Diverse and yet unified: A comparative study of the supramolecular assemblies of three diastereomeric perhydro-2,3,4a,6,7,8a-naphthalenehexols

Article abstract of DOI:10.1002/ejoc.200800905

Self-assemblies of three crystalline perhydro-2,3,4a,6,7,8a- naphthalenehexols 3-5, all constructed on a trans-decalin framework, were compared with each other and to that of their diastereomeric all axial hydroxy sibling 2, which was previously reported. The presence of the peripheral equatorial OH groups in 3-5 severs, to varying extents, the end-to-end intramolecular O-H...O hydrogen-bonding chain linking the 1,3-diaxial hydroxy groups on both faces of hexol 2. Hence, the crystal packing in 3-5 deviates from the simple qualitative model proposed and observed in 2. Though complex and seemingly individualistic upon a cursory glance, the supramolecular assemblies of all three hexols underscore two primary concepts of O-H...O hydrogen bonding, namely, maximization of the total number of hydrogen bonds per molecule and maximization of O-H...O hydrogen-bond cooperativity by forming as many finite and infinite chains of hydrogen bonds as possible. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Full text of DOI:10.1002/ejoc.200800905

FULL PAPER
DOI: 10.1002/ejoc.200800905
Diverse and Yet Unified: A Comparative Study of the Supramolecular
Assemblies of Three Diastereomeric Perhydro-2,3,4a,6,7,8a-naphthalenehexols
Goverdhan Mehta*[a] and Saikat Sen[a]
Keywords: Chirality / Hydrogen bonds / Supramolecular chemistry / Conformational locking
Self-assemblies of three crystalline perhydro-2,3,4a,6,7,8a-
naphthalenehexols 3–5, all constructed on a trans-decalin
framework, were compared with each other and to that of
their diastereomeric all axial hydroxy sibling 2, which was
previously reported. The presence of the peripheral equato-
rial OH groups in 3–5 severs, to varying extents, the end-to-
end intramolecular O–H···O hydrogen-bonding chain linking
the 1,3-diaxial hydroxy groups on both faces of hexol 2.
Hence, the crystal packing in 3–5 deviates from the simple
plex and seemingly individualistic upon a cursory glance, the
supramolecular assemblies of all three hexols underscore two
primary concepts of O–H···O hydrogen bonding, namely,
maximization of the total number of hydrogen bonds per
molecule and maximization of O–H···O hydrogen-bond coo-
perativity by forming as many finite and infinite chains of
hydrogen bonds as possible.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
qualitative model proposed and observed in 2. Though com- Germany, 2009)
drogen-bond donors and acceptors, which not only simpli-
Introduction
fied a qualitative visualization of the various packing pat-
terns in 2, but also allowed us to propose, on the basis of
previously reported CSD analyses, the packing motifs most
likely to converge with the experimental results (Figure 1).
Albeit qualitative in nature, the O–H···O hydrogen-bonding
pattern proposed for 2 was found to conform well with that
observed experimentally for the two observed polymorphs
of hexol 2.[2d,2e]
With only one functional group, namely, the hydroxy
group, functioning as both donor and acceptor of hydrogen
bonds in the molecule, polyols, such as carbohydrates and
inositols, have constituted one of the earliest and simplest
systems for the analysis of O–H···O hydrogen bonding.[1]
However, in most cases, logical anticipation of the mode of
molecular association in such molecules becomes a difficult
proposition owing to the orientational flexibility of the C–
OH groups.[1c] Proposing the hydrogen-bonded architecture
in polyols, with little or no constraints to the internal de-
grees of freedom, proves to be even more complicated, as
the final spatial disposition of the hydroxy groups, realized
in the crystal structure of such molecules, is often largely
determined by the crystal packing itself.
Against this background, we have been actively involved,
for quite some time now, in the pursuit of elucidating the
patterns of self-assembly in conformationally locked poly-
cyclitols, specially crafted on a rigid trans-decalin carbocy-
clic backbone 1 in order to obtain a ground-state axial rich
disposition of the hydroxy groups.[2] As a part of this ongo-
ing research, we recently reported the crystal packing in
bicyclic, C2h-symmetric hexol 2, having a novel all axial dis-
position of the six hydroxy functionalities.[2d] Intramolecu-
lar H-bonding between the 1,3-diaxial OH groups in 2 pre-
ordained the positions of the intermolecular O–H···O hy-
The deterministic role played by intramolecular O–H···O
hydrogen bonding in the supramolecular assembly of 2
prompted us to study the crystal packing of diastereomeric
perhydro-2,3,4a,6,7,8a-naphthalenehexols 3–5, all confor-
mationally locked like 2 owing to their elaboration on a
trans-decalin scaffold. Polyols 3–5 were conceptualized with
the intent of severing the end-to-end cooperative intramo-
lecular O–H···O–H hydrogen-bonding chain on both faces
of the molecule, as observed in 2, through an axial–equato-
rial transposition of one or more of the peripheral hydroxy
groups (Figure 2). With increased freedom now allowed to
[a] Department of Organic Chemistry, Indian Institute of Science,
Bangalore 560012, India
Fax: +91-80-23600283
E-mail: gm@orgchem.iisc.ernet.in
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2009, 123–131
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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G. Mehta, S. Sen
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hydrogen bonds (Figure 1). In this context, the present
study analyzes the extent to which the supramolecular as-
semblies of isomeric hexols 3–5 correlate with or differ from
each other.
Figure 1. One of the packing modes proposed and observed experi-
mentally for hexol 2. Note that the H-bonding pattern involves all
donor/acceptor oxygen atoms and incorporates infinite chains of
O–H···O bonds.
the OH groups in the choice of their H-bonding partners,
in comparison to 2, crystal packing in polycyclitols 3–5 was
expected to evolve from the simplistic model of hydrogen
bonding proposed and observed for 2 to invoke more com-
plex patterns of self-assembly mediated through O–H···O
Results and Discussion
Synthesis of Isomeric Hexols 3–5
Synthesis of Cs-symmetric hexol 3 commenced from
trans-diol 6, conveniently prepared from Birch reduction
product 7 of naphthalene according to an earlier reported
procedure.[4] Catalytic OsO4 mediated exhaustive dihydrox-
ylation of 6 furnished 3, which was isolated from the reac-
tion mixture as tetraacetate 8. Exposure of 8 to K2CO3/
MeOH gave hexol 3 in quantitative yield (Scheme 1).
Though tlc and spectroscopic means of characterization
pointed towards hexol 3 being the sole product of the dihy-
droxylation step, a miniscule amount (Ͻ0.01 mg) of iso-
meric hexol 4 could be isolated as a sole crystal from one
of the crystallization batches of 3, carried out on a 25-mg
scale.[5]
Scheme 1. Reagents and conditions: (a) Ref.[4]; (b) (i) OsO4 (5 mol-
%), NMMO, acetone/water (4:1), room temp., 8 h; (ii) Ac2O,
DMAP, room temp., 6 h, 60% over two steps; (c) K2CO3, MeOH,
room temp., 5 h, quant. [Note: a trace amount of hexol 4 was also
formed during the dihydroxylation step].[5]
syn-Diol 9, obtained upon regioselective dihydroxylation
of 7 at low temperature, formed the starting material for
the synthesis of hexol 5.[6] Exhaustive epoxidation of 9 with
m-CPBA, followed by mild acid-catalyzed ring opening in
the mixture of diepoxides thus obtained, afforded 5 as a
single diastereomer. In order to facilitate purification of po-
lar hexol 5, the latter was first converted into tetraacetate
Figure 2. Modes of intramolecular O–H···O hydrogen bonding
most likely to be observed in hexols 3 (a), 4 (b) and (c), and 5 (d–
g). In proposing the H-bonding patterns (b) and (c), it was assumed
that Ci-symmetric hexol 4 occupies a crystallographic inversion
center.[2d,3]
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Comparative Study of Supramolecular Assemblies
10, from which polyol 5 was regenerated almost quan-
titatively
through
base-catalyzed
transesterification
(Scheme 2).[5b]
Scheme 2. Reagents and conditions: (a) Ref.[6]; (b) m-CPBA,
CH2Cl2, room temp., 3 h; (c) (i) 10% AcOH (aq.), 55 °C, 4 h; (ii)
Ac2O, DMAP, room temp., 6 h, 75% over steps (b) and (c); (d)
K2CO3, MeOH, room temp., 6 h, quant.
Figure 3. ORTEP diagram of hexol 3, with the atom numbering
scheme for the asymmetric unit. Displacement ellipsoids are drawn
at the 50% probability level, and H atoms are shown as small
spheres of arbitrary radii. The grey dotted lines indicate the intra-
molecular O–H···O hydrogen bonds.
X-ray Crystallographic Studies on Hexols 3–5
Crystals of isomeric hexols 3 and 5, suitable for single-
crystal X-ray crystallography, were grown under ambient
temperature and pressure from their solutions in methanol/
ethyl acetate (1:1) by slow solvent evaporation. As described
in the preceding section, a tiny block-like single crystal of
hexol 4 was obtained in one of the crystallization batches
of 3, and it was used in toto for the X-ray diffraction stud-
ies. The details of the packing patterns in polycyclitols 3–5,
as gleaned from analysis of their respective crystal data (see
Table 4), are discussed below.
Crystal Structure of Hexol 3
Achiral, Cs-symmetric hexol 3 packed in the chiral ortho-
rhombic space group P212121 (Z = 8).[7] The 1,3-diaxial hy-
droxy groups in both of the two symmetry independent
hexol molecules (arbitrarily designated as A and B) in the
asymmetric unit participate in intramolecular O–H···O hy-
drogen bonding (Figures 2a and 3). Intermolecular O–
H···O hydrogen bonding, involving O1···O11 (AǞB),
O11···O3 (BǞA), O12···O2 (BǞA), and O7···O8 (BǞB),
link the hexol molecules in a ···BǞBǞAǞBǞBǞAǞB···
arrangement to form helical molecular chains, growing es-
sentially parallel to the longest c axis (Figure 4). The heli-
ces, translated along the a axis, are further connected by
hydrogen bonds involving O5···O2 (AǞA), O2···O6
(AǞA), and O8···O12 (BǞB) to form H-bonded tapes.
These molecular tapes then interconnect with each other
along the b axis through the intermediacy of a “connector”
A molecule with O6···O4 hydrogen bonds to generate an
intricate three-dimensional supramolecular assembly (Fig-
ure 5, Table 1). Interestingly, an alternate tracing of the O–
H···O hydrogen bond connectivity between the helices
along the b axis reveal, as shown in Figure 6, a complex
intertwined double helical self-assembly of the hexol mole-
cules.
Figure 4. Ball-and-stick representation of the molecular packing in
hexol 3, showing details of the helical self-assembly mediated by
O–H···O hydrogen bonds.
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Table 1. Hydrogen bond geometry in hexol 3.[a]
D–H···A
D–H [Å]
H···A [Å] D···A [Å] D–H···A [°]
O1–H1O···O11i
O2–H2O···O6ii
O3–H3O···O4iii
O4–H4O···O5iii
O5–H5O···O2iv
O6–H6O···O4v
O7–H7O···O8vi
O8–H8O···O12ii
O9–H9O···O10iii
O10–H10O···O11iii
O11–H11O···O3vii
O12–H12O···O2vii
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
2.11
1.91
2.26
1.99
2.12
2.00
2.01
1.92
2.04
1.97
1.96
1.96
2.928(3)
2.684(3)
2.827(3)
2.703(3)
2.929(3)
2.806(3)
2.817(3)
2.655(3)
2.736(3)
2.695(3)
2.755(3)
2.766(3)
172
158
127
145
171
170
170
149
142
147
165
170
[a] Symmetry codes: (i) –x + 3/2, –y + 1, z – 1/2; (ii) x – 1, y, z;
(iii) x, y, z; (iv) x + 1, y, z; (v) –x + 2, y – 1/2, –z + 1/2; (vi) x +
1/2, –y + 3/2, –z + 2; (vii) x + 1/2, –y + 3/2, –z + 1.
Figure 5. Molecular packing in hexol 3, showing details of the O–
H···O hydrogen-bonding interconnectivity between the helical
strands, translated along (a) the a axis and (b) the b axis. In both
figures, the constituent A and B molecules of each helix are colored
in light and dark shades of grey respectively. In (b), the arrows
indicate the “connector A molecules”, linking the helices along the
b axis. H atoms bonded to C atoms are omitted for the sake of
clarity.
A novel feature of the molecular packing in crystalline 3
should be noted at this point. It is well known that achiral
molecules prefer to crystallize in centrosymmetric space
groups.[9] In this context, the supramolecular assembly of
hexol 3 is reminiscent of that observed in quartz and γ-
glycine,[10] wherein the chirality of the crystal is derived
from the handedness of the helical assembly of the mole-
cules.[1a,11] Although it is difficult to provide the raison
d’être for the chiral molecular packing of hexol 3, a clue
can still be gleaned from the CSD analysis, carried out by
Figure 6. An intertwined double-helical self-assembly, identified
through an alternate tracing of the O–H···O hydrogen bond con-
nectivity in the crystal structure of hexol 3. Color coding of the A
and B molecules follows from that of Figure 5. The “connector A
molecules” are darkened slightly and indicated by arrows. Notice
that the intermolecular O–H···O hydrogen bonds in the helical
strand on the left thread through the “connector A molecules” and
follow an antiparallel sense in their sequence to those present in
Pidcock on the structural determinants of space group pref- the right helix.
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Comparative Study of Supramolecular Assemblies
erences in achiral molecules.[12] The study had concluded
that conformationally rigid molecules, particularly those
like 3, possessing a mirror symmetry, exhibit an increased
propensity to crystallize in a chiral space group, possibly on
account of the equivalence of an inversion operation, car-
ried out on a Cs symmetric molecule, to a rotation sym-
metry. Although it is interesting to note that hexol 3 sub-
scribes to the choice of space group laid down in the afore-
said CSD analysis, an alternate explanation to the chirality
in the solid-state supramolecular assembly of 3 also exists.
The crystal structure of 3 would have been centrosymmetric
if the translated helical chains, built of molecules following
the 21 symmetry parallel to the a and c axes, ran antiparallel
to each other. However, the helical chains, translated along
the [010] direction, are also threaded through by A mole-
cules that follow the 21 symmetry parallel to the b axis (a
symmetry operation arising from the combination of 21
symmetry parallel to the a and c axes; Figure 5b). This re-
sults in a transmission of polarity among the translationally
related helical chains and eventually culminates in the chiral
molecular self-assembly of hexol 3.
Crystal Structure of the Hemihydrate of Hexol 4
Ci-symmetric hexol 4 crystallized as a hemihydrate in the
centrosymmetric monoclinic space group C2/c (Z = 4).
Analysis of the crystal structure revealed that the asymmet-
Figure 8. Molecular packing in the hemihydrate of hexol 4, show-
ing details of the O–H···O hydrogen-bond interconnectivity in the
ric unit contains two symmetry independent hexol mole- hydrated layers of B molecules.
Figure 7. ORTEP diagram of the hemihydrate of hexol 4, with the
atom numbering scheme for the asymmetric unit. Displacement el-
lipsoids are drawn at the 50% probability level, and H atoms are
shown as small spheres of arbitrary radii. The grey dotted lines
indicate the intramolecular O–H···O hydrogen bonds.
Figure 9. Molecular packing in the hemihydrate of hexol 4, show-
ing details of the O–H···O hydrogen-bond interconnectivity in the
layers of A molecules.
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G. Mehta, S. Sen
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cules (designated arbitrarily as A and B), occupying the in- ures 9 and 10, Table 2). The self-assembly of hexol 4 thus
version centers at (0.25, 0.25, 0) and (0, 0, 0), respectively, exhibits self complexation, wherein layers of A molecules
and a molecule of water lying on the twofold axis passing are sandwiched between and H-bonded to hydrated layers
through (0, 0 0.75; Figure 7). As seen in its sibling 3, the of B molecules.
1,3-diaxial hydroxy groups of hexol 4 participate in intra-
molecular O–H···O hydrogen bonding, and the A and B
Crystal Structure of Hexol 5
The crystal structure of hexol 5 was solved and refined
in the centrosymmetric monoclinic space group P21/n (Z =
8) (Figure 11). The 1,3-diaxial hydroxy groups in both of
molecules correspond to the H-bonded molecular motifs
represented by Figure 2c,b. Each water molecule in the sup-
ramolecular assembly of 4 exhibits a near tetrahedral coor-
dination around the oxygen atom, and is linked to four B
molecules through O–H···O hydrogen bonds, involving the
axial O6 acting as the H-bond donor and the equatorial O4
acting as the H bond acceptor. The vicinal hydroxy groups
of the B molecules link to each other through intermo-
lecular O–H···O hydrogen bonds in a commonly encoun-
tered R2 (10) dimeric motif[13] to form wave-like molecular
2
tapes, growing parallel to the c axis (Figure 8). Sandwiched
between and interconnecting the H-bonded tapes of B
molecules translated along the a axis, through hydrogen
bonds involving O1···O4 and O5···O3, are the A molecules.
The A molecules are also H-bonded (O2···O1) to each other
to exhibit a centrosymmetric tetrameric arrangement of the
hexol molecules, reminiscent of that observed in 2 (Fig-
Figure 11. ORTEP diagram of hexol 5, with the atom numbering
scheme for the asymmetric unit. Displacement ellipsoids are drawn
at the 50% probability level, and H atoms are shown as small
spheres of arbitrary radii. The grey dotted lines indicate the intra-
molecular O–H···O hydrogen bonds.
Figure 10. Self complexation in the hemihydrate of hexol 4. Note
the layers of A molecules sandwiched between layers of hydrated B
molecules.
Table 2. Hydrogen-bond geometry in the hemihydrate of hexol 4.[a]
D–H···A
D–H [Å]
H···A [Å]
D···A [Å] D–H···A [°]
O1–H1O···O4i
0.82
0.82
0.82
0.82
0.82
1.93
1.94
1.92
1.94
1.97
2.745(3)
2.749(3)
2.665(3)
2.757(4)
2.784(3)
2.976(4)
2.982(4)
178
168
150
171
169
O2–H2O···O1ii
O3–H3O···O2iii
O4–H4O···O6iv
O5–H5O···O3iii
O6–H6O···O1Wv,vi
O1W–H1W···O4vii
0.82
0.78(5)
2.26
2.27(5)
146
152(4)
[a] Symmetry codes: (i) –x + 1/2, y – 1/2, –z + 1/2; (ii) –x + 1/2, y
+ 1/2, –z + 1/2; (iii) x, y, z; (iv) x, –y, z + 1/2; (v) x – 1, y, z – 1; Figure 12. Molecular packing in hexol 5. The A and B molecules
(vi) –x + 1, y, –z + 1/2; (vii) –x + 1, –y + 1, –z + 1. are colored in light and dark shades of grey, respectively.
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Comparative Study of Supramolecular Assemblies
the two symmetry independent hexol molecules in the
To summarize, the results on the self-assembly of three
asymmetric unit, arbitrarily designated as A and B, partici- conformationally locked polycyclitols, crafted through ax-
pate in intramolecular O–H···O hydrogen bonding and ex- ial–equatorial transposition of hydroxy groups, clearly es-
hibit the H-bonding patterns depicted in Figure 2d,f. Inter- tablish that supramolecular assemblies can evolve along
molecular O–H···O hydrogen bonding, involving O3···O7 separate paths on account of subtle stereochemical varia-
(AǞB), O6···O6 (AǞA), O10···O11 (BǞB), and O12···O4 tion in their hydroxylation pattern while still conforming to
(BǞA),
link
the
hexol
molecules
in
a
the core concepts of H-bonding, identified in the crystal
···BǞBǞAǞAǞBǞB··· arrangement to form zigzag structures of alcohols and sugars. In addition to advancing
tapes, growing essentially parallel to the longest b axis. The the understanding of the modalities of molecular packing
molecular tapes, translated along the [101] direction, are mediated through O–H···O hydrogen bonding, the present
linked through H-bonds involving O9···O12 and O10···O11 study also points to the importance of crystal structures of
to form sheets, which are in turn hydrogen bonded “locked” polycyclitols as promising leads for the identifica-
(O4···O1) along the c axis (Figure 12, Table 3).
tion of novel supramolecular synthons.
Table 3. Hydrogen bond geometry in hexol 5.[a]
Experimental Section
D–H···A
D–H [Å]
H···A [Å]
D···A [Å] D–H···A [°]
Synthesis of Hexol 3: To a solution of trans-diol 6 (200 mg,
1.205 mmol) in acetone/water (4:1, 2 mL) was added a catalytic
amount of solid osmium tetroxide (15 mg, 5 mol-%), followed by
4-methylmorpholine N-oxide (50 wt.-% in water, 0.850 mL,
3.614 mmol). The resulting solution was allowed to stir at ambient
temperature for 8 h, after which the reaction was quenched by the
addition of solid sodium bisulfite (600 mg). The mixture was then
diluted with acetone to precipitate the inorganic salts, and filtered
through a short pad of Celite. After washing the filter bed thor-
oughly with acetone, the combined filtrate and washings were con-
centrated under reduced pressure to obtain crude hexol 2 as a
gummy mass. Compound 2 underwent acetylation in the presence
of acetic anhydride (1 mL) and 4-dimethylaminopyridine (600 mg)
at ambient temperature. After completion of the reaction (about
6 h as indicated by tlc), the solution was cooled in an ice bath and
carefully diluted with methanol (2 mL). The volatiles were removed
under reduced pressure, and the crude solid thus obtained was puri-
fied by column chromatography (65% ethyl acetate/petroleum
O1–H1O···O2i
O2–H2O···O3i
O3–H3O···O74ii
O4–H4O···O1iii
O5–H5O···O6i
O6–H6O···O6iv
O7–H7O···O8i
O8–H8O···O9i
O9–H9O···O12ii
O10–H10O···O11iii
O11–H11O···O7i
O12–H12O···O4vi
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
1.98
1.90
1.95
1.93
1.88
2.04
2.08
1.97
1.93
1.95
1.92
1.95
2.670(2)
2.629(2)
2.734(2)
2.741(3)
2.625(3)
2.738(2)
2.768(2)
2.701(2)
2.740(2)
2.765(2)
2.656(2)
2.764(3)
141
158
161
174
171
143
141
147
169
178
148
172
[a] Symmetry codes: (i) x, y, z; (ii) x – 1, y, z – 1; (iii) x, y, z – 1;
(iv) –x + 2, –y, –z + 2; (v) x – 1/2, –y + 1/2, z – 1/2; (vi) x + 1, y,
z + 1.
Concluding Remarks
ether) to afford tetraacetate 8 (290 mg, 60%). IR (thin film): ν =
˜
1
3460, 1732 cm–1. H NMR (300 MHz, CDCl3): δ = 5.39–5.14 (m,
The present study compares the modes of self-assembly
in hexols 3–5, all of which are formally diastereomers of
perhydro-2,3,4a,6,7,8a-naphthalenehexol, constructed on a
conformationally locked trans-decalin scaffold. On a cur-
sory glance, each hexol would appear individualistic, dif-
fering from its siblings in the pattern of O–H···O hydrogen
bonding and complexity of its crystal packing. However,
upon closer analysis, two salient features of commonality
emerge in the self-assemblies of the three hexols under
study, namely, (a) maximization of the total number of hy-
drogen bonds per molecule by using as many donor/ac-
ceptor oxygen atoms as possible and (b) maximization of
cooperativity by forming as many finite and infinite chains
of hydrogen bonds as possible. These two general concepts
of O–H···O hydrogen bonding, proposed by Jeffrey and
Saenger for carbohydrates, were in fact at the crux of our
arguments in proposing the pattern of hydrogen bonding,
most likely to be observed in the crystal structure of 2.[1c,2d]
The fact that the asymmetric unit of all three hexols under
study contains two symmetry independent molecules
should also be noted and compared with the crystal struc-
ture of 2 in which ZЈ = 1/2. It is likely that the awkward
shape of hexols 3–5, resulting from the “bumps” created by
the equatorial hydroxy groups, prevent the molecules from
adopting a simple packing mode.[14]
4 H), 2.35 (dd appearing as a triplet, J = 12 Hz, 2 H), 2.13 (s, 6
H), 2.05–1.98 (m, 8 H), 1.86 (d, J = 16 Hz, 2 H), 1.64 (dd, J = 13,
5 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.6 (2 C),
169.9 (2 C), 75.3, 70.9, 69.3 (2 C), 68.3 (2 C), 35.1 (2 C), 34.4 (2
C), 21.2 (2 C), 21.0 (2 C) ppm. LRMS (ES, 70 eV): m/z = 425 [M
+ Na]+. HRMS (ES): calcd. for C18H26O10Na [M + Na]+ 425.1424;
found 425.1413.
To a solution of pure tetraacetate 8 (150 mg, 0.373 mmol) thus ob-
tained dissolved in dry methanol (1 mL) was added solid potassium
carbonate (206 mg, 1.493 mmol). The reaction mixture was allowed
to stir at room temperature for 5 h. The solvent was then removed
completely under vacuum, and the residue was dissolved in a mini-
mum amount of deionized water. The aqueous solution was passed
through a short column of pretreated DOWEX®50Wϫ8–200 ion-
exchange resin (acidic cation) and washed with deionized water.
The aqueous solution of the product thus obtained was concen-
trated under vacuum to obtain hexol 3 (87 mg) in quantitative
yield. M.p. 232.8–233.3 °C. IR (KBr disc): ν = 3390 cm–1. 1H NMR
˜
(300 MHz, D2O): δ = 3.87–3.84 (m, 4 H), 1.92 (dd appearing as a
triplet, J = 13 Hz, 2 H), 1.83–1.52 (m, 4 H), 1.46 (dd, J = 13, 4 Hz,
2 H) ppm. 13C NMR (75 MHz, D2O): δ = 76.3, 74.3, 70.9 (2 C),
67.9 (2 C), 36.5 (2 C), 36.4 (2 C) ppm. LRMS (ES, 70 eV): m/z =
257 [M + Na]+. HRMS (ES): calcd. for C10H18O6Na [M + Na]+
257.1001; found 257.0998.
Synthesis of Hexol 5: syn-Diol 9 (300 mg, 1.807 mmol) was treated
at ambient temperature with m-CPBA (980 mg, 3.976 mmol, 70%
Eur. J. Org. Chem. 2009, 123–131
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129

G. Mehta, S. Sen
FULL PAPER
purity) in dry dichloromethane (4 mL) for 3 h. The reaction was
then quenched by the addition of saturated aqueous sodium bisul-
fite solution. The product was extracted with dichloromethane
(3ϫ30 mL); the combined extracts were washed successively with
saturated sodium hydrogen carbonate solution and brine and then
dried with anhydrous sodium sulfate. Removal of the solvent af-
forded a crude mixture of diepoxides, which was used directly for
acid-catalyzed ring opening with aqueous acetic acid (10%v/v,
4 mL) at 55 °C. After complete consumption of the staring material
(about 4 h as indicated by tlc), the solvent was removed under re-
duced pressure to furnish crude hexol 5 as a sticky gum. To hexol
5 was added acetic anhydride (2 mL), followed by 4-dimethylami-
nopyridine (883 mg), and the resulting solution was allowed to stir
at ambient temperature for 6 h. The reaction mixture was then co-
oled in an ice bath and carefully diluted with methanol (2 mL).
The volatiles were removed under reduced pressure, and the crude
solid thus obtained was purified by column chromatography (50%
ethyl acetate/petroleum ether) to afford tetraacetate 10 (545 mg,
was, however, allowed to rotate freely about its C–O bond. The
positions of the H atoms of the water molecule in the hemihydrate
of hexol 4 were refined freely, along with an isotropic displacement
parameter (Table 4). CCDC-688248 (hexol 3), -688249 (hexol 4),
and -688250 (hexol 5) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
Table 4. Summary of crystal data, data collection, structure solu-
tion, and refinement details.
3
4
5
Formula
Mr
C10H18O6
234.24
2(C10H18O6)·H2O C10H18O6
486.50
234.24
Crystal size [mm] 0.31, 0.23, 0.21 0.20, 0.17, 0.16
0.39, 0.32, 0.25
monoclinic
P21/n
6.520(2)
38.751(13)
8.715(3)
90
Crystal system
Space group
a [Å]
orthorhombic
P212121
9.279(3)
11.439(3)
20.199(6)
90
monoclinic
P21/n
22.278(5)
6.5821(14)
15.698(3)
90
1
75%). H NMR (300 MHz, CDCl3): δ = 5.49 (d, J = 3 Hz, 1 H),
b [Å]
c [Å]
5.35 (ddd, J = 12, 4, 4 Hz, 1 H), 5.16 (br. s, 1 H), 4.99 (br. s, 1 H),
3.38 (s, 1 H), 3.22 (s, 1 H), 2.48 (dd, J = 14, 4 Hz, 1 H), 2.22–1.64
(m, 19 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.0, 169.6,
169.3, 168.4, 73.6, 71.6, 70.1, 69.9, 69.1, 68.0, 35.6, 33.8, 32.8, 32.0,
21.2, 21.1, 20.9 ppm. LRMS (ES, 70 eV): m/z = 425 [M + Na]+.
HRMS (ES): calcd. for C18H26O10Na [M + Na]+ 425.1424; found
425.1418.
α [°]
β [°]
90
90
111.356(4)
90
2143.8(8)
4
107.640(6)
90
2098.3(12)
8
γ [°]
V [Å3]
2143.9(10)
8
Z
F (000)
1008
1048
1008
ρcalcd. [gcm–3]
µ [mm–1]
Reflns. collected
l.s. Parameters
Unique reflns
Observed reflns
Index range
1.451
0.120
15767
301
2240
1960
–11ՅhՅ11
–13ՅkՅ13
–24ՅlՅ23
0.0362
0.0813
1.086
1.507
0.126
8258
160
2186
1634
–27ՅhՅ27
–8ՅkՅ8
–18ՅlՅ19
0.0645
0.1555
1.013
1.483
0.122
15666
301
3877
2602
–7ՅhՅ7
–46ՅkՅ43
–10ՅlՅ9
0.0514
Pure tetraacetate 10 (200 mg, 0.498 mmol) was taken up in dry
methanol (2 mL) and stirred at ambient temperature with solid po-
tassium carbonate (275 mg, 1.990 mmol) for 6 h. The solvent was
then removed completely under vacuum, and the residue was dis-
solved in a minimum amount of deionized water. The aqueous
solution was passed through a short column of pretreated DOW-
EX®50Wϫ8–200 ion-exchange resin (acidic cation) and washed
with deionized water. The aqueous solution of the product thus
obtained was concentrated under vacuum to obtain hexol 5
R1 [I Ͼ 2σ(I)]
wR2 [I Ͼ 2σ(I)]
Goodness of fit
∆ρmax/min [eÅ–3]
0.1061
1.022
0.291/–0.221
(116 mg) in quantitative yield. IR (KBr disc): ν = 3390 cm–1. 1H
˜
NMR (300 MHz, D2O): δ = 3.89–3.85 (m, 4 H), 2.11 (dd, J = 15,
2 Hz, 2 H), 1.91–1.46 (m, 7 H) ppm. 13C NMR (75 MHz, D2O): δ
= 76.0, 75.0, 70.8, 70.7, 67.4, 36.7, 35.9, 33.4, 32.7 ppm. LRMS
(ES, 70 eV): m/z = 257 [M + Na]+. HRMS (ES): calcd. for
C10H18O6Na [M + Na]+ 257.1001; found 257.1006.
0.189/–0.161
0.220/–0.239
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of hexols 3 and 5.
Crystal Structure Analysis: Single crystal X-ray diffraction data
were collected with a Bruker AXS SMART APEX CCD dif-
fractometer at 291 K. The X-ray generator was operated at 50 KV
and 35 mA by using Mo-Kα radiation. The data was collected with
a ω scan width of 0.3°. A total of 606 frames per set were collected
by using SMART[15] in three different settings of φ (0, 90, and 180°)
keeping a sample-to-detector distance of 6.062 cm and a 2θ value
fixed at –28°. The data were reduced by SAINTPLUS;[15] an empir-
ical absorption correction was applied by using the package SAD-
ABS,[16] and XPREP[15] was used to determine the space group.
The crystal structures were solved by direct methods with the use
of SIR92[17] and refined by full-matrix least-squares methods with
SHELXL97.[18] Molecular and packing diagrams were generated
by using ORTEP32,[19] CAMERON,[20] and MERCURY.[21] The
geometric calculations were done by PARST[22] and PLATON.[23]
All hydrogen atoms were initially located in a difference Fourier
map. The methine (CH) and methylene (CH2) H atoms were then
placed in geometrically idealized positions and allowed to ride on
their parent atoms with C–H distances in the range 0.97–0.98 Å
and Uiso(H) = 1.2Ueq(C). The OH hydrogen atoms were con-
strained to an ideal geometry with O–H distances fixed at 0.82 Å
and Uiso(H) = 1.5Ueq(O). During refinement, each hydroxy group
Acknowledgments
We thank the Department of Science and Technology (DST), India
for the CCD facility at the Indian Institute of Science (IISc), Ban-
galore. We sincerely acknowledge Prof. K. Venkatesan for his criti-
cal comments and helpful advice in preparing the manuscript.
G. M. thanks the Council for Scientific and Industrial Research
(CSIR), India for research support and the award of the Bhatnagar
Fellowship.
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Published Online: November 27, 2008
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