HClO4?SiO2 catalysed synthesis of alkyl 3-deoxy-hex-2-enopyranosides from 2-hydroxy glucal ester: Application in the synthesis of a cis-fused bicyclic ether and a 4-amino-C-glucoside

Article abstract of DOI:10.1039/b810654a

A variety of alcohols react with 2,3,4,6-tetra-O-acetyl-1,5-anhydro-d- arabino-hex-1-enopyranose 1 in the presence of a catalytic amount of HClO ₄ supported on silica gel to give the corresponding alkyl 3-deoxy-hex-2-enopyranosides 2 in high yield, with short reaction times (10-45 mins) and good α-selectivity. Work-up merely involves filtration of the reagent, followed by chromatographic purification of the crude product. This methodology has also been employed in the synthesis of a bicyclic ether, a useful precursor for cyclic polyethers, and a 4-amino-C-glucoside. The 2008 Royal Society of Chemistry.

Full text of DOI:10.1039/b810654a

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www.rsc.org/obc | Organic & Biomolecular Chemistry
HClO4·SiO2 catalysed synthesis of alkyl 3-deoxy-hex-2-enopyranosides from
2-hydroxy glucal ester: application in the synthesis of a cis-fused bicyclic ether
and a 4-amino-C-glucoside†
Preeti Gupta, Nitee Kumari, Aditi Agarwal and Yashwant D. Vankar*
Received 23rd June 2008, Accepted 29th July 2008
First published as an Advance Article on the web 5th September 2008
DOI: 10.1039/b810654a
A variety of alcohols react with 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enopyranose 1 in
the presence of a catalytic amount of HClO4 supported on silica gel to give the corresponding alkyl
3-deoxy-hex-2-enopyranosides 2 in high yield, with short reaction times (10–45 mins) and good
a-selectivity. Work-up merely involves filtration of the reagent, followed by chromatographic
purification of the crude product. This methodology has also been employed in the synthesis of a
bicyclic ether, a useful precursor for cyclic polyethers, and a 4-amino-C-glucoside.
the glycosyl acceptors. Further, in the literature this reaction has
not been reported using allylic alcohols as the glycosyl acceptors
where the products could be useful in organic synthesis. Also, only
one report is known for this reaction using p-methoxy phenol as
Introduction
2-Hydroxy glucal ester1 1 (Fig. 1) and its analogues are impor-
tant intermediates in organic synthesis because of the presence
of a masked carbonyl group at C-2. These molecules react
a glycosyl acceptor in the presence of BF3·Et2O. Moreover, the
product is formed in only 49% yield.13
with alcohols in the presence of a Lewis acid to undergo
allylic rearrangement,2 forming the corresponding 3-deoxy-hex-
2-enopyranosides 2 or 3,4-dideoxy-hex-3-enopyranoside-2-uloses
3. These enosides, in turn, are useful building blocks in organic
synthesis since they make provision for substitutions at C-2, C-3,
and C-4. This has led to the synthesis of a number of biologically
active natural products.3–10 The Lewis acids that have been used
in the allylic rearrangement of 2-hydroxy glycal esters include
BF3·Et2O,2 NIS11 and SnCl4,12 and depending upon the reaction
conditions, enosides 2 or enones 3 are the preferred products.
Also, allylic rearrangements employing thiols are not reported
in the literature except for one recent report14 wherein LiBF4
and BF3·Et2O have been used as Lewis acids to obtain S-linked
disaccharides and the yields range from 15–60% depending on the
Lewis acid used. Keeping these developments in mind it appeared
that there is a need to develop methods that can be applicable to
a wide range of alcohols and thiols, and give only one of the two
products, viz. 2 or 3.
Recently, ‘perchloric acid supported on silica gel’ (HClO4·SiO2)
has been used for the acetylation of simple alcohols and sugars,15
one pot acetylation–acylation of sugars,16 O- and C-Ferrier rear-
rangement of glycals,17 glycosylation of disarmed thioglycoside18
and in the deprotection19 of terminal isopropylidenes and trityl
ethers. In continuation of our efforts17a,19 to explore the potential of
this reagent system, herein we wish to report the reaction of 2,3,4,6-
tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-eno-pyranose 1 with
various primary, secondary, tertiary, and allylic alcohols, phenols
and thiols in the presence of HClO4·SiO2.
Fig. 1 Allylic rearrangement of 1 to products 2 and 3.
Despite their importance, there are very few methods for the
synthesis of enosides 2 or enones 3 from 1, and many of these have
some drawbacks. Thus, for example, in the synthesis of enone 3
from 1 using N-iodosuccinimide (NIS) longer reaction times (2.5–
60 h) were generally needed, and most of the time the product 3
was accompanied by a small amount of 2. With SnCl4, though
it gave only the a-anomer, in most of the cases a 2-furaldehyde
derivative was formed as a side product.
The above methodology has also been used in the synthesis of
a cis-fused 6/7 membered bicyclic ether 24. Such types of fused
ethers are present in natural products of marine origin20 such
as brevetoxins, ciguatoxins, maitotoxins, halichondrins etc. These
molecules have a ladder like framework with contiguous trans-
and/or cis- fused five to nine membered polyether rings. Structural
complexity, coupled with the impressive biological properties of
these natural products, has been the main attraction for the
development of new synthetic methods for their construction.21
Furthermore, the present methodology has also been extended
towards the synthesis of a 4-amino-2,3-diacetoxy-C-glucoside 30.
Additionally, the double bond in its precursor viz. 29, can also
be easily functionalised into different 4-aminosugars.22 Very few
methods are known in the literature for the synthesis of such
compounds, which mostly involve the allyl cyanate-to-isocyanate
Furthermore, it was necessary to use a large excess of BF3·Et2O
in the conversion of 1 to 2, and the amount varied depending on
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016,
India. E-mail: vankar@iitk.ac.in; Fax: 0091-512-259 7492
† Electronic supplementary information (ESI) available: Spectroscopic
data for new compounds and copies of spectra for compounds 21–30.
See DOI: 10.1039/b810654a
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rearrangement of hex-3-enopyranosides and the palladium catal-
ysed allylic substitution by amines or azides of suitable hex-
2-enopyranosides.23 Recently, glycal derived activated allylic
aziridines have also been used as precursors for the synthesis
of 4-amino-derived-2,3-unsaturated glycosides.24 In this paper, we
have utilised the Overman rearrangement25 for the stereoselective
introduction of nitrogen functionality at the C-4 position of the
sugar derivative and later transformed it into an amino sugar.
Results and discussion
Scheme 2 Reagents and conditions: (a) NaBH4, CeCl3·7H2O, MeOH,
0 ◦C, 2 h, 56% (major isomer); (b) (i) NaOMe–MeOH, 0 ◦C, 1 h; (ii) TrCl,
Et3N, CH2Cl2, 0 ◦C → rt, 8 h, 92% over 2 steps; (c) NaH, allyl bromide,
THF, reflux, 3 h, 86%; (d) 1st generation Grubbs’ catalyst, toluene, rt,
overnight, 88%.
The reaction of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-
hex-1-enopyranose 1 with various primary, secondary, tertiary,
and allylic alcohols, phenols and thiols in the presence of
HClO4·SiO2 went smoothly, leading to the corresponding alkyl-
3-deoxy-hex-2-enopyranosides 2 in good to excellent yields with
high a-selectivity, and required short reaction times (10–45 min).
The work-up involved merely filtration of the reagent followed
by chromatographic purification. Our results are summarised in
Table 1. For aliphatic alcohols (entries 1 to 10, Table 1) 10 mg
of HClO4·SiO2 was needed per 100 mg of 1, and for phenols and
thiols (entries 11 to 15, Table 1) 5 mg of the reagent was needed
per 100 mg of 1 for optimum yields. As mentioned above, primary
and secondary aliphatic thiols do react14 with 1 using LiBF4 or
BF3·Et2O as Lewis acids. With BF3·Et2O, although a-selectivity
was observed, the yields were moderate.14 On the other hand,
in the present study, although we have not used aliphatic thiols,
the reactions with aromatic thiols required low catalyst loading
and good yields of the products were obtained with reasonably
We proceeded further with the major alcohol 21, but the relative
stereochemistry at C-1 and C-2 could not be determined at this
stage. Deacetylation of 21 using sodium methoxide in methanol
(Zemple´n procedure),32 followed by regioselective protection of
the primary alcohol as the trityl ether gave 22 in 92% yield over
two steps. Allylation of the secondary alcohol in the presence of
allyl bromide and sodium hydride provided triene 23 in 86% yield.
The stereochemistry at C-1 and C-2 was confirmed through NOE
experiments. Thus, when the signal for H-5 was irradiated the
signal for H-1 was not enhanced (Fig. 2) indicating that H-1 and
H-5 are trans oriented. Furthermore, irradiation of the signal for
H-2 led to the enhancement of the signals for H-1 and the olefinic
hydrogen H-3 present in the ring, suggesting that H-1 and H-2
are cis oriented. Finally the ring closing metathesis of 23, using
Grubbs’ 1st generation ruthenium catalyst33 (6 mol%), proceeded
smoothly in toluene at room temperature to furnish the cis-fused
bicyclic ether 24 which was characterised by 1H, 13C NMR, COSY
experiments. The stereochemistry at the A–B ring junction was
further confirmed from the NOE experiments, wherein irradiation
of the signal for H-2 led to the enhancement of the signal for H-1,
suggesting cis stereochemistry at the ring junction and thus
supporting its stereochemical assignment. (Fig. 2)
1
good selectivity. All the products were characterised by H and
13C NMR, IR and mass spectral data and further by comparison
with literature data wherever available.
In order to extend the scope of this methodology, 100 mg of
1 was treated with 3 equivalents of allyl trimethylsilane in the
presence of 10 mg of the HClO4·SiO2 reagent system, which led
to the formation of the C-glycosidic enone 20 instead of the
enoside 19 (Scheme 1) in 75% yield. The product was obtained
as a 3 : 1 mixture of a and b anomers, which was characterised
by spectroscopic means and compared with the literature data.26
C-Glycosyl enones of the type 20 serve as valuable precursors
in organic synthesis.27–31The reactions of vinyl trimethylsilane
and trimethylsilyl cyanide with 1 were extremely sluggish, and
the increased amount of HClO4·SiO2 used led to extensive
decomposition from which no product could be identified.
Fig. 2 NOE correlations.
For the synthesis of the 4-amino-C-glucoside (Scheme 3) the
allyl alcohol 22 was reacted with trichloroacetonitrile in the pres-
ence of DBU to afford trichloroacetimidate 25 in 95% yield. This
imidate 25 was then subjected to the Overman rearrangement34
by refluxing in xylene in the presence of K2CO3,35 to provide
the corresponding trichloroacetyl amide 26 in 80% yield and
with total stereocontrol. The product was well characterised by
analysing its H NMR spectral data, in addition to other data,
which showed the disappearance of the imine proton singlet at d
8.27 and the appearance of the amine proton as a doublet at d 6.73.
=
1 Reagents and conditions: (a) CH2 CH–CH2SiMe3,
HClO4·SiO2, CH3CN, reflux, 5 h, 75%.
Scheme
We have also utilised the enone 20 in the synthesis of a bicyclic
ether 24 (Scheme 2). Thus, enone 20, which was present as an
inseparable 3 : 1 mixture of a and b anomers, was treated with
NaBH4 in the presence of CeCl3·7H2O to get a separable mixture
of 3 diastereomers in the ratio of 7 : 2 : 1 and 80% combined yield.
1
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Table 1 Reaction of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enopyranose 1 with alcohols in the presence of HClO4·SiO2
Entry
1
Product structure
Product no.
Time/min
20a
Yield (%)
90
a : b
4
13 : 22
2
3
5
20a
20a
45a
10a
20a
10a
15a
10a
10a
95
90
86
82
85
93
75
82
80
4 : 111
7 : 111
6 : 111
5 : 1
6
4
7
5
8
6
9
10 : 1
8 : 1
7
10
11
12
13
8
3 : 1
9
2 : 1
10
3 : 1
11
12
14
15
15b
30b
84
85
8 : 1
14 : 1
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Table 1 (Contd.)
Entry
13
Product structure
Product no.
Time/min
30b
Yield (%)
87
a : b
16
10 : 113
14
15
17
18
30b
30b
80
82
4 : 1
5 : 1
a 10 mg, b 5 mg of HClO4·SiO2 used per 100 mg of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enopyranose 1.
configuration of 30 was assigned based on the coupling constant
values, where J3,4 = 10.76 Hz, and J2,3 = 2.92 Hz were observed.
Since H-2 and H-3 have to be cis to each other because of the cis
dihydroxylation, and the larger coupling of J = 10.76 Hz must be
due to the coupling of protons H-3 and H-4, a diaxial disposition
of H-3 and H-4 is suggested and thus the trans relationship between
them confirmed.
Conclusion
In conclusion, we have developed an efficient method for the allylic
rearrangement of 2-hydroxy glucal ester 1 leading to 3-deoxy-
hex-2-enopyranosides 2. Furthermore, only enopyranosides 2 are
formed in the present work and no trace of 3 was seen to form.
Also, a specific C-glucoside 20 could be readily formed under
these conditions. The advantages of this method are the ease of
handling, short reaction times, high yields and good anomeric
selectivity. This methodology also provides easy access to a bicyclic
ether 24 and a highly functionalised 4-amino-C-glucoside, which
can serve as chiral building blocks allowing a variety of synthetic
transformations.
Scheme 3 Reagents and conditions: (a) Cl3CCN, DBU, CH2Cl2, 0 ◦C → rt,
30 min, 95%; (b) K2CO3, xylene, reflux, 12 h, 80%; (c) (i) OsO4 cat., NMO,
acetone : water (1 : 2), rt, 3 h; (ii) NaIO4, MeOH, 0 ◦C → rt, 30 min, 71%
over 2 steps (based on starting material recovered); (d) NaBH4, MeOH,
0 ◦C → rt, 30 min, 95%; (e) TBDMSCl, Et3N, DMAP cat., CH2Cl2, reflux,
5 h, 94%; (f) (i) OsO4 cat., NMO, t-BuOH : acetone : water (1 : 2 : 2), rt, 12 h;
(ii) Ac2O, Et3N, DMAP cat., CH2Cl2, 0 ◦C → rt, 3 h, 89% over 2 steps.
Experimental
Infrared spectra were recorded on a Bruker FT/IR Vector 22
spectrophotometer. H and 13C NMR spectra were recorded on
1
a JEOL LA-400 (400 and 100 MHz respectively) spectrometer in
solutions of CDCl3 as a solvent. Chemical shifts are reported in
d units (ppm) with reference to tetramethylsilane as an internal
standard and J values are given in Hz. The mass spectra were
recorded on a Micromass Quattro II triple quadrupole mass
spectrometer. Rotation values were recorded on an Autopol II
automatic polarimeter at the wavelength of the sodium D-line
(589 nm) at 25 ◦C. Elemental analyses were carried out on
a Thermoquest CE-instruments EA-1110C, H, N, S analyser.
Column chromatography was performed on silica gel (100–
200 mesh) and thin layer chromatography (TLC) was performed
on silica gel plates made by using grade G silica gel obtained from
Regioselective dihydroxylation of the terminal olefin in 26, fol-
lowed by oxidation with sodium periodate, produced the aldehyde
27 in 71% combined yield. Reduction using sodium borohydride
gave alcohol 28 whose protection as a tert-butyldimethylsilyl ether
furnished 29 in 94% yield after chromatographic purification. The
exposure of 29 to a catalytic amount of OsO4 in the presence
of NMO, followed by acetylation, afforded 30 as the major
diastereomer in 89% yield. As expected, the dihydroxylation of
29 took place from the less hindered side of the double bond. The
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S. D. Fine-Chem Ltd., Mumbai or precoated plates (E. Merck,
Germany). The visualisation of spots on TLC plates was effected
by exposure to iodine and spraying with 10% aqueous H2SO4,
followed by charring. Melting points were determined using
a Fischer-John melting point apparatus and are uncorrected.
The reactions were carried out in oven-dried glassware under a
N2 atmosphere. In extractive work-up, aqueous solutions were
always extracted thrice with the appropriate organic solvent. The
combined organic extracts were washed with water and brine,
dried over anhydrous sodium sulfate, then evaporated under
reduced pressure. All solvents and common reagents were purified
by established procedures. The HClO4·SiO2 reagent system was
prepared by following the literature procedure.15a
Allyl 2,4,6-tri-O-acetyl-3-deoxy-a/b-D-erythro-hex-2-
eno-pyranoside (12)
Yield: 82% (2 : 1 mixture of a : b anomers). Found: C, 54.92; H,
6.11. Calc. for C15H20O8 C, 54.87; H, 6.14%; Rf 0.5 (hexane : ethyl
acetate, 7 : 3); IR (neat) nmax/cm-1 1749; dH (400 MHz, CDCl3)
(a-anomer) 2.07 (3H, s, COCH3), 2.10 (3H, s, COCH3), 2.17
(3H, s, COCH3), 4.07–4.34 (5H, m, H-1¢, H-1¢¢, H-5, H-6, H-
=
6¢), 5.10 (1H, s, H-1), 5.19–5.34 (2H, m, CH CH2), 5.47 (1H, br
d, J = 8.6 Hz, H-4), 5.75 (1H, d, J = 2.2 Hz, H-3), 5.87–5.97
=
(1H, m, CH CH2); (b-anomer) 5.78 (1H, d, J = 4.9 Hz, H-3); dC
(100 MHz, CDCl3) (a-anomer) 20.9, 29.6, 31.8, 62.4, 65.2, 67.1,
69.3, 92.9, 115.3, 117.7, 133.6, 146.3, 168.1, 170.1, 170.6; MSES+:
351 [M + Na]+.
General experimental procedure for the synthesis of
3-deoxy-hex-2-enopyranosides
p-Methylphenyl 2,4,6-tri-O-acetyl-3-deoxy-a/b-D-erythro-hex-2-
enopyranoside (15)
To a stirred mixture of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-
arabino-hex-1-enopyranose 1 (100 mg, 0.33 mmol) and an alcohol
[1 equiv. (2 equiv. in the case of the methyl, ethyl and allyl alcohols)]
in anhydrous acetonitrile (1.5 mL), was added “HClO4·SiO2”
(10 mg in the case of entries 1–10; 5 mg in the case of entries
11–15). The reaction mixture was refluxed for the appropriate
time (Table 1) and completion of the reaction was monitored
by TLC analysis. The reaction mixture was then filtered, washed
with acetonitrile, and then the combined organic extracts were
concentrated under vacuum. The products were purified by silica
gel column chromatography.
Yield: 85% (14 : 1 mixture of a : b anomers). Found: C, 60.37;
H, 5.82. Calc. for C19H22O8 C, 60.31; H, 5.86%; Rf 0.5 (hexane :
ethyl acetate, 7 : 3); IR (neat) nmax/cm-1 2923, 1741; dH (400 MHz,
CDCl3) (a-anomer) 2.01 (3H, s, COCH3), 2.10 (3H, s, COCH3),
2.18 (3H, s, COCH3), 2.29 (3H, s, pCH3-C6H4), 4.16–4.34 (3H, m,
H-5, H-6, H-6¢), 5.52 (1H, dd, J = 2.0, 9.5 Hz, H-4), 5.62 (1H, s,
H-1), 5.87 (1H, d, J = 2.2 Hz, H-3), 6.96–7.11 (4H, m, C6H4);
(b-anomer) 5.79 (1H, s, H-1), 5.34 (1H, m, H-4), 5.95 (1H, d, J =
5.4 Hz, H-3); dC (100 MHz, CDCl3) (a-anomer) 20.5, 20.6, 20.9,
22.6, 29.6, 62.2, 65.1, 67.8, 93.1, 116.0, 117.2, 129.9, 132.4, 145.6,
154.8, 164.3, 168.1, 170.0, 170.6; MSES+: 401 [M + Na]+.
Benzyl 2,4,6-tri-O-acetyl-3-deoxy-a/b-D-erythro-hex-2-
eno-pyranoside (8)
Thiophenyl 2,4,6-tri-O-acetyl-3-deoxy-a/b-D-erythro-hex-2-
enopyranoside (17)
Yield: 82% (5 : 1 mixture of a : b anomers). Found: C, 60.39;
H, 5.82. Calc. for C19H22O8 C, 60.31; H, 5.86%; Rf 0.5 (hexane :
ethyl acetate, 7 : 3); IR (neat) nmax/cm-1 2925, 1740; dH (400 MHz,
CDCl3) (a-anomer) 1.99 (3H, s, COCH3), 2.02 (3H, s, COCH3),
2.04 (3H, s, COCH3), 4.04–4.18 (3H, m, H-5, H-6, H-6¢), 4.54
(2H, s, OCH2C6H5), 5.05 (1H, br s, H-1), 5.39 (1H, dd, J = 2.2,
9.5 Hz, H-4), 5.64 (1H, d, J = 2.0 Hz, H-3), 7.21–7.29 (5H, m,
OCH2C6H5); (b-anomer) 5.23 (1H, s, H-1), 5.26 (1H, dd, J =
4.4, 8.6 Hz, H-4), 5.73 (1H, d, J = 4.6 Hz, H-3); dC (100 MHz,
CDCl3) (a-anomer) 20.7, 20.8, 20.9, 29.6, 62.4, 65.2, 67.3, 70.5,
72.6, 93.0, 115.4, 112.1, 127.8, 128.6, 137.2, 146.3, 168.1, 170.0,
170.7; MSES+: 401 [M + Na]+
Yield: 80% (4 : 1 mixture of a : b anomers). Found: C, 56.79; H,
5.31; S, 8.42. Calc. for C18H20O7S C, 56.83; H, 5.30; S, 8.43%; Rf 0.6
(hexane : ethyl acetate, 7 : 3); IR (neat) nmax/cm-1 2928, 1746; dH
(400 MHz, CDCl3) (a-anomer) 2.07 (3H, s, COCH3), 2.11 (3H, s,
COCH3), 2.20 (3H, s, COCH3), 4.23–4.33 (2H, m, H-6, H-6¢),
4.48–4.52 (1H, m, H-5), 5.48 (1H, br d, J = 9.5 Hz, H-4), 5.72
(1H, d, J = 2.2 Hz, H-3), 5.75 (1H, s, H-1), 7.27–7.34 (3H, m,
C6H4), 7.53–7.55 (2H, m, C6H4); (b-anomer) 5.81 (1H, s, H-1); dC
(100 MHz, CDCl3) (a-anomer) 20.7, 20.9, 62.6, 64.7, 67.5, 67.6,
83.4, 115.3, 127.8, 128.9, 129.0, 131.9, 132.0, 133.8, 146.4, 167.9,
170.1, 170.6; MSES+: 403 [M + Na]+, 271 [M - 109]+.
Tetrahydrofurfuryl 2,4,6-tri-O-acetyl-3-deoxy-a/b-D-erythro-hex-
Allyl 6-O-acetyl-3,4-dideoxy-a/b-D-glycero-hex-3-
2-enopyranoside (11)
eno-pyranoside-2-ulose (20)
Yield: 75% (3 : 1 mixture of a : b anomers). Found: C, 54.79;
H, 6.55. Calc. for C17H24O9 C, 54.83; H, 6.50%; Rf 0.6 (hexane :
ethyl acetate, 7 : 3); IR (neat) nmax/cm-1 2925, 1746; dH (400 MHz,
CDCl3) (a-anomer) 1.56–2.05 (4H, m, H-3¢, H-3¢¢, H-4¢, H-4¢¢),
2.08 (3H, s, COCH3), 2.10 (3H, s, COCH3), 2.17 (3H, s, COCH3),
3.46–3.59 (1H, m, H-2¢), 3.74–3.81 (2H, m, H-5¢,H-5¢¢), 3.83–3.89
(1H, m, H-1¢), 4.06–4.11 (1H, m, H-1¢¢), 4.19–4.32 (3H, m, H-5,
H-6, H-6¢), 5.31 (1H, s, H-1), 5.46 (1H, br d, J = 9.3 Hz, H-4), 5.73
(1H, d, J = 2.2 Hz, H-3); (b-anomer) 5.78 (1H, d, J = 4.1 Hz, H-
3); dC (100 MHz, CDCl3) (a-anomer) 20.7, 20.9, 25.5, 25.7, 27.9,
28.2, 62.5, 65.2, 67.1, 68.3, 71.6, 94.1, 115.2, 146.3, 168.2, 170.1,
170.7; MSES+: 390 [M + NH4]+, 271 [M - 101]+.
To a stirred mixture of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-
arabino-hex-1-enopyranose 1 (0.100 g, 0.33 mmol) and allyl
trimethylsilane (0.113 g, 0.16 mL, 0.99 mmol) in anhydrous
acetonitrile (2 mL), was added HClO4·SiO2 (10 mg). The reaction
mixture was refluxed for 5 h. After completion of the reaction, the
reaction mixture was filtered, washed with acetonitrile, and then
the combined organic extracts were concentrated under vacuum.
Purification by silica gel chromatography (hexane : ethyl acetate =
4 : 1) afforded compound 20 (0.048 g, 75%, 3 : 1 mixture of a :
b anomers) as a colourless viscous liquid. Found: C, 62.89; H,
6.69. Calc. for C11H14O4 C, 62.85; H, 6.71%; Rf 0.5 (hexane : ethyl
acetate, 7 : 3); dH (400 MHz, CDCl3) 2.10 (3H, s, COCH3), 2.52
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(2H, m, H-1¢, H-1¢¢), 4.11 (1H, dd, J = 4.2, 11.7 Hz, H-6), 4.34–
4.44 (2H, m, H-6¢, H-1), 4.67 (1H, m, H-5), 5.12–5.19 (2H, m, H-3¢,
H-3¢¢), 5.79–5.89 (1H, m, H-2¢), 6.15 (1H, dd, J = 2.2, 10.5 Hz,
H-3), 6.91 (1H, dd, J = 2.7, 10.5 Hz, H-4); (b-anomer) 6.19 (1H,
dd, J = 2.6, 10.3 Hz, H-3), 6.95 (1H, dd, J = 1.6, 10.3 Hz, H-4); dC
(100 MHz, CDCl3) (a-anomer) 20.8, 34.0, 63.7, 68.7, 77.5, 117.9,
127.4, 133.3, 146.2, 170.7, 195.3; MSES+: 228 [M + NH4]+.
H-3¢), 5.19 (1H, dd, J = 1.6, 17.0 Hz, H-3¢¢), 5.81–5.91 (2H, m,
H-4, H-2¢), 6.11 (1H, ddd, J = 2.2, 5.6, 10.0 Hz, H-3), 7.21–7.32
(9H, m, C(C6H5)3), 7.41–7.47 (6H, m, C(C6H5)3); dC (100 MHz,
CDCl3) 35.3, 62.7, 63.4, 72.4, 73.1, 86.5, 117.3, 126.9, 127.7, 128.1,
128.6, 130.1, 134.4, 143.7; MSES+: 435.4 [M + NH4]+.
(2R,3R,6S)-2-Allyl-3-(allyloxy)-6-(trityloxymethyl)-3,6-dihydro-
2H-pyran (23)
((2S,5R,6R)-6-Allyl-5-hydroxy-5,6-dihydro-2H-pyran-2-yl)methyl
acetate (21)
To a stirred suspension of NaH (0.015 g, 0.36 mmol, 60%
suspension in mineral oil) in dry THF (2 mL) was added
compound 22 (0.100 g, 0.24 mmol). The reaction mixture was
stirred at room temperature for 30 min followed by reflux for
1 h. It was cooled to room temperature, allyl bromide added
(0.035 g, 0.025 mL, 0.29 mmol) and again it was refluxed for 2 h.
The reaction was cooled to room temperature and quenched with
saturated NH4Cl solution, extracted with ethyl acetate (3 ¥ 10 mL)
and the combined organic extracts were washed with water,
brine and dried over anhydrous Na2SO4. After concentration, the
residue was purified by silica gel chromatography (hexane : ethyl
acetate = 9 : 1) to furnish 23 (0.095 g, 86.6%) as a colourless liquid.
Found: C, 82.30; H, 7.11. Calc. for C31H32O3 C, 82.27; H, 7.13%;
Rf 0.6 (hexane : ethyl acetate, 9 : 1); [a]2D5 -133.0 (c 1.0, CH2Cl2);
IR (neat) nmax/cm-1 3060, 2923, 1642, 1072; dH (400 MHz, CDCl3)
2.48 (2H, t, J = 7.0 Hz, H-1¢, H-1¢¢), 3.05 (1H, dd, J = 4.6, 9.5 Hz,
H-6), 3.28 (1H, dd, J = 6.6, 9.5 Hz, H-6¢), 3.70 (1H, br s, H-2),
3.89 (1H, dt, J = 2.9, 7.0 Hz, H-1), 4.02 (1H, dd, J = 5.6, 12.6 Hz,
H-7), 4.15 (1H, dd, J = 5.6, 12.6 Hz, H-7¢), 4.45 (1H, br s, H-5),
5.08 (1H, dd, J = 1.2, 10.0 Hz, H-3¢), 5.15 (1H, d, J = 1.2 Hz,
H-3¢¢), 5.18 (1H, dd, J = 1.4, 6.6 Hz, H-9), 5.29 (1H, dd, J =
1.4, 17.0 Hz, H-9¢), 5.83–5.97 (3H, m, H-4, H-2¢, H-8), 6.04 (1H,
ddd, J = 1.9, 4.4, 10.2 Hz, H-3), 7.21–7.31 (9H, m, C(C6H5)3),
7.44–7.46 (6H, m, C(C6H5)3); dC (100 MHz, CDCl3) 34.4, 64.2,
68.8, 69.6, 72.0, 72.5, 86.4, 116.7, 117.0, 125.3, 126.9, 127.7, 128.6,
131.0, 135.0, 135.1, 143.8; MSES+: 475.2 [M + Na]+.
To a solution of enone 20 (1.20 g, 5.71 mmol, 3 : 1 diastereomeric
mixture) in methanol (10 mL) was added CeCl3·7H2O (2.552 g,
6.85 mmol) at 0 ◦C. The mixture was stirred for 5 min at 0 ◦C
followed by the addition of NaBH4 (0.260 g, 6.85 mmol). The
resulting mixture was stirred for 2 h at the same temperature
and then quenched with saturated NH4Cl solution (10 mL). The
reaction mixture was concentrated under high vacuum to remove
methanol. The aqueous phase was extracted with ethyl acetate
(3 ¥ 30 mL), then the combined organic extracts were washed with
brine and dried over anhydrous Na2SO4. After concentration, the
residue was purified by silica gel chromatography (hexane : ethyl
acetate = 3 : 1) to afford alcohol 21 (0.678 g, 56%) as a colourless
viscous liquid along with other diastereomers in 16% (0.194 g) and
8% (0.097 g) yield respectively. Found: C, 62.23; H, 7.64. Calc. for
C11H16O4 C, 62.25; H, 7.60%; Rf 0.5 (hexane : ethyl acetate, 3 : 2);
[a]D25 -186.1 (c 2.4, CH2Cl2); IR (neat) nmax/cm-1 3442, 3076, 2919,
1742, 1642, 1040; dH (400 MHz, CDCl3) 2.10 (3H, s, COCH3), 2.34
(1H, br s, OH), 2.41 (2H, t, J = 7.0 Hz, H-1¢, H-1¢¢), 3.76–3.82 (2H,
m, H-1, H-2), 3.98 (1H, dd, J = 3.6, 11.7 Hz, H-6), 4.35 (1H, dd,
J = 8.2, 11.7 Hz, H-6¢), 4.43–4.46 (1H, m, H-5), 5.09 (1H, bd, J =
10.4 Hz, H-3¢), 5.18 (1H, dd, J = 1.7, 17.3 Hz, H-3¢¢), 5.82–5.89
(2H, m, H-4, H-2¢), 6.17 (1H, ddd, J = 1.9, 5.3, 10.0 Hz, H-3); dC
(100 MHz, CDCl3) 20.7, 34.8, 62.5, 62.6, 71.3, 72.0, 117.1, 127.9,
129.4, 134.3, 170.8; MSES+: 213.2 [M + H]+.
(2R,3R,6S)-2-Allyl-6-(trityloxymethyl)-3,6-dihydro-2H-pyran-3-
ol (22)
(2S,4aR,9aR,Z)-2-(Trityloxymethyl)-4a,6,9,9a-tetrahydro-2H-
pyrano[3,2-b]oxepine (24)
To a solution of compound 21 (0.200 g, 0.94 mmol) in dry
methanol (5 mL) at 0 ◦C was added a catalytic amount of sodium
methoxide. The mixture was stirred for 1 h at the same temperature.
Evaporation of the solvent under vacuum gave a residue which
was passed through a short pad of silica gel (eluent ethyl acetate)
to afford diol as a yellowish oil, which was subjected to trityl
protection without any further purification. To a solution of crude
diol in CH2Cl2 (2 mL) at 0 ◦C were added Et3N (0.286 g, 0.4 mL,
2.82 mmol) and TrCl (0.288 g, 1.03 mmol). The reaction mixture
was stirred for 8 h at room temperature and then extraction with
CH2Cl2 followed by the usual work up gave a crude product
which after purification by column chromatography (hexane :
ethyl acetate = 4 : 1) afforded compound 22 (0.358 g, 92%) as
a colourless liquid. Found: C, 81.48; H, 6.87. Calc. for C28H28O3
C, 81.52; H, 6.84%; Rf 0.5 (hexane : ethyl acetate, 4 : 1); [a]2D5 -112.2
(c 1.2, CH2Cl2); IR (neat) nmax/cm-1 3431, 3059, 2919, 1641, 1075;
Bis-(tricyclohexylphosphine)benzylidine ruthenium(IV) dichlo-
ride (0.011 g, 6 mol%) was added to a stirred solution of 23 (0.100 g,
0.22 mmol) in toluene (5 mL) under a nitrogen atmosphere. The
reaction mixture was stirred at room temperature for 8 h and
then filtered through a pad of celite and concentrated in vacuo.
Purification by silica gel chromatography (hexane : ethyl acetate =
9 : 1) gave 24 (0.083 g, 88%) as a colourless solid, mp 136 ◦C. Found:
C, 82.09; H, 6.69. Calc. for C29H28O3 C, 82.05; H, 6.65%; Rf 0.5
(hexane : ethyl acetate, 9 : 1); [a]2D5 -104.8 (c 0.7, CH2Cl2); IR (neat)
n
max/cm-1 3057, 2923, 1597, 1091, 1072; dH (400 MHz, CDCl3)
2.43–2.46 (1H, m, H-10), 2.74–2.77 (1H, m, H-10¢), 3.01 (1H, dd,
J = 4.3, 9.7 Hz, H-6), 3.28 (1H, dd, J = 6.8, 9.7 Hz, H-6¢), 3.97
(1H, t, J = 4.1 Hz, H-2), 4.13 (1H, br d, J = 16.6 Hz, H-7),
4.17–4.21 (1H, m, H-1), 4.42–4.46 (2H, m, H-5, H-7¢), 5.57–5.60
(1H, m, H-8), 5.68–5.71 (1H, m, H-9), 5.87 (1H, ddd, J = 2.2, 4.1,
10.4 Hz, H-3), 6.00 (1H, ddd, J = 1.5, 3.5, 10.4 Hz, H-4), 7.21–7.32
(9H, m, C(C6H5)3), 7.45–7.47 (6H, m, C(C6H5)3); dC (100 MHz,
CDCl3) 30.0, 64.1, 68.2, 71.0, 71.1, 72.9, 86.5, 125.0, 125.1, 126.9,
127.7, 128.6, 129.9, 130.8, 143.9; MSES+: 447.5 [M + Na]+.
d
H (400 MHz, CDCl3) 1.66 (1H, br s, OH), 2.48 (2H, t, J = 7.0 Hz,
H-1¢, H-1¢¢), 3.05 (1H, dd, J = 3.9, 9.7 Hz, H-6), 3.33 (1H, dd,
J = 7.0, 9.7 Hz, H-6¢), 3.72 (1H, br s, H-2), 3.78 (1H, dt, J = 1.9,
7.0 Hz, H-1), 4.44–4.47 (1H, m, H-5), 5.09 (1H, bd, J = 10.0 Hz,
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(2R,3R,6S)-2-Allyl-6-(trityloxymethyl)-3,6-dihydro-2H-pyran-3-
yl 2,2,2-trichloroacetimidate (25)
To a solution of diol (0.060 g, 0.10 mmol) in methanol (2 mL)
was added NaIO4 (0.032 g, 0.15 mmol) dissolved in water, at
0 C. The reaction mixture was stirred for 30 min and quenched
◦
Alcohol 22 (0.100 g, 0.24 mmol) was dissolved in CH2Cl2 (2 mL)
and cooled to 0 ◦C. DBU (0.04 mL, 0.24 mmol) was added to
it, followed by trichloroacetonitrile (0.03 mL, 0.29 mmol). The
reaction mixture was stirred at the same temperature for 1 h and
then the CH2Cl2 evaporated. The crude product was purified by
column chromatography (hexane : ethyl acetate = 4 : 1) to afford
trichloroacetimidate 25 (0.1283 g, 95%) as a viscous liquid. Found:
C, 64.74; H, 5.09; N, 2.49. Calc. for C30H28Cl3NO3 C, 64.70; H,
5.07; N, 2.52%; Rf 0.7 (hexane : ethyl acetate, 4 : 1); [a]2D5 -35.1
(c 0.6, CH2Cl2); IR (neat) nmax/cm-1 3340, 2924, 1660, 1002; dH
(400 MHz, CDCl3) 2.51–2.59 (2H, m, H-1¢, H-1¢¢), 3.10 (1H, dd,
J = 3.9, 10.0 Hz, H-6), 3.34 (1H, dd, J = 6.8, 10.0 Hz, H-6¢),
4.06 (1H, dt, J = 2.4, 7.0 Hz), 4.56 (1H, t, J = 2.9 Hz), 5.08–5.10
(2H, m), 5.17 (1H, dd, J = 1.7, 17.1 Hz), 5.78–5.88 (1H, m), 6.02
(1H, dd, J = 3.1, 10.2 Hz), 6.22 (1H, ddd, J = 2.4, 5.3, 10.2 Hz),
7.22–7.32 (9H, m, C(C6H5)3), 7.45–7.47 (6H, m, C(C6H5)3), 8.27
(1H, s, NH); dC (100 MHz, CDCl3) 34.9, 63.9, 69.2, 71.2, 72.6,
86.6, 91.5, 117.7, 122.5, 127.0, 127.7, 128.6, 133.2, 133.9, 143.8,
162.1; MSES+: 578.4 [M + Na]+.
with water. Evaporation in vacuo gave a residue which was
extracted with ethyl acetate (3 ¥ 10 mL) and the combined
organic layers were washed with water, brine and concentrated.
The residual oil was purified by silica gel chromatography (hexane :
ethyl acetate = 7 : 3) to give the aldehyde 27 (0.052 g, 91.5%)
as a colourless oil. Found: C, 62.36; H, 4.66; N, 2.49. Calc. for
C29H26Cl3NO4 C, 62.32; H, 4.69; N, 2.51%; Rf 0.6 (hexane : ethyl
acetate, 3 : 2); [a]D25 + 48.4 (c 0.5, CH2Cl2); IR (neat) nmax/cm-1
3332, 2924, 1714, 1596, 1079; dH (400 MHz, CDCl3) 2.65–2.75
(2H, m, H-1¢, H-1¢¢), 3.26 (1H, dd, J = 4.8, 10.0 Hz, H-6), 3.35
(1H, dd, J = 7.0, 10.0 Hz, H-6¢), 3.93–3.97 (1H, m), 4.35 (1H,
dd, J = 3.2, 8.3 Hz), 4.44–4.45 (1H, m), 5.82 (2H, s), 7.06 (1H,
d, J = 8.5 Hz, NH), 7.21–7.32 (9H, m, C(C6H5)3), 7.44–7.46 (6H,
m, C(C6H5)3), 9.78 (1H, s, CHO); dC (100 MHz, CDCl3) 45.6,
47.0, 62.2, 66.1, 73.7, 86.9, 92.4, 123.7, 127.1, 127.8, 128.6, 131.8,
143.6, 161.3, 199.4; HRMS (ESI): 556.0843 [M - H]-. Calc. for
C29H26Cl3NO4 [M - H]-: 556.0849.
2,2,2-Trichloro-N-((2S,3S,6R)-6-(2-hydroxyethyl)-2-
(trityloxymethyl)-3,6-dihydro-2H-pyran-3-yl)acetamide (28)
N-((2S,3S,6R)-6-Allyl-2-(trityloxymethyl)-3,6-dihydro-2H-pyran-
To a stirred solution of compound 27 (0.100 g, 0.18 mmol) in
methanol (2 mL), cooled to 0 ◦C, was added NaBH4 (0.008 g,
0.198 mmol). The reaction mixture was stirred at the same
temperature for 30 min and then quenched with saturated NH4Cl
solution. The reaction mixture was concentrated under high
vacuum to remove methanol. The aqueous phase was extracted
with ethyl acetate (3 ¥ 15 mL), the combined organic extracts
were washed with water and brine, then dried over anhydrous
Na2SO4. After concentration, the residue was purified by silica gel
chromatography (hexane : ethyl acetate = 1 : 1) to afford alcohol
28 (0.095 g, 95%) as a colourless viscous liquid. Found: C, 62.14;
H, 5.05; N, 2.51. Calc. for C29H28Cl3NO4 C, 62.10; H, 5.03; N,
2.50%; Rf 0.5 (hexane : ethyl acetate, 1 : 1); [a]2D5 +54.4 (c 0.7,
CH2Cl2); IR (neat) nmax/cm-1 3410, 3322, 3033, 1701, 1597, 1033;
dH (400 MHz, CDCl3) 1.78–1.85 (2H, m, H-1¢, H-1¢¢), 2.40 (1H,
br s, OH), 3.27 (1H, dd, J = 4.4, 10.4 Hz, H-6), 3.35 (1H, dd,
J = 7.6, 10.4 Hz, H-6¢), 3.83–3.86 (2H, m), 3.91–3.95 (1H, m),
4.25–4.28 (2H, m), 5.71–5.74 (1H, m), 5.82 (1H, bd, J = 10.4 Hz),
6.82 (1H, d, J = 8.4 Hz, NH), 7.21–7.32 (9H, m, C(C6H5)3), 7.44–
7.46 (6H, m, C(C6H5)3); dC (100 MHz, CDCl3) 35.7, 45.8, 60.5,
62.6, 70.1, 73.3, 87.1, 92.8, 123.1, 127.1, 127.8, 128.6, 133.3, 143.6,
161.3.
3-yl)-2,2,2-trichloroacetamide (26)
A mixture of imidate 25 (0.100 g, 0.18 mmol) and K2CO3 (10 mg) in
xylene (5 mL) was refluxed (150 ◦C) for 12 h. The reaction mixture
was cooled to room temperature and the solvent evaporated,
followed by silica gel chromatography (hexane : ethyl acetate = 4 :
1) giving 26 (0.080 g, 80%) as a white solid along with recovered
starting material (0.008 g, 8%). Found: C, 64.66; H, 5.10; N,
2.54. Calc. for C30H28Cl3NO3 C, 64.70; H, 5.07; N, 2.52%; Rf
0.6 (hexane : ethyl acetate, 4 : 1); [a]2D5 -56.17 (c 1.2, CH2Cl2); IR
(neat) nmax/cm-1 3409, 3325, 2925, 1711, 1597, 1082; dH (400 MHz,
CDCl3) 2.30–2.40 (2H, m, H-1¢, H-1¢¢), 3.22 (1H, dd, J = 4.8,
9.7 Hz, H-6), 3.35 (1H, dd, J = 6.8, 9.7 Hz, H-6¢), 3.97–4.01 (1H,
m, H-5), 4.08–4.11 (1H, m, H-1), 4.28–4.30 (1H, m, H-4), 5.12–
5.18 (2H, m, H-3¢, H-3¢¢), 5.74–5.88 (3H, m, H-2, H-2¢, H-3), 6.72
(1H, d, J = 8.5 Hz, NH), 7.21–7.31 (9H, m, C(C6H5)3), 7.45–7.47
(6H, m, C(C6H5)3); dC (100 MHz, CDCl3) 38.2, 45.7, 62.3, 69.8,
73.7, 86.7, 92.3, 118.1, 122.9, 127.0, 127.8, 128.6, 133.1, 133.6,
143.6, 161.1; MSES+: 578.4 [M + Na]+.
2,2,2-Trichloro-N-((2S,3S,6R)-6-(2-oxoethyl)-2-
(trityloxymethyl)-3,6-dihydro-2H-pyran-3-yl)acetamide (27)
To a stirred solution of compound 26 (0.100 g, 0.18 mmol) in
acetone : water (1 : 2, 1.5 mL) at room temperature, were added
NMO·H2O (0.027 g, 0.198 mmol) and OsO4 (a 25 mg ml-1 solution
N-((2S,3S,6R)-6-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-
(trityloxymethyl)-3,6-dihydro-2H-pyran-3-yl)-2,2,2-
trichloroacetamide (29)
t
in BuOH, 9 mL, 0.005 eq.). After stirring for 3 h, a solution of
Na2S2O5 (0.041 g, 0.216 mmol dissolved in water) was added and
the resulting mixture was stirred for 10 min. After removal of the
acetone, the residue was extracted with ethyl acetate (3 ¥ 15 mL)
and washed with brine solution. The combined organic layers
were dried and concentrated in vacuo, and the residual oil was
purified by silica gel chromatography to give diol (0.066 g, 62%)
as a colourless liquid along with recovered starting material 26
(0.020 g, 20%).
tert-Butyldimethylsilyl chloride (0.025 g, 0.165 mmol) was added
to a solution of alcohol 28 (0.060 g, 0.11 mmol), triethylamine
(0.02 mL, 0.165 mmol) and 4-dimethylaminopyridine (catalytic
amount) in CH2Cl2 (4 mL). The reaction mixture was refluxed for
5 h and then cooled to room temperature. The resultant solution
was diluted with CH2Cl2 and washed with water and brine then
dried over anhydrous Na2SO4. Concentration in vacuo, followed
by silica gel chromatography (hexane : ethyl acetate = 9 : 1) gave 29
3954 | Org. Biomol. Chem., 2008, 6, 3948–3956
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(0.068 g, 94.3%) as a colourless liquid. Found: C, 62.28; H, 6.30;
N, 2.04. Calc. for C35H42Cl3NO4Si C, 62.26; H, 6.27; N 2.07%;
Rf 0.6 (hexane : ethyl acetate, 9 : 1); [a]2D5+ 40.2 (c 1.7, CH2Cl2);
IR (neat) nmax/cm-1 3326, 2952, 1697, 1958, 1019; dH (400 MHz,
CDCl3) 0.01 (s, 6H, Si(CH3)2), 0.84 (s, 9H, C(CH3)3), 1.67–1.70
(m, 1H, H-1¢), 1.74–1.78 (m, 1H, H-1¢¢), 3.17 (dd, 1H, J = 4.4,
10.0 Hz, H-6), 3.31 (dd, 1H, J = 6.8, 10.0 Hz, H-6¢), 3.72–3.82 (m,
3H), 4.23–4.28 (m, 2H), 5.64 (ddd, 1H, J = 2.2, 3.2, 10.2 Hz), 5.83
(bd, 1H, J = 10.2 Hz), 6.53 (d, 1H, J = 8.5 Hz, NH), 7.15–7.26
(m, 9H, C(C6H5)3), 7.40–7.42 (m, 6H, C(C6H5)3); dC (100 MHz,
CDCl3) -5.3, 18.2, 25.9, 36.6, 46.2, 59.3, 62.9, 68.0, 72.5, 86.8,
92.3, 122.9, 127.0, 127.8, 128.6, 134.0, 143.6, 161.2; HRMS
(ESI): 672.1875 [M - H]-. Calc. for C35H42Cl3NO4Si [M - H]-:
672.1870.
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To a stirred solution of compound 29 (0.100 g, 0.148 mmol)
in acetone : water : t-BuOH (4 mL, 1 : 1 : 0.5) at ambient
temperature, were added NMO·H2O (0.024 g, 0.178 mmol) and
t
OsO4 (a 25 mg ml-1 solution in BuOH, 6 mL, 0.004 equiv.). The
reaction mixture was stirred for 12 h and then it was treated
with Na2S2O5 (0.036 g, 0.192 mmol). The reaction mixture was
stirred for a further 0.5 h and extracted with ethyl acetate (3 ¥
15 mL). The organic layer was washed with water and finally
with brine. Evaporation of the organic layer gave a crude product
which was dissolved in CH2Cl2 and treated with Ac2O (0.04 mL,
0.444 mmol), Et3N (0.06 mL, 0.444 mmol) and a catalytic amount
of DMAP. The reaction mixture was stirred for 3 h and then
extracted with CH2Cl2. The usual work up gave a crude product
which after purification by column chromatography (hexane : ethyl
acetate = 9 : 1) afforded 30 (0.104g, 89%)as the major isomer along
with 7% minor isomer. Found: C, 59.09; H, 6.11; N, 1.74. Calc. for
C39H48Cl3NO8Si C, 59.05; H, 6.10; N 1.77%; Rf 0.5 (hexane : ethyl
acetate, 9 : 1); [a]D25 + 19.3 (c 1.5, CH2Cl2); IR (neat) nmax/cm-1 3422,
2924, 1754, 1722, 1093; dH (400 MHz, CDCl3) 0.00 (3H, s, SiCH3),
0.01 (3H, s, SiCH3), 0.83 (9H, s, C(CH3)3), 1.72–1.75 (1H, m, H-
1¢), 1.95 (3H, s, COCH3), 1.97–2.01 (1H, m, H-1¢¢), 2.08 (3H, s,
COCH3), 3.17 (1H, dd, J = 2.2, 10.4 Hz, H-6), 3.25 (1H, dd, J =
6.0, 10.4 Hz, H-6¢), 3.71–3.79 (3H, m, H-5, H-2¢, H-2¢¢), 4.09–4.18
(2H, m, H-4, H-1), 5.16 (1H, br s, H-2), 5.30 (1H, dd, J = 2.9,
10.7 Hz, H-3), 6.31 (1H, d, J = 8.7 Hz, NH), 7.12–7.23 (9H, m,
C(C6H5)3), 7.38–7.40 (6H, m, C(C6H5)3); dC (100 MHz, CDCl3)
-5.3, 18.2, 20.6, 20.9, 25.8, 31.5, 50.1, 58.7, 63.6, 68.2, 71.0, 71.9,
73.1, 86.7, 92.0, 127.0, 127.8, 128.6, 143.7, 161.7, 170.1, 170.7;
HRMS (ESI): 790.2138 [M - H]-. Calc. for C39H48Cl3NO8Si [M -
H]-: 790.2137.
Acknowledgements
We thank the Department of Science and Technology (DST), New
Delhi, for financial support to Y.D.V. in the form of a Ramanna
Fellowship (Grant No. SR/S1/RFOC-04/2006). P.G. and N.K.
thank the University Grant Commission, New Delhi, for Senior
Research Fellowships.
25 For selected examples of Overman rearrangements from the C-4 to
C-2 position, and synthetic applications of related compounds, see:
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