reaction of the alcohol 5 with ethanol in the presence of montmo-
rillonite K-10 at ambient temperature did not furnish the Ferrier-
rearranged product 37, but led to the formation of an interesting
enal 36 (Scheme 6, Table 2, entry 8). It is probable that the mois-
ture present in ethanol triggers a Ferrier rearrangement of 5,
resulting in the formation of an unstable hemiacetal that opens
As expected, the acetate 24 also underwent the montmorillon-
ite K-10-catalyzed glycosidation with the alcohol 31 and 32 to af-
ford 33 and 28, respectively, in reasonable yields (Table 2, entries 5
and 6). In both the cases the yields and
a selectivity are compara-
ble with those reported in literature,28 while the reaction is faster
with 4 as compared to 24.
2.3. Reaction of 3,4,6-tri-O-acetyl-D-glycals with 2,6-
dimethylphenol
out to give an open chain
a,b-unsaturated primary alcohol,
The reaction of 3,4,6-tri-O-acetyl-
D
-glycals with phenols with
5-hydroxy-2-methylenepentenal. Subsequent Ferrier rearrange-
ment involving this aldehydic alcohol to another molecule of 5
could account for the formation of 36. But the reaction of the alco-
hol 5 with benzyl alcohol afforded the normal Ferrier-rearranged
product 38 (Scheme 6, Table 2, entry 9).
montmorillonite K-10 is quite well known,23 but it has not been re-
ported with 2,6-dimethylphenol (25). In contrast to the behavior of
the glycals 4, the reaction of 3,4,6-tri-O-acetyl-
2,6-dimethylphenol (25) in the presence of montmorillonite K-10
D-glucal (7) with
2.5. Reaction of 3,4-(dihydro-2H-pyran-5-yl)methanol (5) with
phenols
OBn
OBn
O
OR
O
Mont. K10
DCE
Yet another unexpected domino transformation was encoun-
tered when 3,4-(dihydro-2H-pyran-5-yl)methanol (5) was reacted
with phenols. The montmorillonite K-10-catalyzed reaction of the
alcohol 5 with p-cresol in DCE at ambient conditions for 3 h, fur-
nished an unexpected product 40 in 60% yield (Scheme 6, Table
2, entry 10).
The structure of 40 was established and confirmed from its
HRMS and HMBC spectral data. The formation of 40 can be ratio-
nalized as a domino process involving an initial Ferrier rearrange-
ment of 5 with p-cresol to furnish 40a that can further undergo an
acid-catalyzed Claisen rearrangement to form the phenolic inter-
mediate 40b. A final concomitant cyclization and nucleophilic sub-
stitution could lead to the formation of 40 (Scheme 8).
ROH
+
CH2
BnO
BnO
R
OBn
31-32
OBn
33, 28
4 R = OH
24 R = OAc
Ac2O
31, 33 R = Et
32, 28 R = Bn
Pyr.
Scheme 4. Synthesis of 2-C-exo-methylene-
D
-galactosides.
H3C
OAc
OAc
OH
O
Mont. K10
O
O
H3C
CH3
+
ClCH2CH2Cl
H3C
The reaction of 5 with 2,6-dimethylphenol (25) in the presence
of montmorillonite K-10 was similar to that of the glycal 1 and
afforded the 4-(3,4-dihyro-2H-pyran-5-yl)-2,6-dimethylphenol
(41) (Scheme 7, Table 2, entry 11). Noteworthy here is the high
propensity exhibited by the glycals and the alcohol 5 to undergo
AcO
AcO
OAc
7
25
34
D-glucal (7) with 2,6-dimethylphenol (25).
Scheme 5. Reaction of 3,4,6-tri-O-acetyl-
OEt
CH2
O
CH2
CHO
O
O
Mont. K10
EtOH
CH2
37
36
O
DCE
O
NaBH4
MeOH
CHO
Mont. K10
BnOH
OH
OBn
CH2
O
5
35
DCE
38
Scheme 6. Montmorillonite K-10-catalyzed reaction of 5 with alcohols.

1658
E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
25
p-cresol
Mont. K10
O
O
O
H3C
HO
H3C
O
Mont. K10
CH3
DCE
DCE
OH
O
40
41
5
Scheme 7. Montmorillonite K-10-catalyzed reaction of 5 with phenols.
OR
O
OR
OH
OR
O
OBn
O
Mont K-10
DCE
O
O
O
H+
R2
R1
+
O
O
CH
3
R2
R1
CH3
CH2
OR
O
BnO
CH
3
OH
5
H
46
47-50
42-45
H
40a
42, 47 R1=OBn, R2 = H, R = Bn
43, 48 R1 =H, R2 = OBn, R = Bn
44, 49 R1 = OMe, R2 = H, R = Me
45, 50 R1 = H, R2 = OMe, R = Me
HO
O
O
O
40b
CH3
Scheme 9. Isomerization of per-O-alkyl-D-glycals
CH
3
H
O
O
40
H
O
Table 3
Isomerization of per-O-alkyl-D-glycals
Scheme 8. Probable mechanistic pathway for the formation of 40.
S. No
Substrate
Time (h)
Product
Yielda (%)
a
:bb
Ref.
1
2
3
4
42
43
44
45
8
8
6
6
47
48
49
50
75
62
53
48
4:1
Only
4:1
10,48,49
—
50,51
—
a
a
normal substitution in preference Ferrier rearrangement with 2,6-
dimethylphenol. Also noteworthy is their preference for C-alkyl-
ation over O-alkylation. The generality and mechanism of these
transformations are under investigation.
Only
a
Yield after column chromatography.
Ratio obtained from the 1H NMR spectrum of the crude product.
b
2.6. Allylic transposition of the ether group in peralkyl glycals
Finally, we focused on the montmorillonite K-10-catalyzed
Ferrier rearrangement of peralkyl glycals. Treatment of 2,3,6-tri-
K-10-catalyzed reactions of 3,4-(dihydro-2H-pyran-5-yl)methanol
(5) with p-cresol (9) and 2,6-dimethylphenol (25) are in remark-
O-benzyl-D-glucal (42) with p-cresol in the presence of montmoril-
able contrast to that of 2-C-hydroxymethyl-D-glycals resulting in
lonite K-10 at room temperature led to the corresponding Ferrier
product 46 as the minor product (10%), while the transposed prod-
uct 47 was obtained as the major product (56%) (Scheme 9). The
use of alcohols as nucleophiles with the glucal 42 led only to the
isomerized product and no trace of Ferrier-rearranged product
was obtained.
This isomerization reaction involving the allylic transposition of
the ether group was found to be a general one in the cases of other
glycals 43, 44, and 45 (Scheme 9). In the case of glucals 42 and 44,
few interesting synthons. This methodology offers an attractive
way to synthesize a new class of dihydropyran derivatives that
would find applications as chiral synthons for synthesizing various
pharmaceutically important molecules.
4. Experimental section
4.1. General
the reaction yielded a mixture of
1 and 3), while in the case of galactal 43 and 45, it selectively
yielded only the anomer (Table 3, entries 2 and 4). Our findings
reveal that per-O-alkyl-
a and b anomers (Table 3, entries
For all reactions dry dichloroethane and activated montmoril-
lonite K-10 was used. Montmorillonite K-10 purchased from Sig-
ma–Aldrich was activated by heating it at 150 °C for 2 h in a
furnace. Unless otherwise stated, all reactions are performed under
an N2 atmosphere. All microwave reactions were conducted in a
closed vessel with a CEMs Discover Benchmate model 2455 MHz
microwave oven. NMR spectra were recorded on a Bruker DPX-
300 (300 MHz) in CDCl3 containing trimethylsilane. Melting points
were determined on a Veego (VMP-PM) apparatus and are uncor-
rected. Specific rotations were recorded on an Autopol-V80000
instrument. IR spectra were recorded on a Perkin–Elmer instru-
ment. High-resolution mass spectra were recorded on a QSTAR
instrument. For TLC hexane–EtOAc was used as the eluant.
a
D
-glycals are more prone to undergo allylic
transposition44 than Ferrier rearrangement in the presence of
montmorillonite K-10 as catalyst.
3. Conclusions
We have developed a mild and convenient method for the di-
rect glycosylation of a few 2-C-hydroxymethyl glycals, without
the need to activate the alcohol as the acetate, using the eco-
friendly catalyst, montmorillonite K-10. The reaction of 3,4,6-tri-
O-alkyl-2-C-hydroxymethyl-
rillonite K-10 provides a milder method for the synthesis of chiral
-pyrano[2,3-b]benzopyrans. These reactions were extremely fast
D-glycal with phenols using montmo-
4.2. Typical experimental procedure
a
under microwave irradiation conditions. 2,6-Dimethylphenol (25)
exhibited a totally different behavior compared to that of simple
phenols and led to unexpected transformations. Montmorillonite
4.2.1. Method 1
To a solution of glycal substrate 1, 5, or 24 (0.5 mol) and phenol
or alcohol (2 equiv) in 1,2-dichloroethane (10 mL) was added

E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
1659
activated montmorillonite K-10 (100% w/w). The mixture was stir-
red at rt for the specified time. The reactions were monitored by
TLC. The reaction mixture was filtered and extracted with EtOAc.
The organic layer was washed with 10% NaOH followed by brine,
dried over anhyd Na2SO4, and concentrated under vacuum. The
crude product was purified by flash column chromatography on
silica gel (230–400 mesh) using 7:3 hexane–EtOAc as eluant.
4.3.4. (2R,3R,10aS)-3,10a-Dihydro-2-benzyloxymethyl-3-
benzyloxy-7-methy1–2H,5H pyrano[2,3-b][1]benzopyran (18b)
Mp 84–85 °C. Rf 0.46. ½a D25
ꢁ
ꢃ11.0 (c 0.3, CH2Cl2). IR (cmꢃ1): 3003,
2924, 2855, 1587, 1495, 1212, 1098, 951. 1H NMR (300 MHz,
5B
CDCl3, 25 °C):
d
3.36 (d,
J
= 18 Hz, 1H, H-5A), 3.64 (d,
H,H
5A
2
J
= 18 Hz, 1H, H-5B), 3.75 (s, 3H, OCH3), 3.84 (br d, JH,H
H,H
3
ꢄ6.0 Hz, 2H, H-20), 4.01–4.05 (m, 1H, H-3), 4.11 (td, JH,H = 3.0,
20
J
= 6.0 Hz, 1H, H-2), 4.52–4.70 (m, 4H, 2 ꢂ PhCH2), 5.60 (s,
H,H
4.2.2. Method 2
1H, H-10a), 5.96 (br t, 3JH,H ꢄ3.0 Hz, 1H, H-4), 6.57 (d, 8JH,H = 3.0 Hz,
6
9
To a solution of glycal substrate 1, 5, or 24 (0.5 mol) and phenol
or alcohol (2 equiv) in 1,2-dichloroethane (1 mL) in a 10 mL micro-
wave vessel was added activated montmorillonite K-10 (100% w/
w). The vessel was purged with N2 and closed. The reaction mix-
ture was irradiated with microwaves at 80 °C, 300 W with stirring
for the specified time. The reactions were monitored by TLC. Work
up done as in Method 1.
1H, H-6), 6.70 (dd, JH,H = 3.0, JH,H = 9.0 Hz, 1H, H-8), 6.87 (d,
8JH,H = 9.0 Hz, 1H, H-9), 7.25–7.35 (m, 10H, HAr). 13C NMR
(75 MHz, CDCl3, 25 °C): d 31.48 (t, 5-C), 55.71 (q, OCH3), 68.94 (d,
C-3), 69.19 (t, C-20), 70.71 (t, CH2), 73.72 (t, CH2), 74.57 (d, C-2),
95.18 (d, C-10a), 112.87 (d, C-6), 113.59 (d, C-8), 117.91 (d, C-9),
121.73 (d, C-4), 127.60, 127.66, 127.77, 127.90, 128.32, 128.39 (d,
CHAr), 129.72, 134.73, 138.16, 138.46, 146.52, 154.30 (6s, C-4a,
CAr). HRESIMS: calcd for C28H28O5Na, m/z 467.1834; found; m/z
467.1832.
4.3. Experimental data
4.3.1. (2R,3S,10aS)-3,10a-Dihydro-2-methoxymethyl-3,7-
dimethoxy-2H,5H-pyrano[2,3-b][1]benzopyran (12b)
4.3.5. (2R,3R,12aS)-2,3,5,12a-Tetrahydro-2-benzyloxymethyl-3-
benzyloxy-[2,3-b]naphtho[1,2-e]pyran (23b)
Oil. Rf 0.25. ½a 2D9
ꢁ
+255 (c 0.9, CH2Cl2). 1H NMR (300 MHz, CDCl3,
Mp 131–132 °C. Rf 0.58. ½a D25
ꢁ
ꢃ115.28 (c 0.5, CH2Cl2). IR (cmꢃ1):
5B
25 °C): d 3.34 (d,
J
= 18.0 Hz, 1H, H-5A), 3.40, 3.44 (2s, 6H,
2923, 2854, 1600, 1515, 1468, 1232, 1098, 1027, 968. 1H NMR
H,H
5B
2 ꢂ OCH3), 3.53–3.67 (m, 3H, 5B-H, H-20), 3.74 (s, 3H, OCH3),
(300 MHz, CDCl3, 25 °C): d 3.76 (d,
J
= 18 Hz, 1H, H-5A), 3.81
H,H
2
4
3
2
3.76–3.79 (m, 1H, H-2), 4.05 (dd, JH,H = 6.0, JH,H = 9.0 Hz, 1H, H-
(m, 1H, H-5B), 3.88 (dd, JH,H = 1.8, JH,H = 6.0 Hz, 2H, H-20), 4.11–
4.13 (m, 1H, H-3), 4.18–4.23 (m, 1H, H-2), 4.55–4.70 (m, 4H,
2 ꢂ CH2), 5.73 (br s, 1H, H-12a), 6.13 (br s, 1H, H-4), 7.16 (d,
8
3), 5.60 (s, 1H, H-10a), 6.03 (br s, 1H, H-4), 6.58 (d, JH,H = 3.0 Hz,
6
9
1H, H-6), 6.71 (dd, JH,H = 3.0, JH,H = 9.0 Hz, 1H, H-8), 6.83 (d,
8JH,H = 9.0 Hz, 1H, H-9). 13C NMR (75 MHz, CDCl3, 25 °C): d 32.15
(t, C-5), 55.71, 56.67, 59.24 (3q, 3 ꢂ OCH3), 71.55 (d, C-3), 72.16
(t, C-20), 74.55 (d, C-2), 93.78 (d, C-10a), 112.91, 113.67, 117.90
(3d, CHAr), 120.32 (d, C-4), 121.89 (s, C-4a), 133.33, 146.61,
154.24 (3s, CAr). IR (cmꢃ1): 3012, 2928, 2856, 1613, 1496, 1216,
1095, 954. ESIMS: m/z 315 [M+Na], 261 [MꢃOCH3]. HRESIMS:
calcd for C16H20O5Na, m/z 315.1208; found, m/z 315.1206.
11
10
J
= 9.0 Hz, 1H, H-10), 7.66 (d,
J
= 9.0 Hz, 1H, H-11), 7.28–
H,H
H,H
6
9,7
7.40 (m, 11H, HAr, H-7), 7.50 (td, JH,H = 1.2,
J
= 6.9 Hz, 1H, H-
H,H
8), 7.72–7.79 (m, 2H, H-6, H-9). 13C NMR (75 MHz, CDCl3, 25 °C):
d 28.51 (t, C-5), 69.13 (d, C-3), 69.17 (t, C-20), 70.82 (t, CH2),
73.75 (t, CH2), 74.60 (d, C-2), 94.73 (d, C-12a), 112.30 (s, C-4a),
118.90, 121.77, 122.24, 123.84, 126.68, 127.68, 127.81, 127.92,
128.35, 128.40, 128.61 (11d, CHAr), 128.93, 129.44, 134.15,
138.14, 138.42, 149.93 (6s, CAr). HRESIMS: calcd for C31H28O4+Na,
m/z 487.1885; found, m/z 487.1888.
4.3.2. (2R,3R,10aS)-3,10a-Dihydro-2-methoxymethyl-3,7-
dimethoxy-2H,5H-pyrano[2,3-b][1]benzopyran (14b)
Mp 95–96 °C. Rf 0.28. ½a D25
ꢁ
ꢃ51.5 (c 0.45, CH2Cl2). IR (cmꢃ1):
4.3.6. Benzyl 4,6-di-O-benzyl-2,3-dideoxy-2-C -(40-hydroxy-30,50-
dimethyl)phenylmethyl-a-D-threo-hex-2-enopyranoside (26)
2928, 2831, 1496, 1464, 1213, 1096, 1041, 960. 1H NMR
(300 MHz, CDCl3, 25 °C): d 3.37 (d,
J
= 18.0 Hz, 1H, H-5A),
Oil. Rf 0.20. ½a 2D5
ꢁ
ꢃ111 (c 0.5, CH2Cl2). IR (cmꢃ1): 3485–3300,
5B
H,H
3.39 (s, 3H, OCH3), 3.42 (s, 3H, OCH3), 3.62–3.70 (m, 3H, 5B-H, H-
3088, 3030, 2918, 2869, 1606, 1586, 1494, 1455, 1305, 1204,
1095, 1023, 956. 1H NMR (300 MHz, CDCl3, 25 °C): d 2.17 (s, 6H,
2 ꢂ CH3), 3.28 (AB quartet, JH,H = 15.5 Hz, 2H, H-20A, H-20B), 3.71–
20), 3.74 (s, 3H, OCH3), 3.83 (m, 1H, H-3), 4.03–4.08 (m, 1H, H-2),
3
5.66 (s, 1H, H-10a), 6.04 (br t, JH,H ꢄ3.0 Hz, 1H, H-4), 6.58 (dd,
6
9
5
6A
8JH,H = 2.4 Hz, 1H, H-6), 6.70 (dd, JH,H = 2.7, JH,H = 8.9 Hz, 1H, H-
3.77 (m, 2H, H-4, H-6A), 3.83 (dd, JH,H = 5.1,
J
= 10.1 Hz, 1H,
H,H
8), 6.86 (d, JH,H = 9.0 Hz, 1H, H-9). 13C NMR (75 MHz, CDCl3,
H-6B), 4.29 (td, JH,H = 3.0, JH,H = 6.5 Hz, 1H, H-5), 4.44–4.75 (m,
8
6
4
25 °C): d 31.54 (t, C-5), 55.72, 55.56, 59.29 (3q, 3 ꢂ OCH3), 70.77
(d, C-3), 71.47 (t, C-20), 74.38 (d, C-2), 95.14 (d, C-10a), 112.85 (d,
C-6), 113.59 (d, C-8), 117.94 (d, C-9), 121.17 (d, C-4), 121.84 (d,
C-4a), 135.02, 146.53, 154.37 (3d, CAr). HRESIMS: calcd for
C16H20O5+Na, m/z 315.1208; found, m/z 315.1212.
6H, 2.5 ꢂ CH2, OH exch. with D2O), 4.79 (d, CH2J = 11.7 Hz, 1H,
5
0.5 ꢂ CH2), 4.91 (s, 1H, H-1), 5.77 (d, JH,H = 5.5 Hz, 1H, H-3), 6.68
(s, 2H, HAr), 7.25–7.37 (m, 15H, HAr). 13C NMR (75 MHz, CDCl3,
25 °C): d 15.87 (q, CH3), 38.43 (t, C-20), 68.34 (d, C-4), 69.62 (d, C-
5), 69.64 (t, C-6), 69.74, 70.59, 73.39 (3t, 3 ꢂ CH2), 94.98 (d, C-1),
122.13 (d, C-3), 122.89 (s, C-2), 127.53, 127.67, 128.29, 128.36,
128.84, 129.35 (6d, CHAr), 137.97, 138.43, 138.75, 141.70, 150.69
(5s, CAr). HRESIMS: calcd for C36H38O6+Na, m/z 573.2617; found,
m/z 573.2622.
4.3.3. (2R,3R,10aS)-3,10a-Dihydro-2-benzyloxymethyl-3-
benzyloxy-7-methy1–2H,5H-pyrano[2,3-b][1]benzopyran (17b)
Mp 72–73 °C. Rf 0.54. ½a D25
ꢁ
+1.72 (c 0.35, CH2Cl2). IR (cmꢃ1):
3002, 2924, 2856, 1600, 1497, 1454, 958. 1H NMR (300 MHz, CDCl3,
25 °C): d 2.25 (s, 3H, CH3), 3.31–3.37 (m, 1H, H-5A), 3.54–3.58 (m,
1H, H-5B), 3.84 (br d, 2JH,H ꢄ6.0 Hz, 2H, H-20), 4.03–4.05 (m, 1H, H-
3), 4.10–4.14 (m, 1H, H-2), 4.45–4.67 (m, 4H, 2 ꢂ PhCH2), 5.62 (br s,
1H, H-10a), 5.96 (br t, 3JH,H ꢄ3.4 Hz, 1H, H-4), 6.82–6.94 (m, 3H, 6-
H, H-8, H-9), 7.22–7.34 (m, 10H, HAr). 13C NMR (75 MHz, CDCl3,
25 °C): d 20.53 (q, CH3), 31.24 (t, C-5), 68.98 (d, C-3), 69.18 (t, C-
20), 70.68 (t, CH2), 73.71 (t, CH2), 74.54 (d, C-2), 95.10 (d, C-10a),
116.98 (d, CHAr), 120.70 (s, C-4a), 121.63 (d, C-4), 127.59, 127.65,
127.77, 127.91, 128.32, 128.38, 128.55 (7d, CHAr), 130.83, 134.76,
138.18, 138.46, 150.30 (5s, CAr). HRESIMS: calcd for C28H28O4Na,
m/z 451.1885; found, m/z 451.1887.
4.3.7. Benzyl 2-C-(40-acetoxy-30,50-dimethyl)phenylmethyl-4,6-
di-O-benzyl-2,3-dideoxy-
a
ꢁ
-
-threo-hex-2-enopyranoside (27)
Mp 78–80 °C. Rf 0.26. ½a D25
Dꢃ142 (c 0.5, CH2Cl2). IR (cmꢃ1): 3032,
2924, 2855, 1757, 1605, 1484, 1454, 1369, 1265, 1096, 965. 1H
NMR (300 MHz, CDCl3, 25 °C): d 2.08 (s, 6H, 2 ꢂ CH3), 2.32 (s, 3H,
COCH3), 3.30 (AB quartet, JH,H ꢄ15.5 Hz, 2H, 20A-H, H-20B), 3.71–
5
6A
3.77 (m, 2H, H-4, H-6A), 3.80 (dd, JH,H = 5.1,
J
= 10.5 Hz, 1H,
H,H
4
6
H-6B), 4.29 (td, JH,H = 2.5, JH,H = 6.1 Hz, 1H, H-5), 4.50–4.65 (m,
CH2
5H, 2.5 ꢂ CH2), 4.80 (d,
J
= 11.7 Hz, 1H, 0.5 ꢂ CH2), 4.92 (s,
H,H
4
1H, H-1), 5.73 (d, JH,H = 5.1 Hz, 1H, H-3), 6.77 (s, 2H, HAr), 7.24–
7.34 (m, 15H, HAr). 13C NMR (75 MHz, CDCl3, 25 °C): d 16.28 (q,

1660
E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
CH3), 20.46 (q, COCH3), 38.58 (t, C-20), 68.26 (d, C-4), 69.60 (d, C-5),
69.70 (t, C-6), 69.72, 70.73, 73.41 (3t, 3 ꢂ CH2), 94.93 (d, C-1),
122.73 (d, C-3), 127.53, 127.55, 127.68, 127.71, 128.30, 128.35,
128.37, 129.34 (8d, CHAr), 129.96, 135.37, 137.92, 138.60, 138.69,
141.06, 146.81 (7s, C-2, CAr), 168.83 (s, C@O). HRESIMS: calcd for
CDCl3, 25 °C): d 20.54 (q, CH3), 21.36 (t, C-3), 22.57 (t, C-50),
26.62 (t, C-40), 30.11 (t, C-5), 30.52 (t, C-4), 34.80 (s, C-30), 39.48
(t, C-300), 65.22 (t, C-60), 65.54 (t, C-2), 100.80 (d, C-10a), 107.37
(s, C-4a), 115.97 (d, C-9), 119.92 (s, C-7), 127.98 (d, C-8), 129.99
(d, C-6), 130.32 (s, C-5a), 142.50 (d, C-20), 149.08 (s, C-9a). ESIMS:
m/z 300 [M]+, 179 [MꢃCH3C6H3(OH)CH2]+, 97 [C6H9O]+. HRESIMS:
calcd for C19H24O3+H, m/z 301.1815; found, m/z 301.1804.
C38H40O7+Na, m/z 615.2723; found, m/z 615.2727.
4.3.8. 2,6-Dimethylphenyl 4,6-di-O-acetyl-2,3-dideoxy-
a-D-
4.3.12. 4-(50,60-Dihydro-4H-pyran-30-ylmethyl)-2,6-
dimethylphenol (41)
erythro-hex-2-enopyranoside (34)
Oil. Rf 0.52. IR (cmꢃ1): 3021, 2927, 1744, 1740, 1662, 1475,
1370, 1184, 1047, 962, 911. 1H NMR (300 MHz, CDCl3, 25 °C): d
2.08 (s, 3H, COCH3), 2.13 (s, 3H, COCH3), 2.31 (s, 6H, 2 ꢂ CH3),
4.25–4.28 (m, 2H, H-6), 4.39–4.43 (m, 1H, H-5), 5.34–5.38 (m,
Mp 79–81 °C. Rf 0.47. IR (cmꢃ1): 3434, 3012, 2927, 2855, 1488,
1265, 1133, 1022, 934. 1H NMR (300 MHz, CDCl3, 25 °C): d 1.79 (m,
4H, 3A-H, 3B-H, 4A-H, 4B-H), 2.22 (s, 6H, 2 ꢂ CH3), 3.03 (s, 2H, Ben-
zylic CH2), 3.90 (br s, 2H, 2A-H, 2B-H), 4.50 (s, 1H, OH exch. with
D2O), 6.32 (s, 1H, 6-H), 6.78 (s, 2H, HAr). 13C NMR (75 MHz, CDCl3,
25 °C): d 15.92 (q, CH3), 22.55, 22.80 (2t, 3-C, 4-C), 38.86 (t, ben-
zylic CH2), 65.34 (t, 2-C), 128.72 (d, CHAr), 139.68 (d, 6-C),
112.87, 122.77, 131.75, 150.45 (4s, 5-C, CAr). HRESIMS: calcd for
C14H18O2+H, m/z 219.1385; found, m/z 219.1388.
3
2H, H-1, H-4), 6.02–6.06 (br d, JH,H ꢄ10.5 Hz, 1H, H-2), 6.12–
6.16 (m, 1H, H-3), 6.92–6.96 (m, 1H, HAr), 7.00–7.03 (m, 2H, HAr).
13C NMR (75 MHz, CDCl3, 25 °C): d 17.15 (q, CH3), 20.75, 21.01
(2q, 2 ꢂ COCH3), 63.03 (t, C-6), 64.98 (d, C-4), 67.97 (d, C-5),
97.09 (d, C-1), 124.43 (d, CHAr), 127.11 (d, C-3), 129.03 (d, CHAr),
129.86 (d, C-2), 130.77, 155.20 (2s, CAr), 170.22, 170.84 (2s,
2 ꢂ C@O). HRESIMS: calcd for C18H22O6+Na, m/z 357.1314; found,
m/z 357.1400.
4.3.13. p-Methylphenyl 4,6-di-O-benzyl-2,3-dideoxy-
a-D-
erythro-hex-2-enopyranoside (46)
Mp 75–77 °C. Rf 0.56. IR (cmꢃ1): 2985, 2924, 2857, 1508, 1265,
1100, 985. 1H NMR (300 MHz, CDCl3, 25 °C): d 2.29 (s, 3H, CH3),
4.3.9. 200-[30-(3-Methylene-2,3,5,6-tetrahydropyran-2-
yloxy)propyl]propenal (36)
5
6B
3.68 (dd, JH,H = 1.5,
J
= 12.1 Hz, 1H, H-6A), 3.75 (dd,
H,H
Oil. Rf 0.50. IR (cmꢃ1): 3076, 2940, 2705, 1686, 1438, 1341,
1235, 1160, 1039, 947, 887. 1H NMR (300 MHz, CDCl3, 25 °C): d
6A
6B
5JH,H = 3.9,
J
= 12.0 Hz, 1H, H-6B), 4.08 (br t,
J
ꢄ3.3 Hz,
H,H
H,H
3
1H, H-5), 4.27 (br d, JH,H ꢄ9.6 Hz, 1H, H-4), 4.46, 4.48 (2d,
1.67–1.75 (m, 2H, H-5), 1.80–1.84 (m, 2H, H-20), 2.23 (br d,
JH,H = 12.0 Hz, 2H, CH2), 4.61, 4.63 (2d, JH,H = 12.0 Hz, 2H, CH2),
4B
= 13.0 Hz, 1H, H-4A), 2.33–2.38 (m, 2H, H-10), 2.46–2.57 (m,
1
3
J
H,H
5.65 (br s, 1H, H-1), 5.91 (dt, JH,H = 2.4, JH,H = 10.2 Hz, 1H, H-2),
6.20 (d, JH,H = 10.2 Hz, 1H, H-3), 7.04 (AB quartet, JH,H = 8.7 Hz,
1H, H-4B), 3.40–3.47 (m, 1H, H-30A), 3.57–3.60 (m, 1H, H-6A),
2
5
6A
3.68–3.76 (m, 1H, H-30B), 3.92 (td, JH,H = 3.6,
J
= 11.0 Hz, 1H,
4H, HAr), 7.25–7.34 (m, 10H, HAr). 13C NMR (75 MHz, CDCl3,
25 °C): d 20.57 (q, CH3), 68.64 (t, C-6), 70.06, 70.07 (2d, C-5, C-4),
71.7, 73.31 (2t, 2 ꢂ CH2), 93.54 (d, C-1), 117.04 (d, CHAr), 125.88
(d, C-2), 127.58, 127.86, 128.30, 128.40, 129.85, 131.45, 131.60
(7d, CHAr, C-3), 138.01, 138.14, 155.26 (3s, CAr). HRESIMS: calcd
for C27H28O4+Na, m/z 439.1885; found, m/z 439.1883.
H,H
H-6B), 4.85–4.90 (m, 3H, H-2, @CH2 of pyran), 6.02 (br s, 1H,
@CH), 6.28 (br s, 1H, @CH), 9.55 (s, 1H, CHO). 13C NMR (75 MHz,
CDCl3, 25 °C): d 24.70 (t, C-10), 27.70 (t, C-5), 27.71 (t, C-20), 28.38
(t, C-4), 60.01 (t, C-30), 66.30 (t, C-6), 100.59 (d, C-2), 110.34 (t,
@CH2 of pyran), 134.16 (t, C-300), 144.07, 149.77 (2s, C-3, C-200),
194.54 (d, CHO). HRESIMS: calcd for C12H18O3+H, m/z 211.1334;
found, m/z 211. 1324.
4.3.14. Benzyl 4,6-di-O-benzyl-2,3-dideoxy-a-D-threo-hex-2-
enopyranoside (48)
Mp 50–52 °C. Rf 0.67. IR (cmꢃ1): 2918, 2868, 1496, 1453, 1190,
4.3.10. 2-Benzyloxy-3-methylenetetrahydropyran (38)
Viscous oil. Rf 0.6. IR (cmꢃ1): 3033, 2944, 2876, 1660, 1454,
1099, 910. 1H NMR (300 MHz, CDCl3, 25 °C): d 3.70–3.75 (m, 2H, H-
1266, 1099, 978. 1H NMR (300 MHz, CDCl3, 25 °C): d 1.73–1.82
5
6A
4, H-6A), 3.83 (dd, JH,H = 6.0,
J
= 10.2 Hz, 1H, H-6B), 4.33 (td,
H,H
4B
4JH,H = 2.4, JH,H = 6.3 Hz, 1H, H-5), 4.53–4.60 (m, 4H, 2 ꢂ CH2),
6
(m, 2H, H-5A, H-5B), 2.27 (br d,
J
ꢄ12.9 Hz, 1H, H-4A), 2.56
H,H
5
4A
6B
CH2
CH2
(td, JH,H = 3.9,
J
= 8.1 Hz, 1H, H-4B), 3.65 (br d,
J
H,H
4.63 (d,
J
= 11.7 Hz, 1H, 0.5 ꢂ CH2), 4.81 (d,
J
= 11.7 Hz,
H,H
H,H
H,H
5
6A
2
ꢄ12.1 Hz, 1H, H-6A), 3.99 (td, JH,H = 3.3,
J
= 11.2 Hz, 1H, H-
1H, 0.5 ꢂ CH2), 5.16 (d, JH,H = 3.0 Hz, 1H, H-1), 6.00 (dd,
1JH,H = 3.0, 3JH,H = 10.2 Hz, 1H, H-2), 6.13 (dd, 4JH,H = 5.1,
2JH,H = 10.2 Hz, 1H, H-3), 7.24–7.34 (m, 15H, HAr). 13C NMR
(75 MHz, CDCl3, 25 °C): d 67.35 (d, C-4), 69.39, 69.62 (2t, CH2, C-
6), 69.71 (d, C-5), 71.02, 73.46 (2t, 2 ꢂ CH2), 93.26 (d, C-1),
127.17 (d, C-3), 127.59, 127.66, 127.69, 127.77, 128.25, 128.36,
128.38, 129.66 (8d, CHAr), 137.90, 138.36, 138.49 (3s, CAr). HRE-
SIMS: calcd for C27H28O4+Na, m/z 439.1885; found, m/z 439.1887.
H,H
6B), 4.55, 4.76 (2d, JH,H = 12.1 Hz, 2H, benzylic CH2), 4.86, 4.89
(2s, 2H, @CH2), 4.99 (s, 1H, H-2), 7.25–7.36 (m, 5H, HAr). 13C NMR
(75 MHz, CDCl3, 25 °C): d 27.66 (t, C-5), 28.32 (t, C-4), 60.08 (t, C-
6), 68.45 (t, benzylic CH2), 99.74 (d, C-2), 110.09 (t, @CH2),
127.55, 127.82, 128.37 (3d, CHAr), 138.05, 143.85 (2s, C-3, CAr).
HRESIMS: calcd for
227.1044.
C13H16O2+Na, m/z 227.1048; found, m/z
4.3.11. 4a-(50,60-Dihydro-4H-pyran-30-ylmethyl)-7-methyl-
3,4,4a,10a-tetrahydro-2H,5H-pyrano[2,3-b]chromene (40)
Oil. Rf 0.6. IR (cmꢃ1): 3058, 2927, 2859, 1655, 1594, 1500, 1445,
1212, 1088, 971. 1H NMR (300 MHz, CDCl3, 25 °C): d 1.50–1.61 (m,
4.3.15. Methyl 2,3-dideoxy-4,6-di-O-methyl-a-D-threo-hex-2-
enopyranoside (50)
Oil. Rf 0.54. IR (cmꢃ1): 2979, 2928, 2829, 1598, 1451, 1192,
1099, 965. 1H NMR (300 MHz, CDCl3, 25 °C): d 3.40, 3.43, 3.44
(3s, 9H, 3 ꢂ OCH3), 3.49–3.52 (m, 1H, H-4), 3.62–3.68 (m, 2H, H-
2H, H-3A, H-4A), 1.65–1.73 (m, 2H, H-3B, H-4B), 1.78–1.85 (m, 2H,
300B
4
6
H-50A, H-50B), 1.93 (d,
J
= 14.7 Hz, 1H, H-300A), 1.98 (d,
H,H
6A, H-6B), 4.18 (td, JH,H = 2.4, JH,H = 6.5 Hz, 1H, H-5), 4.94 (d,
300A
2JH,H = 3.0 Hz, 1H, H-1), 6.01 (dd, JH,H = 3.0, JH,H = 10.2 Hz, 1H, H-
1
3
J
= 14.5 Hz, 1H, H-300B), 2.01–2.05 (m, 2H, H-40A, H-40B), 2.24
H,H
5B
2), 6.20 (dd, JH,H = 5.1, JH,H = 10.3 Hz, 1H, H-3). 13C NMR
(75 MHz, CDCl3, 25 °C): d 55.48, 56.72, 59.25 (3q, 3 ꢂ OCH3),
69.03 (d, C-4), 69.25 (d, C-5), 71.92 (t, C-6), 95.07 (d, C-1), 126.53
(d, C-3), 129.75 (d, C-2). HRESIMS: calcd for C9H16O4+Na, m/z
211.0946; found, m/z 211.0947.
4
2
(s, 3H, CH3), 2.38 (d,
J
= 12 Hz, 1H, H-5A), 2.93 (d,
H,H
5A
J
= 12 Hz, 1H, H-5B), 3.57–3.65 (m, 1H, H-2A), 3.91 (br t, 2H,
H,H
60A-H, H-60B), 4.02–4.08 (m, 1H, H-2B), 4.80 (s, 1H, H-10a), 6.15
8
(s, 1H, H-2), 6.76 (d, JH,H = 8.4 Hz, 1H, H-9), 6.82 (br s, 1H, H-6),
6.90 (dd, JH,H = 1.8, JH,H = 8.1 Hz, 1H, H-8). 13C NMR (75 MHz,
6
9

E. Kumaran et al. / Carbohydrate Research 346 (2011) 1654–1661
1661
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Acknowledgments
The authors thank the management of Shasun Research Centre
(SRC) for providing the facility and encouragement. Our thanks are
due to SRC-QC for analytical data.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2011.03.027.
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