Glass-catalyzed conversion of boronic esters of asymmetric diols to diol sulfites and amine complexes of boron halides

Article abstract of DOI:10.1021/om001053s

Sterically hindered boronic esters of (R,R)-1,2-dicyclohexyl-1,2-ethanediol or pinanediol react with thionyl chloride and excess imidazole in acetonitrile on a borosilicate glass surface (but not on silica or sodalime glass) to form the corresponding cyclic sulfite of the diol and the easily separable organoborane derivative containing one boron-bound chloride and two imidazole groups, which may cross link with additional organoborane moieties to form oligomeric species. Other heterocyclic amines react similarly but usually less efficiently. With excess pyridine, the 1:1 complex PhBCl₂(py) rapidly forms the 2:1 complex, PhBCl(py)₂⁺Cl^-. Hydrolysis of the amino boron chlorides to boronic acids in near neutral aqueous solution provides a mild process for the net hydrolysis of hindered boronic esters, many of which cannot be hydrolyzed by ordinary means, though yields were only 54-82%. The diol sulfites are stable toward water or aqueous acid but rapidly hydrolyzed by base to the diol and inorganic sulfite.

Full text of DOI:10.1021/om001053s

2920
Organometallics 2001, 20, 2920-2923
Notes
Gla ss-Ca ta lyzed Con ver sion of Bor on ic Ester s of
Asym m etr ic Diols to Diol Su lfites a n d Am in e Com p lexes
of Bor on Ha lid es
Donald S. Matteson,* William C. Hiscox, Levente Fabry-Asztalos,
Gyung-Youn Kim, and William F. Siems, III
Department of Chemistry, Washington State University, Pullman, Washington 99164-4630
Received December 11, 2000
Summary: Sterically hindered boronic esters of (R,R)-
1,2-dicyclohexyl-1,2-ethanediol or pinanediol react with
thionyl chloride and excess imidazole in acetonitrile on
a borosilicate glass surface (but not on silica or soda-
lime glass) to form the corresponding cyclic sulfite of the
diol and the easily separable organoborane derivative
containing one boron-bound chloride and two imidazole
groups, which may cross link with additional organobo-
rane moieties to form oligomeric species. Other hetero-
cyclic amines react similarly but usually less efficiently.
With excess pyridine, the 1:1 complex PhBCl2(py) rapidly
forms the 2:1 complex, PhBCl(py)2+Cl-. Hydrolysis of the
amino boron chlorides to boronic acids in near neutral
aqueous solution provides a mild process for the net
hydrolysis of hindered boronic esters, many of which
cannot be hydrolyzed by ordinary means, though yields
were only 54-82%. The diol sulfites are stable toward
water or aqueous acid but rapidly hydrolyzed by base
to the diol and inorganic sulfite.
esterification in a two-phase system have been used to
sequester the desired boronic acid in a separate phase
from the diol group.2-4,6 Sufficiently exothermic ligand
transfers can overcome the entropic barrier and lead
indirectly to the boronic acid.5,7,8
Resu lts
The present investigation began with the discovery
that (R,R)-1,2-dicyclohexyl-1,2-ethanediol [“(R)-DICHED”]
benzylboronate (1, R ) PhCH2)9 reacts with thionyl
chloride and excess pyridine to form (R)-DICHED sulfite
(2) and a benzylboron dichloride-pyridine complex,
which was later found to contain 2 mol of pyridine (3,
R ) PhCH2). The reaction was faster in acetonitrile than
in dichloromethane, and the sulfite ester 2 could be
extracted with pentane while the polar boron halide
pyridine complex 3 remained in the separate acetonitrile
phase. Hydrolysis of 2 to sulfite ion and free DICHED
was easily accomplished by treatment with aqueous
base. The relatively slow hydrolysis of haloborane
complex 3 to benzylboronic acid with water in acetoni-
trile-d3 was found by NMR to follow good pseudo-first-
order kinetics.
The utility of boronic esters of chiral diols for the
precise control of stereochemistry in asymmetric syn-
thesis is well established.1 Occasions arise in which it
is necessary to hydrolyze or otherwise separate the
boronic acid from the diol to which it is esterified, for
example, to obtain a boronic acid of biomedical interest,2
to avoid interference of the diol fragment with subse-
quent reaction steps,3 to replace the chiral director with
its enantiomer,4 or to obtain a more reactive organobo-
rane intermediate for use in subsequent reactions.5
However, hydrolyses of boronic esters of (R,R)- or (S,S)-
1,2-dialkyl-1,2-ethanediols or pinanediol are thermody-
namically disfavored at synthetically useful concentra-
tions of the boronic esters.3
The model system worked very well, as indicated by
the complete disappearance of the characteristic mul-
1
tiplet at δ 3.82 (2H, CHOB) in the 300 MHz H NMR
Compensation for the thermodynamic barrier has
been achieved in several ways. Various means of trans-
spectrum of DICHED boronate 1 (R ) PhCH2) and the
overnight appearance of the corresponding diaste-
reotopic pair of protons of sulfite ester 2 as two double
doublets at δ 4.07 and 4.58 (2H, CHOS). A number of
* Corresponding author. E-mail: dmatteson@wsu.edu.
(1) (a) Matteson, D. S. Tetrahedron 1998, 54, 10555-10607. (b)
Matteson, D. S. J . Organomet. Chem. 1999, 581, 51-65. (c) Matteson,
D. S. Chem. Rev. 1989, 89, 1535-1551.
(2) Wityak, J .; Earl, R. A.; Abelman, M. M.; Bethel, Y. B.; Fisher,
B. N.; Kauffman, G. S.; Kettner, C. A.; Ma, P.; McMillan, J . L.;
Mersinger, L. J .; Pesti, J .; Pierce, M. E.; Rankin., F. W.; Chorvat, R.
J .; Confalone, P. N. J . Org. Chem. 1995, 60, 3717-3722.
(3) Matteson, D. S.; Man, H.-W.; Ho, O. C. J . Am. Chem. Soc. 1996,
118, 4560-4566.
(4) Matteson, D. S.; Man, H.-W. J . Org. Chem. 1996, 61, 6047-6051.
(5) Brown, H. C.; Rangaishenvi, M. V. J . Organomet. Chem. 1988,
358, 15-30.
(6) Tripathy, P. B.; Matteson, D. S. Synthesis 1990, 200-206.
(7) Matteson, D. S.; Ray, R.; Rocks, R. R.; Tsai, D. J . S. Organome-
tallics 1983, 2, 1536-1543.
(8) (a) Matteson, D. S.; Sadhu, K. M.; Lienhard, G. E. J . Am. Chem.
Soc. 1981, 103, 5241-5242. (b) Matteson, D. S.; Sadhu, K. M.
Organometallics 1984, 3, 614-618.
(9) (a) Pivazyan, A. D.; Matteson, D. S.; Fabry-Asztalos, L.; Singh,
R. P.; Lin, P.; Blair, W.; Guo, K.; Robinson, B.; Prusoff, W. H.,
Biochemical Pharmacology 2000, 60, 927-936. (b) Systematic name:
(R,R)-2-(phenylmethyl)-4,5-dicyclohexyl-1,3,2-dioxaborolane.
10.1021/om001053s CCC: $20.00 © 2001 American Chemical Society
Publication on Web 05/24/2001

Notes
Organometallics, Vol. 20, No. 13, 2001 2921
Ta ble 1. Con ver sion s of (R)-DICHED Bor on ic
Ester s (1) to (R)-DICHED Su lfite (2) a n d
Or ga n obor on Ch lor id e Com p lexes w ith Am in es (3,
6, or Oth er s)
other DICHED boronic esters 1 were screened by NMR
and generally found to react similarly, though reactions
were often incomplete. Imidazole was found to react
faster than pyridine as the amine component.
The more hindered pinanediol phenylboronate 4 (R
) Ph; CHOB δ 4.45) was inert to thionyl chloride and
pyridine but with imidazole was partially converted to
pinanediol sulfites 5 (diastereomeric pair, δ 4.72 and
4.94) and a phenylboron chloride imidazole derivative
6 in a mixture with analogous, more complex products.
R of 1
aminea
t (h)
T (°C)
2 (%)
Ph
Ph
Ph
Ph
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
ima
pya
py
1.5
24
200
170
0.5
24
20
18
48
4
22
55
55
55
22
22
22
22
22
22
22
65
22
22
22
95
67
98
77
99
98
81
21
80
99
99
16
99
68
99
bipya
im
py
Me-ima
pyzla
pyzl
im
(S)-PhCH2CH(CH3)
(R)-PhCH2CH(OCH2Ph)
im
im
im
im
24
(R)-PhCH2CH(c-C6H11
(R)-PhCH2CH(Cl)
)
100
0.5
24
(R)-(c-C6H11)CH(CH3)b
(R)-CH3CH(OCH2Ph)b
Gla ss Su r fa ce Ca ta lysis. Our initial success came
unraveled when a new investigator attempted to define
practical process conditions. No reaction at all occurred
when 1 (R ) PhCH2) was treated with thionyl chloride
from a fresh bottle in anhydrous acetonitrile in a clean
new flask and either anhydrous pyridine or imidazole!
Subsequently, older samples of thionyl chloride with
imidazole produced small conversions of 1 to sulfite
ester 2. Reactions would proceed part way within a few
hours and then stop at some erratic final conversion.
With a recent case of catalysis by a reagent impurity in
mind,10 we tested small amounts of several additives
to the thionyl chloride, including water, sulfuryl chlo-
ride, chlorosulfonic acid, azobis(isobutyronitrile), disul-
fur dichloride, titanium trichloride, and ferrous chloride.
None of these produced any consistent effect. For
example, triplicate reactions in the presence of excess
imidazole and a small amount of ferrous chloride
produced random conversions of 91, 10, and 15%.
The mystery was solved after Professor D. C. Dittmer
suggested glass surface catalysis, with which he had had
previous experience.11 Addition of borosilicate glass
powder (0.1-1 mm particles, 5 times the weight of 1)
to the reaction mixture of 1 (R ) PhCH2) with pyridine
and thionyl chloride resulted in 65% conversion to 2
after 17 h at room temperature. Pyridine and 1 consis-
tently failed to react at all with thionyl chloride in the
absence of a catalyst, and silica gel led to only 5%
conversion. Evidently the first investigator was able to
discover the reaction because he routinely cleaned his
glassware with alcoholic potassium hydroxide and thus
was working with well-etched glass surfaces. As the new
flasks used by the second investigator became scratched,
his reactions began to proceed.
im
24
a
Amines: im, imidazole; py, pyridine; bipy, 2,2′-dipyridyl; Me-
b
im, N-methylimidazole; pyzl, pyrazole. Enantiomer of this com-
pound was used.
only a few percent of additional conversion, as if the
glass surface becomes coated with the reaction products
and consequently inactivated. Glass added after the
reaction has stopped will catalyze only a small amount
of further reaction. Reactions involving pyridine and
DICHED esters are considerably slower, to the point
that they may not go to completion if a (sec-alkyl)boronic
ester is involved. Other bases such as N-methylimida-
zole and pyrazole also react but have not been tested
extensively. Typical conversions of DICHED boronic
1
esters measured by H NMR are summarized in Table
1.
Reactions of pinanediol esters (4) usually fail with
pyridine and are sluggish with imidazole. There is
usually an induction period of a few hours before a
significant amount of reaction occurs. Only partial
cleavage of pinanediol esters has been achieved when
the boron bears a sec-alkyl substituent. Pinanediol
esters provide a particularly sensitive test of catalyst
effectiveness, and soda-lime glass as well as silica
proved inactive. Results with and without added crushed
borosilicate glass are summarized in the Supporting
Information.
MALDI mass spectroscopic analysis of the imidazole-
chloroborane adducts showed molecular fragments con-
taining alkylborane and imidazole units in ratios of 1
to 2, corresponding to the cation of 6. Higher molecular
weight species were also present, indicating bridging of
an imidazole unit between two boron atoms, with the
species having 2 boranes to 3 imidazoles being promi-
nent. Ions from the pyridine derivatives contained 1 or
2 pyridines, and bipyridyl showed only the 1:1 adduct.
Details of the MALDI spectra are summarized in the
Supporting Information.
Although we had no difficulty preparing an analyti-
cally pure sample of the known 1:1 adduct of phenyl-
boron dichloride with pyridine, we were unable to obtain
the 1:2 adduct in satisfactory analytical purity in several
attempts. NMR evidence indicated that the 1:1 adduct
is converted to a 1:2 adduct as soon as more than 1 equiv
of pyridine is added. 2,2′-Dipyridyl yields a 1:1 adduct
with phenylboron dichloride. The inherent complexity
of the imidazole system discouraged any attempt to
isolate its components.
Reactions of DICHED boronic esters 1 with thionyl
chloride do not occur at all in the absence of a hetero-
cyclic amine. Reactions involving DICHED esters and
imidazole are often virtually complete within a few
minutes at room temperature. To get complete conver-
sion, at least 4 mol of imidazole are required. Charac-
teristically, if reactions are not complete within an hour,
stirring the mixture for another day or two produces
(10) Man, H.-W.; Hiscox, W. C.; Matteson, D. S. Org. Lett. 1999, 1,
379-382.
(11) (a) Dittmer, D. C.; Marcantonio, A. F. J . Org. Chem. 1964, 29,
3473-3475. (b) (R-Chloroallylic)boronic esters, which can be useful
synthetic intermediates, are in some cases difficult to make and to
substitute.1b Allylic isomerization on glass surfaces as described by
Dittmer and Marcantonio is a likely side reaction that has been
overlooked.

2922 Organometallics, Vol. 20, No. 13, 2001
Notes
Recover y of Bor on ic Acid a n d Diol. Diol recovery
from the sulfite ester is simple and quantitative.
DICHED sulfite (2) is stable to aqueous acid or neutral
water but very rapidly hydrolyzed by aqueous base.
Extraction with pentane leaves the polar organoboron
dichloride amine adducts in the acetonitrile phase and
extracts 2 into the pentane phase, together with any
unchanged boronic ester. Separation of the polar and
nonpolar products is sometimes more efficient if some
water is added, provided the aqueous acetonitrile phase
is kept acidic to prevent hydrolysis of the diol sulfite.
The organoboron dichloride imidazole adducts are
more resistant to hydrolysis. The overall yield of phe-
nylboronic acid from (S,S)-DICHED phenylboronate
(en t-1, R ) Ph) via refluxing crude 6 (R ) Ph) in
aqueous acetonitrile was 82%. Similar treatment of
other 1 or en t-1 (R ) PhCH2, PhCH2CH(OBn), PhCH2-
CH(Me), cyclohexyl) yielded 54-69% of the correspond-
ing boronic acids.
catalytic activities of silica and glass are comparable and
may be attributed to hydroxyl groups on the surfaces.
Glass, quartz, or silica surfaces are covered with Si-
OH groups at an estimated packing density ∼4.7/100
Å2.16 It is plausible that a boronic ester bound diol might
exchange to a tricoordinate boron oxide/hydroxide site
in the glass, perhaps to form a tetracoordinate borate
site, but that silica sites do not provide a thermody-
namically competitive possibility for binding to diols.
Bor on Ha lid e Am in e Ad d u cts. Most reports of
reactions of amines with alkylboron dichlorides have
described 1:1 adducts. A computer search of Chemical
Abstracts for compounds containing the tetracoordinate
boron grouping CBCl2N yielded 21 citations, all in the
period 1943-1981. A search for CBClN2 structures
produced only two, not including MeB(Cl)(NHMe2)2 Cl-,17
+
found via the report of CF3B(Cl)(NHMe2)2+Cl-.18 The
1:1 adduct of pyridine with phenylboron dichloride,
PhBCl2(py), has been described.19
Boronic acids are hard to purify, and to get a
representative accurate yield as well as demonstrate a
potential use of the process, the (R)-(+)-DICHED ester
7 was cleaved with thionyl chloride and imidazole. The
resulting mixture of haloborane amine complex 8 and
related compounds was hydrolyzed and treated with
(S,S)-DICHED to form (-)-9, 56% after chromatogra-
phy. The diastereomers 7 and 9 showed small differ-
ences in chemical shifts in the 13C NMR spectra, and
no 7 was detected in 9 at a signal-to-noise ratio of 200:
1.
A closer analogy to the chemistry reported here is the
reaction of aminodichloroboranes with 2 or 3 mol of
pyridine, as in the conversion of Me2NBCl2 to the 1:2
adduct Me2NBCl(py)2+Cl- and of Et2NBCl2 to Et2NB-
(py)32+‚2Cl-.20 In other work, the possibility that orga-
noboron dichlorides might react with more than 1 equiv
of amine has been overlooked.21
Another precedent for reaction of more than one
amine is provided by tris(pyrazolyl)borates (“pyraza-
boles”),22 especially their stepwise synthesis from orga-
noboron halide precursors,23 though no evidence for tris-
(amino)alkylborates was seen in the present work.
Nucleophilic substitutions at tetracoordinate boron are
known to proceed either via direct “SN2” displacements
or “SN1” dissociation to tricoordinate boron intermedi-
ates.24
The molecular masses indicated by MALDI data are
consistent with the type and variety of organoboron
dichloride imidazole adducts that would be expected.
The stoichiometry of formation of cations containing
bridging imidazole units requires formation of an equiva-
lent amount of imidazole hydrochloride, in accord with
observations that complete conversion of boronic esters
to their imidazole boron dichloride derivatives requires
at least 4 equiv of imidazole and works better with 5 or
6.
Discu ssion
Gla ss Ca ta lysis. Glass surface catalyzed reactions
are reported sporadically, but usually involve a nonpolar
medium in contact with the polar surface, as in the ionic
equilibration of crotyl and methallyl chlorides.11 Glass-
catalyzed fluorinations by xenon difluoride, presumably
via XeF+, are inhibited by acetonitrile.12 Polar solvents
diminish catalysis of Diels-Alder reactions by silica or
glass.13 Isotopic O-exchange between sulfate, phosphate,
or chromate and strongly basic water is apparently
catalyzed by silicate etched from the glass rather than
the surface itself.14 Other miscellaneous examples of
surface catalysis show a wide variety of behavior.15
The specific activity of borosilicate glass and the
failure of silica to catalyze these boronic ester reactions
appears to be a unique phenomenon. Ordinarily the
(15) (a) Reiser, U.; J auch, J .; and Herdtweck, E. Tetrahedron:
Asymmetry 2000, 11, 3345-3349. (b) Lindner, P. E.; Correa, R. A.;
Gino, J .; Lemal, D. M. J . Am. Chem. Soc. 1996, 118, 2556-2563. (c)
Crivello, J . V.; Lai, Y.-L.; Malik, R. J . Polym. Sci. Part A: Polym. Chem.
1996, 34, 3103-3120. (d) Hugel, G.; Royer, D.; Le Men-Olivier, L.;
Richard, B.; J acquier, M.-J .; Le´vy, J . J . Org. Chem. 1997, 62, 578-
583. (e) Barney, W. S.; Finlayson-Pitts, B. J . J . Phys. Chem. A 2000,
104, 171-175. (f) Sehested, K.; Corfitzen, H.; Holcman, J .; Hart, E. J .;
J . Phys. Chem. A 1998, 102, 2667-2672.
(16) (a) Zhuravlev, L. T. Colloids Surf., A 1993, 74, 71-90. (b)
Petrucci, M. G. L.; Kakkar, A. K. Organometallics 1998, 17, 1798-
1811.
(17) No¨th, H.; Fritz, P. Z Anorg. Allg. Chem. 1963, 322, 297-309.
(18) Brauer, D. J .; Buerger, H.; Pawelke, G.; Weuter, W.; Wilke, J .
J . Organomet. Chem. 1987, 329, 293-304.
(19) Lappert, M. F.; Pyszora, H. J . Chem. Soc. A 1968, 1024-1031.
(20) Lappert, M. F.; Srivastava, G. J . Chem. Soc. A 1967, 602-603.
(21) Kotz, J . C.; Post, E. W. Inorg. Chem. 1970, 9, 1661-1669.
(22) Trofimenko, S. Chem. Rev. 1993, 93, 943-980.
(23) Herdtweck, E.; J a¨kle, F.; Opromolla, G.; Spiegler, M.; Wagner,
M.; Zanello, P. Organometallics 1996, 15, 5524-5535.
(24) (a) Hawthorne, M. F.; Budde, W. L. J . Am. Chem. Soc. 1964,
86, 5337. (b) Hawthorne, M. F.; Budde, W. L.; Walmsley, D. J . Am.
Chem. Soc. 1964, 86, 5337-5338.
(12) Ramsden, C. A.; Smith, R. G. J . Am. Chem. Soc. 1998, 120,
6842-6843.
(13) (a) Veselovsky, V. V.; Gybin, A. S.; Lozanova, A. V.; Moiseenkov,
A. M.; Smit, W. A.; Caple, R. Tetrahedron Lett. 1988, 29, 175-178. (b)
Schuster, T.; Markus Kurz, M.; Go¨bel, M. W. J . Org. Chem. 2000, 65,
1697-1701.
(14) (a) Winter, E. R. S.; Carlton, M.; Briscoe, H. V. A. J . Chem.
Soc. 1940, 131-138. (b) Brasch, N. E.; Buckingham, D. A.; Evans, A.
B.; Clark, C. R. J . Am. Chem. Soc. 1996, 118, 7969-7980.

Notes
Organometallics, Vol. 20, No. 13, 2001 2923
was concentrated on a rotary evaporator. A mixture of water
(50 mL) and methanol (150 mL) was added until the granular
tan yellow solid dissolved. The mixture was refluxed for 15 h.
After cooling to room temperature, (S,S)-DICHED (1.34 g, 5.93
mmol) was added to the boronic acid solution. The solution
was stirred at 60 °C overnight. Methanol was evaporated by
a rotary evaporator, and ether (150 mL) was added to the
granular tan solid. The mixture was shaken and separated,
and the extraction with ether was repeated (3 × 150 mL). The
ether phase was dried over magnesium sulfate and concen-
trated in a rotary evaporator. Analytically pure compound was
obtained by flash chromatography on silica with ether/pentane
(1:20) (1.07 g, 56.4%): Rf ) 0.5 (silica gel 5% ether in pentane);
Exp er im en ta l Section
Rea ction of DICHED Bor on ic Ester s (1) w ith Im id a -
zole a n d Th ion yl Ch lor id e. Crushed borosilicate glass
(particle size ∼0.1-1 mm) was cleaned with hydrochloric acid,
treated with methanolic potassium hydroxide for several
hours, washed thoroughly with deionized water, and dried in
an oven. Imidazole was dried under vacuum (1 Torr) at 20-
25 °C for 1-2 days. The DICHED boronic ester (1) (0.5 mmol,
150-200 mg) and imidazole (136 mg, 2.0 mmol) were dissolved
in anhydrous acetonitrile (2.5 mL) under an inert atmosphere
(argon) with the aid of a magnetic stirrer. After the imidazole
had dissolved, crushed borosilicate glass (1 g) was added.
Thionyl chloride (360 mg, 3 mmol) was added dropwise, and
vigorous stirring was continued. After the time indicated in
Table 1, the reaction mixture was filtered (suction). The
acetonitrile solution was extracted with pentane (3 × 5 mL).
Concentration of the pentane phase yielded DICHED sulfite
(2) and any unchanged boronic ester (1), the ratio of which
was determined by comparison of the integrals of the 300 MHz
1H NMR signals of 1 near δ 3.8 and the corresponding
diastereotopic pair of signals of DICHED sulfite at δ 4.05 and
4.56. Concentration of the acetonitrile phase yielded a mixture
of boron chloride imidazole complexes (6 and related oligo-
mers).
1
oil, [R]22 -37.7°, [R]22 ) -44.6° (c 0.79, CH2Cl2); H NMR
D
546
(300 MHz, CDCl3) δ 0.83-1.75 (m, 26H), 2.56 (dd, J ) 13.5
Hz, J ) 8.4 Hz, 1H), 2.83 (dd, J ) 13.2 Hz, J ) 7.2 Hz, 1H),
3.80 (d, J ) 4.5 Hz, 2H), 7.1-7.3 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 16.6, 25.9, 26.0, 26.5, 27.3, 28.2, 39.3, 42.9, 83.2,
125.4, 127.8, 128.7, 142.1; HRMS calcd for C23H25BO2 354.2730,
found 354.2727. Anal. Calcd for C23H25BO2: C, 77.95; H, 9.96;
B, 3.05. Found: C, 78.25; H, 10.23; B, 2.75.
Ack n ow led gm en t. We thank the National Science
Foundation for support (grant numbers CHE-9613857
and CHE-0072788). The WSU NMR Center equipment
was supported by NIH grants RR0631401 and RR12948,
NSF grants CHE-9115282 and DBI-9604689, and a
grant from the Murdock Charitable Trust. The PerSep-
tive Biosystems Voyager DE/RP mass spectrometer was
obtained with funds from an NIH Shared Instrumenta-
tion Grant, 1 S10 RR11290-01.
Rea ction of DICHED Bor on ic Ester s w ith P yr id in e
a n d Th ion yl Ch lor id e. The procedure was the same as that
described for reactions with imidazole, but with the following
modifications. Boronic ester 1 (0.5 mmol) in acetonitrile (2.5
mL) was stirred with crushed borosilicate glass (1 g) during
the dropwise addition of thionyl chloride (120 mg, 1 mmol)
followed by the dropwise addition of pyridine (200 mg, 2.5
mmol).
[2(1R),4R,5R]-4,5-Dicycloh exyl-2-(1-m et h yl-2-p h en yl-
eth yl)-1,3,2-d ioxa bor ola n e (9) fr om [2(1R),4S,5S]-4,5-Di-
cycloh exyl-2-(1-m et h yl-2-p h en ylet h yl)-1,3,2-d ioxa b or o-
la n e (7). A slurry of crushed borosilicate glass (10 g, pretreated
as described above) in a solution of anhydrous imidazole (3.65
Su p p or tin g In for m a tion Ava ila ble: Data for reactions
with and without added glass; preparation and characteriza-
tion data for 1 or en t-1 [R ) Ph, n-hexyl, cyclohexyl, PhCH2-
CH(CH3), PhCH2CH(C6H11), PhCH2CH(OCH2Ph), CH3CH-
(C6H11), H2CdCH-CH2CH(CH3)], cyclohexylboronic acid, (S)-
(1-phenylmethoxy-2-phenylethyl)boronic acid, pinacol esters
of (1-methyl-2-phenylethyl)boronic acid and (1-benzyloxy-2-
phenylethyl)boronic acid, (R)-DICHED sulfite (2), pinanediol
sulfites (5); hydrolysis of imidazole borates 6 to boronic acids;
summary of MALDI-TOF measurements; rate of hydrolysis
of pyridine adduct of benzylboron dichloride; 1H and 13C NMR
curves for compounds 7 and 9. This material is available free
of charge via the Internet at http://pubs.acs.org.
g, 53.6 mmol) and (R)-DICHED ester 7 (1.9 g, 5.37 mmol; [R]22
D
+29.2°, [R]22
+35.6° (c 0.24, CH2Cl2)) in anhydrous aceto-
546
nitrile (130 mL) was stirred under argon during the dropwise
addition of thionyl chloride (5.87 mL, 80.5 mmol) and stirred
for an additional 24 h at 20-25 °C. NMR analysis of an aliquot
indicated >98% conversion of 7 to DICHED sulfite. Water was
added until the yellow organic solid was dissolved, leaving the
solid (glass) phase colorless. The aqueous acetonitrile phase
was extracted with pentane (5 × 150 mL) to remove DICHED
sulfite and unconverted boronic ester. The acetonitrile solution
OM001053S