The first optically pure nido-monothiocarborane cluster

Article abstract of DOI:10.1021/om990653s

One of the enantiomers of racemic [NMe₄][7-SPh-8-CH₂OH-7,8-C₂B₉H ₁₀] is isolated in 68% yield. Resolution is achieved by means of differential crystallization of the diastereoisomeric camphanate ester

Full text of DOI:10.1021/om990653s

Organometallics 1999, 18, 5409-5411
5409
Notes
Th e F ir st Op tica lly P u r e n id o-Mon oth ioca r bor a n e
Clu ster
Francesc Teixidor,* Miguel A. Flores, and Clara Vin˜as
Institut de Cie`ncia de Materials de Barcelona, CSIC, Campus de Bellaterra,
Cerdanyola, 08193 Barcelona, Spain
Received August 13, 1999
Summary: One of the enantiomers of racemic [NMe4][7-
SPh-8-CH2OH-7,8-C2B9H10] is isolated in 68% yield.
Resolution is achieved by means of differential crystal-
lization of the diastereoisomeric camphanate ester de-
rivatives.
preparative HPLC on chiral stationary phases has been
reported.5 The species resolved were mainly zwitterionic
7,8-C2B9H10 and 5,10-C2B8H10 clusters and a variety of
metallaboranes. Recently, this technique has been ap-
plied to the resolution of [6,6-µ-Me2P-(1,7-(C2B9H10)2)-
2-Co], and their absolute configurations have been
elucidated by X-ray diffraction.6 Although HPLC is not
so convenient for large-scale preparation, it provided a
In tr od u ction
The preparation and properties of chiral ligands have
attracted considerable attention from a wide range of
chemists especially in the field of organic, biological, and
medicinal chemistry. Their applications have been
further widened to include some currently most focused
areas such as chiral recognition and chiral catalysis.1
One of the main principles in designing asymmetric
reagents and catalysts is to allow the reaction center to
be surrounded by a recognition site and a chiral moiety,
as the former governs the substance selectivity and the
latter the stereoselectivity.2 In contrast, despite the
great development of boron chemistry produced in the
past decades, the chemistry of chiral compounds with
borane framework remains relatively unexplored. A
dreaded easy boron or carbon rearrangement in the
cluster leading to rapid racemization of a pure enanti-
omer may account for it. Until 1991 only 10 papers
dealing with optically active boron cage compounds had
been published, concerning approximately 20 individual
route for the resolution of racemic [7-SR-8-R′-7,8-
-
C2B9H10
]
anionic compounds. The interest in these
anions was motivated by the fact that exo-nido7 and
closo8 derivatives of [7-SR-8-R′-7,8-C2B9H10]- have been
demonstrated to be efficient hydrogenation catalysts for
terminal and internal alkenes, respectively, and we
wanted to find a suitable procedure to get the nido-
monothiocarborane ligands in pure enantiomeric form.
However, continued efforts to resolve [7-SR-8-R′-C2-
B9H10]- anions using several types of chiral stationary
phases were unsuccessful.9 At this point we turned to
the idea of racemic resolution via diastereoisomeric
derivatives. The classical methods of resolution seem
to have been improved by the simultaneous addition of
more than one member of a “family” of resolving agents
to a solution of a racemate to produce the crystallization
of one diastereomeric salt.10,11 However, previous nega-
tive results attempting the crystallization with only one
resolving cationic agent motivated us to form covalent
diastereoisomers that could result in a more efficient
resolution.
compounds,3 of which only four were nido-C2B9 deriva-
-
tives.4 The resolution of derivatives of [7,8-C2B9H12
]
-
or [7,9-C2B9H12
]
was accomplished via differential
crystallization of their diastereoisomeric l-N,N,N-tri-
methyl-R-phenylethylammonium salts.4 For these C2B9
derivatives a high number of recrystallizations were
required to achieve resolution, and low yields of pure
enantiomers were obtained in all cases. The successful
resolution of more than 35 racemic boron cage com-
pounds into optically pure enantiomers using semi-
Resu lts a n d Discu ssion
Diastereoisomeric esters have been used extensively
in the resolution of organic compounds containing
hydroxyl groups, in part due to the ease of formation of
(5) Gru¨ner, B.; Plesek, J . Current Topics in the Chemistry of Boron;
The Royal Society of Chemistry: Cambridge, UK, 1994; p 371.
(6) Gruner, B.; Cisarova I.; Franken, A.; Plesek, J . Tetrahedron:
Asymmetry 1998, 9, 79.
(7) Teixidor, F.; Flores, M. A.; Vin˜as, C.; Kiveka¨s, R.; Sillanpa¨a´, R.
Angew. Chem., Int. Ed. Engl. 196, 35, 2251.
* Corresponding author. E-mail: teixidor@icmab.es.
(1) (a) Lehn, J .-M. Supramolecular Chemistry: Concepts and Per-
spectives; VCH: Wenheim, 1995. (b) Webb, T. H.; Wilcox, C. S. Chem.
Soc. Rev. 1993, 22, 383.
(2) Trost, B. M. Acc. Chem. Res. 1996, 29, 355.
(3) Plesek, J .; Hermanek, S.; Stibr, B. Pure Appl. Chem. 1991, 63,
399.
(4) (a) Hawthorne, M. F.; Young, D. C.; Garrett, P. M.; Owen, D.
A.; Schwerin, S. G.; Tebbe, F. N.; Wegner, P. A. J . Am. Chem. Soc.
1968, 90, 862. (b) Baker, R. T.; Delaney, M. S., King, R. E.; Knobler,
C. B.; Long, J . A.; Marder, T. B.; Paxson, T. E.; Teller, R. G.; M. F.
Hawthorne. J . Am. Chem. Soc. 1984, 106, 2965.
(8) Teixidor, F.; Flores, M. A.; Vin˜as, C.; Sillanpa¨a¨, R.; Kiveka¨s, R.
J . Am. Chem. Soc., submitted.
(9) Teixidor, F.; Traufetter, B.; Vin˜as, C. Unpublished results.
(10) Vries, T.; Wynberg, H.; van Echten, E.; Koek, J .; ten Hoeve,
W.; Kellog, R. M.; Broxterman, Q. B.; Minnaard, A.; Kaptein, B.; van
der Sluis, S.; Hulhof, L.; Kooistra, J . Angew. Chem., Int. Ed. Engl. 1998,
37, 2349.
(11) Collet, A. Angew. Chem., Int. Ed. Engl. 1998, 37, 3239.
10.1021/om990653s CCC: $18.00 © 1999 American Chemical Society
Publication on Web 11/13/1999

5410 Organometallics, Vol. 18, No. 25, 1999
Notes
Sch em e 1
same solvent afforded virtually 100% pure diastereo-
isomer [NMe4][3a ] in 68% yield (step 6). Attempts to
isolate the more soluble diastereoisomer [NMe4][3b]
from the mother liquor were unsuccessful. Diastereo-
isomeric salt [NMe4][3a ] is stable both in the solid state
and in acetone solutions, showing no sign of decomposi-
tion or conversion to its diastereoisomer [NMe4][3b]
after several months.
To regenerate [2]-, several procedures were at-
tempted. Saponification of [NMe4][3a ] in H2O/ethanol
yielded a mixture of the alcohol [2]- and the ether
derivative [NMe4][7-SPh-8-CH2OEt-7,8-C2B9H10] ac-
cording to 1H, 13C, and 11B NMR spectroscopy. Also,
transesterification in KOH/methanol yielded a mixture
of [2]- and the methyl ether derivative [NMe4][7-SPh-
8-CH2OMe-7,8-C2B9H10]. These results suggest that
nucleophilic attack to the alkyl carbon of the Ccage
-
CH2-O-CO group is a competitive reaction in saponi-
fication conditions. Nevertheless, reduction of the ester
derivative [NMe4][3a ] with LiAlH4 in THF yielded pure
enantiomer (+)-[NMe4][2] in 90% yield (step 7). To check
whether racemization had occurred during the reduction
step, (+)-[NMe4][2] was reacted again with (-)-cam-
phanic acid chloride to regenerate the ester derivative.
1H and 13C{1H} NMR spectroscopy showed no signals
belonging to [NMe4][3b], thus confirming that the
reduction step had proceeded without racemization. In
summary, the first chiral nido-monothiocarborane clus-
ter has been isolated in good yield. The method can be
extended to other nido-carboranes provided that the
hydroxyl functionality not be an obstacle in the future
application for which the molecule has been conceived.
the ester and regeneration of the starting alcohol.12 On
this basis we designed a synthetic procedure to incor-
porate the hydroxyl group to nido-monothiocarborane
ligands, which is depicted in Scheme 1.
Compound closo-1-CH2OH-1,2-C2B10H11 was chosen
as starting material. This 1,2-C2B10 cluster incorporates
the desired hydroxyl group and can be prepared from
decaborane in good yield (steps 1 and 2 in Scheme 1).
The reaction of closo-1-CH2OH-1,2-C2B10H11 with 2
equiv of BuLi followed by reaction with diphenyl di-
sulfide led to the isolation of closo-1-SPh-2-CH2OH-1,2-
C2B10H11 (1) (step 3). Subsequent partial degradation
of 1 in KOH/methanol afforded the nido derivative
[NMe4][7-SPh-8-CH2OH-7,8-C2B9H10] ([NMe4][2], step
4). (-)-Camphanic acid chloride, which has been suc-
cessfully used in the resolution of alcohols,13 was chosen
as resolving agent. The camphanate derivative [NMe4][7-
SPh-8-CH2OOC(C9H13O2)-7,8-C2B9H10] ([NMe4][3]) was
obtained by reaction of [NMe4][2] with (-)-camphanic
Exp er im en ta l Section
In str u m en ta tion . Elemental analyses were performed
using a Carlo Erba EA1108 microanalyzer. IR spectra were
recorded with KBr pellets on a Nicolet 710 FT spectropho-
tometer. The 1H NMR (300.13 MHz), 13C{1H} NMR (75.47
MHz), and 11B NMR (96.29 MHz) spectra were recorded at
room temperature using a Bruker ARX 300 instrument
equipped with the appropriate decoupling accessories. Chemi-
cal shift values for 11B NMR spectra were referenced to
1
external BF3‚OEt2, and those for H and 13C{1H} NMR spectra
were referenced to SiMe4. Chemical shifts are reported in units
of parts per million downfield from tetramethylsilane, and all
coupling constants are reported in hertz. The specific rotation
was measured using a Dr. Kernchen Optik+Electronik Propol
polarimeter.
1
acid chloride in dry pyridine (step 5), and H and 13C-
{1H} NMR spectra confirmed the formation of two
diastereomers. TLC in silica gel using different solvent
mixtures was performed to investigate whether chro-
matographic separation could be convenient for resolu-
tion, but no sign of separation was observed probably
due to the long tails inherent to the ionic nature of the
diastereoisomers. Also ionic chromatographic separation
was attempted, but we found no success. Nevertheless,
the diastereoisomeric esters displayed quite distinct
solubility properties. A single recrystallization of the
diastereoisomeric mixture in methanol yielded one of
Ma ter ia ls. Unless otherwise noted, all manipulations were
carried out under a dinitrogen atmosphere using standard
vacuum line techniques. Diethyl ether was distilled from
sodium benzophenone prior to use. The rest of the solvents
were of reagent grade quality and were used without further
purification. Decaborane (KATCHEM) and (1S)-(-)-camphanic
acid chloride (Aldrich) were purchased from commercial
sources and used as received. Propargyl acetate14 was prepared
according to the literature methods. closo-1-CH2OH-1,2-
C2B10H1115 was prepared from closo-1-CH2OOCMe-1,2-C2B10H11
,
which in turn was prepared from decaborane and propargyl
acetate according to the literature.
Syn th esis of 1-SP h -2-CH2OH-1,2-C2B10H10 (1). A solution
of 1-CH2OH-1,2-C2B10H11 (1.00 g, 5.74 mmol) in 40 mL of ether
1
the diastereoisomers in ca. 95% purity according to H
NMR spectroscopy. A second recrystallization in the
(12) J acques, J .; Collet, A.; Wilhen, S. H. Enantiomers, Racemates
and Resolutions, 3rd ed.; Krieger Publishing Company: Malabar, FL,
1994; p 332.
(13) a) Gerlach. H. Helv. Chim. Acta 1968, 51, 1587. (b) Collet. A.;
Brienne, M. J .; J acques, J . Tetrahedron Lett. 1975, 2349. (c) Potter,
B. L. V.; Mills, S. J .; Lampe, D. J . Chem. Soc., Perkin Trans. 1 1992,
2899.
(14) Vogel, A. I. Practical Organic Chemistry, 5th ed.; Longman:
Essex, UK, 1989.
(15) Heying, T. L.; Ager, J . W.; Clark, S. L.; Mangold, H. L.;
Goldstein, H. L.; Hillman, M.; Polak, R. J .; Szymanski, J . W. Inorg.
Chem. 1963, 2, 1089.

Notes
Organometallics, Vol. 18, No. 25, 1999 5411
was cooled to -78 °C, and 7.4 mL of BuLi (1.55 M, 11.5 mmol)
was added dropwise with vigorous stirring. After half of the
BuLi solution had been added, the cooling bath was removed
and the addition continued, precipitating a white solid. The
suspension was vigorously stirred for 1 h at room temperature,
after which time Ph-S-S-Ph (1.26 g, 5.77 mmol) was added
as a solid, and the suspension was stirred for 2 h. Next, water
(40 mL) and additional ether (40 mL) were added, and the
organic phase was decanted, washed with water (3 × 40 mL),
and dried with MgSO4. The ether was removed on a rotary
evaporator, obtaining a pale yellow oil which contains the
desired product and a small amount of hexylphenylsulfide. The
oil was chromatographed on silica gel (eluent: CH2Cl2) to
afford a colorless viscous oil which slowly crystallizes on
cooling. Yield: 1.4 g (86%). IR (KBr): ν [cm-1] ) 2593, 2568
solution of the solid (50 mL overall). The heating and stirring
was stopped, and the clear solution was left aside for 5 h.
Compound [NMe4][3a ] slowly crystallized during this time and
was isolated by filtration, washed with cold methanol (2 × 3
mL), and dried in vacuo, yielding 0.78 g. The purity was 95%
according to 1H NMR spectroscopy. The solid was again
suspended in methanol (7 mL) and refluxed for 15 min, and
the suspension was left aside for 2 h. The solid was isolated
by filtration and washed with methanol (2 × 2 mL). Yield: 0.68
22
g (68%). [R]D ) +37.6 (c ) 2.33, acetone). IR (KBr): ν [cm-1
]
) 2540 (B-H). 1H NMR ((CD3)2CO): 7.3-7.0 (m, 5, Haryl), 4.58
(d, 2J (H,H) ) 11.8 Hz, 1, Ccage-CH2O-), 4.52 (d, 2J (H,H) )
11.8 Hz, 1, Ccage-CH2O-), 2.34 (ddd, 2J (Ha,Hc) ) 13.2 Hz,
3J (Ha,Hb) ) 10.8 Hz, 3J (Ha,Hd) ) 4.1 Hz, 1, Ha), 1.93 (ddd,
2J (Hb,Hd) ) 12.7 Hz, J (Hb,Ha) ) 10.8 Hz, J (Hb,Hc) ) 4.4 Hz,
1, Hb), 1.69 (ddd, 2J (Hc,Ha) ) 13.2 Hz, 3J (Hc,Hd) ) 9.3 Hz,
3J (Hc,Hb) ) 4.4 Hz, 1, Hc), 1.51 (ddd, 2J (Hd,Hb) ) 12.7 Hz,
3J (Hd,Hc) ) 9.3 Hz, 3J (Hd,Ha) ) 4.1 Hz, 1, Hd), 1.02 (s, 3, CH3),
0.92 (s, 3, CH3), 0.90 (s, 3, CH3). 13C{1H} NMR ((CD3)2CO):
178.6, 167.5, 142.7, 129.1, 128.1, 125.1 (Caryl), 91.8, 69.9
(-CH2O-), 56.0 (N(CH3)4), 55.3, 54.4, 31.0, 29.4, 17.0, 16.8,
9.9. 11B NMR ((CD3)2CO): -6.2 (d, 1J (B,H) ) 143 Hz, 1B), -9.1
(d, 1J (B,H) ) 139 Hz, 1B), -13.5 (d, 1J (B,H) ) 165 Hz, 1B),
3
3
1
3
(B-H). H NMR (CDCl3): 7.6-7.5 (m, 5, Haryl), 5.32 (t, J (H-
3
H) ) 6.6 Hz, 1, CH2OH), 4.48 (d, J (H-H) ) 6.6 Hz, 2, CH2-
OH). 13C{1H} NMR (CDCl3): 138.4, 132.5, 130.4 (Caryl), 87.2,
83.9 (Ccage), 63.5 (CH2OH). 11B{1H} NMR (CDCl3): -3.7 (2B),
-8.9 (2B), -10.2 (4B), -12.0 (2B). Anal. Calcd for C9H18B10S:
C, 38.28; H, 6.42; S, 11.35. Found: C, 38.33; H, 6.07; S, 11.15.
Syn t h esis of [NMe4][7-SP h -8-CH2OH -7,8-C2B9H 10]-
([NMe4][2]). A solution of 1 (0.990 g, 3.51 mmol) in methanol
(25 mL) containing KOH (1.40 g, 21.2 mmol) was refluxed for
6 h. After this time, the solution was cooled to room temper-
ature and the solvent was evaporated. Water was added (10
mL), and the solution was acidified to pH ) 7 with HCl 35%
and was filtered through Celite. To the resulting clear solution
was added slowly with stirring [NMe4]Cl (1.15 g, 10.5 mmol)
dissolved in water (2 mL), producing a white precipitate, which
was filtered, washed with cold water (3 × 5 mL), and dried in
vacuo. Yield: 1.25 g (93%). IR (KBr): ν [cm-1] ) 3563(m), 2534-
(s) (B-H). 1H NMR ((CD3)2CO): 7.3-7.0 (m, 5, Haryl), 3.90 (m,
1, CH2OH), 3.71 (m, 1, CH2OH), 2.48 (m, 1, CH2OH), -2.42 (b
s, 1, B-H-B). 13C{1H} NMR ((CD3)2CO): 143.2, 128.9, 127.8,
124.9 (Caryl), 66.9 (CH2OH), 55.9 (N(CH3)4). 11B NMR ((CD3)2-
1
1
-14.4 (d, J (B,H) ) 145 Hz, 1B), -17.7 (d, J (B,H) ) 132 Hz,
3B), -33.0 (d, 1J (B,H) ) 130 Hz, 1B), -36.0 (d, 1J (B,H) ) 139
Hz, 1B). Anal. Calcd for C23H42B9NO4S: C, 52.52; H, 8.05; N,
2.66; S, 6.10. Found: C, 52.14; H, 7.90; N, 2.63; S, 6.02.
Syn t h esis of [NMe4][7-SP h -8-CH 2OOC(C9H 13O2)-7,8-
C2B9H10] ([NMe4][3b]). The filtrate from de recrystallization
of [NMe4][3] (see above) contains diastereoisomer [NMe4][3b]
in ca. 75% purity. 1H NMR (300.2 MHz, (CD3)2CO, 25 °C,
TMS): 1.18 (s, 3, CH3), 1.02 (s, 3, CH3), 0.79 (s, 3, CH3). The
rest of resonances were overlapped with those of the diaste-
reoisomer [NMe4][3a ]. 13C{1H} NMR ((CD3)2CO): 178.4, 167.5,
142.7, 129.0, 127.8, 125.1 (Caryl), 91.9, 70.4 (-CH2O-), 56.0
(N(CH3)4), 55.2, 54.5, 30.9, 17.3, 16.7, 9.9.
1
1
CO): -6.5 (d, J (B,H) ) 143 Hz, 1B), -9.8 (d, J (B,H) ) 139
Syn t h esis of (+)-[NMe4][7-SP h -8-CH2OH-7,8-C2B9H10
]
1
1
Hz, 1B), -13.4 (d, J (B,H)) 165 Hz, 1B), -15.0 (d, J (B,H) )
((+)-[NMe4][2]). To a suspension of LiAlH4 (63 mg, 1.7 mmol)
in THF (6 mL) was added a solution of [NMe4][3a ] (0.651 g,
1.24 mmol) in THF (10 mL), and the suspension was stirred
at room temperature for 1 h. After this time the reaction was
quenched with water (0.5 mL) and the suspension was filtered
through Celite. The solvent was removed, methanol (1 mL)
was added to dissolve the residue, and a solution of [NMe4]Cl
(0.420 g, 3.83 mmol) in water was added with stirring,
precipitating a white solid. The methanol was evaporated to
complete precipitation, and the solid was isolated by filtration,
washed with cold water (3 × 5 mL), and dried in vacuo. The
product was dissolved in acetone and filtered through Celite
to remove a solid impurity. The acetone was evaporated, and
the product was treated with ether (3 mL). The solvent was
removed in vacuo to yield 0.40 g (93%) of product. The IR and
NMR spectra were identical to those of racemic product [NMe4]-
145 Hz, 1B), -17.8 (d, 1J (B,H) ) 132 Hz, 3B), -33.3 (d, 1J (B,H)
1
) 130 Hz, 1B), -36.3 (d, J (B,H) ) 139 Hz, 1B). Anal. Calcd
for C13H30B9NOS: C, 45.16; H, 8.75; N, 4.05; S, 9.27. Found:
C, 45.06; H, 8.51; N, 4.02; S, 9.16.
Syn t h esis of [NMe4][7-SP h -8-CH 2OOC(C9H 13O2)-7,8-
C2B9H10] ([NMe4][3]). A 25 mL Schlenk flask was charged
with 2 (1.437 g, 4.156 mmol), (-)-camphanic acid chloride
(0.970 g, 4.48 mmol), a magnetic stirring bar, and 6 mL of
pyridine. Upon stirring, the solids dissolved, precipitating a
white solid within minutes. The suspension was stirred at
room temperature for 12 h, after which time the pyridine was
removed in vacuo, affording a syrup, which was taken up with
THF (10 mL), followed by the addition of a solution of [NMe4]-
Cl (1.37 g, 12.5 mmol) in water (6 mL). The THF was removed
in vacuo until a solid appeared, and methanol (2 mL) was
added with stirring, precipitating a white solid. The methanol
and the rest of the THF were evaporated to complete precipi-
tation, and the resulting solid was filtered, washed with water
(3 × 5 mL), and dried in vacuo. Yield: 2.0 g (91%). The
isolation of diastereoisomer [NMe4][3a ] is described below.
Syn t h esis of [NMe4][7-SP h -8-CH 2OOC(C9H 13O2)-7,8-
C2B9H10] ([NMe4][3a ]). A 250 mL flask equipped with a
sidearm was charged with [NMe4][3] (2.0 g, mmol), methanol
(10 mL), and a magnetic stirring bar. The suspension was
brought to reflux, and methanol was added until total dis-
22
[2]. [R]D ) +34.1 (c ) 2.11, acetone). To check whether the
reaction had proceeded with racemization, (+)-[NMe4][2] and
(-)-camphanic acid chloride were allowed to react as for [NMe4]-
1
[3], and H and 13C{1H} NMR showed no traces of [NMe4][3b].
Ack n ow led gm en t. This work was supported by
CIRIT (project QFN95-4721) and DGICYT (project
PB94-0226).
OM990653S