Tetrabutylammonium fluoride promoted novel reactions of o- carborane: Inter- and intramolecular additions to aldehydes and ketones and annulation via enals and enones

Article abstract of DOI:10.1021/ja973832e

The addition of o-carborane (1) to aldehydes 2 proceeded very smoothly in the presence of aqueous tetrabutylammonium fluoride (tbaf: 3 equiv) at room temperature, giving the corresponding carbinols 3 in high yeilds. The Tbaf-mediated reaction was appiled

Full text of DOI:10.1021/ja973832e

J. Am. Chem. Soc. 1998, 120, 1167-1171
1167
Tetrabutylammonium Fluoride Promoted Novel Reactions of
o-Carborane: Inter- and Intramolecular Additions to Aldehydes and
Ketones and Annulation via Enals and Enones
Hiroyuki Nakamura, Kouichi Aoyagi, and Yoshinori Yamamoto*
Contribution from the Department of Chemistry, Graduate School of Science, Tohoku UniVersity,
Sendai 980-77, Japan
ReceiVed NoVember 7, 1997
Abstract: The addition of o-carborane (1) to aldehydes 2 proceeded very smoothly in the presence of aqueous
tetrabutylammonium fluoride (TBAF; 3 equiv) at room temperature, giving the corresponding carbinols 3 in
high yields. The TBAF-mediated reaction was applied to the intramolecular cycloaddition of o-carboranyl
aldehydes and ketones 4, and the corresponding five-, six-, and seven-membered carboracycles were obtained
in good-to-high yields. Further, [3 + 2] annulation between o-carborane (dianionic C2 synthons) and R,â-
unsaturated aldehydes and ketones (dicationic C3 synthons) proceeded very smoothly in the presence of TBAF
to give the corresponding five-membered carbocycles in good-to-high yields. Detailed mechanistic studies
revealed that the [3 + 2] annulation proceeded through kinetically controlled 1,2-addition and thermodynamically
controlled 1,4-addition.
Introduction
carborane is highly activated. Shatenshtein reported that the
pKa value of this proton is 23.9 It occurred to us that a proton
attached to the carbon of o-carborane could be deprotonated
easily by a weak base and the resulting carbanion could react
with electrophiles. Actually, we have found that o-carborane
undergoes an addition reaction to carbonyl compounds in the
presence of tetrabutylammonium fluoride (TBAF). In this
paper, we report the first direct addition of o-carborane to
carbonyl compounds without using any metalated carborane
species; the reaction of o-carborane (1) with aldehydes 2 in the
presence of TBAF in THF at room temperature gave the
corresponding o-carboranyl carbinols 3 in high-to-good yields
(eq 1). The intramolecular cycloadditions of o-carboranes
The addition of o-carborane to electrophiles is one of the most
important reactions to synthesize carboranes containing organic
functional groups, which could be useful as multifunctional
molecules for material science1 and/or as boron carriers for
boron neutron capture therapy.2 Lithiocarboranes, which are
readily prepared from butyllithium with carboranes, are widely
utilized for C-C bond formation of various functional groups
with carboranes.3,4 We have developed the addition reactions
of stannyl-5 and silylcarboranes6,7 to various electrophiles, which
proceed under very mild conditions and therefore are potentially
useful for synthesizing biologically active functionalized car-
boranes sensitive to strong basic or acidic conditions.8
On the other hand, it is known that a carborane framework
involves three-center two-electron bonding and is thus an
electron-deficient cluster.3a Therefore, the C-H bond of
(1) (a) Yang, X.; Jiang, W.; Knobler, C. B.; Hawthorne, M. F. J. Am.
Chem. Soc. 1992, 114, 9719. (b) Mu¨ller, J.; Base, K.; Magnera, T. F.; Michl,
J. J. Am. Chem. Soc. 1992, 114, 9721. (c) Chizhevsky, I. T.; Johnson, S.
E.; Knobler, C. B.; Gomez, F. A.; Hawthorne, M. F. J. Am. Chem. Soc.
1993, 115, 6981. (d) Zinn, A. A.; Zheng, Z.; Knobler, C. B.; Hawthorne,
M. F. J. Am. Chem. Soc. 1996, 118, 70.
(2) For recent reviews: Yamamoto, Y. Pure. Appl. Chem. 1991, 63, 423.
Hawthorne, M. F. Angew. Chem., Int. Ed. Engl. 1993, 32, 950. Barth, R.
F.; Soloway, A. H.; Fairchild, R. G. Cancer Res. 1990, 50, 1061.
(3) (a) Carboranes; Grimes, R. N., Ed.; Academic: New York, 1970;
pp 1-22. (b) Ibid., pp 66-150. (c) Williams, R. E. Chem. ReV. 1992, 92,
177.
(4) Maurer, J. L.; Berchier, F.; Serino, A. J.; Knobler, C. B.; Hawthorne,
M. F. J. Org. Chem. 1990, 55, 838.
(5) Nakamura, H.; Sadayori, N.; Sekido, M.; Yamamoto, Y. J. Chem.
Soc., Chem. Commun. 1994, 2581.
(6) Cai, J.; Nemoto, H.; Nakamura, H.; Singaram, B.; Yamamoto, Y.
Chem. Lett. 1996, 791.
(7) Nakamura, H.; Aoyagi, K.; Singaram, B.; Cai, J.; Nemoto, H.;
Yamamoto, Y. Angew. Chem., Int. Ed. Engl. 1997, 36, 367.
(8) Nakamura, H.; Sekido, M.; Yamamoto, Y. J. Med. Chem. 1997, 40,
2825.
containing carbonyl moieties proceeded very smoothly by
treatment with TBAF to give the corresponding five-, six-, and
seven-membered carboracycles 5 (eq 2). o-Carborane under-
went a facile annulation reaction with various R,â-unsaturated
enals and enones in the presence of aqueous TBAF, giving the
(9) Shatenshtein, A. I.; Zakharkin, L. I.; Petrov, E. S.; Yakoleva, E. A.;
Yakushin, F. S.; Vukmirovich, Z.; Isaeva, G. G.; Kalinin, V. N. J.
Organomet. Chem. 1970, 23, 313.
S0002-7863(97)03832-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/30/1998

1168 J. Am. Chem. Soc., Vol. 120, No. 6, 1998
Nakamura et al.
Table 1. 1,2-Addition of o-Carborane 1 to Aldehydes 2 in the
Presence of TBAF
entry
aldehyde 2
R
product 3
yield,a %
1
2
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
88
88
p-CF3C6H4
p-BrC6H4
2-naphthyl
p-MeC6H4
p-MeOC6H4
PhCH2CH2
Bu
3
96
4
76
5
71
6
48
7
76
8
93
9
i-Pr
>99
10
2j
2k
Me
3j
3k
86
11b
H
86
a Yields of isolated products. b Formaldehyde contained 37% w/w
in water was used.
corresponding five-membered carboracyclic products 7 in high-
to-good yields (eq 3).
Table 2. Intramolecular Cycloaddition of Carboranes 4 Prompted
by TBAF
entry
carboranes 4
cyclic products 5
yield,a %
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
49b
99
99
0c
79b
82
0c
4g
5g
Results and Discussion
a Yield of isolated products. b Yields were determined by H NMR
using p-xylene as an internal standard, since these products were
synthesized by the different procedures developed in our laboratory
(ref 7), and their structures were determined unambiguously. c In the
cases of entries 4 and 7, the complex mixtures were obtained including
the reduced products, 6-(o-carboranyl)hexanol and 6-(o-carboranyl)-
2-hexanol, in 17% and 35% yield, respectively.
1
Addition of Nonmetalated o-Carborane to Aldehydes. The
addition of 1 to aldehydes 2 proceeded very smoothly in the
presence of aqueous TBAF (3 equiv) at room temperature,
giving the corresponding carbinols 3 in high yields (eq 1). The
results are summarized in Table 1. The reaction of 1 with
benzaldehyde 2a was complete within 10 min and the carbinol
3a was obtained in 88% yield (entry 1). The use of less than
or greater than 3 equiv of TBAF resulted in lower yields. Other
ammonium salts, such as tetraethylammonium iodide, tetrabu-
tylammonium chloride, and tetrabutylammonium hydroxide, did
not give the desired product. Not only aromatic aldehydes 2a-f
(entries 1-6) but also aliphatic aldehydes 2g-j (entries 7-10)
underwent the addition reaction, affording the corresponding
carbinols 3a-f and 3g-j, respectively, in high yields. This
addition reaction proceeded very smoothly even in an aqueous
medium. The reaction of 1 with aqueous formaldehyde (37%
w/w in water) gave o-carboranylmethanol (3k) in 86% yield
(entry 11). No double addition of 2a to 1 was observed even
when excess amounts of 2a and TBAF were used. Selective
monolithiation of 1 is not necessarily easy, and in certain cases,
double-addition products are obtained in addition to the desired
monoadducts, since the facile disproportionation of the mono-
lithio species takes place. Therefore, the present TBAF method
is quite useful for the selective formation of monoadducts.10
Intramolecular Cycloaddition of o-Carboranes Bearing
Carbonyl Groups. The intramolecular cycloaddition of o-
carboranyl aldehydes and ketones 4 via the traditional lithio-
carborane method is difficult since the carbonyl groups are
reactive toward lithium organometallics which are needed to
produce the lithiocarboranes. We examined the TBAF-mediated
intramolecular cycloaddition of 4 and found that the five-, six-,
and seven-membered carboracycles 5 can be synthesized in
good-to-high yields (eq 2). The results are summarized in Table
2. 3-Carboranylpropanal (4a; n ) 1) underwent the cycload-
dition reaction by treatment with TBAF (3 equiv) in THF, giving
the corresponding five-membered cyclic product 5a in 49% yield
(entry 1). Very interestingly, the six- and seven-membered-
ring products 5b and 5c (n ) 2, 3) were obtained in higher
yields from the corresponding aldehydes 4b and 4c, respectively
(entries 2 and 3). However, in the case of 4d, the eight-
membered cyclic product 5d was not obtained. The cycload-
dition of carbonyl ketones 4e-g was also examined. The
reaction of 4e and 4f gave the corresponding five- and
six-membered carboracycles 5e and 5f in 79% and 82% yields,
respectively (entries 5 and 6). However, the seven-membered-
ring product 5g was not obtained from 4g but the reduced
product (6-(o-carboranyl)-2-hexanol) was obtained in 35% yield
(entry 7).
[3 + 2] Annulation Reaction of o-Carborane with Enals
and Enones. Next we examined the TBAF-promoted addition
to R,â-unsaturated enals and enones and found that o-carborane
underwent a [3 + 2] annulation reaction with conjugated
carbonyl compounds.7 A [3 + 2] annulation is one of the most
efficient methods for the construction of five-membered car-
bocyclic rings.11 Perhaps the most widely utilized strategy in
this regard is one in which dipolar C3 synthons are utilized in
conjunction with electron-deficient olefins (dipolar C2 synthons)
to achieve [3 + 2] annulation (Scheme 1a).11,12 However, [3
+ 2] annulations between dianionic C2 synthons and dicationic
C3 synthons are less common than the dipolar annulations.13
The coupling reaction of the 1,3-dihalides or â-haloesters with
the doubly charged succinate anions14 or tetraethoxycarbonyl-
ethyl anions15 has been investigated in the latter approach. We
found that [3 + 2] annulation between o-carborane (dianionic
C2 synthons) and R,â-unsaturated aldehydes and ketones (di-
cationic C3 synthons) gave the corresponding five-membered
carbocycles (Scheme 1b). o-Carborane underwent a facile
annulation reaction with various R,â-unsaturated carbonyl
(10) Gomez, F. A.; Johnson, S. E.; Hawthorne, M. F. J. Am. Chem. Soc.
1991, 113, 5915. Gomez, F. A.; Hawthorne, M. F. J. Org. Chem. 1992, 57,
1384.
(11) Reviews: ComprehensiVe Organic Synthesis; Trost, B. M., Ed.;
Pergamon: Oxford, 1991; Vol. 5, pp 240-314.

TBAF-Promoted NoVel Reactions of o-Carborane
J. Am. Chem. Soc., Vol. 120, No. 6, 1998 1169
Table 3. [3 + 2] Annulation of 1 with 6
Scheme 1
compounds under aqueous TBAF-promoted conditions, giving
the corresponding five-membered carboracyclic products 7
(or 5) (eq 3).
The results are summarized in Table 3. The reaction of 1
with crotonaldehyde 6a gave carboracyclopentane 7a in 90%
yield with a 52:48 mixture of syn and anti diastereomers (entry
1). The syn configuration of the major diastereoisomer of 7a
was confirmed unambiguously by X-ray analysis (Figure 1).
Enals with bulky groups on the â-position such as 6b underwent
a facile annulation to give the corresponding cyclic product 7b
in 77% yield (entry 2). The reaction of cinnamaldehyde 6c
gave 7c in 74% yield with a syn/anti ratio of 63:37 (entry 3).
The configuration of the major isomer of 7c was determined
by comparison with the chemical shifts of 1H NMR of the major
isomer of 7a. The reaction of acrolein 6d gave 5a in 40% yield
(entry 4) and that of methacrolein 6e gave 7e in 65% yield with
a syn/anti ratio of 20:80 (entry 5). The stereochemistry of the
major isomer of 7e was determined by NOE experiments. Since
NOEs were observed between CH3 protons and Hb but not
between Hb and Ha, the configuration of the major isomer was
anti. The stereochemistry of the minor isomer (syn) was also
determined by NOE experiments. The yields in the reactions
with 3-substituted aldehydes (6a-c) were higher than those with
3-unsubstituted aldehydes (6d and 6e). The reactions of R,â-
unsaturated ketones were also examined. The reaction of enone
6f gave the corresponding cyclic adduct 7f in 42% yield with
a syn/anti ratio of 40:60 (entry 6). NOEs were obtained between
Ha and Hb and between Hc and the protons of CH3 attached to
the OH-substituted C atom of 7f, thus indicating that the
configuration of the major isomer was anti (see 7f). A phenyl
group at the â-position of the enone led to higher diastereose-
lectivity (syn/anti ) 26/74, entry 7), although the substituent
groups at the â-position of the enals did not affect the
a When the stereochemistry of 7 was determined unambiguously,
that of a major isomer is shown in the column. b Yield of isolated
products. Syn:anti ratios determined by 1H NMR are shown in
parentheses. c The reactions did not complete within 40 min.
(12) (a) Allylic transition-metal complexes: Cutler, A.; Ehntholt, D.;
Giering, W. P.; Lennon, P.; Raghu, S.; Rosan, A.; Rosenblum, M.; Tancrede,
J.; Wells, D. J. Am. Chem. Soc. 1976, 98, 3495. Calligaris, M.; Carturan,
G.; Nardin, G,; Scrivanti, A.; Wojcicki, A. Organometallics 1983, 2, 865.
Kurosawa, H.; Urabe, A.; Miki, K.; Kasai, N. Organometallics 1986, 5,
2002. (b) Allylic silane: Danheiser, R. L.; Carini, D. J.; Basak, A. J. Am.
Chem. Soc. 1981, 103, 1604. (c) Trimethylenemethane: Trost, B. M.; Chan,
D. M. T. J. Am. Chem. Soc. 1979, 101, 6432. Trost, B. M. Angew. Chem.,
Int. Ed. Engl. 1986, 25, 1. (d) Cyclopropenone ketal: Boger, D. L.;
Brotherton, C. E. J. Am. Chem. Soc. 1984, 106, 805. (e) Nitrones: Stevens,
R. V.; Christensen, C. G.; Cory, R. M.; Thorsett, E. Angew. Chem., Int.
Ed. Engl. 1973, 12, 914. Funk, R. L.; Bolton, G. L.; Daggett, J. U.; Hansen,
M. M.; Horcher, L. H. M. Tetrahedron 1985, 41, 3479. Oppolzer, W.; Siles,
S.; Snowden, R. L.; Bakker, B. H.; Petrzilka, M. Tetrahedron 1985, 41,
3497. Padwa, A.; Kline, D. N.; Koehler, K. F.; Matzinger, M.; Venkatra-
manan, M. K. J. Org. Chem. 1987, 52, 3909. Curran, D. P.; Fenk, C. J.
Tetrahedron. Lett. 1986, 27, 4865.
(13) The reaction between dicationic substrates (x-x) and dianionic
synthons (Qk&kQ) has been reported. Molander, G. A.; Shubert, D. C. J.
Am. Chem. Soc. 1986, 108, 4683.
(14) Misumi, A.; Iwanaga, K.; Furuta, K.; Yamamoto, H. J. Am. Chem.
Soc. 1985, 107, 3343. Furuta, K.; Misumi, A.; Mori, A.; Ikeda, N.;
Yamamoto, H. Tetrahedron Lett. 1984, 25, 669. Misumi, A.; Furuta, K.;
Yamamoto, H. Tetrahedron Lett. 1984, 25, 671.
(15) Ibuka, T.; Aoyagi, T.; Yoneda, F.; Yamamoto, Y. J. Organomet.
Chem. 1985, 287, C18.
Figure 1. X-ray structure of cyclic adduct 7a.
diastereoselectivity (entries 1 and 3). 3-Unsubstituted enone
6h underwent the annulation, giving the corresponding product
5e in lower yield (entry 8).

1170 J. Am. Chem. Soc., Vol. 120, No. 6, 1998
Nakamura et al.
Scheme 2
Pseudo-1,4-addition of o-Carborane to the Enone. 1,4-
Addition of o-carborane to conjugated carbonyl compounds is
an attractive reaction to synthesize the carboranes containing a
carbonyl moiety, which are very useful for the synthesis of
functionalized carborane compounds since further functional-
ization is possible via the manipulation of the carbonyl group.
There are few examples of the 1,4-addition of carboranes to
conjugated carbonyl compounds. The R,â-unsaturated ketones
substituted by bulky groups, such as phenyl and tert-butyl at
the R′ position, underwent 1,4-addition with o-carborane.18 It
was thought that the carbocyclic products derived from enones,
if a hydroxy proton is deprotonated, would undergo the retro
cyclization via the equilibration process (7′ f 10 f 9) and the
1,4-addition products might be obtained under certain reaction
conditions. This hypothesis proved to be practical. Accord-
ingly, even in the case of less bulky methyl vinyl ketone, the
1,4-addition of o-carborane is possible by the two-step sequential
reaction. The reaction of 1 with 6h in the presence of TBAF
in THF, followed by the retro 1,2-addition by the treatment with
catalytic amounts of KOH (0.15 equiv) in THF-H2O (100:1),
gave the corresponding 1,4-adduct 4e in 48% yield (eq 4).17
Scheme 3
Conclusion
We have developed a new method for the C-C bond
formation between o-carborane and carbonyl compounds. A
selective monoaddition reaction of 1 to aldehydes 2 is ac-
complished by treating the two substrates with TBAF at room
temperature: the corresponding carbinols 3 are obtained in high
yields even in aqueous medium. Intramolecular cycloaddition
of o-carborane containing carbonyl moieties is also accom-
plished by the treatment with TBAF. Further, [3 + 2]
annulation between o-carborane and R,â-unsaturated aldehydes
and ketones proceeds in the presence of TBAF to give the
corresponding five-, six-, and seven-membered carboracycles.
Finally, pseudo-1,4-addition of o-carborane to a less hindered
enone is demonstrated as an extension of the annulation reaction.
We are now in a position to synthesize a variety of carborane
derivatives, some of which are difficult to synthesize via the
previously known methods.
Mechanism. To clarify the mechanism of the annulation
reaction, we monitored the reaction of 1 with crotonaldehyde
6a by 1H NMR (Scheme 2). When the reaction was quenched
after 1 min, the 1,2-adduct 8 was obtained in 63% yield along
with the recovery of o-carborane in 36% yield. However, the
cyclic product 7a was obtained exclusively after 10 min.
Furthermore, the cyclic product 7a was also obtained in 58%
yield by the treatment of allylic alcohol 8, which was synthesized
independently by the 1,2-addition reaction of lithiocarborane
and enal 6a, with TBAF (3 equiv).
Based upon these observations, it was considered that the [3
+ 2] annulation would proceed through kinetically controlled
1,2-addition followed by a thermodynamically controlled cy-
clization process. According to a possible mechanism for this
unprecedented annulation reaction (Scheme 3), an anionic
intermediate 1′, which would produce by the reaction of 1 with
TBAF (or from 1,2-adduct 8′), would undergo addition to 6
either in a 1,2- or in a 1,4-manner to give the 1,2-adduct 8′ or
1,4-adduct 9, respectively. There would be an equilibrium
between 8′ and 9, and the formation of 8 would be a kinetically
controlled process as is apparent from the result of Scheme 2.
The thermodynamically favored 9 would undergo proton
exchange to afford the o-carborane anion 10, which would give
7 via an intramolecular ring closure.16 The methylated 1,2-
adduct analogue 11 and allylcarborane 12 did not undergo the
[3 + 2] annulation reaction by treatment with TBAF. These
results support that a hydroxy group at the allylic position is
essential for the equilibrium between 1 and 1,2-adduct 8 and
for the annulation reaction.17
Experimental Section
General Information. 1H and 13C NMR spectra were recorded on
a JEOL GSX-270 spectrometer. The chemical shifts are reported in δ
units relative to internal tetramethylsilane. IR spectra were recorded
on a Shimadzu FTIR-8200A spectrometer. High-resolution mass
spectra were recorded on a JEOL JMS-HX110. Most commercially
supplied chemicals were distilled and stored over molecular sieves.
Addition to Aldehydes. A typical procedure for the TBAF-
promoted addition is as follows. To a solution of o-carborane 1 (290
mg, 2.01 mmol) and hydrocinnamaldehyde 2g (290 µL, 2.2 mmol) in
THF (10 mL) was added TBAF (1.0 M in THF, 6 mL) under Ar
atmosphere, and the mixture was stirred at room temperature for 30
min. The reaction was quenched by saturated aqueous NH4Cl, and
the mixture was extracted with ether, washed with saturated aqueous
(17) Nakamura, H.; Aoyagi, K.; Yamamoto, Y. J. Org. Chem. 1997,
62, 780.
(18) (a) Zakharkin, L. I.; Kazantsev, A. V. Zh. Obshch. Khim. 1967, 37,
554. (b) Carboranes: Grimes, R. N., Ed.; Academic: New York, 1970; p
102 and references therein.
(16) The mechanism of this reaction involving a 1,4-addition-proton
exchange-addition sequence is quite similar to that of 2,3-bis(phenylsul-
fonyl)-1,3-butadiene with activated methylenes: Padwa, A.; Murphree, S.
S.; Ni, Z.; Watterson, S. H. J. Org. Chem. 1996, 61, 3829.

TBAF-Promoted NoVel Reactions of o-Carborane
J. Am. Chem. Soc., Vol. 120, No. 6, 1998 1171
NaCl, dried over anhydrous MgSO4, and then concentrated. Purification
by silica gel column chromatography (hexane:ethyl acetate ) 15:1)
gave the carbinol 3g in 76% yield (423 mg, 1.52 mmol).
The structure of 3k were determined unambiguously by comparison
with an authentic sample, prepared by the literature procedure.10
Spectral data of compounds 3f-j are given in the supporting informa-
tion.
1,2-Carboracyclohexan-3-ol (5b). White solid. IR (KBr) 3303,
2962, 2933, 2873, 2580, 1743, 1452, 1346, 1178, 1147 cm-1 1H NMR
.
(CDCl3) δ 4.35 (dd, J ) 10.0, 5.0, Hz, 1 H), 2.38 (m, 2 H), 2.30 (d, J
) 5.0 Hz, 1 H), 1.96-1.52 (m, 4 H). 13C NMR (CDCl3) δ 68.76,
32.88, 28.22, 17.19. HRMS (EI) Calcd for C6H18OB10: m/z 216.2289.
Found: m/z 216.2280.
1,2-Carboracycloheptan-3-ol (5c). White solid. IR (KBr) 3452,
2931, 2866, 2648, 2580, 1446, 1112, 1060 cm-1 1H NMR (CDCl3) δ
.
1-(o-Carboranyl)benzyl Alcohol (3a). Colorless solid: mp 70 °C.
IR (KBr) 3550, 3100, 2550, 1490, 1460, 1100, 1040, 770, 710 cm-1
.
4.37 (m, 1 H), 2.64-2.45 (m, 2 H), 2.26 (d, J ) 4.8 Hz, 1 H), 2.08-
1.68 (m, 6H). 13C NMR (CDCl3) δ 82.59, 74.26, 38.76, 33.66, 30.32,
25.92, 24.07. HRMS (EI) Calcd for C7H20OB10: m/z 230.2445.
Found: m/z 230.2427. Anal. Calcd for C7H20OB10: C, 36.82; H, 8.83.
Found: C, 37.12; H, 8.90.
1H NMR (CDCl3) δ 7.36 (m, 5 H), 5.27 (d, J ) 3.5 Hz, 1 H), 3.81 (br
s, 1 H), 2.56 (d, J ) 3.5 Hz, 1 H). MS (EI) m/z 250 (M+), 233 (M+
- OH), 108 (M+ - carborane), 77 (Ar). Anal. Calcd for C9H18OB10:
C, 43.18; H, 7.25. Found: C, 42.98; H, 7.09.
1-(o-Carboranyl)-p-(trifluoromethyl)benzyl Alcohol (3b). Color-
less solid: mp 70 °C. IR (KBr) 3674, 3549, 3444, 3087, 2937, 2900,
3-Methyl-1,2-carboracyclopentan-3-ol (5e). White solid. IR (KBr)
3583, 3467, 2991, 2956, 2592, 1452, 1379 cm-1 1H NMR (CDCl3) δ
.
2582, 1622, 1419, 1384, 1325, 1247, 1168 cm-1 1H NMR (CDCl3) δ
.
2.33-2.63 (m, 4 H), 2.08 (s, 1 H), 1.62 (s, 1 H). Anal. Calcd for
C6H18OB10: C, 33.63; H, 8.47. Found: C, 33.50; H, 8.81.
3-Methyl-1,2-carboracyclohexan-3-ol (5f). White solid. IR (KBr)
7.67 (d, J ) 8.0 Hz, 2 H), 7.48 (d, J ) 8.0 Hz, 2 H), 5.34 (d, J ) 3.0
Hz, 1 H), 3.94 (br s, 1 H), 2.73 (d, J ) 3.0 Hz, 1 H). HRMS (EI)
Calcd for C10H17OB10F: m/z 320.2162. Found: m/z 320.2152. Anal.
Calcd for C10H17OB10F; C, 37.7; H, 5.38. Found: C, 38.1; H, 5.21.
1-(o-Carboranyl)-p-bromobenzyl Alcohol (3c). White solid. IR
(CHCl3) 3600, 3500-3150, 3050, 2570, 1600, 1480, 1400, 1090, 1070,
3469, 2952, 2873, 2578, 1452, 1380, 1132 cm-1 1H NMR (CDCl3) δ
.
2.49 (m, 1 H), 2.32 (m, 1 H), 2.13 (s, 1 H), 1.87-1.73 (m, 2 H), 1.62-
1.50 (m, 2 H), 1.52 (s, 3 H). 13C NMR (CDCl3) δ 70.18, 35.16, 33.69,
32.57, 17.10. HRMS (EI) Calcd for C7H20OB10: m/z 230.2445.
Found: m/z 230.2444.
1010 cm-1 1H NMR (CDCl3) δ 7.54 (d, J ) 8.5 Hz, 2 H), 7.22 (d, J
.
) 8.5 Hz, 2 H), 5.25 (d, J ) 3.5 Hz, 1 H), 3.88 (br s, 1 H), 2.61 (d,
J ) 3.5 Hz, 1 H). MS (EI) m/z 329 (M+), 249 (M+ - Br), 157 (BrPh),
143 (carborane). HRMS (EI) Calcd for C9H17OB10Br: m/z 330.1393.
Found: m/z 330.1405.
[3 + 2]Annulation of 1 with 6. A typical procedure for the TBAF-
promoted [3 + 2] annulation is as follows. To a solution of 1 (74 mg,
0.51 mmol) and 3-methyl-2-butanal (6b. 46 µL, 0.48 mmol) in THF
(10 mL) was added TBAF (1.0 M in THF, 1.5 mL) under Ar
atmosphere, and the mixture was stirred at room temperature for 10
min. The reaction was quenched by saturated aqueous NH4Cl, and
the mixture was extracted with ether, washed with saturated aqueous
NaCl, dried over anhydrous MgSO4, and then concentrated. Purification
by silica gel column chromatography (hexane:ethyl acetate ) 4:1) gave
the annulated product 7b in 77% yield (84 mg, 0.37 mmol). Spectral
data of compounds 7e-g are given in the supporting information.
5-Methyl-1,2-carboracyclopentan-3-ol (7a). White solid. IR
1-(o-Carboranyl)-2-naphthylmethanol (3d). Colorless solid. IR
(KBr) 3585, 3086, 2633, 2603, 2580, 1356, 1315, 1247, 1184, 1166,
1083, 1020 cm-1 1H NMR (CDCl3) δ 7.87 (m, 3 H), 7.78 (s, 1 H),
.
7.54 (m, 2 H), 7.45 (m, 1 H), 5.44 (d, J ) 3.5 Hz, 1 H), 3.84 (br s, 1
H), 2.72 (d, J ) 3.5 Hz, 1 H). HRMS (EI) Calcd for C13H20OB10: m/z
302.2445. Found: m/z 302.2450. Anal. Calcd for C13H20OB10: C,
51.9; H, 6.71. Found: C, 51.7; H, 6.41.
1-(o-Carboranyl)-p-methylbenzyl Alcohol (3e). Liquid. IR (CHCl3)
3600, 3500-3150, 3150-2800, 2570, 1730, 1650, 1610, 1095, 1010,
(KBr) 3325, 2976, 2586, 1458, 1384, 1342, 1166, 731 cm-1 1H NMR
.
900 cm-1 1H NMR (CDCl3) δ 7.20 (s, 4 H), 5.23 (d, J ) 3.0 Hz, 1
.
(CDCl3) syn isomer δ 4.72 (m, 1 H), 2.82 (m, 2 H), 2.24 (d, J ) 5.5
Hz, 1 H), 1.71 (m, 1 H), 1.17 (d, J ) 6.0 Hz, 3 H), anti isomer δ 4.65
(m, 1 H), 3.01 (m, 1 H), 2.36 (m, 1 H), 2.25 (m, 1 H), 2.05 (d, J ) 5.0
Hz, 1 H), 1.13 (d, J ) 6.0 Hz, 3 H). Anal. Calcd for C6H18OB10: C,
33.63; H, 8.47. Found: C, 33.98; H, 8.41.
H), 3.77 (br s, 1 H), 2.51 (d, J ) 3.0 Hz, 1 H), 2.37 (s, 3 H). MS (EI)
m/z 264 (M+), 143 (carborane), 121 (M+ - carborane), 93 (MePh).
HRMS (EI) Calcd for C10H20OB10: m/z 266.2445. Found: m/z
266.2448.
Intramolecular Cycloaddition of 4. o-Carboranyl aldehydes and
ketones 4a-g were prepared from the corresponding ynals and ynones
by using the standard Lewis base promoted addition of decaborane to
acetylene derivatives. Spectral data of compounds 4b-d, 4f, and 4g
are given in the supporting information.
5,5-Dimethyl-1,2-carboracyclopentan-3-ol (7b). White solid. IR
(KBr) 3367, 2978, 2596, 1334, 1074 cm-1 1H NMR (CDCl3) δ 4.67
.
(ddd, J ) 8.0, 5.1, 5.0 Hz, 1 H), 2.54 (dd, J ) 14.8, 8.0 Hz, 2 H), 2.18
(d, J ) 5.0 Hz, 1 H), 2.02 (dd, J ) 14.8, 5.1 Hz, 1 H), 1.37 (d, J ) 5.0
Hz, 3 H), 1.32 (d, J ) 5.0 Hz, 3 H). HRMS (EI) Calcd for C7H20-
OB10: m/z 230.2445. Found: m/z 230.2443. Anal. Calcd for C7H20-
OB10: C, 36.82; H, 8.83. Found: C, 36.45; H, 8.95.
3-(o-Carboranyl)propanal (4a). White solid. IR (KBr) 3057,
2842, 2578, 1724, 727 cm-1 1H NMR (CDCl3) δ 9.74 (s, 1 H), 3.67
.
(br s, 1 H), 2.74 (t, J ) 7.0 Hz, 2 H), 2.55 (t, J ) 7.0 Hz, 2 H). 13C
NMR (CDCl3) δ 198.54, 73.86, 61.73, 42.98, 30.07. HRMS (EI) Calcd
for C5H16OB10: m/z 202.2132. Found: m/z 202.2130. Anal. Calcd
for C5H16OB10: C, 29.98; H, 8.05. Found: C, 29.76; H, 7.90.
4-(o-Carboranyl)-2-butanone (4e). White solid. IR (KBr) 3055,
5-Phenyl-1,2-carboracyclopentan-3-ol (7c). White solid. IR
(CCl4) 3583, 3413, 2586, 1748, 1074, 794 cm-1 1H NMR (CDCl3)
.
syn isomer δ 7.15-7.34 (m, 5 H), 4.82 (m, 1 H), 4.16 (dd, J ) 9.5,
9.0 Hz, 1 H), 2.83-3.05 (m, 1 H), 2.39-2.53 (m, 1 H), 2.10 (d, J )
3.0 Hz, 1 H), anti isomer δ 7.15-7.34 (m, 5 H), 4.82 (m, 1 H), 3.92
(dd, J ) 9.0, 8.5 Hz, 1 H), 2.83-3.05 (m, 1 H), 2.39-2.53 (m, 1 H),
2.10 (d, J ) 3.0 Hz, 1 H). HRMS (EI) Calcd for C11H20OB10: m/z
278.2452. Found: m/z 278.2452. Anal. Calcd for C11H20OB10: C,
47.80; H, 7.29. Found: C, 47.95; H, 7.30.
2956, 2923, 2850, 2597, 1712 cm-1 1H NMR (CDCl3) δ 3.72 (br s,
.
1 H), 2.68 (t, J ) 7.0 Hz, 2 H), 2.51 (t, J ) 7.0 Hz, 2 H), 2.19 (s, 3
H). 13C NMR (CDCl3) δ 205.64, 74.38, 61.77, 42.53, 31.30, 29.69.
HRMS (EI) Calcd for C6H18OB10: m/z 216.2289. Found: m/z
216.2294.
A typical procedure for the TBAF-promoted intramolecular cycload-
dition of 4c is as follows. To a solution of 4c (99 mg, 0.43 mmol) in
THF (5 mL) was added TBAF (1.0 M solution in THF, 1.3 mL), and
the mixture was stirred at room temperature for 35 min. The reaction
was quenched with saturated aqueous NH4Cl, and the mixture was
extracted with ether, washed with saturated aqueous NaCl, dried over
anhydrous MgSO4, and concentrated. Purification by silica gel column
chromatography (hexane:ethyl acetate ) 5:1) gave the cyclic product
5e in 99% yield (98 mg, 0.429 mmol).
Acknowledgment. We thank Prof. B. Singaram, University
of California at Santa Cruz, who contributed very much to the
discovery of the carborane C-C bond formation reaction via
TBAF.
Supporting Information Available: Spectral data for
compounds 3f-j, 4b-d, 4f, 4g, and 7e-g, NMR spectra for
compounds 3c, 3e, 3g, 3h, 4b-g, 5b, and 5f, and X-ray
crystallographic data for compound 7a (25 pages). See any
current masthead page for ordering and Internet access
instructions.
1,2-Carboracyclopentan-3-ol (5a). White solid. IR (KBr) 3317,
2954, 2592, 1444, 1350, 1315, 1163, 1099 cm-1 1H NMR (CDCl3) δ
.
4.79 (m, 1 H), 2.84-2.70 (m, 1 H), 2.59-2.12 (m, 4 H). HRMS (EI)
Calcd for C5H16OB10: m/z 202.2132. Found: m/z 202.2125. Anal.
Calcd for C7H20OB10: C, 29.98; H, 8.05. Found: C, 29.54; H, 7.83.
JA973832E