Asymmetric synthesis of aryl cyclitols based on 1,2,3,4 tetrahydronaphthalene scaffolds

Article abstract of DOI:10.1016/j.tetasy.2011.02.009

A series of aryl cyclitols based on a 1,2,3,4-tetrahydronaphthalene scaffold have been synthesized in a stereocontrolled manner. These cyclitols possess four contiguous stereocenters amongst which one is a quaternary stereocenter, which has been construct

Full text of DOI:10.1016/j.tetasy.2011.02.009

Tetrahedron: Asymmetry 22 (2011) 406–412
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric synthesis of aryl cyclitols based
on 1,2,3,4-tetrahydronaphthalene scaffolds
⇑
Tridib Mahapatra, Samik Nanda
Department of Chemistry, Indian Institute of Technology, Kharagpur, 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of aryl cyclitols based on a 1,2,3,4-tetrahydronaphthalene scaffold have been synthesized in a
stereocontrolled manner. These cyclitols possess four contiguous stereocenters amongst which one is a
quaternary stereocenter, which has been constructed by applying enzymatic kinetic resolution reaction.
The remaining stereocenters have been created by substrate directed asymmetric dihydroxylation reac-
tion and stereoselective keto-reduction process.
Received 8 November 2010
Revised 4 February 2011
Accepted 10 February 2011
Available online 30 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
have an extra aromatic ring, which could possess interesting
features such as stacking properties and enhanced lipophilicity
Cyclitols are small organic molecules with a cyclic ring as the
core structural scaffold and the ring is highly substituted with hy-
droxy functional groups. Inositol, the most widely known natural
cyclitol (cyclohexanehexols) is a sugar like molecule1 and has nine
existing stereoisomers altogether in nature, all of which may be re-
ferred to as inositol. The most prominent naturally occurring form is
myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol), which plays
a significant role as the structural basis for a number of secondary
messengers in eukaryotic cells, including inositol phosphates, phos-
phatidylinositol (PI) and phosphatidylinositol phosphate (PIP) lip-
(Scheme 1).6e Herein we report the asymmetric synthesis of such
aryl cyclitols, in which one of the hydroxy group has been replaced
by a hydroxymethyl substituent and also bears a quaternary stereo-
center (Scheme 1). The cyclitols are based on a stereochemically
pure 1,2,3,4-tetrahydronapthalene scaffold, which are thought to
be synthesized by enzymatic kinetic resolution, asymmetric dihydr-
oxylation and stereoselective reduction of carbonyl functionality.
2. Results and discussion
ids.2 Since the discovery that
D-myo-inositol 1,4,5-triphosphate
We were interested in developing new asymmetric routes for
obtaining designed aryl cyclitols based on tetrahydronapthalene
scaffold. The parent scaffold can be easily constructed by applying
an enzymatic kinetic resolution reaction developed earlier in our
group, which generates the required quaternary stereocenters. By
applying the enzymatic kinetic resolution strategy, both enantio-
mers of the parent scaffold can be efficiently prepared. In the
majority of the biocatalytic methods available for the synthesis
of cyclitols, arene-dioxygenase is one of the enzymes used in almost
all cases. Although the reaction is very useful in terms of chemical
yield and enantioselectivity, it is often difficult to obtain those
microbial strains and the reaction always gives the syn-1,2-diols.
In terms of developing general and appealing asymmetric pro-
cesses for novel aryl cyclitols, we intended to carry out a unique
strategy which employs commercially available enzymes coupled
with chemical reagents in an efficient way.
acts as a Ca2+ mobilizing intracellular secondary messenger, many
other inositol phosphates have been discovered, although it is only
in recent years that their physiological functions have begun to be
understood.3 Condutirols (cyclohex-5-ene-1,2,3,4-tetrols) are an-
other class of natural cyclitols, which have a wide range of biological
activities such as insulin modulators and glycosidase inhibition.4
Many designed synthetic analogues of conduritols are known in
the literature and have attracted significant attention from the sci-
entific community due to their interesting structural features.5,6
Aryl cyclitols are analogues of conduritols which can be regarded
as locked cyclitols, in which the ring double bond is replaced by
an aromatic ring. The search for new designed synthetic analogues
of conduritols has mainly focused on ring modification and sidearm
variation in the core structure; aryl cyclitols are such analogues gen-
erated from ring modifications.6 Many unnatural synthetic
analogues with the basic core structural units of conduritols have
been synthesized; aryl cyclitols the bicyclic mimic of conduritols,
Herein we have synthesized eight aryl cyclitols 1–8 (four pair of
enantiomers) based on 1,2,3,4-tetrahydronapthalene scaffolds
(Scheme 2). The retrosynthetic analysis of all the stereoisomers re-
veals that the quaternary stereocenter can be efficiently con-
structed by adopting an enzymatic kinetic resolution reaction of
⇑
Corresponding author.
E-mail address: snanda@chem.iitkgp.ernet.in (S. Nanda).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.02.009

T. Mahapatra, S. Nanda / Tetrahedron: Asymmetry 22 (2011) 406–412
407
OH
OH
OH
OH
OH
OH
R
OH
OH
OH
OH
HO
HO
OH
OH
HO
HO
OH
OH
OH
OH
conduritols
myo-inositol
R = H, OMe, COMe ; aryl cyclitols
scyllo-inositol
O
OH
OH
OH
OH
O
OH
OH
O
HO
HO
O
R
O
OH
OH
OH
R'
HO
OH
OH OH
OH OH
LuicolsB
Luicols A
locked cyclitols
R = CH2OH = R'
cyclitols reported
Naturally occurring aromatic tetrols
in this article
Scheme 1. Few naturally occurring and designed cyclitols.
OH
OH
OH
OH
MeO
OH
OP
MeO
OH
OP
OH
OP
OH
OP
OH
OH
OH
OH
OH
OH
OH
OH
4
3
1
2
P = TBDPS
Me
OH
OH
OH
OH
Me
OH
OH
OP
OH
OP
OH
OP
OH
OP
MeO
MeO
OH
OH
OH
OH
OH
OH
5
OH
8
6
7
enzymatic
OH(d)
OH(d)
OH(a)
asymmetric
dihydroxylation
kinetic
OH(c)
OP
OH(c)
OP
resolution
OH
OH
OP
OH
OH
OH
O
O
O
Scheme 2. Designed aryl cyclitols and a general retrosynthetic disconnection.
the properly substituted bis-hydroxymethylated derivative of
1-tetralone. The hydroxyl stereocenters c and d can be obtained
via a substrate directed asymmetric dihydroxylation reaction
while the hydroxyl stereocenter a can be assembled through
the substrate directed reduction of a carbonyl functionality
(Scheme 2).
yields 14 and 15 (Scheme 3). In a similar fashion olefins 16 and
17 were also synthesized starting from 6-methoxy-1-tetralone.
Compounds 18 and 19 were prepared from 7-methoxy-1-tetralone
in good yield. Compounds 20 and 21 were obtained starting from 4-
methyl-1-tetralone (Scheme 3) by adopting a similar approach.
The next step was to access the syn-diol moiety from the olefinic
compounds by employing an asymmetric dihydroxylation reac-
tion.8 For this reason, compound 14 was subjected to a dihydroxy-
lation reaction with OsO4, to afford the corresponding diol 22 with
absolute stereocontrol (yield = 78%). The origin of this excellent
diastereoselection in favor of the diol 22, can be explained by
assuming a sofa like conformation of the parent olefin 14 in which
the bottom face is shielded by the bulky tert-butyldiphenylsilyl
ether (OTBDPS) group. Hence the dihydroxylation exclusively
occurs from the top face of the olefin to afford diol 22. The similar
analogy can also be made when olefin 13 was subjected to an
asymmetric dihydroxylation reaction with OsO4 to afford diol 23
(yield = 74%) as the sole product (Scheme 4). The acetate groups
in diols 22 and 23 were removed with K2CO3/MeOH to afford the
deacetylated product, which upon subsequent reduction with
NaBH4 in MeOH afforded the target compounds 1 and 2 in almost
quantitative yield. Similar reaction sequences were performed to
The starting material bis-hydroxymethylated 1-tetralone deriv-
atives are easily prepared as described earlier.7 The initial enzy-
matic kinetic resolution reaction went smoothly with CAL-B as an
enzyme and vinyl acetate as the acyl donor to afford the (S)-acetate
10 (fast reacting enantiomer) and (R)-alcohol (11; slow reacting
enantiomer). The enantioselectivity of enzymatic kinetic resolution
was determined by chiral HPLC analysis. For the creation of the
benzylic unsaturation, (R)- and (S)-acetates were subjected to
bromination by using NBS (bromine source) and Bz2O (radical initi-
ator) to afford the corresponding bromo compounds as diastereo-
meric mixtures 12 and 13. It is worth mentioning that the free
hydroxyl group in the (R)-alcohol needs to be protected as its ace-
tate prior to bromination, otherwise unusual intramolecular (SN2
type) cyclization occurs with the generated bromo species and free
hydroxyl groups. Dehydrobromination with DBU as a base in reflux-
ing THF afforded the corresponding elimination products in good

408
T. Mahapatra, S. Nanda / Tetrahedron: Asymmetry 22 (2011) 406–412
CALB
OAc
OP
OH
OP
OP
OH
+
OAc
O
10
O
O
9
11
(R)-alcohol; ee = 97%
(S)-acetate; ee = 98%
P = TBDPS
(ii) NBS, Bz2O
(i) Ac2O
NBS, Bz2O
Br
Br
DBU
DBU
MeO
OP
OP
OP
OP
OAc
OAc
O
OAc
OAc
O
O
O
O
14
12
15
19
13
MeO
MeO
OP
OP
OP
OP
MeO
OAc
OAc
OAc
OAc
O
O
O
16
17
18
Me
Me
O
OP
OP
OAc
OAc
O
20
21
Scheme 3. Enzymatic kinetic resolution and dehydrobromination reactions for the synthesis of useful intermediates for aryl cyclitol preparation.
OH
O
OH
O
OH
OH
MeO
MeO
OAc
OTBDPS
Ph
OAc
OAc
O
Si tBu
Ph
OAc
O
O
OTBDPS
Ph
O
14
13
26
3
27
4
Si
tBu
Ph
OsO4
OsO4
OH
OH
OH
OH
OH
OH
OAc
OAc
OH
OH
OTBDPS
OTBDPS
OAc
OAc
OTBDPS
O
O
22
23
MeO
MeO
OTBDPS
31
O
a
30
a
O
OH
OH
OH
OH
OH
6
5
OH
OH
Me
OH
Me
OH
OH
OH
OTBDPS
OTBDPS
O
25 O
24
OAc
OAc
OTBDPS
OTBDPS
35
b
b
34
O
O
OH
OH
OH
OH
OH
OTBDPS
OTBDPS
8
7
1
2
OH
OH
Scheme 4. Asymmetric dihydroxylation and substrate directed keto-reduction for the synthesis of aryl cyclitols 1–8. Reagents and conditions: (a) K2CO3, MeOH, 0 °C; (b)
NaBH4, MeOH.
access the remaining aryl cyclitols 3–8 (Scheme 4). The TBDPS
group can be subsequently removed to afford the corresponding
pentols with the loss of the quaternary stereocenters. We kept
the TBDPS group intact in all the aryl cyclitols to retain the
quaternary stereocenters. Cyclitols 7 and 8 possess an additional
quaternary stereocenter (benzylic) originating from the starting
material 4-methyl-1-tetralone.
3. Conclusion
In conclusion, the asymmetric synthesis of eight aryl cyclitols
containing 1,2,3,4-tetrahydronapthalene scaffolds has been carried
out in a stereocontrolled way. All of the aryl cyclitols synthesized
have four contiguous stereocenters, one of which is quaternary.
The lipase catalyzed (CAL-B) enzymatic kinetic resolution reaction

T. Mahapatra, S. Nanda / Tetrahedron: Asymmetry 22 (2011) 406–412
409
is one of the key reactions to generate enantiomerically pure 1-tet-
ralone scaffolds, which have been used to construct the cyclitols.
Asymmetric dihydroxylation and the substrate directed reduction
of the keto functionality are the other key reactions we have
employed to obtain a structurally diverse set of aryl cyclitols in
an efficient way. Studies directed toward the synthesis of novel
aryl cyclitols and their potential use as glycosidase inhibitors are
currently underway in our laboratory.
130.5, 129.8, 128.9, 127.7, 127.6, 126.4, 65.5, 64.9, 52.4, 44.7,
38.2, 26.8, 20.6, 19.3. ½a D29
¼ ꢂ32:1 (c 1.5, CHCl3).
ꢁ
4.4. Acetic acid (S)-2-(tert-butyl-phenyl-silanyloxymethyl)-1-
oxo-1,2-dihydronaphthalen-2-ylmethyl ester 14
Bromo compound 12 (1 g, 1.9 mmol) was dissolved in tetrahy-
drofuran (25 mL) after which DBU (0.42 mL, 2.85 mmol) was then
added in one portion. The solution was refluxed for 24 h and the
solvent was then removed under reduced pressure. Water
(10 mL) was added to the brown oily residue and the mixture
was extracted with diethyl ether (2 ꢀ 50 mL). The combined or-
ganic extracts were washed with HCl (1 M), then with sodium
bicarbonate solution and finally with brine solution. The solution
was dried over anhydrous sodium sulfate and the solvent was re-
moved under reduced pressure. The residue was purified by silica
gel chromatography through silica gel 230–400 using a 95:5 mix-
ture of petroleum ether/ethylacetate as eluent to give the olefinic
4. Experimental
4.1. General
Unless otherwise stated, materials were obtained from com-
mercial suppliers and used without further purification. THF
and diethyl ether were distilled from sodiumbenzophenone ke-
tyl. Dimethylformamide (DMF) and dimethylsulfoxide (DMSO)
were distilled from calcium hydride. Reactions were monitored
by thin-layer chromatography (TLC) carried out on 0.25 mm sil-
ica gel plates (Merck) with UV light, ethanolic anisaldehyde and
phosphomolybdic acid/heat as developing agents. Silica gel 100–
200 mesh was used for column chromatography. Yields refer to
chromatographically and spectroscopically homogeneous materi-
als unless otherwise stated. NMR spectra were recorded on
Bruker 200 and 400 MHz spectrometers at 25 °C in CDCl3 using
TMS as the internal standard. Chemical shifts are shown in d.
13C NMR spectra were recorded with a complete proton decou-
pling environment. The chemical shift value is listed as dH and
dC for 1H and 13C, respectively. Optical rotations were measured
on a JASCO P1020 digital polarimeter. Mass spectral analysis was
performed at CRF, IIT-Kharagpur. Chiral HPLC was performed
using Chiral AD-H column (0.46 ꢀ 25 cm, Daicel industries) with
Shimadzu Prominence LC-20AT chromatograph coupled with
UV–vis detector (254 nm). Eluting solvent used was different ra-
tio of hexane and 2-propanol.
compound 14 as
a
colorless oily liquid. 1H NMR (CDCl3,
200 MHz), d: 8.06 (d, J = 7.8 Hz, 1H), 7.61–7.45 (m, 5H), 7.44–7.24
(m, 8H), 6.80 (d, J = 9.8 Hz, 1H), 6.26 (d, J = 9.8 Hz, 1H), 4.50 (d,
J = 10.4 Hz, 1H), 4.41 (d, J = 10.6 Hz, 1H), 3.92 (d, J = 9.4 Hz, 1H),
3.79 (d, J = 9.2 Hz, 1H), 1.89 (s, 3H), 0.89 (s, 9H). 13C NMR (CDCl3,
50 MHz), d: 199.5, 170.6, 138.1, 135.6, 134.5, 133.5, 132.7, 131.2,
129.8, 128.5, 128.0, 127.7, 127.5, 126.7, 67.6, 66.1, 55.5, 26.5,
20.6, 19.2. ½a 2D9
ꢁ
¼ ꢂ7:9 (c 0.9, CHCl3). ESI MS for (M++Na) =
507.6248.
4.5. Acetic acid (R)-2-(tert-butyl-phenyl-silanyloxymethyl)-1-
oxo-1,2-dihydronaphthalen-2-ylmethyl ester 15
Benzylic bromination followed by elimination with DBU affor-
ded compound 15 as described earlier. ½a D29
¼ þ8:3 (c 1.0, CHCl3).
ꢁ
4.6. Acetic acid (S)-4-bromo-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl-
methyl ester
4.2. HPLC data for compounds 10 and 11
The bromination reaction was performed as described in the
synthesis of compound 12. 1H NMR (CDCl3, 200 MHz), d: 7.93 (d,
J = 8.8 Hz, 1H), 7.89–7.56 (m, 4H), 7.45–7.29 (m, 6H), 7.1 (br s,
1H), 6.91–6.85 (m, 1H), 5.64–5.57 (m, 1H), 4.38 (d, J = 11.0 Hz,
1H), 4.23 (d, J = 11.0 Hz, 1H), 4.05 (d, J = 10.0 Hz, 1H), 3.91–3.78
(m, 4H), 2.88–2.77 (m, 2H), 1.88 (s, 3H), 1.00 (s, 9H). 13C NMR
(CDCl3, 50 MHz), d: 194.9, 170.4, 164.0, 144.1, 135.7, 135.6,
135.5, 132.9, 132.8, 130.1, 129.7, 127.6, 127.6, 124.8, 115.4,
114.3, 65.7, 65.0, 55.6, 52.2, 45.1, 38.3, 26.8, 20.6, 19.3.
(CHIRALCEL AD-H, mobile phase: hexane/2-propanol = 9:1; flow
rate: 1 mL/min; tS-acetate: 4.01 min; tR-acetate: 4.74 min; tR-alcohol
:
4.91 min; tS-alcohol: 5.44 min).
4.3. Acetic acid (S)-4-bromo-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl methyl ester 12
Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-1-oxo-
1,2,3,4-tetrahydro-naphthalen-2-ylmethyl ester 10 (930 mg,
1.9 mmol) was taken in anhydrous CCl4 (20 mL). A small amount
of Bz2O was added to the reaction mixture followed by the addition
of NBS (408 mg, 1.2 mmol). The reaction mixture was exposed to a
100 W mercury lamp for 1 h (as indicated by TLC analysis). After
that time the reaction was cooled to room temperature and the so-
lid succinimide was filtered off. The organic solvent was washed
with first sodium thiosulfate solution and then sodium bicarbonate
solution. The organic solvent was washed with water and then
brine. The solution was dried over anhydrous sodium sulfate and
the solvent was removed under reduced pressure. The residue
was purified through silica gel chromatography with silica gel
230–400 using a 95:5 mixture of petroleum ether/ethylacetate as
eluent to afford the bromo compound as brownish oil. 1H NMR
(CDCl3, 200 MHz), d: 7.98 (d, J = 7.8 Hz, 1H), 7.70–7.56 (m, 6H),
7.45–7.32 (m, 7H), 5.67 (t, J = 7.0 Hz, 1H), 4.43 (d, J = 11.2 Hz,
1H), 4.30 (d, J = 11.0 Hz, 1H), 4.09 (d, J = 11.2 Hz, 1H), 4.00 (d,
J = 11.2 Hz, 1H), 2.92–2.87 (m, 2H), 1.91 (s, 3H), 1.04 (s, 9H). 13C
NMR (CDCl3, 50 MHz), d: 196.4, 170.1, 141.8, 135.7, 134.1, 132.9,
4.7. Acetic acid (S)-2-(tert-butyl-phenyl-silanyloxymethyl)-6-
methoxy-1-oxo-1,2-dihydronaphthalen-2-ylmethyl ester 16
The DBU elimination reaction was performed as described in
the synthesis of compound 14. 1H NMR (CDCl3, 200 MHz), d: 8.05
(d, J = 8.6 Hz, 1H), 7.58–7.54 (m, 4H), 7.45–7.30 (m, 6H), 6.90–
6.84 (m, 1H), 6.75–6.71 (m, 2H), 6.30 (d, J = 10.0 Hz, 1H), 4.51–
4.35 (m, 2H), 3.93–3.75 (m, 5H), 1.89 (s, 3H), 0.92 (s, 9H). 13C
NMR (CDCl3, 50 MHz), d: 197.7, 170.7, 164.7, 140.4, 135.6, 134.9,
132.9, 132.8, 129.8, 129.3, 127.7, 123.7, 113.9, 111.8, 67.8, 66.4,
55.6, 55.3, 26.6, 20.7, 19.2. ½a D29
¼ þ16:5 (c 1.0, CHCl3). ESI MS for
ꢁ
(M++Na) = 537.4352.
4.8. Acetic acid (R)-2-(tert-butyl-phenyl-silanyloxymethyl)-
6-methoxy-1-oxo-1,2-dihydronaphthalen-2-ylmethyl ester 17
The DBU elimination reaction was performed as described in
the synthesis of compound 14. ½a D29
¼ ꢂ14:6 (c 0.8, CHCl3).
ꢁ

410
T. Mahapatra, S. Nanda / Tetrahedron: Asymmetry 22 (2011) 406–412
4.9. Acetic acid (S)-2-(tert-butyl-phenyl-silanyloxymethyl)-7-
methoxy-1-oxo-1,2-dihydronaphthalen-2-ylmethyl ester 18
reaction mixture was extracted with EtOAc (4 ꢀ 100 mL) and then
brine. The organic layer was dried (Na2SO4) and evaporated in va-
cuo. The diol was purified by flash chromatography with silica gel
230–400 using a 70:30 mixture of petroleum ether/ethylacetate as
eluent to afford compound 22. 1H NMR (CDCl3, 400 MHz), d: 8.03
(d, J = 7.6 Hz, 1H), 7.31–7.64 (m, 2H), 7.59–7.56 (m, 4H), 7.46–
7.37 (m, 7H), 5.01 (br s, 1H), 4.93 (d, J = 12.0 Hz, 1H), 4.68 (d,
J = 11.2 Hz, 1H), 4.13 (d, J = 3.4 Hz, 1H), 3.92 (d, J = 10.2 Hz, 1H),
3.82 (d, J = 10.2 Hz, 1H), 3.80 (br s, 1H, -OH), 3.39 (br s, 1H, -OH),
1.90 (s, 3H), 0.92 (s, 9H). 13C NMR (CDCl3, 100 MHz), d: 196.0,
170.4, 141.3, 135.6, 135.4, 134.5, 131.8, 131.3, 131.1, 130.2,
130.1, 129.2, 128.5, 127.9, 127.9, 126.9, 70.5, 68.0, 63.1, 62.8,
1H NMR (CDCl3, 200 MHz), d: 7.73–7.65 (m, 4H), 7.48–7.24 (m,
9H), 6.66 (d, J = 10.0 Hz, 1H), 6.46 (d, J = 10.0 Hz, 1H). 4.44–4.21 (m,
2H), 3.79–3.62 (m, 5H), 1.95 (s, 3H), 0.90 (s, 9H).13C NMR (CDCl3,
50 MHz), d: 199.0, 170.5, 161.3, 136.1, 135.4, 135.3, 134.5, 132.2,
129.2, 127.6, 127.1, 126.9, 117.4, 114.1, 64.1, 63.5, 55.5, 50.2,
26.5, 20.6, 19.1.
½
a 2D9
ꢁ
¼ þ21:58 (c 1.0, CHCl3). ESI MS for
(M++Na) = 537.4112.
4.10. Acetic acid (R)-2-(tert-butyl-phenyl-silanyloxymethyl)-7-
methoxy-1-oxo-1,2-dihydronaphthalen-2-ylmethyl ester 19
55.3, 26.6, 20.5, 19.0. ½a D29
¼ þ20:1 (c 0.2, CHCl3).
ꢁ
½
a 2D9
ꢁ
¼ ꢂ22:0 (c 1.1, CHCl3).
4.16. (2S,3S,4R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-3,4-dihydro-2H-naphthalen-1-one
4.11. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-hydroxymethyl-
4-methyl-3,4-dihydro-2H-naphthalen-1-one
24
Diol compound 22 (100 mg, 0.19 mmol) in aqueous methanol
(10 mL) was treated with potassium carbonate (8 mg, 0.057
mmol) at 0 °C. The reaction temperature rose to room tempera-
ture and was stirred for 2 h whereupon a more polar product
was observed by TLC. The methanol was removed by evapora-
tion and the resulting residue was partitioned between water
and ethyl acetate. The organic layer was separated, dried
(MgSO4), and the solvent was removed under reduced pressure
to afford the crude product. Flash chromatography with silica
gel 230–400 using a 75:35 mixture of petroleum ether/ethylace-
tate as eluent afforded the corresponding triol 24. 1H NMR
(CDCl3, 400 MHz), d: 7.99 (d, J = 7.6 Hz, 1H), 7.69–7.50 (m, 6H),
7.42–7.31 (m, 7H), 5.01 (d, J = 3.2 Hz, 1H), 4.74 (d, J = 3.2 Hz,
1H), 4.18 (d, J = 11.6 Hz, 1H), 4.09 (d, J = 11.6 Hz, 1H), 3.85 (d,
J = 10.4 Hz, 1H), 3.78 (d, J = 10.4 Hz, 1H), 2.89 (br s, 4H, -OH),
0.94 (s, 9H). 13C NMR (CDCl3, 100 MHz), d: 198.8, 142.1, 135.5,
135.4, 134.5, 132.1, 131.3, 130.4, 129.9, 129.9, 128.6, 128.2,
127.8, 127.8, 126.5, 73.9, 67.9, 64.9, 94.8, 57.3, 26.5, 19.0.
1H NMR (CDCl3, 200 MHz), d: 7.98 (d, J = 8.0 Hz, 1H), 7.63–7.49
(m, 5H), 7.42–7.29 (m, 8H), 4.00 (d, J = 7.0 Hz, 1H), 3.9 (d, J = 5.8 Hz,
1H), 3.81 (d, J = 4.2 Hz, 1H), 3.76 (d, J = 3.0 Hz, 1H), 3.09–2.97 (m,
1H), 2.28–2.19 (m, 1H), 1.83–1.70 (m, 1H), 1.76 (d, J = 13.0 Hz,
3H), 0.97 (s, 9H). 13C NMR (CDCl3, 50 MHz), d: 202.6, 148.0,
135.6, 134.0, 133.0, 132.8, 131.8, 129.8, 127.8, 127.5, 126.5, 66.1,
63.4, 52.6, 36.0, 28.2, 26.8, 20.6, 19.3.
4.12. Acetic acid (R)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
4-methyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylmethyl ester
1H NMR (CDCl3, 200 MHz), d: 8.05 (d, J = 8.2 Hz, 1H), 7.60–7.24
(m, 12H), 4.62 (d, J = 10.8 Hz, 1H), 4.49 (d, J = 11.0 Hz, 1H), 3.77 (br
s, 2H), 3.03–2.92 (m, 1H), 2.31–2.18 (m, 1H), 2.01 (s, 3H), 1.98–1.85
(m, 1H), 1.37 (d, J = 6.6 Hz, 3H), 1.00 (s, 9H). 13C NMR (CDCl3,
50 MHz), d: 198.0, 170.9, 147.2, 135.6, 135.5, 133.6, 132.8, 132.6,
131.8, 129.8, 127.8, 126.5, 66.4, 64.1, 51.6, 35.9, 28.0, 26.7, 20.9,
20.7, 19.2.
½
a 2D9
ꢁ
¼ þ22:1 (c 0.1, CHCl3). ESI MS for (M++Na) = 499.1917.
4.13. Acetic acid (S)-2-(tert-butyl-phenyl-silanyloxymethyl)-4-
4.17. (1R,2S,3R,4R)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
methyl-1-oxo-1,2-dihydronaphthalen-2-ylmethyl ester 20
hydroxymethyl-1,2,3,4-tetrahydronaphthalene-1,2,4-triol 1
1H NMR (CDCl3, 200 MHz), d: 8.10 (d, J = 7.8 Hz, 1H), 7.67–
7.53 (m, 4H), 7.48–7.28 (m, 9H), 6.01 (s, 1H), 4.42 (s, 2H), 3.93
(d, J = 9.2 Hz, 1H), 3.77 (d, J = 9.2 Hz, 1H), 2.22 (s, 3H), 1.91 (s,
3H), 0.9. (s, 9H). 13C NMR (CDCl3, 50 MHz), d: 200.1, 170.9,
139.2, 135.8, 134.6, 133.1, 132.3, 130.3, 129.9, 127.9, 127.0,
The triol compound 24 prepared in the previous step (50 mg,
0.1 mmol) was taken in anhydrous MeOH. Next, NaBH4 (4 mg,
0.1 mmol) was added to the reaction mixture at 0 °C. The reac-
tion mixture was allowed to return to room temperature. After
completion of the reaction as indicated by TLC analysis, the con-
tents of the flask were evaporated and the residue was taken in
DCM. The organic layer was washed with water and brine. The
organic layer was dried (MgSO4) and evaporated. The crude te-
trol was purified further by silica gel chromatography (1:1; hex-
ane/EtOAc) to afford the tetrol in 90% yield. 1H NMR (CDCl3,
400 MHz), d: 7.62 (d, J = 6.8 Hz, 2H), 7.56–7.32 (m, 13H), 5.04
(s, 1H), 4.71 (d, J = 4.0 Hz, 1H), 4.26 (d, J = 4.0 Hz, 1H), 4.01 (d,
J = 2.0 Hz, 1H), 3.93 (d, J = 10.8 Hz, 1H), 3.79 (d, J = 10.8 Hz, 1H),
1.05 (s, 9H). 13C NMR (CDCl3, 100 MHz), d: 138.6, 137.3, 135.5,
135.4, 135.1, 132.0, 130.1, 130.0, 129.2, 128.6, 128.4, 127.9,
127.8, 127.3, 71.4, 70.3, 68.2, 64.4, 64.2, 47.3, 26.8, 19.1.
124.5, 67.8, 66.2, 55.3, 26.7, 20.9, 19.8, 19.3. ½a D29
¼ þ6:9 (c 1.0,
ꢁ
CHCl3). ESI MS for (M++Na) = 521.6125.
4.14. Acetic acid (R)-2-(tert-butyl-phenyl-silanyloxymethyl)-4-
methyl-1-oxo-1,2-dihydronaphthalen-2-ylmethyl ester 21
½
a 2D9
ꢁ
¼ ꢂ6:7 (c 0.5, CHCl3).
4.15. Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxy-
methyl)-3,4-dihydroxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-
ylmethyl ester 22
½
a 2D9
ꢁ
¼ þ29:3 (c 0.2, CHCl3). ESI MS for (M++Na) = 501.2101.
Acetone (50 mL), H2O (5 mL), and OsO4 (0.09 mmol, solution in
toluene) were mixed and the mixture was stirred for 15 min.
Compound 3 (50 mg, 0.98 mmol) was then added in one portion,
followed by the addition of N-methylmorpholine N-oxide (NMO,
1.2 mmol) into the solution. The reaction mixture was stirred
vigorously at 20 °C for 24 h. After that time, sodium sulfite (6 g)
was added and stirring was continued for a further 1 h. The
4.18. (2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-3,4-dihydro-2H-naphthalen-1-one
25
The triol 25 was prepared as described earlier. ½a D29
¼ ꢂ23:3 (c
ꢁ
0.25, CHCl3). ESI MS for (M++Na) = 499.1917.

T. Mahapatra, S. Nanda / Tetrahedron: Asymmetry 22 (2011) 406–412
411
4.19. (1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
4.25. (1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-1,2,3,4-tetrahydronaphthalene-1,2,4-triol 2
hydroxymethyl-7-methoxy-1,2,3,4-tetrahydronaphthalene-
1,2,4-triol 4
Reduction of triol 25 afforded tetrol 2 as described previously.
½
a 2D9
ꢁ
¼ ꢂ33:5 (c 0.2, CHCl3). ESI MS for (M++Na) = 501.2101.
Reduction of triol 29 with NaBH4 afforded the tetrol 4. ½a D29
ꢂ19:8 (c 0.8, CHCl3). ESI MS for (M++Na) = 531.2233.
ꢁ
¼
4.20. Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-3,4-dihydroxy-6-methoxy-1-oxo-1,2,3,4-tetrahydronaph-
thalen-2-ylmethyl ester 26
4.26. Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-3,4-dihydroxy-7-methoxy-1-oxo-1,2,3,4-tetrahydronaph-
thalen-2-ylmethyl ester 28
The asymmetric dihydroxylation of compound 16 was per-
formed with OsO4/NMO to afford diol 26 in 78% yield. 1H NMR
(CDCl3, 200 MHz), d: 7.95–7.91 (d, J = 8.8 Hz, 1H), 7.52–7.12 (m,
11H), 6.85 (dd, J = 8.6, 2.2 Hz, 1H), 4.94 (d, J = 2.4 Hz, 1H), 4.87 (d,
J = 11.8 Hz, 1H), 4.64 (d, J = 11.8 Hz, 1H), 4.09 (d, J = 3.4 Hz, 1H),
3.89–3.74 (m, 5H), 2.02 (s, 3H), 0.83 (s, 9H). 13C NMR (CDCl3,
50 MHz), d: 194.8, 172.7, 164.7, 144.8, 135.6, 135.4, 132.3, 132.2,
131.5, 129.9, 129.8, 129.2, 127.8, 126.7, 124.3, 114.9, 11.3, 72.5,
Dihydroxylation of compound 18 with OsO4/NMO afforded
diol 30. 1H NMR (CDCl3, 200 MHz), d: 7.62–7.53 (m, 4H), 7.47–
7.29 (m, 8H), 7.20 (dd, J = 8.6, 2.6 Hz, 1H), 4.93 (d, J = 3.2 Hz,
1H), 4.88 (s, 1H), 4.7 (d, J = 10.8 Hz, 1H), 4.12 (d, J = 3.6 Hz,
1H), 3.96 (d, J = 5.6 Hz, 1H), 3.88–3.80 (m, 4H), 2.66 (br s, 2H,
-OH), 2.08 (s, 3H), 0.90 (s, 9H). 13C NMR (CDCl3, 50 MHz), d:
196.2, 172.5, 159.5, 135.5, 135.4, 134.2, 132.2, 131.7, 129.9,
129.8, 129.5, 127.8, 127.7, 125.6, 122.3, 108.9, 72.2, 66.9, 63.8,
67.4, 64.5, 63.6, 56.6, 55.6, 26.5, 20.9, 19.1. ½a D29
¼ þ11:3 (c 0.5,
ꢁ
CHCl3).
63.0, 57.2, 55.6, 26.5, 20.9, 19.1. ½a D29
¼ þ16:7 (c 0.5, CHCl3).
ꢁ
4.21. (2S,3S,4R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-6-methoxy-3,4-dihydro-2H-nap
hthalen-1-one 28
4.27. (2S,3S,4R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-7-methoxy-3,4-dihydro-2H-naph
thalen-1-one 32
The acetate deprotection with K2CO3 was carried out as de-
scribed in the synthesis of compound 24. 1H NMR (CDCl3,
200 MHz), d: 7.97 (d, J = 8.6 Hz, 1H), 7.59–7.35 (m, 10H), 7.16 (d,
J = 2.4 Hz, 1H), 6.95 (dd, J = 8.4 Hz, 2.6 Hz, 1H), 4.99 (d, J = 3.8 Hz,
1H), 4.51 (d, J = 3.8 Hz, 1H), 4.25 (d, J = 10.6 Hz, 1H), 4.16 (d,
J = 10.6 Hz, 1H), 3.90 (s, 3H), 3.83 (s, 2H), 2.7 (br s, 3H, -OH), 0.9
(s, 9H). 13C NMR (CDCl3, 50 MHz), d: 197.2, 164.9, 144.5, 135.7,
135.5, 131.9, 131.5, 130.3, 130.2, 129.4, 127.9, 126.3, 124.8,
115.6, 112.6, 71.2, 68.2, 64.7, 64.3, 56.4, 55.7, 26.7, 19.1.
Acetate deprotection of diol 30 afforded triol 32. 1H NMR
(CDCl3, 200 MHz), d: 7.59–7.52 (m, 5H), 7.44–7.30 (m, 7H),
7.18 (dd, J = 8.6, 2.8 Hz, 1H), 4.96 (d, J = 3.4 Hz, 1H), 4.73 (d,
J = 3.8 Hz, 1H), 4.09 (s, 2H), 3.9–3.7 (m, 5H), 2.52 (br s, 3H, -
OH), 0.96 (s, 9H). 13C NMR (CDCl3, 50 MHz), d: 198.7, 159.7,
135.5, 132.2, 130.4, 130.0, 127.9, 126.4, 124.7, 122.5, 108.9,
73.5, 67.7, 65.1, 64.6, 57.4, 55.5, 26.7, 19.2. ½a D29
¼ þ9:15 (c 0.5,
ꢁ
CHCl3).
½
a 2D9
ꢁ
¼ ꢂ19:0 (c 0.3, CHCl3). ESI MS for (M++Na) = 571.1729.
4.28. (1R,2S,3R,4R)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-6-methoxy-1,2,3,4-tetrahydronaphthalene-
1,2,4-triol 5
4.22. (1R,2S,3R,4R)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-7-methoxy-1,2,3,4-tetrahydronaphthalene-
1,2,4-triol 3
Triol 32 was reduced with NaBH4 to afford tetrol 5 in quan-
titative yield. 1H NMR (CDCl3, 200 MHz), d: 7.63–7.53 (m, 4H),
7.45–7.30 (m, 7H), 7.07 (d, J = 2.4 Hz, 1H), 6.88 (dd, J = 8.4 Hz,
2.4 Hz, 1H), 5.02 (br s, 1H), 4.65 (d, J = 4.2 Hz, 1H), 4.21 (d,
J = 4.2 Hz, 1H), 4.01 (s, 2H), 3.88 (d, J = 10.6 Hz, 1H), 3.82 (s,
3H), 3.78 (d, J = 10.6 Hz, 1H), 1.05 (s, 9H). 13C NMR (CDCl3,
50 MHz), d: 160.5, 137.0, 135.7, 135.6, 132.3, 132.1, 130.2,
130.1, 129.7, 128.9, 128.0, 122.5, 115.0, 114.0, 83.5, 72.9, 68.7,
The NaBH4 reduction was achieved as reported in the synthesis
of tetrol 3. 1H NMR (CDCl3, 200 MHz), d: 7.63–7.52 (m, 4H), 7.46–
7.28 (m, 7H), 6.99 (d, J = 2.4 Hz, 1H), 6.88 (dd, J = 8.6 Hz, 2.6 Hz,
1H), 4.94 (br s, 1H), 4.59 (d, J = 3.8 Hz, 1H), 4.21 (d, J = 4.0 Hz,
1H), 3.95–3.68 (m, 4H), 3.77 (s, 3H), 2.95 (br s, 4H, -OH), 1.04 (s,
9H). 13C NMR (CDCl3, 50 MHz), d: 159.3, 135.5, 135.4, 132.2,
131.3, 130.0, 128.8, 127.9, 114.9, 112.9, 71.6, 71.1, 69.9, 68.3,
64.2, 55.3, 47.5, 26.9, 19.2. ½a D29
¼ þ17:0 (c 0.1, CHCl3). ESI MS for
ꢁ
64.7, 55.4, 53.6, 33.8, 26.8, 19.2. ½a D29
¼ þ44:1 (c 1.2, CHCl3).
ꢁ
(M++Na) = 531.2233.
ESI MS for (M++Na) = 531.2238.
4.23. Acetic acid (2R,3R,4S)-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-3,4-dihydroxy-6-methoxy-1-oxo-1,2,3,4-tetrahydronaph-
thalen-2-ylmethyl ester 27
4.29. Acetic acid (2R,3R,4S)-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-3,4-dihydroxy-7-methoxy-1-oxo-1,2,3,4-tetrahydronaph-
thalen-2-ylmethyl ester 31
Dihydroxylation of compound 17 with OsO4/NMO afforded the
diol 27. ½a 2D9
¼ ꢂ8:05 (c 0.5, CHCl3).
ꢁ
Dihydroxylation of 19 with OsO4/NMO afforded diol 31.
¼ ꢂ19:25 (c 0.6, CHCl3).
½
a 2D9
ꢁ
4.24. (2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-6-methoxy-3,4-dihydro-2H-naph-
thalen-1-one 29
4.30. (2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-7-methoxy-3,4-dihydro-2H-naph-
thalen-1-one 33
The acetate deprotection was performed as reported earlier to
a 2D9
ꢁ
¼ þ22:65 (c 1.1, CHCl3). ESI MS for
Acetate group in 31 was removed to produce triol 33 as re-
afford triol 29.
½
ported earlier. ½a D29
¼ þ12:3 (c 0.5, CHCl3).
ꢁ
(M++Na) = 571.1729.

412
T. Mahapatra, S. Nanda / Tetrahedron: Asymmetry 22 (2011) 406–412
4.31. (1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-6-methoxy-1,2,3,4-tetrahydronaphthalene-
1,2,4-triol 6
4.37. (1R,2S,3R,4R)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-1-methyl-1,2,3,4-tetrahydronaphthalene-1,2,4-
triol 7
Triol 33 was reduced with NaBH4 to afford tetrol 6 in almost
NaBH4 reduction of triol 36 afforded tetrol 7. ½a D29
¼ þ5:9 (c
ꢁ
quantitative yield.
½
a 2D9
ꢁ
¼ ꢂ34:7 (c 0.75, CHCl3). ESI MS for
0.15, CHCl3).
(M++Na) = 531.2238.
Acknowledgments
4.32. Acetic acid (2R,3R,4S)-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-3,4-dihydroxy-4-methyl-1-oxo-1,2,3,4-tetrahydronaph
thalen-2-ylmethyl ester 35
We are thankful to DST-SERC (New Delhi, India) for providing
financial support. We are also thankful to DST (New Delhi) for pro-
viding the departmental NMR facility under the DST-IRPHA pro-
gram. One of the authors T.M. is thankful to CSIR (New Delhi,
India) for a research fellowship.
Asymmetric dihydroxylation of compound 21 with OsO4/NMO
afforded the diol 35. 1H NMR (CDCl3, 200 MHz), d: 7.89 (d,
J = 7.6 Hz, 1H), 7.76–7.46 (m, 7H), 7.44–7.35 (m, 6H), 4.56 (s, 1H),
4.26 (d, J = 8.7 Hz, 1H), 4.18 (d, J = 8.9 Hz, 1H), 4.05 (d, J = 8.8 Hz,
1H), 3.89 (d, J = 7.8 Hz, 1H), 3.03 (br s, 2H, -OH), 1.95 (s, 3H).
1.76 (s, 3H), 0.97 (s, 9H). 13C NMR (CDCl3, 50 MHz), d: 198.7,
144.2, 143.9, 135.6, 134.7, 132.6, 131.2, 130.1, 128.3, 127.2,
126.9, 126.8, 74.9, 70.1, 65.2, 62.9, 56.6, 26.6, 20.4, 19.3.
References
1. (a) Michell, R. H. Nat. Rev. Mol. Cell Biol. 2008, 9, 151; (b)Inositol Phosphates and
Derivatives: Synthesis, Biochemistry and Therapeutic Potential; Reitz, A. B., Ed.;
American Chemical Society: Washington, DC, 1991; (c) Posternak, T. The
Cyclitols; Holden-Day: San Francisco, CA, 1962; (d) Anderson, L. The Cyclitols,
2nd ed. In The Carbohydrates; Pigman, W., Horton, D., Eds.; Academic: San Diego,
CA, 1972; Vol. 1A, pp 519–579.
2. (a) Best, M. D.; Zhang, H.; Prestwich, G. D. Nat. Prod. Rep. 2010, 27, 1403; (b)
Conway, S. J.; Miller, G. J. Nat. Prod. Rep. 2007, 24, 687; (c) Berridge, M. J.; Irvine,
R. F. Nature 1984, 312, 315; (d)Inositol Lipids in Cell Signalling; Michell, R. H.,
Drummond, A. H., Downes, C. P., Eds.; Academic: San Diego, CA, 1989; (e) Powis,
G.; Kozikowski, A. P. Inhibitors of myo-Inositol Signalling. In New Molecular
Targets for Cancer Chemotherapy; Kerr, D. J., Workman, P., Eds.; CRC: Boca Raton,
LA, 1994; pp 81–95; (f) Kozikowski, A.; Fauq, A.; Malaska, M.; Tuchmantel, W.;
Ognyanov, V.; Powis, G. Curr. Med. Chem. 1994, 1, 1; (g) Schedler, D. J. A.; Baker,
D. C. Carbohydr. Res. 2004, 339, 1585.
½
a 2D9
ꢁ
¼ ꢂ12:3 (c 0.4, CHCl3). ESI MS for (M++Na) = 555.1913.
4.33. (2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-4-methyl-3,4-dihydro-2H-naph-
thalen-1-one 37
Acetate group was deprotected as depicted earlier to afford the
triol 37. 1H NMR (CDCl3, 200 MHz), d: 8.0 (d, J = 7.0 Hz, 1H), 7.77 (d,
J = 7.6 Hz, 1H), 7.66–7.58 (m, 6H), 7.47–7.35 (m, 6H), 4.53 (d,
J = 3.2 Hz, 1H), 4.06 (d, J = 8.8 Hz, 1H), 3.92 (d, J = 9.6 Hz, 1H),
3.72 (d, J = 10.8 Hz, 1H), 3.33 (br s, 3H, -OH), 1.74 (s, 3H), 0.98 (s,
9H). 13C NMR (CDCl3, 50 MHz), d: 198.8, 144.6, 143.4, 135.6,
134.6, 132.5, 131.5, 130.0, 128.4, 127.8, 126.9, 74.10, 70.27,
3. (a) Berridge, M. J. Nature 1993, 361, 315; (b) Irvine, R. F.; Schell, M. J. Nat. Rev.
Mol. Cell Biol. 2001, 2, 327.
4. (a) Balci, M. Pure Appl. Chem. 1997, 69, 97; (b) Carless, M. A. J. Tetrahedron:
Asymmetry 1992, 3, 795; (c) Balci, M.; Sütbeyas, Y.; Secüen, H. Tetrahedron 1990,
46, 3715; (d) Billington, D. C.; Perron-Sierra, F.; Picard, I.; Beaubras, S.; Duhault,
J.; Espinal, J.; Challal, S. In Carbohydrate Mimics: Concepts and Methods; Chapleur,
Y., Ed.; Wiley-VCH: Weinheim, 1998; p 433; (e) Legler, G. Adv. Carbohydr. Chem.
Biochem. 1990, 48, 319.
65.90, 63.07, 57.07, 26.79, 19.22. ½a D29
¼ ꢂ20:9 (c 0.5, CHCl3). ESI
ꢁ
MS for (M++Na) = 513.3526.
5. For reviews on the synthesis of inositols and conduritols, see: (a) Balci, M.;
Sütbeyas, Y.; Secüen, H. Tetrahedron 1990, 46, 3715–3742; (b) Hudlicky, T.;
Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J. Chem. Rev. 1996, 96, 1195–1220.
6. (a) Chen, N.; Carriere, M. B.; Laufer, R. S.; Taylor, N. J.; Dmitrienko, G. I. Org. Lett.
2008, 10, 381; (b) Orsini, F.; Sello, G.; Bernasconi, S.; Fallacara, G. Tetrahedron
Lett. 2004, 45, 9253; (c) Metha, G.; Ramesh, S. S. Chem. Commun. 2000, 2429; (d)
Angelaud, R.; Babot, O.; Charvat, T.; Landais, Y. J. Org. Chem. 1999, 64, 9613; (e)
Desjardins, M.; Lallemand, M.-C.; Freeman, S.; Hudlicky, T.; Abboud, K. A. J.
Chem. Soc., Perkin Trans. 1 1999, 621; (f) Leung-Toung, R.; Liu, Y.; Muchowski, J.
M.; Wu, Y.-L. J. Org. Chem. 1998, 63, 3235; (g) Riley, A. M.; Potter, B. V. L. J. Org.
Chem. 1995, 60, 4970; (h) Liu, C.; Potter, B. V. L. J. Org. Chem. 1997, 62, 8335; (i)
Riley, A. M.; Potter, B. V. L. Tetrahedron Lett. 1999, 40, 2213; (j) Sun, H.; Reddy, G.
B.; George, C.; Meuillet, E. J.; Berggren, M.; Powis, G.; Kozikowski, A. P.
Tetrahedron Lett. 2002, 43, 2835; (k) Jenkins, D. J.; Riley, A. M.; Potter, B. V. L. J.
Org. Chem. 1996, 61, 7719; (l) Kozikowski, A. P.; Fauq, A. H.; Powis, G.; Melder, D.
C. J. Am. Chem. Soc. 1990, 112, 4528; (m) Cheikh, A. B.; Craine, L. E.; Zemlicka, J.;
Heeg, M. H. Carbohydr. Res. 1990, 199, 19; (n) Schnaars, A.; Schultz, C.
Tetrahedron 2001, 57, 519; (o) Kwon, Y. U.; Lee, C.; Chung, S. K. J. Org. Chem.
2002, 67, 3327; (p) Takahashi, H.; Kittaka, H.; Ikegami, S. J. Org. Chem. 2001, 66,
2705; (q) Kim, K. S.; Park, J. I.; Moon, H. K.; Yi, H. Chem. Commun. 1998, 1945; (r)
Landias, Y. Chimia 1998, 52, 104; (s) Riley, A. M.; Jenkins, D. J.; Potter, B. V. L.
Carbohydr. Res. 1998, 314, 277; (t) Motherwell, W.; Williams, A. S. Angew. Chem.
1995, 107, 2207. Angew. Chem. Int., Ed. Engl. 1995, 34, 2031.; (u) Hudlicky, T.;
Mandel, M.; Rouden, J.; Lee, R. S.; Bachmann, B.; Dudding, T.; Yost, K. J.; Merola, J.
S. J. Chem. Soc., Perkin Trans. 1 1994, 1553; (v) Jaramillo, C.; Lomas, M. M.
Tetrahedron Lett. 1991, 32, 2501.
4.34. (1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-1-methyl-1,2,3,4-tetrahydronaphthalene-1,2,4-
triol 8
The NaBH4 reduction of the triol 37 afforded the tetrol 8 in
quantitative yield. 1H NMR (CDCl3, 200 MHz), d: 7.72–7.60 (m,
5H), 7.44–7.31 (m, 9H), 4.79 (s, 1H), 4.12 (s, 1H), 4.07 (d,
J = 4.2 Hz, 2H), 3.77 (s, 2H), 1.65 (s, 3H), 1.19 (s, 9H). 13C NMR
(CDCl3, 50 MHz), d: 135.6, 135.6, 132.4, 130.1, 130.05, 128.9,
128.8, 128.3, 127.9, 127.3, 73.9, 72.0, 70.7, 66.0, 62.4, 46.4, 28.2,
26.9, 19.2.
½
a 2D9
ꢁ
¼ ꢂ7:05 (c 0.4, CHCl3). ESI MS for
(M++Na) = 515.2248.
4.35. Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxym
ethyl)-3,4-dihydroxy-4-methyl-1-oxo-1,2,3,4-tetrahydronaph-
thalen-2-ylmethyl ester 34
Asymmetric dihydroxylation of compound 20 with OsO4/NMO
afforded the diol 34. ½a D29
¼ þ12:65 (c 0.2, CHCl3). ESI MS for
ꢁ
(M++Na) = 555.1913.
7. Mahapatra, T.; Das, T.; Nanda, S. Tetrahedron: Asymmetry 2008, 19, 2497.
8. Tietze, L. F.; Eicher, T.; Diederichsen, U.; Speicher, A. Reactions and Syntheses;
Wiley-VCH: Weinheim, 2007.
4.36. (2S,3S,4R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-
dihydroxy-2-hydroxymethyl-4-methyl-3,4-dihydro-2H-naph-
thalen-1-one 36
Deacetylation of compound 34 with K2CO3/MeOH afforded the
triol 36. ½a 2D9
¼ þ22:3 (c 0.5, CHCl3).
ꢁ