A-Alkylation and S-Amination of Methyl Thioethers - Derivatives of closo-[B12H12]2-. Synthesis of a Boronated Phosphonate, gem-Bisphosphonates, and Dodecarborane-ortho-carborane Oligomers

Article abstract of DOI:10.1021/ja0123857

A variety of S-alkylated products was prepared by alkylation of methyl thioethers [MeSB12H11]^2- (5), [1-(MeS)-2(7,12)-(Me2S)B12H10]^- (6-8), and [1,2(7,12)-(MeS)2B12H10]^2- (9-11) with alkyl halides and tosylates in acetonit

Full text of DOI:10.1021/ja0123857

Published on Web 02/19/2002
S-Alkylation and S-Amination of Methyl Thioethers -
Derivatives of closo-[B12H12]2-. Synthesis of a Boronated
Phosphonate, gem-Bisphosphonates, and
Dodecaborane-ortho-carborane Oligomers
Roman G. Kultyshev, Jianping Liu, Shengming Liu, Werner Tjarks,†
Albert H. Soloway,† and Sheldon G. Shore*
Contribution from the Department of Chemistry and College of Pharmacy,
The Ohio State UniVersity, Columbus, Ohio 43210
Received October 18, 2001
Abstract: A variety of S-alkylated products was prepared by alkylation of methyl thioethers [MeSB12H11]2-
(5), [1-(MeS)-2(7,12)-(Me2S)B12H10]- (6-8), and [1,2(7,12)-(MeS)2B12H10]2- (9-11) with alkyl halides and
tosylates in acetonitrile. Since these methyl thioethers can be prepared easily in B-10-enriched form on a
large scale and due to their chemical versatility, they are potentially very attractive boron entities for the
design and synthesis of therapeutics for boron neutron capture therapy of cancer. It was found that alkylation
of 6-8 can be complicated by an equilibrium which establishes between, on the one hand, one of the
former species and, on the other hand, 1,2(7,12)-(Me2S)2B12H10 (2-4) and [1,2(7,12)-(MeS)2B12H10]2- (9-
11). A boronated phosphonate 1-(MeS(CH2)4P(O)(OEt)2)-7-(Me2S)B12H10 (14g) and a gem-bisphosphonate
1-(MeS(CH2)3CH[P(O)(OEt)2]2)-7-(Me2S)B12H10 (14h) were prepared from thioether 7 and the corresponding
iodide and tosylate, respectively, and subsequently converted to their sodium salts. The propargyl sulfonium
salts obtained by alkylation of thioethers 7, 8, 10, and 11 with propargyl bromide have been further converted
to two- and three-cage oligomers containing both ortho-carborane and dodecaborane moieties. Methyl
thioethers derived from closo-[B12H12]2- are excellent participants in Michael addition reactions in the
presence of a strong acid. The sulfonium salts with tertiary alkyl and vinyl substituents have been prepared
by this method. Methyl thioethers 5-11 react with hydroxylamine-O-sulfonate yielding the corresponding
aminosulfonium salts, albeit in lower yields as compared to those in the alkylation reactions. Several
derivatives of methyl thioethers 5-11 have been characterized by single-crystal X-ray diffraction.
Introduction
Our interests are centered around the chemistry of dimethyl
sulfide derivatives of closo-[B12H12]2-: [Me2SB12H11]- (1), 1,2-
Interest in the chemistry of the icosahedral closo-[B12H12]2-
anion has been rekindled, with increasing recognition of its
versatility in forming exopolyhedral derivatives that have the
potential for a wide range of applications. Hawthorne and co-
workers,1 for example, have recently reported on a series of
seminal investigations that have produced and characterized
several closomeric derivatives of closo-[B12H12]2- that are not
only extremely interesting but also, as they have indicated,
possess the potential for a wide range of applications, from
materials to medicine. Other groups2 have also reported on
recent derivative chemistry of this ion in general, with a
particular emphasis upon derivatives that might have medical
applications.
(Me2S)2B12H10 (2), 1,7-(Me2S)2B12H10 (3), and 1,12-(Me2S)2-
B12H10 (4), most of which are readily produced from neat BH3-
SMe2.3 This presents, of course, the possibility for feasible large-
scale syntheses of these compounds which offer many possi-
bilities for applications. In a sense, 2, 3, and 4 can be viewed
as exopolyhedral analogues of 1,2-, 1,7-, and 1,12-isomers of
(2) (a) Bregadze, V. I.; Sivaev, I. B.; Bruskin, A. B.; Sjoberg, S.; Nesterov, V.
V.; Antipin, M. Y. In Contemporary Boron Chemistry; Davidson, M.,
Hughes, A. K., Marder, T. B., Wade, K., Eds.; The Royal Society of
Chemistry: Cambridge, 2000; pp 163-166. (b) Lebeda, O.; Orlova, A.;
Tolmachev, V.; Lundqvist, H.; Carlsson, J.; Sjoberg, S. In Contemporary
Boron Chemistry; Davidson, M., Hughes, A. K., Marder, T. B., Wade, K.,
Eds.; The Royal Society of Chemistry: Cambridge, 2000; pp 148-151.
(c) Orlova, A.; Lebeda, O.; Tolmachev, V.; Sjoberg, S.; Carlsson, J.;
Lundqvist, H. In Contemporary Boron Chemistry; Davidson, M., Hughes,
A. K., Marder, T. B., Wade, K., Eds.; The Royal Society of Chemistry:
Cambridge, 2000; pp 144-147. (d) Sivaev, I. B.; Bregadze, V. I.; Sjoberg,
S. In Contemporary Boron Chemistry; Davidson, M., Hughes, A. K.,
Marder, T. B., Wade, K., Eds.; The Royal Society of Chemistry:
Cambridge, 2000; pp 135-138. (e) Orlova, A.; Lebeda, O.; Tolmachev,
V.; Sjoberg, S.; Carlsson, J.; Lundqvist, H. J. Labelled Compd. Radiopharm.
2000, 43, 251-260. (f) Plekhanov, A. I.; Markov, R. V.; Rautian, S. G.;
Orlova, N. A.; Shelkovnikov, V. V.; Volkov, V. V. Proc. SPIE-Int. Soc.
Opt. Eng. 1998, 3473, 20-31.
† College of Pharmacy.
(1) (a) Jason, T.; Hawthorne, M. F. Chem. Commun. 2001, 1884-5. (b)
Peymann, T.; Knobler, C. B.; Khan, S. I.; Hawthorne, M. F. Angew. Chem.,
Int. Ed. 2001, 40, 1664-1667. (c) Maderna, A.; Knobler, C. B.; Hawthorne,
M. F. Angew. Chem., Int. Ed. 2001, 40, 1662-1664. (d) Peymann, T.;
Knobler, C. B.; Khan, S. I.; Hawthorne, M. F. J. Am. Chem. Soc. 2001,
123, 2182-2185. (e) Peymann, T.; Knobler, C. B.; Khan, S. I.; Hawthorne,
M. F. Inorg. Chem. 2001, 40, 1291-1294. (f) Peymann, T.; Knobler, C.
B.; Hawthorne, M. F. J. Am. Chem. Soc. 1999, 121, 5601-5602. (g)
Peymann, T.; Herzog, A.; Knobler, C. B.; Hawthorne, M. F. Angew. Chem.,
Int. Ed. 1999, 38, 1062-1064.
(3) (a) Hamilton, E. J. M.; Jordan, G. T., IV; Meyers, E. A.; Shore, S. G.
Inorg. Chem. 1996, 35, 5335-5341. (b) Kultyshev, R. G.; Liu, J.; Meyers,
E. A.; Shore, S. G. Inorg. Chem. 1999, 38, 4913-4915.
9
2614 VOL. 124, NO. 11, 2002 J. AM. CHEM. SOC.
10.1021/ja0123857 CCC: $22.00 © 2002 American Chemical Society

S-Alkylation and S-Amination of Methyl Thioethers
A R T I C L E S
Chart 1
apparently other processes are competing, and the yields are
significantly lower.
Results and Discussion
Alkylation of Methyl Thioethers 5-11 by Alkyl Halides.
Primary alkyl iodides as well as allyl, benzyl, and propargyl
bromides are excellent alkylating agents for thioethers 5-11
(eqs 1-3, Table 1). Addition of one of these reagents to a
[MeSB12H11]2- + RX CH3CN8 [(MeSR)B12H11]- + X- (1)
5
12a-c
[1-(MeS)-2(7,12)-(Me2S)B12H10]- + RX CH CN8
3
6-8
10 + X- (2)
1-(MeSR)-2(7,12)-(Me2S)B12H
carborane, C2B10H12. The derivative chemistry of sulfur, in
principle, can parallel some of the rich organic chemistry
observed29 on the carbon atoms of the carborane isomers without
disrupting the boron-sulfur bonds. Furthermore, the B-H
vertexes are also accessible. Boron-10-enriched compounds,
which are a crucial factor in the design and synthesis of boron
neutron capture therapy (BNCT) agents,4 could be produced
from the relatively easily prepared isomers 2, 3, and 4. In
principle, analogues of many of the new systems outlined by
Hawthorne1 including their possible applications can be visual-
ized. It should be recognized that the key precursor to icosa-
hedral carboranes is the relatively expensive B10H14, while that
for the dimethyl sulfide derivatives of [B12H12]2- is the much
cheaper NaBH4.
The excellent nucleophilicity of methyl thioethers derived
from closo-[B12H12]2- was first observed by Muetterties and
co-workers who obtained sulfonium salts 1 and (Me2S)2B12H10
(a mixture of isomers 2-4) by alkylation of [MeSB12H11]2-
(5) and [(MeS)2B12H10]2- (a mixture of isomers 9-11, Chart
1), with trimethylsulfonium iodide.5 S-Alkylation of the methyl
thioether [(MeS)(Me2S)B12H10]- (a mixture of isomers 6-8)
by RX, where X is a halogen and R ) m-CH2C6H4COOH,
p-CH2C6H4NO2, and p-CH2C6H4NH2, was used later by Solo-
way and co-workers in the synthesis of protein-binding boranes.6
In this paper, we report the results of extended alkylation
studies using recently characterized methyl thioethers 5-117
and a variety of alkylating reagents. In particular, tertiary alkyl
and vinyl substituents can be easily introduced onto a thioether
sulfur atom of 5-11 in Michael addition-type reactions.
Obviously, the high reactivity of these methyl thioethers would
allow for the facile introduction of these boron clusters into
therapeutic structures either directly or through linkers such as
alkyl-, vinyl-, allenyl-, propargyl-, or other groups. Indeed, using
S-alkylation reactions, a phosphonate, gem-bisphosphonates, and
dodecaborane-ortho-carborane oligomers have been prepared
with the eventual goal of evaluation for BNCT. S-Amination
of methyl thioethers with hydroxylamine-O-sulfonate yielded
aminosulfonium salts. Although this reaction is formally
analogous to the reaction of methyl thioethers with alkyl halides,
13, 14a-l, 15a
[1,2(7,12)-(MeS)2B12H10]2- + 2RX CH CN8
3
9-11
10 + 2X- (3)
1,2(7,12)-(MeSR)2B12H
16, 17a-c, 18a
solution of any thioether 5-11 as a tetramethyl ammonium salt
in acetonitrile at room temperature results in almost immediate
precipitation of the corresponding halide. As expected, second-
ary alkyl iodides and primary alkyl bromides react considerably
more slowly. We were surprised to discover that a product of
alkylation of 6-8 was always accompanied by formation of a
parent sulfonium salt (Me2S)2B12H10 in small quantities, when
a reaction mixture was heated. However, by studying demethy-
lation of isomers of (Me2S)2B12H10 by nucleophiles in DMF
and CH3CN, we noticed that the reaction of 1 equiv of a
nucleophile with (Me2S)2B12H10 produces not only a mono-
thioether, but also a dithioether and a starting bissulfonium salt
in lesser amounts, the ratio of the last two being approximately
1:1. Considering these experimental facts, we proposed that in
these solvents a thioether-sulfonium species is in equilibrium
with dithioether and bissulfonium species as pictured below for
the 1,7-isomer (eq 4). To prove the existence of equilibrium 4,
equimolar amounts of 3 and [Me4N]2[10] were placed in an
NMR tube and dissolved in acetonitrile-d3. The solution was
allowed to stand at room temperature while being occasionally
monitored by 11B{1H} NMR. New signals that could be
attributed to thioether 7 being formed were clearly observed
on the fifth day after mixing. Since the appearance of the
spectrum was changing very slowly at room temperature, the
solution was heated at 70° C to allow for the equilibrium to
establish faster. After heating for 5 days, no further change in
the spectrum, which at this point primarily featured the signals
due to 7, was observed. A similar experiment was run in
acetonitrile with 4 and [Me4N]2[11]. At room temperature this
(4) Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong, F.-G.; Barth, R. F.;
Codogni, I. M; Wilson, J. G. Chem. ReV. 1998, 98, 1515-1562.
(5) Knoth, W. H.; Sauer, J. C.; England, D. C.; Hertler, W. R.; Muetterties, E.
L. J. Am. Chem. Soc. 1964, 86, 3973-3983.
(6) Sneath, R. L., Jr.; Soloway, A. H.; Dey, A. S. J. Med. Chem. 1974, 17,
796-799.
(7) Kultyshev, R. G.; Liu, J.; Meyers, E. A.; Shore, S. G. Inorg. Chem. 2000,
39, 3333-3341.
9
J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002 2615

A R T I C L E S
Kultyshev et al.
Table 1. Alkylation of Methyl Thioethers 5-11 by Alkyl Halides and Tosylates in CH3CN
entry
thioether
alkyl halide or tosylate
alkylation product
yield (%)a
1
2
3
4
5
6
7
5
5
5
6
7
7
7
C2H5I
CH2I2
CH3S(O)(CH2)2Cl
HCtCCH2Br
C2H5I
[(MeSC2H5)B12H11]-, 12a
93/77
80
75/63
95
99
94/88
80
[(MeSCH2I)B12H11]-, 12b
[(MeS(CH2)2S(O)Me)B12H11]-, 12c
1-(MeSC3H3)-2-(Me2S)B12H10, 13
1-(MeSC2H5)-7-(Me2S)B12H10, 14a
1-(MeSCH2I)-7-(Me2S)B12H10, 14b
1-(MeS(CH2)3I)-7-(Me2S)B12H10, 14c
(µ-CH2)[1-(MeSCH2)-7-(Me2S)B12H10]2, 14d
1-(MeS(CH2)3OH)-7-(Me2S)B12H10, 14e
1-(MeS(CH2)2C(O)OMe)-7-(Me2S)B12H10, 14f
1-(MeS(CH2)4P(O)(OEt)2)-7-(Me2S)B12H10, 14g
1-(MeS(CH2)3CH[P(O)(OEt)2]2)-7-(Me2S)B12H10, 14h
CH2I2
I(CH2)3I
8
9
10
11
7
7
7
7
HO(CH2)3Br
97
97
93
85
95
89
94
99/94
96
CH3OC(O)(CH2)2Br
(EtO)2P(O)(CH2)4I
[(EtO)2P(O)]2CH(CH2)3OTs
[(EtO)2P(O)]2CH(CH2)3OMs
i-PrI
12
13
14
15
16
17
18
19
20
21
7
7
7
7
8
1-(i-PrSMe)-7-(Me2S)B12H10, 14i
1-(MeSBn)-7-(Me2S)B12H10, 14j
1-(MeSC3H5)-7-(Me2S)B12H10, 14k
1-(MeSC3H3)-7-(Me2S)B12H10, 14l
1-(MeSC3H3)-12-(Me2S)B12H10, 15a
1,2-(MeSC3H3)2B12H10, 16
1,7-(i-PrSMe)2B12H10, 17a
1,7-(MeSBn)2B12H10, 17b
1,7-(MeSC3H3)2B12H10, 17c
1,12-(MeSC3H3)2B12H10, 18a
PhCH2Cl
H2CdCHCH2Br
HCtCCH2Br
HCtCCH2Br
H2CtCCH2Br
i-PrI
PhCH2Cl
HCtCCH2Br
HCtCCH2Br
94
9
10
10
10
11
99/76
95/90
92
93
a Crude yield/yield after recrystallization.
equilibrium established even more slowly. Thus, 8 was still a
minor component 139 days after mixing. However, heating at
70° C for 6 days resulted in 8 as a major component of the
mixture (see Supporting Information). Thus, mixtures of similar
composition, where the monoanion predominates, can be
obtained from (Me2S)2B12H10 and [(MeS)2B12H10]2-, on the one
hand, and [(MeS)(Me2S)B12H10]- (demonstrated by demethy-
lation reactions of 2-4, 1:1 ratio), on the other hand, proving
the existence of the proposed equilibria. Since they establish
very slowly at room temperature, isomers of (Me2S)2B12H10 are
not usually observed among the products of alkylation of 6-8
by primary alkyl iodides as well as allyl, benzyl, and propargyl
iodides and bromides which react very rapidly. Heating a
reaction mixture to increase the rate of alkylation in the case of
the less reactive alkyl tosylates and chlorides also increases the
rate of establishment of equilibrium 4 or similar to it, producing
(Me2S)2B12H10 and the dialkylated product, (MeSR)2B12H10. As
a matter of fact, these equilibria can be used for the synthesis
of 6-8 from 2-4 and 9-11. Thus, [Me4N][7] was isolated in
75% yield after reflux of a mixture of 3 and [Me4N]2[10] (1
mmol of each) in acetonitrile for 75 h. [Me4N][8] was obtained
in comparable yield (73%) in a similar reaction after 135 h of
reflux. These yields are close to those obtained from reactions
of 3 and 4 with nucleophiles (phthalimide, ethanethiolate),7 and
the simplicity of the preparation may overcome the fact that
these reactions require longer times.
Similar to allyl bromide, propargyl bromide is an excellent
alkylating agent for methyl thioethers 5-11. Reaction takes
place almost instantly in acetonitrile. Interestingly, upon re-
crystallization from ethanol, 1-(MeSC3H3)-7-(Me2S)B12H10 (14l)
partially isomerized to its allenyl isomer (ratio propargyl:allenyl
3.9:1). Surprisingly, under similar conditions the corresponding
1,12-isomer (15a) did not isomerize. The conversion of a
propargyl to a more stable allenyl isomer is known to occur for
prop-2-ynyl sulfones and sulfonium salts.8a This process is
catalyzed by bases. Similarly, addition of a drop of triethylamine
to NMR samples of 13, 14l, and 15a in CD3CN resulted in
almost complete propargyl-allenyl isomerization in a few days.
Reaction of dithioether 10 with excess propargyl bromide in
the presence of potassium phthalimide resulted in a mixture
containing dipropargyl, diallenyl, and mixed propargyl-allenyl
isomers. This mixture was separated by medium-pressure
column chromatography (MPLC) using EtOAc-hexane (1:1)
as an eluent yielding 14% of dipropargyl, 37% of diallenyl, and
43% of the mixed propargyl-allenyl isomer. When heated in
ethanol, the propargyl-allenyl isomer produced a mixture of
all three isomers. Isomerization of propargyl or allenyl groups
of these sulfonium salts to a 1-methylethynyl (CH3-CC-)
group was never observed, although the allenyl to 1-methyl-
ethynyl isomerization has been reported previously by Zakharkin
and co-workers8b for ortho- and meta-allenylcarboranes in the
presence of a stronger base, t-BuOK.
Interestingly, when either 5 or 7 is alkylated by CH2I2 (Table
1, entries 2 and 6), only the product of monosubstitution is
formed, even if the reaction mixture containing excess borane
is refluxed. The carbon atom is presumably too hindered for
the substitution of the second iodide by the bulky sulfur
nucleophile. However, the smaller ethanethiolate anion displaces
iodide from [(MeSCH2I)B12H11]- (12b) yielding [(MeSCH2SEt)-
B12H11]- (12d) upon reflux. As expected, a small amount of
disubstitution product 14d (a mixture of meso- and D,L-
diastereomers) is formed in the reaction of thioether 7 with
excess 1,3-diiodopropane (Table 1, entry 7).
Stereochemistry of Alkylation. When R is not a methyl
group (eqs 1-3), prochiral methyl thioethers 5 and 6-8 yield
racemic sulfonium salts [(MeSR)B12H11]- and (MeSR)(Me2S)-
B12H10. Thus, the X-ray structures of 1-(MeSR)-7-(Me2S)B12H10
(14i, R ) i-Pr, Figure 1; 14j, R ) Bn, see Supporting
Information) determined by single-crystal X-ray diffraction
reveal that every molecule in a unit cell is related to its
(8) (a) Appleyard, G. D.; Stirling, C. J. M. J. Chem. Soc. C 1969, 1904-
1908. (b) Zakharkin, L. I.; Kovredov, A. I.; Shaugumbekova, Z. S.;
Vinogradova, L. E.; Leites, L. A. Russ. J. Gen. Chem. 1981, 51, 1337-
1342.
9
2616 J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002

S-Alkylation and S-Amination of Methyl Thioethers
A R T I C L E S
Figure 1. The molecular structure of 1-(i-PrSMe)-7-(Me2S)B12H10 (14i)
with 25% thermal ellipsoids.
Figure 2. The molecular structure of meso-1,7-(MeSBn)2B12H10 (17b) with
25% thermal ellipsoids.
Chart 2
Figure 3. The molecular structure of meso-1,2-(MeSC3H3)2B12H10 (16)
with 25% thermal ellipsoids. Hydrogen atoms on carbons are omitted for
clarity.
NMR. The molecular structure of 1,7-(MeSBn)2B12H10 (17b)
(Figure 2) revealed that the chosen crystal was of the meso-
diastereomer, but other crystals were not examined for the
presence of the D,L-diastereomer. However, the asymmetric
centers in 1,2-(MeSR)2B12H10 are close to each other; therefore,
1
enantiomer via a center of symmetry. Prochiral methyl dithio-
ethers 9-11 produce racemic [(MeSR)(MeS)B12H10]- upon
reaction with 1 equiv of RX. Addition of a second equivalent
of RX should lead to formation of diastereomers (Chart 2). In
the case of 9 and 10, which have the same symmetry (C2V),
these would be a racemic mixture of (R,R)- and (S,S)-1,2(7)-
(MeSR)2B12H10 (both C2) and achiral diastereomer meso-(R,S)-
1,2(7)-(MeSR)2B12H10 (Cs) possessing a mirror plane. Similarly,
dialkylation of 11 would result in a racemic mixture of (R,R)-
and (S,S)-1,12-(MeSR)2B12H10 (both C2) and meso-(R,S)-1,12-
(MeSR)2B12H10 (Ci), the latter compound being achiral by virtue
of a center of symmetry. The presence of diastereomers is not
the H NMR spectrum of 16 displays two sets of signals, one
for the meso- and another for the D,L-diastereomer. Unfortu-
nately, only the meso-diastereomer of 16 produced X-ray quality
crystals from a dichloromethane solution of the mixture of
diastereomers (Figure 3).
Synthesis of Boronated Phosphonate and gem-Bisphos-
phonates by Alkylation of 7 with Primary Alkyl Iodides and
Tosylates. A phosphonate and a gem-bisphosphonate containing
an icosahedral borane cage were synthesized for potential use
as BNCT agents. The rationale for their syntheses stems from
previous biological studies indicating that certain phosphorus-
containing boron clusters are selectively taken up to a high
extent in tumor/rodent models.9a Also, due to their selective
uptake in primary and metastatic bone tumors, bis- and
polyphosphonates have found wide application in the diagnosis
and therapy of these cancers.9b-e Recently, targeted radiotherapy
of bone tumors with R-emitter-containing phosphonates has been
proposed.9f,g Thus, boronated derivatives of bisphosphonates
1
supported by H NMR for either 1,7- or 1,12-(MeSR)2B12H10,
as only one set of signals is observed, regardless of the identity
of R. A possible explanation is that the asymmetric centers in
the 1,7- and 1,12-isomers are too far from each other, which
renders the environment of the corresponding protons in two
diastereomers to be very similar and thus indistinguishable by
9
J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002 2617

A R T I C L E S
Kultyshev et al.
Scheme 1. Synthesis of Boronated Phosphonate 14g and Its
Sodium Salt 20
alkylating reagent. Since the resulting mixtures containing the
monoalkylated product along with some dialkylated product and
TEMBP were difficult to separate, the entire mixture was usually
subjected to the hydroboration-oxidation procedure.11 Tosylation
or mesylation of a residue consisting of monoalcohol and
TEMBP (diol is lost in the workup) afforded a mixture of
sulfonate ester 22b (22c) and TEMBP, which was easier to
separate. Reaction of a sulfonate ester with the tetramethylam-
monium salt of 7 in acetonitrile is sluggish even upon heating;
however, addition of dry NaI dramatically improves the rate of
conversion. An alternative procedure for the preparation of 22a
has been recently reported by Sturtz and co-workers.13 Ethyl
esters 14g and 14h were converted into the sodium salts of the
corresponding phosphonic and bisphosphonic acids, respectively,
by treatment with excess bromotrimethylsilane (TMSBr) fol-
lowed by the carbonate-buffered hydrolysis of the resulting
trimethylsilyl esters and adjusting the pH of solutions to 11 with
aqueous NaOH.14 Ethyl esters 14g and 14h are the first examples
of compounds containing both a closo-B12 moiety and a
phosphonate or bisphosphonate group, although similar com-
pounds based on ortho-carborane have been reported.15 The
sodium salts 20 and 23 were subjected to in vivo evaluation
for BNCT using various tumor/rodent models.16 In particular,
23 showed very promising results in an osteosarcoma/mouse
model.
Scheme 2. Synthesis of gem-Bisphosphonate 14h and Its Sodium
Salt 23
may have potential for the palliative and possibly curative
treatment of primary and metastatic bone tumors by BNCT.
Taking advantage of the excellent reactivity of methyl
thioether 7 toward primary alkyl iodides and the hydrolytic
stability of the resulting S-C linkage, a boronated diethyl
butylphosphonate 14g was synthesized according to Scheme 1.
Synthesis of a similar compound containing a terminal gem-
bisphosphonate group presented a greater challenge. Tetraethyl
1-iodo-4,4-bisphosphonobutane (19b) is not available via the
alkylation of tetraethyl methylene bisphosphonate (TEMBP) by
1,3-diiodopropane (Scheme 2). From the reaction in THF only
the elimination product, tetraethyl 1,1-bisphosphonobut-3-ene
(21a), was isolated, while the reaction in toluene produced
tetraethyl cyclobutane-1,1-bisphosphonate (21b) and 21a. Ebe-
tino et al.10 isolated tetraisopropyl cyclobutane-1,1-bisphospho-
nate in 70% yield from the reaction of tetraisopropyl methyl-
enebisphosphonate with propane-1,3-ditosylate under similar
conditions. An attempt to alkylate TEMBP with a sulfonium
salt bearing a terminal iodide (14c) was also unsuccessful as
iodide was mostly eliminated under the reaction conditions
yielding 14k, identified by comparison with the spectrum of
the authentic sample prepared according to eq 2. The desired
bisphosphonate 14h was obtained in only 19% yield; therefore,
it was decided to return to a synthetic scheme where 14h is
obtained by alkylation of thioether 7 by a halide or tosylate
already bearing the bisphosphonate moiety. Keeping in mind
that 21a formed easily in the alkylation of TEMBP by 1,3-
diiodopropane, we prepared 21a using allylbromide as an
Nucleophilic Addition of Methyl Thioethers to Activated
Alkenes and Alkynes. Alkylation of methyl thioethers by alkyl
halides and tosylates has its usual limitations. Only primary and
secondary alkyl groups can be introduced. However, addition
of a nucleophile to an electron-deficient alkene (Michael
addition) is not affected by steric problems nearly as much since
the carbon to be attacked is sp2-hybridized. Organic thioethers
are known to form sulfonium salts upon reaction with activated
alkenes.17 Similarly, thioethers 5-11 react with a variety of R,â-
unsaturated substrates (Table 2, Scheme 3) in the presence of a
strong acid, such as HCl. As expected, tertiary substituents can
be introduced easily by this method. When an electron-deficient
alkyne was used (propiolic acid), vinyl sulfonium salts 25a,b
were produced, a result not available by a simple alkylation.
The presence of a strong acid is absolutely necessary to drive
the reaction to completion by trapping the intermediate carban-
ion, which is in equilibrium with the starting materials. The
reaction of methyl thioethers with acrylonitrile under acidic
conditions reported here is a reverse of the retro-Michael
reaction reported by Gabel and co-workers18 in which [(RSCH2-
CH2CN)B12H11]- and [Me4N]OH yielded acrylonitrile and
(11) The alternative preparation of 21a by phosphonylation of diethyl phospho-
nobut-3-ene12 did not produce a higher yield of the desired bisphosphonate
in our hands.
(12) Dufau, C.; Sturtz, G. Phosphorus, Sulfur Silicon Relat. Elem. 1992, 69,
93-102.
(13) Gourves, J.-P.; Couthon, H.; Sturtz, G. Phosphorus, Sulfur Silicon Relat.
Elem. 1998, 132, 219-229.
(14) Gross, H.; Keitel, I.; Costisella, B.; McKenna, C. E. Phosphorus, Sulfur
Silicon Relat. Elem. 1991, 61, 177-181.
(9) (a) Bechtold, R. A.; Kaczmarczyk, A.; Messer, J. R. J. Med. Chem. 1975,
18, 371-376. (b) Brown, D. L.; Robbins, R. J. Clin. Pharmacol. 1999,
39, 651-660. (c) Bruland, O. S.; Aas, M.; Solheim, O. P.; Vindern, M.;
Hoie, J. Bone Miner. 1994, 25, 497-499. (d) Bruland, O. S.; Skretting,
A.; Solheim, O. P.; Aas, M. Acta Oncol. 1996, 35, 380-384. (e) Lattimer,
J. C.; Corwin, L. A. J.; Stapleton, J.; Volkert, W. A.; Ehrhardt, G. J.;
Ketring, A. L.; Anderson, S. K.; Simon, J.; Goeckler, W. F. J. Nucl. Med.
1990, 31, 1316-1325. (f) Hassfjell, S. P.; Hoff, P.; Bruland, O. S.; Alstad,
J. J. Labelled Compd. Radiopharm. 1994, 34, 717-734. (g) Hassfjell, S.
P.; Bruland, O. S.; Hoff, P. Nucl. Med. Biol. 1997, 24, 231-237.
(10) Ebetino, F. H.; Degenhardt, C. R.; Jamieson, L. A.; Burdsall, D. C.
Heterocycles 1990, 30, 855-862.
(15) (a) Semioshkin, A.; Lemmen, P.; Inyushin, S.; Ermanson, L. In AdVances
In Boron Chemistry; Siebert, W., Ed.; The Royal Society of Chemistry:
Cambridge, 1997; pp 311-314. (b) Komagata, T.; Kawanabe, T.; Mat-
sushita, T. Japanese Patent 11080177 A2 990326 Heisei, 1999.
(16) (a) Kultyshev, R. G.; Tjarks, W.; Adams, D. M.; Rotaru, J.; Barth, R. F.;
Soloway, A. H.; Shore, S. G. Abstracts of ACS 31st Central Regional
Meeting; The Ohio State University, Columbus, Ohio, June 21-23, 1999.
(b) Tjarks, W.; Barth, R. F.; Rotaru, J.; Adams, D. M.; Yang, W.; Kultyshev,
R. G.; Forrester, J.; Barnum, B. A.; Soloway, A. H.; Shore, S. G. Anticancer
Res. 2001, 21, 841-846.
(17) Stirling, C. J. M. In Organic Chemistry of Sulfur; Oae, S., Ed.; Plenum
Press: New York, 1977; pp 473-525.
9
2618 J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002

S-Alkylation and S-Amination of Methyl Thioethers
A R T I C L E S
Table 2. Alkylation of Methyl Thioethers 5 and 10 by Activated Alkenes (Michael Addition)
a
b
entry
thioether
R
1
R
2
R
3
EWG
product
yield, %
1
2
3
4
5
5
5
5
5
10
H
Ph
H
Me
Me
H
H
H
Me
Me
H
H
CN
Ac
P(O)(OEt2)2
Ac
Ac
[(MeSCH2CH2CN)B12H11]-, 24a
85/70c
93c
[(MeSCHPhCH2C(O)Me)B12H11]-, 24b
[(MeSCH2CH[P(O)(OEt)2]2)B12H11]-, 24c
[(MeSCMe2CH2C(O)Me)B12H11]-, 24d
1,7-(MeSCMe2CH2C(O)Me)2B12H10, 26
P(O)(OEt2)2
H
H
89c
88/52c
92
a Electron-withdrawing group. b Crude yield/yield after recrystallization. c Isolated as tetramethylammonium salt.
Scheme 3. Alkylation of Methyl Thioethers by Activated Alkenes
and Alkynes (Michael Addition)
Figure 4. The molecular structure of [(MeSCH2CH[P(O)(OEt)2]2)B12H11]-
(24c) with 25% thermal ellipsoids. Hydrogen atoms on carbons are omitted
for clarity.
after 45 min and 1:1.15 after 20 h. Similarly, when 8 was used
as a nucleophile, the Z/E product ratio also decreased as the
reaction time increased from 40 min to 24 h (1.7:1 vs 1.3:1,
respectively). The E- and Z-proton signals were assigned from
the values of the coupling constants of the vicinal vinyl
protons.19
Hutchinson and Thornton20 have shown that tetraalkyl ethen-
ylidene bisphosphonates can participate in Michael addition
reactions with various nucleophiles, giving especially good
results with thiols. Keeping in mind that methyl thioethers 5-11
are excellent nucleophiles, Michael addition was used as an
alternative route to the boronated gem-bisphosphonates. Reaction
of the readily available tetraethyl ethenylidene bisphosphonate21
with thioether 5 afforded 24c (Figure 4), a charged homologue
of bisphosphonobutane 14h having one less Me2S substituent,
in 89% yield.
[RSB12H11]2- (a leaving group) via â-hydrogen abstraction.
Although we did not attempt similar retro-Michael reactions
using [Me4N]OH, the same result was obtained when we tried
to remove both methyl groups in 26 by excess NaSEt or
potassium phthalimide. Instead of the expected dithioether
featuring tertiary substituents on each sulfur atom, dithioether
10 was obtained as the only boron product (Scheme 3). This
was confirmed by methylation of the reaction product with
methyl iodide and isolation of 3.
NMR Spectra of the Alkylation Products. When R is a
primary alkyl group, the 11B{1H} NMR spectra of [(MeSR)-
B12H11]-, (MeSR)(Me2S)B12H10, and (MeSR)2B12H10 are not
very different from those of [Me2SB12H11]- and (Me2S)2B12H10
and therefore are not reported in the Experimental Section.
However, replacing R with a secondary or tertiary alkyl group
significantly modifies the appearance of the spectrum. Thus,
while the signals due to the B(5,12) and B(4,6,8,11) overlap in
the spectra of 1,7-(Me2S)2B12H10 and 1-(MeSR)-7-(Me2S)B12H10
(R ) Et, CH2I, (CH2)3I) even at 160.5 MHz, all signals are
resolved in the spectra of 14i (R ) i-Pr) and 1,7-(i-
PrSMe)2B12H10 (17a) because of the shift of the peak of intensity
A modest degree of diastereoselectivity was observed in the
conjugate addition reactions of substrates possessing two
different substituents at the â-carbon. Thus, for trans-4-phenyl-
3-butene-2-one and 5 the ratio of diastereomeric products is
1
4.4:1, as calculated from the integration data of the H NMR
spectrum. Unfortunately, it was not possible to determine
whether the major product has a syn or anti relative stereo-
chemistry. A lower degree of diastereoselectivity (approximately
3:2 ratio) was observed when the same thioether reacted with
3-methyl-2-cyclohexen-1-one. The Z/E product ratio for the
reaction of thioethers 7 and 8 with an excess of propiolic acid
seems to depend on the time of stirring and favors the more
stable E-isomer at longer reaction times. Thus, for 7 it was 1.8:1
(19) Silverstein, R. M.; Webster, F. X. Spectrometric Identification of Organic
Compounds; Wiley: New York, 1998.
(20) Hutchinson, D. W.; Thornton, D. M. J. Organomet. Chem. 1988, 346, 341-
(18) Gabel, D.; Moller, D.; Harfst, S.; Rosler, J.; Ketz, H. Inorg. Chem. 1993,
32, 2276-2278.
348.
(21) Degenhardt, C. R.; Burdsall, D. C. J. Org. Chem. 1986, 51, 3488-3490.
9
J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002 2619

A R T I C L E S
Kultyshev et al.
Scheme 4. Synthesis of ortho-Carborane-dodecaborane
Oligomers 14m and 17d
2 downfield. In the case of compound 26, this signal moves
downfield even further and overlaps with another signal of
intensity 2 due to B(9,10) (see Supporting Information). The
presence of the vinyl substituent on a sulfur atom (25a,b) does
not lead to any significant changes in the 11B{1H} NMR spectra
of these compounds as compared to those of 3 and 4. The
characteristic feature of 1H NMR spectra of alkylated products
is the presence of two diastereotopic methylene hydrogens (or
any other identical groups attached to the carbon atom next to
asymmetric sulfur atom). These hydrogens usually appear
downfield from the Me2S singlet as an “AB quartet”. For
(MeSR)(Me2S)B12H10 the MeS signal is upfield from the Me2S
when R is an alkyl group such as Et, i-Pr, Bn, or allyl. The
presence of an electron-withdrawing group in R causes this order
to reverse (R ) CH2I (12b), (CH2)2C(O)OMe (14f), C3H3 (13,
14l, and 15a)). When an electron-withdrawing group is attached
to a γ-carbon and further, the Me2S and MeS resonances have
almost the same chemical shifts as in 14c, 14e, 14g, and 14h.
Synthesis of Dodecaborane-ortho-carborane Oligomers. A
number of open-chain and macrocyclic compounds containing
several carborane nuclei have been reported.22 In these com-
pounds the cages are linked either by vertexes (C-C, C-B) or
some spacer like -(CH2)3- or a disubstituted benzene ring.
Recently, oligomeric structures containing a number of nido-
o-carboranyl clusters have received considerable attention as
potential BNCT agents.23a However, similar systems incorporat-
ing the closo-B12 cage, which may also serve as valuable boron
moieties in BNCT agents, have been less well studied.23b The
use of boron cluster entities containing different types of boron
cages has been proposed as an innovative strategy in the
synthesis of BNCT agents.2d,23c We used propargyl sulfonium
salts 14l, 15a, 17c, and 18a as starting materials in the synthesis
of two- and three-cage compounds 14m, 15b, 17d, and 18b,
respectively, containing both o-carborane and dodecaborane
cages linked together via -CH2-S(Me)- units as shown in
Scheme 4 for 14l and 17c. The isolated yields are moderate in
the case of two-cage compounds (40-50%) and even lower
for three-cage compounds (25-40%). Both B10H12(SEt2)2 and
B10H12(CH3CN)2 complexes were used as starting materials to
form the o-carborane nucleus, and neither was of particular
advantage. Since the presence of allenyl isomers was never
Figure 5. The molecular structure of 1-(1′,2′-C2B10H11CH2SMe)-12-
(Me2S)B12H10 (15b) with 25% thermal ellipsoids.
detected after these reactions, it seems unlikely that the partial
isomerization of propargyl sulfonium salts is responsible for
these moderate yields. The yields can be definitely improved if
a better way of separation of the two- and three-cage products
from the unreacted propargyl starting materials can be found.
The molecular structures of both 14m and 15b were determined;
the latter is shown in Figure 5 (see Supporting Information for
the structure of 14m). The 11B{1H} NMR spectrum of a two-
or three-cage compound appears to be a sum of the spectra of
the corresponding sulfonium salt (3 or 4) and monoalkyl
C-substituted ortho-carborane, 1-R-1,2-C2B10H11, taken with a
coefficient 1 or 2 depending on the number of the ortho-
carborane units present. Ten signals can be found in the spectra
of 14m and 17d (see Supporting Information). Among those,
five belong to the 1,7-disubstituted dodecaborane unit, and the
other six can be assigned to the ortho-carborane unit(s), with
the overall number of signals being reduced to 10 due to the
overlap of the borane B(1,7) singlet and one of the ortho-
carborane signals at -8.5 ppm. There is no such overlap in the
spectra of 15b and 18b; therefore, the expected number of
signals (eight) is observed, two of which are due to the 1,12-
disubstituted dodecaborane unit. The 1H{11B} NMR spectra of
these compounds are also sums of the spectra of the ap-
propriately substituted B12H10 and 1,2-C2B10H11 units. Structure
17d in Scheme 4 can be considered as a model building block
for the possible preparation of novel boron oligomers and
polymers composed of different types of boron clusters.
Variation of length and type of the spacer arms as well as
specific removal of some or all S-methyl groups in such
oligopolymers could potentially produce “custom-tailored”
boron trailers for various types of receptor-targeting approaches
in BNCT.
(22) (a) Chizhevsky, I. T.; Johnson, S. E.; Knobler, C. B.; Gomez, F. A.;
Hawthorne, M. F. J. Am. Chem. Soc. 1993, 115, 6981-6982. (b) Clegg,
W.; Gill, W. R.; MacBride, J. A. H.; Wade, K. Angew. Chem., Int. Ed.
Engl. 1993, 32, 1328-1329.
(23) (a) Nakanishi, A.; Guan, L.; Kane, R. R.; Kasamatsu, H.; Hawthorne, M.
F. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 238-241. (b) Gula, M.; Perleberg,
O.; Gabel, D. In Contemporary Boron Chemistry; Davidson, M., Hughes,
A. K., Marder, T. B., Wade, K., Eds.; The Royal Society of Chemistry:
Cambridge, 2000; pp 115-119. (c) Hosmane, N. S.; Franken, A.; Zhang,
G.; Srivastava, R. R.; Smith, R. Y.; Spielvogel, B. F. Main Group Met.
Chem. 1998, 21, 319-324.
Amination of Methyl Thioethers with Hydroxylamine-O-
sulfonate. Hertler and Raasch reported24 that closo-[B12H12]2-
and [Me3NB12H11]- react with potassium hydroxylamine-O-
sulfonate to yield B-substituted products, (H3N)2B12H10 and
(Me3N)(H3N)B12H10, believed to be mostly 1,7-isomers.
(24) Hertler, W. R.; Raasch, M. S. J. Am. Chem. Soc. 1964, 86, 3661-3668.
9
2620 J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002

S-Alkylation and S-Amination of Methyl Thioethers
A R T I C L E S
[1-(Me2S)B10H9]- produced 1-(Me2S)-6-(H3N)B10H8. Since the
directive effect of the electron-rich methylthio group might be
the opposite of that of the dimethyl sulfide substituent, it was
hoped that methyl thioethers would react with substitution on
the boron adjacent to the already substituted boron atom. Thus,
[Me2SB12H11]- would form 1-(Me2S)-2-(H3N)B12H10, which
may be envisioned as a precursor for an interesting S,N-bidentate
ligand [1-(MeS)-2-(H2N)B12H10]2-. Unfortunately, the sulfur
atoms in methyl thioethers are too nucleophilic for the amination
to occur at a boron site, and aminosulfonium salts are produced
instead (eqs 5-7) in a reaction similar to S-alkylation by alkyl
[MeSB12H11]2- + [H2NOSO3]- CH CN, H O8
3
2
5
2-
[(MeSNH2)B12H11]- + SO4 (5)
27
[1-(MeS)-7(12)-(Me2S)B12H10]- +
Figure 6. The molecular structure of meso-1,2-(MeSNH2)2B12H10 (31) with
25% thermal ellipsoids.
7-8
[H2NOSO3]- CH CN, H O8
search). For separation of boron compounds, fractions obtained after
chromatography were analyzed by TLC using the palladium dichloride
stain. 1H NMR spectra were obtained on Bruker DRX-500, DPX-400,
and AM-250 spectrometers at 500.1, 400.1, and 250.1 MHz, respec-
tively, and referenced to residual solvent protons. 13C NMR spectra
were obtained on Bruker DRX-500, DPX-400, and AM-250 spectrom-
eters operating at 125.8, 100.6, and 62.9 MHz, respectively, and
referenced to deuterated solvent signals. 11B spectra were obtained on
the Bruker DRX-500 spectrometer at 160.5 MHz and referenced
externally to BF3‚OEt2 in C6D6 (δ ) 0.00 ppm). 31P NMR spectra were
obtained on Bruker DRX-500 and AM-250 spectrometers operating at
202.5 and 101.3 MHz, respectively, and referenced externally to 85%
H3PO4. Coupling constants are reported in Hertz. The mass spectra
were recorded either on the Micromass QTOF Electrospray (ESI) or
on the VG-70 (EI) mass spectrometers. Elemental analyses were
performed by Galbraith Laboratories, Inc., of Knoxville, TN. Complete
syntheses are described in Supporting Information.
General Procedure for the Synthesis of [(MeSR)B12H11]- by
Reaction of 5 with Alkyl Halides. To a solution of [Me4N]2[5] (1-2
mmol) in acetonitrile (15-20 mL) was added an excess of alkyl halide,
and the resulting mixture was stirred overnight at room temperature.
The volatile materials were removed in vacuo leaving behind a residue,
which was washed with water, cold ethanol, and pentane and was dried
overnight at 70 °C.
3
2
2-
1-(MeSNH2)-7(12)-(Me2S)B12H
10 + SO4 (6)
28-29
[1,7(12)-(MeS)2B12H10]2- + 2[H2NOSO3]- CH CN, H O8
10-11
3
2
2-
1,7(12)-(MeSNH2)2B12H
10 + 2SO4 (7)
30-31
halides or tosylates. Despite this similarity, the yields of
S-aminated products are generally lower than those of the
sulfonium salts, and their isolation always requires chromatog-
raphy due to the presence of unidentified side products.
The 11B{1H} NMR spectra of 27 and 30-31 are very similar
to those of their parent sulfonium salts, except that the
substituted boron atoms resonate at a slightly lower field in the
former case. The ipso-boron atoms in 28 and 29 give rise to
two distinct singlets in a 1:1 ratio due to the MeSNH2 and Me2S
substituents. Presumably, the most downfield signal is due to
the boron bearing the MeSNH2 group. S-Amination results in
1
a downfield shift of methyl resonances in H NMR spectra of
the aminosulfonium salts as compared to those of the parent
sulfonium compounds. All resonances in the spectra of com-
pounds with the 1,7-substitution pattern are located slightly
downfield from the corresponding resonances of the 1,12-
substituted aminosulfonium salts, as was the case with parent
sulfonium salts 3 and 4. The molecular structure of meso-1,12-
(H2NSMe)2B12H10 (31) was determined by single-crystal X-ray
diffraction (Figure 6).
General Procedure for the Synthesis of [(MeSR)B12H11]- by
Reaction of 5 with Activated Alkenes (Michael Addition). Concen-
trated HCl (0.3-0.5 mL) was added to a solution containing 0.8-1.0
mmol of [Me4N]2[5] and an excess of an activated alkene in 20-30
mL of acetonitrile. The resulting mixture was stirred overnight and
concentrated in vacuo. The residue was washed with water, cold ethanol,
and pentane and was dried overnight at 70 °C.
General Procedure for the Synthesis of (MeSR)(Me2S)B12H10 and
(MeSR)2B12H10. In a typical experiment, 0.5-1.0 mmol of [Me4N]-
[(MeS)(Me2S)B12H10] or [Me4N]2 [(MeS)2B12H10] in a 100 mL round-
bottom flask is dissolved in 15-25 mL of acetonitrile, and excess alkyl
halide is added. After overnight stirring, volatiles are removed on a
flash evaporator, and a residue is partitioned between dichloromethane
and water. After phase separation, an aqueous phase is extracted with
a fresh portion of CH2Cl2, and the organic phases are combined and
dried over MgSO4. The crude products are obtained after solvent
removal under reduced pressure and purified by chromatography and/
or recrystallization.
Experimental Section
General Methods. Tetramethylammonium salts of methyl thioethers
5-11 were prepared according to the previously published methods.7
Diethyl 1-iodo-4-phosphonobutane (19a) was obtained according to the
procedure of Kim et al.25 All alkylating reagents except mesityl oxide
(Acros Organics) were purchased from Aldrich. Chromatography was
performed on Selecto silica gel (230-430 mesh). Radial chromatog-
raphy was performed on Chromatotron (model 8924, Harrison Re-
[Me4N][(MeSCH2SEt)B12H11] ([Me4N][12d]). A 50 mL three-neck
round-bottom flask equipped with a condenser, stirbar, and rubber
(25) Kim, C. U.; Luh, B. Y.; Misco, P. F.; Bronson, J. J.; Hitchcock, M. J. M.;
Ghazzouli, I.; Martin, J. C. J. Med. Chem. 1990, 33, 1207-1213.
9
J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002 2621

A R T I C L E S
Kultyshev et al.
septum was charged in a drybox with 0.0406 g of sodium (1.76 mmol)
followed by addition of 5 mL of ethanol. When gas evolution ceased,
0.13 mL of ethanethiol (1.703 mmol) was added by syringe followed
by a solution of 0.6401 g of [Me4N][12b] (1.588 mmol) in 10 mL of
acetonitrile. The resulting mixture was refluxed for 2.5 h, the volatile
materials were removed under reduced pressure, and the residue was
recrystallized from water providing the title compound as a white solid
pressure leaving behind the desired alcohol as a colorless oil (0.428 g,
1
68%). H NMR (CDCl3, 250 MHz): δ 4.17 and 4.15 (2 quintets, 8H,
3JHP ) 3JHH ) 7.1, OCH2CH3), 3.65 (t, 2H, 3JHH ) 5.9, CH2OH), 3.17
(br s, 1H, OH), 2.36 (tt, 1H, 2JHP ) 24.3, 3JHH ) 5.5; CH[P(O)(OEt)2]2),
3
2.15-1.93 (m, 2H, CH2CH), 1.80 (quintet, JHH ) 6.6, CH2CH2OH),
1.33 (t, 12H, 3JHH ) 7.1, OCH2CH3). 13C{1H} NMR (CDCl3): δ 63.0
2
1
and 62.8 (2d, JCP ) 6.6; OCH2), 61.6 (s, CH2OH), 36.0 (t, JCP
)
)
1
2
(0.3947 g, 74%). H NMR (CD3CN, 500 MHz): δ 4.17 (d, 1H, JHH
) 13.9, SCHaHbS), 3.87 (d, 1H, 2JHH ) 13.9, SCHaHbS), 3.08 (s, 12H,
N(CH3)4), 2.73-2.67 (m, 2H, SCH2CH3), 2.54 (s, 3H, SCH3), 1.26 (t,
133.5, CH[P(O)(OEt)2]2), 31.9 (t, 2JCP ) 6.1, CH2CH), 21.9 (t, 3JCP
4.8, CH2CH2CH2), 16.4 (d, JCP ) 6.1, OCH2CH3). 31P{1H} NMR
3
(CHCl3): δ 25.4.
3H, 3JHH ) 7.4, CH2CH3). 13C{1H} NMR (CD3CN): δ 56.3 (t, JCN
)
MsO(CH2)3CH[P(O)(OEt)2]2 (22b). The general procedure for
mesylation of alcohols by Grossland and Servis26 was used. In a typical
experiment, 0.3 mL of triethylamine and 8 mL of dry dichloromethane
were condensed onto 0.428 g of alcohol 22a (1.236 mmol) in a three-
neck 50 mL round-bottom flask equipped with a stirbar and rubber
septum. The flask was placed in an ice-water bath, and the solution
was stirred for 1 h under nitrogen. Mesyl chloride (0.12 mL) was added
slowly by syringe (within 15 min). After appearance of precipitate,
the solution was stirred for an additional 1 h followed by the standard
workup procedure. The title compound, a colorless liquid, was held
on the vacuum line overnight to remove the residual solvent (0.450 g,
11
4), 47.1, 27.2, 23.3, 14.6. MS (ESI): calcd for C4H2110B2 B10S2, m/z
) 263.2278. Obsd, m/z ) 263.2290 (M-).
1-(MeS(CH2)4P(O)(OEt)2)-7-(Me2S)B12H10 (14g). A solution of
[Me4N][7] (0.9605 g, 2.972 mmol) and 19a (1.0366 g, 3.24 mmol) in
20 mL of acetonitrile was stirred for 22.5 h. After a standard workup
procedure the crude product was chromatographed using a EtOAc-
MeOH mixture (9:1) as an eluent. The product free of solvents was
obtained as a colorless oil (1.2202 g, 93%) after 2 days of heating on
the vacuum line at 100 °C (oil bath). 1H NMR (CDCl3): δ 4.14-4.04
(m, 4H, OCH2CH3), 3.10-3.02 (m, 1H, SCHaHb), 2.81-2.74 (m, 1H,
SCHaHb), 2.53 (s, 6H, S(CH3)2), 2.52 (s, 3H, SCH3), 1.94-1.68 (m,
6H, CH2CH2CH2P), 1.33 (t, 6H, OCH2CH3). 13C{1H} NMR (CDCl3):
δ 61.8 (d, 2JCP ) 6.3, OCH2), 42.4 (s, SCH2), 26.7 (d, J ) 14.8), 25.8
1
3
86%). H NMR (CDCl3, 500 MHz): δ 4.20 (t, 2H, JHH ) 5.8, CH2-
OMs), 4.18-4.10 (m, 8H, OCH2CH3), 2.98 (s, 3H, CH3SO2), 2.28 (tt,
2
3
1H, JHP ) 24.0, JHH ) 5.5; CH[P(O)(OEt)2]2), 2.05-1.98 (m, 4H,
CH2CH2), 1.31 (t, 12H, 3JHH ) 7.0, OCH2CH3). 31P{1H} NMR (CDCl3,
202.5 MHz): δ 24.3.
1
(s, S(CH3)2), 25.0 (d, JCP ) 141.9, CH2P), 23.6 (s, SCH3), 21.7 (d, J
3
) 4.5), 16.6 (d, JCP ) 5.8). 31P{1H} NMR (CDCl3): δ 31.2. Anal.
Calcd: C, 29.87; H, 8.43. Found: C, 29.61; H, 8.74.
1-(MeS(CH2)3CH[P(O)(OEt)2]2)-7-(Me2S)B12H10 (14h). A. From
22c. In a drybox, 0.304 g of NaI (2.03 mmol) was added to a 100 mL
round-bottom flask containing 0.9229 g of tosylate (1.837 mmol) and
a stirbar. Dry acetonitrile (10 mL) was condensed, and the resulting
solution was stirred at room temperature for 1.5 h. To the cloudy
yellowish solution was added [Me4N][7] (0.564 g, 1.745 mmol), and
the resulting mixture was heated at 70 °C under nitrogen with a
condenser for 7 h. The solvent was removed under reduced pressure,
and a residue was partitioned between dichloromethane and water. The
organic phase was separated and dried with sodium sulfate. The crude
yellowish oil obtained after the solvent removal was purified by radial
chromatography on a 4 mm layer plate using a EtOAc-MeOH mixture
(4:1) as an eluent. The mixture was introduced as a solution in
dichloromethane. After combining the appropriate fractions and remov-
ing solvents on a flash evaporator, the residual solvents were removed
on the vacuum line by heating at 80 °C for 36 h providing 0.8627 g of
14h (85%) as a thick white oil.
1-(MeS(CH2)4P(O)(ONa)2)-7-(Me2S)B12H10.xH2O (20). Dry dichlo-
romethane (15 mL) was condensed on the vacuum line into a 100 mL
round-bottom flask containing 1.0139 g of diethyl ester 14g and a
stirbar. In the drybox, 1.22 mL of 97% TMSBr (8.97 mmol) was added
by syringe. After the solution was stirred in the sealed flask for 24 h,
the 31P{1H} NMR spectrum of the solution indicated the complete
conversion of the diethyl ester to the bis(trimethylsilyl) ester having a
single signal at 15.3 ppm. The volatile materials were removed under
reduced pressure, and the solution of sodium carbonate (0.302 g, 2.85
mmol) in 6 mL of water was added to the residue causing a white
solid to precipitate. A small amount of acetone was added to dissolve
the precipitate, and the resulting solution was stirred overnight in a
beaker. After filtration, 1 mL of aqueous 3M NaOH was added to the
solution to adjust the pH approximately to 11. The solution was
transferred into a 250 mL round-bottom flask followed by removal of
water on the rotary evaporator with heating. The off-white residue was
redissolved in 10 mL of water and transferred into a 500 mL Erlenmeyer
flask followed by addition of 350 mL of 2-propanol. The white
precipitate was filtered off, washed with 10 mL of ethanol (95%) and
pentane, and dried overnight at 70 °C. The product (0.7459 g, 76%) is
hygroscopic; therefore, the yield is only approximate. 1H NMR (CD3-
OD, 500 MHz): δ 3.05-2.99 (m, 1H, SCHaHb), 2.88-2.82 (m, 1H,
SCHaHb), 2.511 (s, 6H, S(CH3)2), 2.508 (s, 3H, SCH3), 1.85-1.65 (m,
4H, S(Me)CH2CH2), 1.50-1.44 (m, 2H, CH2P(O)(ONa)2). 13C{1H}
B. From 22b. In a procedure similar to the one described above for
tosylate, 0.9933 g of mesylate (2.341 mmol), 0.330 g of NaI (2.20
mmol), and 0.6680 g of [Me4N][7] (2.067 mmol) afforded 1.1414 g of
14h (95%). 1H NMR (CDCl3, 300 MHz): δ 4.17-4.05 (m, 8H, OCH2-
CH3), 3.02-2.92 (m, 1H, SCHaHb), 2.81-2.72 (m, 1H, SCHaHb), 2.49
(s, 6H, S(CH3)2), 2.47 (s, 3H, SCH3), 2.23 (tt, 1H, 2JHP ) 24.0, 3JHH
)
5.3; CH[P(O)(OEt)2]2), 2.10-1.90 (m, 4H, SCH2CH2CH2), 1.29 (t, 12H,
3JHH ) 7.0, OCH2CH3). 13C{1H} NMR (CDCl3): δ 62.9 and 62.7 (2d,
1
1
2JCP ) 6.7, 6.8; OCH2), 42.4 (s, SCH2), 36.1 (t, JCP ) 134.0, CH-
NMR (CD3OD, 125.8 MHz): δ 44.0, 30.8 (d, JCP ) 130), 29.1 (d,
3
2JCP ) 17), 26.0, 25.2 (d, JCP ) 3.4), 23.7. 31P{1H} NMR (CD3OD,
3
[P(O)(OEt)2]2), 25.7 (s, S(CH3)2), 25.0 (t, JCP ) 6.7, CH2CH2), 24.5
202.5 MHz): δ 22.7. MS (ESI): calcd for C7H28O310B2 B10PS2Na2,
11
2
3
(t, JCP ) 5.1, SCH2CH2CH2), 23.2 (s, SCH3), 16.4 (d, JCP ) 6.1,
m/z ) 431.2203. Obsd, m/z ) 431.2205 (M + H)+.
OCH2CH3). 31P{1H} NMR (CDCl3): δ 23.1.
‚
1-(MeS(CH2)3CH[P(O)(ONa)2]2)-7-(Me2S)B12H10 xH2O (23). In a
HO(CH2)3CH[P(O)(OEt)2]2 (22a). Dry THF (5 mL) was condensed
into a 25 mL three-neck round-bottom flask containing 0.6004 g of
21a (1.829 mmol) and a stirbar. The flask was placed into an ice-
water bath for 30 min followed by the addition of 3.0 mL of a 1.0 M
solution of BH3THF in THF under nitrogen. After stirring for 1.5 h,
the reaction mixture was quenched with methanol followed by the
addition of 1.0 mL of aqueous 3M NaOH and 1.0 mL of 30% H2O2
and heating at 50 °C for 1 h. Aqueous potassium chloride solution
was added, and the product was extracted with 40 mL of chloroform.
After the second extraction with a fresh portion of chloroform, the
extracts were combined, and the solvent was removed under reduced
drybox, 1.20 mL of 97% TMSBr (8.82 mmol) was added to a solution
of 0.8627 g of 14h (1.487 mmol) in 10 mL of dry dichloromethane,
and the resulting solution was stirred under nitrogen for 40 h. The
volatile materials were removed under reduced pressure followed by
addition of 0.68 g of anhydrous sodium carbonate in 5 mL of water. A
white precipitate appeared that was dissolved upon addition of acetone.
After standing overnight, the solution was filtered, and its pH was
adjusted approximately to 11 by addition of aqueous 3M NaOH. After
(26) Grossland, R. K.; Servis, K. L. J. Org. Chem. 1970, 35, 3195-3196.
9
2622 J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002

S-Alkylation and S-Amination of Methyl Thioethers
A R T I C L E S
Table 3. Crystallographic Data for 1-(i-PrSMe)-7-(Me2S)B12H10
(14i), meso-1,2-(MeSC3H3)2B12H10 (16), and
meso-1,7-(MeSBn)2B12H10 (17b)
water removal on the flash evaporator, the yellowish solid residue was
dissolved in 10 mL of water and filtered. To the filtrate in a 500 mL
Erlenmeyer flask was added 300 mL of 2-propanol causing a white
solid to precipitate. It was extracted with 120 mL of the boiling
methanol-water mixture (5:1), washed with pentane, and dried for 2
days at 70 °C. The resulting sodium salt is a white solid very soluble
in water (0.6941 g, 88% estimated yield assuming no water of
crystallization). 1H NMR (D2O, 500 MHz): δ 3.06-3.01 (m, 1H,
SCHaHb), 2.94-2.89 (m, 1H, SCHaHb), 2.54 (s, 3H, SCH3), 2.52 (s,
6H, S(CH3)2), 2.03-1.76 (m, 4H, CH2CH2), 1.68 (tt, 1H, 2JHP ) 21.5,
3JHH ) 6.2, CH[P(O)(ONa)2]). 13C{1H} NMR (D2O, 100.6 MHz): δ
14i
16
17b
empirical formula C6H25B12S2
C8H22B12S2
312.10
colorless
C16H30B12S2
416.24
colorless
formula weight
crystal color
cryst size, mm
space group
a, Å
291.10
colorless
0.31 × 0.31 × 0.15 0.42 × 0.31 × 0.15 0.50 × 0.15 × 0.08
P21/c
Pbca
P1h
11.593(1)
12.754(1)
11.543(1)
90
91.95(1)
90
16.579(3)
11.322(2)
19.758(4)
90
90
90
3708.8(1)
8
1.118
7.266(2)
11.976(4)
14.488(4)
93.65(3)
104.41(2)
105.43(3)
1165.6(6)
2
b, Å
c, Å
R, deg
1
42.8, 41.0 (t, JCP ) 116), 27.2 (t, JCP ) 7.3), 26.9 (br s), 25.2, 22.6.
â, deg
11B{1H} NMR (D2O, 128.4 MHz): δ -5.7 (s, B(1,7)), -12.3 (d, all
other borons). 31P{1H} NMR (D2O, 202.5 MHz): δ 21.0. MS (ESI):
γ, deg
vol, Å3
1705.7(2)
4
11
calcd for C7H26O610B2 B10P2S2Na4, m/z ) 555.1506. Obsd, m/z )
Z
F (calcd), Mg m-3 1.134
1.186
293
555.1512 (M + H)+.
temp, K
150
150
1-(E/Z-MeSCHCHCOOH)-7-(Me2S)B12H10 (25a). Concentrated
HCl (0.4 mL) was added to a solution of [Me4N][7] (0.2425 g, 0.750
mmol) and 0.06 mL of propiolic acid (0.94 mmol) in 20 mL of
acetonitrile, and the resulting solution was stirred for 40 min. The
volatile materials were removed in vacuo, and an oily residue was
partitioned between CH2Cl2 and water. The organic phase was washed
with a fresh portion of water and dried over MgSO4. The solvent was
removed under reduced pressure providing the title compound as a fluffy
radiation (λ, Å)
2θ limits, deg
µ, mm-1
0.71073
4.74-50.06
0.288
0.0394
0.1260
1.041
0.71073
4.80-50.06
0.269
0.0416
0.1302
1.078
0.71073
4.28-44.96
0.231
0.0631
0.1962
1.073
R1a [I > 2σ(I)]
wR2b (all data)
GOF on F2
a R1 ) ∑||Fo| - |Fc||/∑|Fo|. b wR2 ) {∑[w(Fo2 - Fc )2]/∑[w(Fo )2]}1/2
.
2
2
Table 4. Crystallographic Data for
1
white hygroscopic material (0.1820 g, 76%). H NMR (CD3CN, 500
[Me4N][(MeSCH2CH[P(O)(OEt)2]2)B12H11] ([Me4N][24c]),
1-(1′,2′-C2B10H11CH2SMe)-12-(Me2S)B12H10 (15b), and
meso-1,12-(MeSNH2)2B12H10 (31)
3
3
MHz): δ 7.15* (d, 1H, JHH ) 15.2, CHSMe), 6.70 (d, 1H, JHH
)
9.6, CHSMe), 6.63 (d, 1H, 3JHH ) 9.6, CHCOOH), 6.44* (d, 1H, 3JHH
) 15.2, CHCOOH), 2.74* and 2.68 (2s, 3H, SCH3), 2.483* and 2.479
(2s, 6H, S(CH3)2) (*E-isomer). 13C{1H} NMR (CD3CN): δ 164.5,
164.1, 135.8, 135.0, 132.5, 131.7, 27.8, 26.0, 25.2.
[Me4N][24c]
15b
31
empirical formula C15H49B12NO6P2S C6H32B22S2
C2H20B12N2S2
226.04
colorless
formula weight
crystal color
cryst size, mm
space group
a, Å
563.27
colorless
406.26
colorless
1-(1′,2′-C2B10H11CH2SMe)-7-(Me2S)B12H10 (14m). A 25 mL three-
neck round-bottom flask was charged with 0.1717 g of 14l (0.596
mmol), 0.0729 g of B10H14 (0.596 mmol), and a stirbar. Dry acetonitrile
(10 mL) was condensed onto the reagents, and the resulting solution
was refluxed overnight under continuous nitrogen flow. The volatile
materials were removed under reduced pressure, and the residue was
extracted with CH2Cl2. The dichloromethane solution was filtered,
concentrated, and chromatographed using CH2Cl2 as an eluent. The
pure title compound was obtained as a white powder (0.1168 g, 48%).
1H NMR (CD3CN, 250 MHz): δ 4.45 (br s, 1H, CH), 3.90 (d, 1H, J
) 15.7, SCHaHb), 3.84 (d, 1H, J ) 15.7, SCHaHb), 2.72 (s, 3H, SCH3),
2.50 (s, 6H, S(CH3)2). 13C{1H} NMR (CD3CN, 125.8 M): δ 71.1, 64.5,
0.23 × 0.15 × 0.15 0.53 × 0.31 × 0.15 0.38 × 0.31 × 0.12
P212121
8.955(1)
14.566(1)
24.271(1)
90
Cc
P21/n
7.481(1)
29.578(1)
10.573(1)
90
90.21(1)
90
2339.4(4)
4
1.153
7.933(1)
8.780(1)
10.925(1)
90
108.45(1)
90
721.8(1)
2
1.224
b, Å
c, Å
R, deg
â, deg
90
90
3166.0(4)
4
γ, deg
vol, Å3
Z
F (calcd), Mg m-3 1.182
temp, K
150
150
173
radiation (λ, Å)
2θ limits, deg
µ, mm-1
0.71073
4.84-50.02
0.234
0.0477
0.1047
1.028
0.71073
4.74-50.10
0.222
0.0430
0.1074
1.071
0.71073
5.60-50.04
0.337
0.0480
0.1301
1.030
48.9, 27.2, 26.0. 11B NMR (CD3CN, 160.5 MHz): δ -2.1 (d, JBH
)
R1a [I > 2σ(I)]
wR2b (all data)
GOF on F2
149, 1B), -4.3 (d, JBH ) 148, 1B), -8.6 (d, JBH ) 128, 2B), -8.6 (s,
B(1,7)), -11.2 (d, 2B), -11.8 (d, 2B), -12.2 (d, 2B), -13.3 (d,
B(9,10)), -14.3 (d, B(5,12)), -15.0 (d, JBH ) 135, B(4,6,8,11)), -16.4
(d, B(2,3)). MS (EI): calcd for C6H3210B411B18S2, m/z ) 406.4140. Obsd,
m/z ) 406.4149 (M+).
a R1 ) ∑| |Fo| - |Fc||/∑|Fo|. b wR2 ) {∑[w(Fo2 - Fc )2]/∑[w(Fo )2]}1/2
.
2
2
(d, JBH ) 146, B(2,3)). MS (ESI): calcd for C8H4210B4 B28S2Na, m/z
11
1,7-(1′,2′-C2B10H11CH2SMe)2B12H10 (17d). A 25 mL three-neck
round-bottom flask was charged with 0.2285 g of 17c (0.732 mmol),
0.4602 g of B10H12(SEt2)2 (1.531 mmol), and a stirbar. Dry acetonitrile
(10 mL) was condensed onto the reagents, and the resulting solution
was refluxed under nitrogen for 16 h. The volatile materials were
removed under reduced pressure, and acetone was added to the residue.
The solution was allowed to evaporate to dryness in a hood. The residue
was partitioned between dichloromethane and water, and the organic
phase was separated and dried over MgSO4. After the solvent removal,
the crude product was chromatographed using a CH2Cl2-toluene
mixture (2:3) as an eluent. The title compound was isolated as a white
powder (0.1504 g, 37%). 1H NMR ((CD3)2CO, 500 MHz): δ 5.06 (br
) 573.5762. Obsd, m/z ) 573.5778 (M + Na)+.
[Me4N][(MeSNH2)B12H11] ([Me4N][27]). A solution of [Me4N]2-
[5] (0.2120 g, 0.631 mmol) in 10 mL of acetonitrile water (1:1) was
added to a solution of H2NOSO3K obtained by mixing 0.0805 g of
hydroxylamine-O-sulfonic acid (0.690 mmol) and 0.0498 g of K2CO3
(0.360 mmol) in 5 mL of water. The resulting solution was stirred
overnight, and most of the acetonitrile was removed on a flash
evaporator. The precipitate was filtered off, washed with cold ethanol
(2-3 mL) and pentane, and dried at 70 °C for 2 h. The title compound
1
was obtained as a white powder (0.1391 g, 79%). H NMR (CD3CN,
400 MHz): δ 3.47 (br s, 2H, SNH2), 3.08 (s, 12H, N(CH3)4), 2.59 (s,
3H, SCH3). 13C{1H} NMR (CD3CN): δ 56.1 (t, JCN ) 4), 33.8. 11B
NMR (CD3CN): δ -7.9 (s), -14.1 (d), -15.8 (d). MS (ESI): calcd
2
2
s, 2H, CH), 4.18 (d, 2H, JHH ) 15.7, SCHaHb), 4.03 (d, 2H, JHH
15.7, SCHaHb), 2.86 (s, 6H, SCH3). 13C{1H} NMR ((CD3)2CO): δ 71.2,
64.5, 49.0, 26.9. 11B NMR ((CD3)2CO, 160.5 MHz): δ -1.9 (d, JBH
)
for CH16N10B2 B10S, m/z ) 204.2193. Obsd, m/z ) 204.2203 (M-).
11
)
149, 2B), -4.1 (d, JBH ) 148, 2B), -8.4 (d, JBH ) 142, 4B), -8.4 (s,
B(1,7)), -10.9 (d, 4B), -11.6 (d, 4B), -12.0 (d, 4B), -12.6 (d,
B(9,10)), -14.0 (d, B(5,12)), -14.7 (d, JBH ) 132, B(4,6,8,11)), -16.3
General Procedure for the Synthesis of (MeSNH2)(Me2S)B12H10
and (MeSNH2)2B12H10. A solution of potassium hydroxylamine-O-
sulfonate obtained by mixing H2NOSO3H and potassium carbonate (2:
9
J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002 2623

A R T I C L E S
Kultyshev et al.
1) in water was added to a solution of the tetramethylammonium salt
of the corresponding thioether in water (10, 11) or acetonitrile (7, 8).
The mixture was stirred at room temperature and concentrated in vacuo.
The resulting solution was extracted with dichloromethane, the organic
phase was dried over MgSO4, and the solvent was removed under
reduced pressure. Aminosulfonium salt products were purified by
column chromatography.
Single-Crystal X-ray Diffraction Analyses. Single-crystal X-ray
diffraction data were collected on an Enraf-Nonius CAD4 (14j, 17b)
and Enraf-Nonius KappaCCD (14i, 15b, 16, [Me4N][24], 31). Crystal
data are given in Tables 3 and 4. A Bruker SMART 1000 CCD
diffractometer was employed for compound 14m. Crystal data for this
compound are given in Supporting Information. All instruments employ
graphite-monochromated Mo KR radiation. When the Enraf-Nonius
CAD4 diffractometer was used, a single crystal was mounted inside a
glass capillary. Unit cell parameters were obtained by a least-squares
refinement of the angular settings from 25 reflections, well distributed
in reciprocal space and lying in the 2θ range of 24-30°. Diffraction
data were corrected for Lorentz and polarization effects. With the Enraf-
Nonius KappaCCD diffraction system, a single crystal was mounted
on the tip of a glass fiber coated with Parabar. Unit cell parameters
were obtained by indexing the peaks in the first 10 frames and refined
employing the whole data set. All frames were integrated and corrected
for Lorentz and polarization effects using DENZO.27 The structures
were solved by the direct method and refined using SHELXTL
(difference electron density calculations, full least-squares refine-
ments).28 After all non-hydrogen atoms were located and refined
anisotropically, H atoms on organic groups (alkyl, phenyl groups) were
calculated assuming standard -CH geometries. All other hydrogen
atoms were located and refined isotropically. In the case of 14m, frames
were integrated with the Bruker SAINT software package using a
narrow-frame integration algorithm. The final structural refinement
required application of a pseudo-orthorhombic twinning law with a
twinning parameter of 0.223.
Acknowledgment. This work was supported by the Petroleum
Research Fund through Grant 31467-AC3.
Supporting Information Available: Complete synthetic pro-
cedures and characterization of compounds, time-evolved 11B-
{1H} NMR spectra of the equimolar mixture of 4 and [Me4N]2-
1
[11], H NMR spectra of 1,7-(MeSR)2B12H10 (R ) CHdCd
CH2, CH2CCH) and 1-(MeSCHdCdCH2)-7-(MeSCH2CCH)-
B12H10, 11B{1H} NMR spectra of 3, 17a, 26, 14m, and 17d,
X-ray molecular structures of 14j and 14m, tables of crystal-
lographic data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
(27) Otwinowsky, Z.; Minor, W. In Methods in Enzymology: Macromolecular
Crystallography, Part A; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic
Press: New York, 1997; Vol. 276, pp 307-326.
(28) SHELXTL (version 5.10), Bruker Analytical X-ray Systems, 1997.
(29) (a) Grimes, R. N.Carboranes; Academic Press: New York, 1970. (b)
Bregadze, V. Chem. ReV. 1992, 92, 209-223.
JA0123857
9
2624 J. AM. CHEM. SOC. VOL. 124, NO. 11, 2002