The Selective Silylation of D-Mannitol Assisted by Phenylboronic Acid and the Solid State and Solution Structures of the Intermediate 1,6-bis(silyl) bis(phenylboronates)

Article abstract of DOI:10.1081/CAR-120026598

The influence of phenylboronic acid on the silylation of D-mannitol by TBDMSCl and TBDPSCl has been investigated. Terminal silyation was found to dominate, with PBA significantly enhancing the yield of 1,6 di-TBDMS D-mannitol compared to the control. The

Full text of DOI:10.1081/CAR-120026598

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The Selective Silylation of d‐Mannitol Assisted
by Phenylboronic Acid and the Solid State and
Solution Structures of the Intermediate 1,6‐bis(silyl)
bis(phenylboronates)
Vijaya Bhaskar a e , Angelo D'Elia a , Peter J. Duggan a , David G. Humphrey d , Guy Y.
Krippner b f , Trang T. Nhan a & Edward M. Tyndall c
a School of Chemistry , Monash University , Clayton, Melbourne, Victoria, 3800, Australia
b Biota Chemistry Laboratory , School of Chemistry , Monash University , Clayton,
Melbourne, Melbourne, Victoria, 3800, Australia
c Centre for Green Chemistry , School of Chemistry , Monash University , Clayton,
Melbourne, Victoria, 3800, Australia
d CSIRO Forestry and Forest Products , Private Bag 10, Clayton South, Melbourne, Victoria,
3169, Australia
e Kinacia Pty Ltd. , Level 5, Clive Ward Centre, 16 Arnold St, Box Hill, Melbourne, Victoria,
3128, Australia
f Starpharma Ltd. , Level 6, Baker Heart Research Building, Commercial Road, Prahran,
Victoria, 3181, Australia
Published online: 02 Feb 2007.
To cite this article: Vijaya Bhaskar , Angelo D'Elia , Peter J. Duggan , David G. Humphrey , Guy Y. Krippner , Trang T. Nhan
& Edward M. Tyndall (2003) The Selective Silylation of d‐Mannitol Assisted by Phenylboronic Acid and the Solid State and
Solution Structures of the Intermediate 1,6‐bis(silyl) bis(phenylboronates), Journal of Carbohydrate Chemistry, 22:9, 867-879,
DOI: 10.1081/CAR-120026598
To link to this article: http://dx.doi.org/10.1081/CAR-120026598
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 22, No. 9, pp. 867–879, 2003
The Selective Silylation of D-Mannitol Assisted by
Phenylboronic Acid and the Solid State and
Solution Structures of the Intermediate
1,6-bis(silyl) bis(phenylboronates)
Vijaya Bhaskar,1,# Angelo D’Elia,1 Peter J. Duggan,1,
*
David G. Humphrey,4 Guy Y. Krippner,2,z Trang T. Nhan,1
and Edward M. Tyndall3
2
1School of Chemistry, Biota Chemistry Laboratory, School of Chemistry, and
3Centre for Green Chemistry, School of Chemistry, Monash University,
Clayton, Melbourne, Victoria, Australia
4CSIRO Forestry and Forest Products, Melbourne, Victoria, Australia
ABSTRACT
The influence of phenylboronic acid on the silylation of D-mannitol by TBDMSCl and
TBDPSCl has been investigated. Terminal silyation was found to dominate, with PBA
significantly enhancing the yield of 1,6 di-TBDMS D-mannitol compared to the
control. The intermediate 1,6-disilyl bis(phenylboronates) showed unusually high
stability, such that oxidative conditions were required to cleave the boronate esters.
X-ray crystal structures of both bis(phenylboronates) were determined, revealing both
diboronate esters to exist as two fused six-membered rings. The results of 11B NMR
experiments suggest that these structures also predominate in solution, whereas the
#Current address: Kinacia Pty Ltd, Melbourne, Victoria, Australia.
*
Correspondence: Peter J. Duggan, School of Chemistry, Monash University, Clayton, Melbourne,
Victoria, 3800, Australia; E-mail: peter.duggan@sci.monash.edu.au.
zCurrent address: Starpharma Ltd, Prahran, Victoria, Australia.
867
DOI: 10.1081/CAR-120026598
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2003 by Marcel Dekker, Inc.

868
Bhaskar et al.
bis(phenylboronate) ester of D-mannitol itself exists as a mixture of five-membered
and six-membered cyclic boronates.
Key Words: Silylation; Mannitol; Boronate; Phenylboronic acid;
1,3,2-Dioxaborolane.
INTRODUCTION
The use of boronic acids as protective agents in organic synthesis was pioneered by
Ferrier and others in the 1960’s and 70’s,[1] and articles describing the use of boronic
acids in this way, and as catalysts for a range of organic transformations, have appeared
intermittently in the intervening years.[2] Our interest in the development of synthetic
procedures that require minimal manipulation and purification steps led us to examine
the selective terminal acylation and alkylation of open chain 1,2,3-triols, assisted by
phenylboronic acid (PBA).[3] These reactions were carried out in a single pot, yielding
analytically pure products in moderate yield, without the need for chromatography or
formal recrystallisation steps. In some cases, PBA could be recovered for re-use. The
structures of the intermediate boronate esters prior to and post derivatisation were not
determined.a
Here we report an extension of this work to the selective 1,6-silylation of D-
mannitol. We have found that the introduction of bulky, hydrophobic silyl ethers onto
the terminal oxygens of D-mannitol results in a significant stabilisation of the inter-
mediate diboronate esters such that recovery of the PBA after completion of the re-
action sequence becomes difficult. However, this added stability has allowed us to
determine the solid-state crystal structures of two intermediate silylated boronate esters,
1 and 2.
RESULTS AND DISCUSSION
Silyation Reactions
Silyl ethers, particularly tert-butyldimethylsilyl ether (TBDMS) and tert-butyldi-
phenylsilyl ether (TBDPS) are used extensively in organic synthesis for the protection
of hydroxyl groups.[5,6] Most procedures for the formation of these ethers involve the
reaction of an alcohol with the appropriate silyl chloride in the presence of a base, such
as imidazole. When the substrate is a polyol, regioselectivity is governed by a balance
between the steric requirements of the bulky TBDMS or TBDPS groups and the nu-
cleophilicity of the hydroxyl groups. The TBDMS protecting group is sometimes
preferred over TBDPS due to its ease of removal. Procedures for the clean preparation
aThe crystal structure of the bis(phenylboronate) of D-mannitol-1,6-dibenzoate, which had been
prepared from D-mannitol by direct benzoylation followed by condensation with phenylboronic acid
has recently been reported.[4]

Selective Silylation of D-Mannitol
869
Scheme 1. Preparation of D-mannitol 1,6-bis(silyl) bis(phenylboronates) and subsequent oxidative
cleavage to D-mannitol 1,6-bis(silylethers).
of the 1,6-diTBDPS ether of D-mannitol (4) have been reported,[7,8] but not for the
corresponding diTBDMS ether (3).
In the present study, solutions of the bis(phenylboronate) of D-mannitolb were
prepared by azeotropic removal of water from a mixture of D-mannitol, two equivalents
of phenylboronic acid (PBA), toluene and N,N-dimethylformamide (DMF). The toluene
was then evaporated, the reaction mixture cooled to 0ꢀC, and imidazole then the silyl
chloride (TBDMSCl or TBDPSCl) was added. Extraction with dichloromethane fol-
lowed by concentration yielded the pure, crystalline 1,6-bis(silyl) D-mannitol bis(phe-
nylboronates) (1 and 2, Scheme 1). In contrast to the 1,6-bis(benzyl) and 1,6-
bis(octanoyl) D-mannitol bis(phenylboronates) obtained in our previous study,[3] both
the 1,6-bis(tert-butyldimethylsilyl) D-mannitol bis(phenylboronate) 1 and the 1,6-bis-
(tert-butyldiphenylsilyl) D-mannitol bis(phenylboronate) 2 were found to be very stable
towards alkaline hydrolysis. Other common techniques used for the cleavage of phe-
nylboronates,[2] such as trans-esterification with neopentylglycol or pinacol also had no
effect on 1 and 2. Instead, the cleavage of these phenylboronates required oxidative
conditions.[2] The presence of terminal bulky and lipophilic silyl groups clearly sta-
bilises these bis-boronates towards nucleophilic attack from hydroxide and alcohols.
Although the oxidation step, which employs hydrogen peroxide, is a very clean process,
it precludes the recovery of PBA, as the boronates are converted irreversibly to phenol
and the readily hydrolysed borates.
In order to evaluate the ability of PBA to enhance the selectivity of silylation of D-
mannitol, identical silylation reactions were performed, with the omission of PBA. The
1
crude reaction mixtures thus obtained were analysed using H NMR spectroscopy and
pre-calibrated electrospray mass spectrometry.c In the reaction that employed
TBDMSCl as the silylating agent, a crude yield of 65% was obtained (cf. 96% for 1),
with two silylated products, the disilylated D-mannitol 3 and a tri-silyated D-mannitol,
present in a ratio of 1.6:1.0, accounting for ꢀ90% of the reaction mixture. In the
reaction that employed TBDPSCl as the silylating agent, a crude yield of 78% was
bFor a preliminary discussion of the structure of the intermediate phenylboronate esters of D-
mannitol see footnote 12 in Ref. [3].
cRelative peak intensities can give an indication of relative abundance of components in a mixture
if the components give similar responses in the spectrometer and, as was the case here, there are
few or no fragment ions.

870
Bhaskar et al.
Figure 1. ORTEP view of 1 with 50% thermal ellipsoids.
Figure 2. ORTEP view of 2 with 50% thermal ellipsoids. The two acetone molecules of
crystallisation have been omitted for clarity.

Selective Silylation of D-Mannitol
871
Table 1. Selected bond angles (ꢀ) with standard deviations
in parentheses for compounds 1 and 2.
Bonds
1
2
C7B1O3
O3B1O2
O2B1C7
C13B2O5
O5B2O4
O4B2C13
118.0(2)
123.0(2)
119.0(2)
118.8(2)
123.5(2)
117.7(2)
119.0(2)
123.6(2)
117.4(2)
116.9(2)
123.8(2)
119.4(2)
obtained (cf. 54% for 2), with two silylated products, the disilylated D-mannitol 4 and a
tri-silylated D-mannitol present in a ratio of 10.0:1.0, accounting for ꢀ85% of the
1
reaction mixture. In contrast to these results, H NMR, 13C NMR and microanalysis of
the crude products from both PBA-assisted reactions indicated that in those cases only
bis-silylation had occured.
Solid State Structures of bis(Phenyl Boronates) 1 and 2
Relatively few crystal structures of cyclic trigonal aryl boronates formed from
polyols with more than one potential diol binding site have so far been reported.[4,9–13]
The structures obtained for 1 and 2 provide insight into their formation and an op-
portunity to expand the limited knowledge of the solid state structures of such com-
pounds. Crystals of 1 suitable for x-ray analysis were obtained directly from the crude
product of the PBA assisted silyation of D-mannitol with TBDMSCl. Single co-crystals
of 2 with two moles of acetone were grown by slow evaporation of an acetone solution
of the crude product of the PBA assisted silyation of D-mannitol with TBDPSCl.
ORTEP diagrams and numbering schemes for 1 and 2 are shown in Figures 1
and 2 respectively.
Compounds 1 and 2 were found to have very similar solid state structures, with
two six-membered dioxaboroline rings fused onto a mannitol backbone, and with two
pseudo-tetrahedral silyl-ether substituents at the terminal positions. The coordination at
all boron centres is distorted trigonal planar with mean bond angles over both structures
being C–B–O 118.3(9)ꢀ and O–B–O 123.5(3)ꢀ (Table 1). The B–O interatomic
˚
Table 2. Selected boron atom bond lengths (A) with
standard deviations in parentheses for 1 and 2.
Bond
1
2
C7B1
B1O3
B1O2
C13B2
B2O5
B2O4
1.560(2)
1.363(2)
1.365(2)
1.562(3)
1.369(2)
1.365(2)
1.570(3)
1.366(2)
1.365(2)
1.566(3)
1.361(2)
1.372(2)

872
Bhaskar et al.
Table 3. Dihedral angles (ꢀ) between selected
mean planes for 1 and 2.
Planes
1
2
1 vs. 2
1 vs. 3
2 vs. 4
5 vs. 3
5 vs. 1
6 vs. 4
6 vs. 2
86.1
4.9
4.2
9.1
5.7
2.3
3.3
86.1
8.4
5.1
9.4
3.5
6.6
4.5
See Table 4 for definition of planes.
˚
distances are typical for such trigonal aromatic boronates (1.361–1.372 A, Table 2,
[14]
˚
compares with the Cambridge Structural Database mean B(3)–O(2) 1.367 A)
as are
the ipso-C–B bond lengths (1.560–1.570 A, Table 2, compares with the Cambridge
˚
[14]
˚
Structural Database mean B(3)-Car 1.556 A).
The six-membered rings in both
structures are almost planar, with one atom, C3 for the ring containing B1, and C4 for
the ring containing B2, lying slightly outside of the main plane. The mean planes
defined by the aryl rings (Planes 1 and 2, Tables 3 and 4) diverge from the backbone
with an angle of 86.1ꢀ for both 1 and 2.
The high degree of co-planarity observed between the boronate aromatic rings and
the corresponding planes defined by ipso-C–BO2 (dihedral angles range from 4.2–8.4ꢀ,
Table 3) in 1 and 2 indicate a general overlap of aromatic p-electrons with the vacant
p-orbital of boron. This type of co-planarity has been observed in related bor-
onates.[4,10,11,15]
The six-membered boronate rings observed for the solid state structures of 1 and 2
contrast with the three five-membered boronate rings observed in the tris(phenyl-
boronate) ester of D-mannitol (5, Figure 3) which crystallizes exclusively from an
aqueous methanol solution of D-mannitol and one or two equivalents of PBA.[9,16,17]
The presence of six-membered boronate rings in 1 and 2 is, however, consistent with a
similar solid state structure obtained by Shinkai and co-workers[11] of a 1:2 threitol-aryl
boronic acid diester (6) which also showed exclusive formation of six-membered
boronate rings. The presence of six-membered boronates in 1 and 2 is also consistent
Table 4. Definition of planes listed in Table 3.
Plane number
Definition
1
2
3
4
5
6
C7B1O2O3
C13B2O4O5
C7C8C9C10C11C12
C13C14C15C16C17C18
C2C3C4O3B1O2
C3C4C5O5B2O4

Selective Silylation of D-Mannitol
873
Figure 3. Tris(phenylboronate) ester formed from D-mannitol (5)[9] and bis(phenylboronate) ester
formed threitol (6). (From Ref. [11].)
with the view that, due to ring strain, six-membered trigonal boronate esters are more
stable, and hence more readily formed than five-membered esters.[1,2]
The IR spectra (KBr) for 1 and 2 show characteristic B–O absorption bands[18] at
1338 cmÀ 1 and 1334 cmÀ 1, respectively, which are at lower frequencies to the B–O
stretch for the tris(phenylboronate) ester of D-mannitol (5)d at 1355 cmÀ 1. These
[11]
findings are also consistent with similar observations by Shinkai et al.
who found
that the B–O stretch for a six-membered boronate appeared at a lower frequency than
the B–O stretch for an electronically similar five-membered boronate.
Solution Structures of Phenylboronates Derived
Directly or Indirectly from D-Mannitol
Shinkai et al.[11] have used 11B NMR spectroscopy to great effect to characterise,
in CDCl3 solution, the ring size of the cyclic boronates present in 6. They found that in
electronically similar model compounds, the 11B NMR signal for a five membered
boronate occurred at a chemical shift more than 4 ppm higher than the corresponding
six-membered boronate, and concluded that 6 existed mainly as the six-membered
bis(arylboronates) in solution, as its 11B NMR signal was closer in chemical shift to the
six-membered model boronate. Following Shinkai’s example, we have identified the
ring sizes of the cyclic boronates present in solutions of 1 and 2. The 11B NMR signals
produced by these compounds, when dissolved in CDCl3, were broad and were both
centred at 30 ppm. The signal for the electronically similar tris(phenylboronate) (5),
was also broad in CDCl3 but appeared at 35 ppm. These chemical shifts are consistent
with the conclusion that, analogous to their solid state forms, in solution, 1 and 2 exist
predominantly as six-membered boronates, whereas the tris(phenylboronate) (5) exists
with five-membered boronate rings. The broadness of the peaks is presumably due to
fluxional behaviour of these esters in solution.
The 11B NMR signal in CDCl3 of the 1:2 mannitol-PBA ester,e likely to be similar
in nature to the initial bis(phenylboronate) of D-mannitol formed in the silylation
d5 was synthesized by a similar method to that used by Kuivila et al.[17] and recrystallized
from methanol.
eThis compound was synthesized by the azeotropic removal of water from a suspension of 3/2 equiv
PBA anhydride and 1 equiv D-mannitol in toluene, followed by removal of the solvent.

874
Bhaskar et al.
Figure 4. Possible bis(phenylboronate) esters formed with D-mannitol.
reactions, as well as in previously reported acylation and alkylation reactions,[3] was
also broad and located at 33 ppm. This intermediate chemical shift suggests that,
consistent with previous findings,b in solution, the bis(phenylboronate) of D-mannitol is
in equilibrium between structures containing five- and six-membered boronate rings
(Figure 4). Coordination of the free hydroxyl groups with the boron atoms in these
bis(phenylboronate) esters, in which the boron atoms would tend towards a tetrahedral
configuration, appears unlikely, as this would produce significantly lower 11B NMR
chemical shifts. In the silylation reactions of this mixture of bis(phenylboronate) esters,
the disilyl ethers (1 and 2) result from the reaction of the silyl chlorides with the more
reactive primary hydroxyl groups present in four of the transient bis(phenylboronate) D-
mannitol esters shown in Figure 4. The unassisted silylation reactions of D-mannitol
show some selectivity towards terminal derivitisation, but the effect of the esterification
of this polyol with PBA is to further shield its secondary hydroxyl groups from attack
by the silyl chloride, thus leading to enhanced 1,6-selectivity.
CONCLUSIONS
The condensation of D-mannitol with two equivalents of PBA followed by sily-
lation with TBDMSCl and TBDPSCl produces two unusually stable bis(phenylbor-

Selective Silylation of D-Mannitol
875
onates) (1 and 2) which were characterised in the solid state by x-ray crystallography. It
was found that both esters exist as two fused six-membered rings. These findings are
consistent with the structure previously determined for the threitol derivative (6),[11] but
contrast with that of the tris(phenylboronate) ester of D-mannitol (5),[9] which possesses
isolated five-membered cyclic boronates. The results of 11B NMR experiments with 1,
2 and 5 suggest that in CDCl3 solution, these esters possess similar ring structures to
those observed in the solid state, whereas the intermediate bis(phenylboronate) formed
prior to silylation exists as a mixture of five- and six-membered cyclic boronates. The
high stability of 1 and 2 and excellent organic solubility suggests that they may have
application as novel chiral hosts for bi-dentate Lewis bases, and as chiral catalysis for a
range of organic transformations.[2]
Oxidative deprotection of 1 leads to the disilylated D-mannitol (3) in higher yield
(60% isolated yield from D-mannitol) and purity than that obtained from direct sily-
lation of D-mannitol with TBDMSCl (ꢀ36% conversion with significant contamination
from the tri-silylated product). In contrast, disilylation of D-mannitol with TBDPSCl
proceeds with higher yield if PBA is omitted from the reaction mixture (ꢀ60% con-
version cf 33% isolated yield of 4 from the two-step procedure) although some con-
tamination with the tri-silylated product is still observed. Thus, the use of PBA
provides the advantage of a cleaner product in the synthesis of the di-TBDPS ether of
D-mannitol (4), and significantly improves the preparation of the corresponding
diTBDMS ether (3), in terms of yield and product purity.
EXPERIMENTAL
General remarks and instrumentation. All non-specialized starting materials
were commercially available research-grade chemicals and were used without further
purification. All solvents were used as supplied except dimethyl formamide, which was
˚
dried over 4 A molecular sieves prior to use. TLC was performed on silica coated
plastic sheets (Macherey-Meigel Polygram SilG/U.V. 254). Plates were viewed using
either Ultraviolet Light (254 nm) or iodine to visually develop the spots. Melting points
of solid compounds were measured on a Stuart Scientific SMP3 capillary tube melting
point apparatus and are uncorrected. Microanalyses were performed by Campbell
Microanalytical Laboratory, University of Otago, Dunedin, New Zealand. IR spectra
were recorded on a Perkin Elmer 1600 Series Fourier Transform Spectrophoto-
meter. Samples were run as neat oils or nujol mulls on sodium chloride plates or as
KBr disks.
1H and 13C NMR spectra were recorded on a Varian 300 MHz spectrometer using
CDCl3 as the solvent and tetramethylsilane (TMS) as the internal standard (d 0.00). 11B
NMR spectra were recorded on a Bruker 400 MHz spectrometer using CDCl3 as the
solvent and BF3 Á Et2O as an external standard. High-resolution mass spectra were
recorded on a Bruker BioApex 47e Fourier Transform mass spectrometer. Samples
were dissolved in methanol and ionized using an electrospray ionisation (ESI) source.
X-Ray data were collected at 123(1) K on an Enraf–Nonius Kappa CCD single crystal
˚
diffractometer with Mo-Ka radiation (l = 0.71073 A). The structures were solved by
direct methods with SHELXS-97 and refined by full or block matrix least-squares on

876
Bhaskar et al.
F2 using SHELXS-97 within the interface WinGX-Version 1.64.03b.[19] All non-hy-
drogen atoms were refined anisotropically, and C–H hydrogen positions included as
invariants at geometrically estimated positions.f
D-Mannitol 1,6-Di-(tert-butyldimethylsilyl)-2:4, 3:5-O2:O4,O3:O5bis(phenyl-
boronate) (1). Under an atmosphere of nitrogen, a solution of D-mannitol (5.0 g, 28
mmol) and phenyl boronic acid (6.8 g, 55 mmol) in DMF (300 mL) and toluene (300
mL) was heated under reflux for 2 h, with azeotropic removal of water. The toluene
was then distilled from the reaction mixture and the resulting solution cooled to 0 ꢀC.
Imidazole (11.2 g, 165 mmol) was then dissolved into the stirring solution, followed by
the addition of TBDMSCl (9.3 g, 62 mmol). The reaction mixture was allowed to warm
to room temperature and stirred for 2 days. Following the addition of water (1250 mL),
the reaction mixture was extracted with dichloromethane. The organic layers were
washed with water then brine and dried over MgSO4. After removal of the solvent in
vacuo, the product was obtained in high purity as a viscous brown oil (15.4 g, 96%).
Upon standing for several weeks, the oil crystallized to form large orange/brown
prismatic crystals suitable for X-ray diffraction; mp 57–62 ꢀC. IR (KBr disk): n
[cmÀ 1] = 2933 (C—H), 2859 (C—H), 1602 (C=C), 1444 (B—C), 1338 (B—O), 1304
(C—O), 1257 (Si—Me), 1146 (C—O), 1128, 1094 (Si O), 838 (Si—Me), 779, 699,
1
647. H NMR (300 MHz; CDCl3) d = 7.79–7.84 (m, 4H, oArH), 7.36–7.43 (m, 2H,
pArH), 7.27–7.35 (m, 4H, mArH), 4.70–4.72 (m, 2H, 3-H, 4-H), 4.37–4.43 (m, 2H, 2-
H, 5-H), 3.94 (dd, J1a,2 = 3.4 Hz, J1a,1b = 10.8 Hz, 2H, 1a-H, 6a-H), 3.88 (dd,
J1b,2 = 5.7 Hz, J1b,1a = 10.8 Hz, 2H, 1b-H, 6b-H), 0.89 (s, 18H, SiC(CH3)3), 0.09 (s,
6H, 2 Â SiCH3), 0.04 (s, 6H, 2 Â SiCH3). 13C NMR (75MHz, CDCl3) 134.1 (oC-
arom.), 130.8 (pC-arom.), 127.5 (mC-arom.), 75.1 (C-2, C-5), 66.9 (C-3, C-4), 64.2
(C-1, C-6), 26.0 (SiC(CH3)3), 18.4 (SiC), À5.3 (SiCH3), À5.4 (SiCH3). C–B signals not
observed due to broadening.
Anal. Calcd for C30H48B2O6Si2: C, 61.86; H, 8.31. Found: C, 61.88; H, 8.15.
Crystal structure determination of 1: C30H48B2O6Si2, Mr = 582.50, ortho-
rhombic, space group P 22121 (no. 18), a = 11.5359(1), b = 11.6136 (1), c = 25.8025
3
3
(1) A; V = 3456.85 A , Z = 4, Dx = 1.119 g/cm , F(000) = 1256, T = 173 K, Enraf
˚
˚
Nonius FR590 diffractometer, graphite monochromator with CCD detector, l(Mo-
Ka) = 0.71073 A, m = 0.14 mm–1, colourless crystal, size 0.21 Â 0.17 Â 0.15 mm3, f
˚
scans with o scans to fit asymmetric unit, 35818 intensities collected 3.61<
q<28.29ꢀ, À13<h<15, À15<k<15, À34<l<34, Lp correction, no absorption correction,
8500 unique intensities (Rint = 0.0392). Structure solved by direct methods, full-matrix
least-squares refinement based on F2 and 361 parameters, all but H atoms refined
anisotropically, H atoms refined with riding model on idealized positions. Refinement
converged at R1(F) = 0.0342, oR2(F2, all data) = 0.0828, S = 1.0230, absolute struc-
ture parameter (Flack) À0.04(7).
fTables of atomic coordinates, bond lengths, and bond angles have been deposited with the
Cambridge Crystallographic Data Centre. These tables may be obtained, on request, from the
Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
Reference numbers; 1: CCDC 201656; 2: CCDC 201657.

Selective Silylation of D-Mannitol
877
D-Mannitol 1,6-Di-(tert-butyldiphenylsilyl)-2:4, 3:5-O2:O4,O3:O5bis(phenyl-
boronate) (2). The title compound was prepared according to the method described
for the preparation of 1, using D-mannitol (2.5 g, 14 mmol), phenylboronic acid (3.4 g,
28 mmol), DMF (150 mL), toluene (150 mL), imidazole (5.6 g, 83 mmol) and
TBDPSCl (8.3 g, 30 mmol). After being allowed to warm to room temperature, the
reaction mixture was stirred overnight. Following the addition of water (750 mL), the
reaction mixture was extracted with dichloromethane. The organic layers were washed
with water then brine and dried over MgSO4. After removal of some of the solvent in
vacuo, the product crystallized as a light tan solid (6.2 g, 54 %); mp 148–149 ꢀC.
Single crystals suitable for X-ray analysis were grown by slow evaporation from an
acetone solution. IR (KBr disk): n [cmÀ 1] = 2932 (C—H), 2858 (C—H), 1601 (C=C),
1472 (C=C), 1444 (B—C), 1428 (C=C), 1334 (B—O), 1303 (C—O), 1151 (C—O),
1
1113 (Si O), 1022, 993, 937, 842, 822, 805, 700, 635, 611, 502. H NMR (300 MHz;
CDCl3): d = 7.86–7.92 (m, 4H, oArH-B), 7.67–7.79 (m, 8H, oArH-Si), 7.29–7.51 (m,
18H, mArH-Si, pArH-Si, pArH-B and mArH-B ), 4.97 (br s, 2H, 3-H, 4-H), 4.42–4.51
(m, 2H, 2-H, 5-H), 4.06 (dd, J1a,1b = 4.5 Hz, J1a,2 = 11.1 Hz, 2H, 1a-H, 6a-H), 3.99 (dd,
J1b,2 = 3.2 Hz, J1b,1a = 11.1 Hz, 2H, 1b-H, 6b-H), 1.06 (s, 18H, Si-C(CH3)3). 13C NMR
(75MHz, CDCl3): d = 135.8, 135.7 (Si-oC-arom.), 134.2 (B-oC-arom.), 133.1, 132.5
(Si-iC-arom.), 130.7 (B-mC-arom.), 130.1, 130.0 (Si-pC-arom.), 128.0, 127.9 (Si-mC-
arom.), 127.6 (B-mC-arom.), 75.0 (C-2, C-5), 67.7 (C-3, C-4), 65.1 (C-1, C-6), 26.9
(Si-C(CH3)3), 19.3 (SiC). C–B signals not observed due to broadening.
Anal. Calcd for C50H56B2O6Si2: C, 72.29; H, 6.79. Found: C, 72.55; H, 7.00.
Crystal structure determination of 2: C56H68B2O8Si2, Mr = 946.94, mono-
˚
clinic, space group P1211 (no. 4), a = 11.8257(1), b = 12.6022 (1), c = 17.8951 (2) A,
3
3
˚
b = 98.273 (1)ꢀ, V = 2639.15 A , Z = 2, Dx = 1.192 g/cm , F(000) = 1012, T = 173 K,
Enraf Nonius FR590 diffractometer, graphite monochromator with CCD detector,
l(Mo-Ka) = 0.71073 A, m = 0.12 mm–1, colourless crystal, size 0.23 Â 0.25 Â 0.20
˚
mm3, f scans with o scans to fit asymmetric unit, 32361 intensities collected
3.08<q<28.29ꢀ, À15<h<15, À 16<k<16, À 21<l<23, Lp correction, no absorption
correction, 12958 unique intensities (Rint = 0.0638). Structure solved by direct methods,
full-matrix least-squares refinement based on F2 and 613 parameters, all but H atoms
refined anisotropically, H atoms refined with riding model on idealized positions.
Refinement converged at R1(F) = 0.0435, oR2(F2, all data) = 0.1018, S = 1.0440,
absolute structure parameter (Flack) À0.08(6).
D-Mannitol 1,6-Di-(tert-butyldimethylsilyl) ether (3). A solution of 1 (0.51 g,
0.88 mmol) in ethyl acetate/acetone (1:1, 20 mL) was treated with aqueous hydrogen
peroxide (30 wt%, 0.54 mL) and the mixture stirred for 4 h. Evaporation of the solvent
yielded a yellow oil containing a white precipitate (0.52 g). A solution of the crude
product in ethyl acetate was washed three times with NaOH (1 moldmÀ 3) then dried
over MgSO4. Removal of the solvent yielded a clear oil which was purified using flash
column chromatography (40% EtOAc/hexane) to give the pure product as a white solid
(0.12 g, 62 %); mp 58–60 ꢀC. [a]2n0 < j1j (c 0.050, CHCl3). IR (nujol): n [cmÀ 1] =
1
3384 (O—H), 1255 (Si—Me), 1111 (Si O), 1058 (C—O), 837 (Si—Me), 777. H
NMR (300 MHz; CDCl3): d = 3.71–3.88 (m, 8H, 1-H, 2-H, 3-H, 4-H, 5-H, 6-H),
3.31–3.38 (br d, J2,OH = 5.7 Hz, 2H, CH2CH(OH), no signal upon D2O exchange),

878
Bhaskar et al.
2.88–2.94 (br d, J3,OH = 3.6 Hz, 2H, CH(OH)CH, no signal upon D2O exchange), 0.90
(s, 18H, Si C(CH3)3), 0.09 (s, 12H, Si(CH3)2). 13C NMR (75MHz, CDCl3): d = 72.3
(C-2, C-5), 71.3 (C-3, C-4), 64.4 (C-1, C-6), 26.0 (Si-C(CH3)3), 18.4 (SiC), À5.2
(Si(CH3)2). MS (ESI, MeOH), m/z: 433.2415 (M + Na+.C18H42O6Si2 Á Na+ requires
m/z, 433.2418).
Anal. Calcd for C18H42O6Si2: C, 52.64; H, 10.31. Found: C, 52.91; H, 10.39.
D-Mannitol 1,6-Di-(tert-butyldiphenylsilyl) ether (4). The diboronate ester 2
(0.61 g, 0.74 mmol) was oxidatively deprotected in an analogous way to 1, using ethyl
acetate/acetone (1:1, 20 mL) and aqueous hydrogen peroxide (30 wt%, 1.3 mL).
Evaporation of the solvent yielded a yellow oil containing a white precipitate (0.82 g).
A similar work-up and purification strategy (35% EtOAc/hexane) as that used for the
preparation of 3 gave 4 as a viscous clear oil (0.30 g, 62 %). [a]2n0 = À3.3 (c 0.03,
CHCl3). IR (film): n [cmÀ 1] = 3415 (O—H), 3071 (C—H), 2931 (C—H), 2858 (C—
H), 1590 (C=C), 1472 (C=C), 1428, 1391, 1362, 1218 (C—O), 1113 (Si O), 1007,
1
824, 758, 741, 702. H NMR (300 MHz; CDCl3): d = 7.63–7.70 (m, 8H, oArH), 7.34–
7.48 (m, 12H, mArH and pArH), 3.76–3.92 (m, 8H, 1-H, 2-H, 3-H, 4-H, 5-H, 6-H),
3.06–3.14 (br s, 2H, CH2CH(OH), no signal upon D2O exchange), 2.80–2.88 (br s, 2H,
CHCH(OH)CH, no signal upon D2O exchange), 1.06 (s, 18H, SiC(CH3)3). 13C NMR
(75MHz, CDCl3): d = 135.67, 135.65 (oC-arom.), 132.9 (iC-arom.), 130.1 (pC-arom.),
128.0 (mC-arom.), 72.5 (C-2 C-5), 71.0 (C-3, C-4), 65.4 (C-1, C-6), 27.0 (SiC(CH3)3),
19.4 (SiC). MS (ESI, MeOH), m/z: 681.3027 (M + Na+. C38H50O6Si2 Á Na+ requires
m/z 681.3044).
Anal. Calcd for C38H50O6Si2: C, 69.26; H, 7.65. Found: C, 69.51; H, 7.99.
ACKNOWLEDGMENTS
This work was funded by Monash University, Biota Holdings Ltd and the Aus-
tralian Research Council. E. M. T. is a recipient of an Australian Postgraduate Award.
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Received April 10, 2003
Accepted August 5, 2003