Synthetic utility of o-carborane: novel protective group for aldehydes and ketones

Article abstract of DOI:10.1016/S0022-328X(98)00922-X

o-Carborane acts as a novel protective group of carbonyl compounds. The reaction of lithiocarborane 2, which was prepared in an essentially quantitative yield from o-carborane and n-butyllithium, with aldehydes or ketones 1 gave the corresponding addition products, o-carboranyl methanol derivatives 3, in high yields. Cleavage of o-carborane from 3 was carried out by treating 3 with catalytic amounts of KOH in THF/H20 (100/1), giving the corresponding aldehydes or ketones in good to high yields along with recovered o-carborane. Accordingly, o-carborane may be utilized as a protective group stable under protic and Lewis acid conditions. Selective alkylation of an ester group, selective reduction of an ester, and selective alkylation of a ketone in the presence of an aldehyde are accomplished by using o-carborane protective groups. - Keywords: o-Carborane; Protective group; Carbonyl compounds

Full text of DOI:10.1016/S0022-328X(98)00922-X

Journal of Organometallic Chemistry 574 (1999) 107–115
Synthetic utility of o-carborane: novel protective group for aldehydes
and ketonesꢀ
Hiroyuki Nakamura, Kouichi Aoyagi, Yoshinori Yamamoto *
Department of Chemistry, Graduate School of Science, Tohoku Uni6ersity, Sendai 980-8578, Japan
Received 26 June 1998; received in revised form 14 August 1998
Abstract
o-Carborane acts as a novel protective group of carbonyl compounds. The reaction of lithiocarborane 2, which was prepared
in an essentially quantitative yield from o-carborane and n-butyllithium, with aldehydes or ketones 1 gave the corresponding
addition products, o-carboranyl methanol derivatives 3, in high yields. Cleavage of o-carborane from 3 was carried out by treating
3 with catalytic amounts of KOH in THF/H2O (100/1), giving the corresponding aldehydes or ketones in good to high yields
along with recovered o-carborane. Accordingly, o-carborane may be utilized as a protective group stable under protic and Lewis
acid conditions. Selective alkylation of an ester group, selective reduction of an ester, and selective alkylation of a ketone in the
presence of an aldehyde are accomplished by using o-carborane protective groups. © 1999 Elsevier Science S.A. All rights
reserved.
Keywords: o-Carborane; Protective group; Carbonyl compounds
1. Introduction
tain dithio acetals and ketals are stable to Lewis acid
but unstable to strong aqueous protic acids. Other
protective groups such as cyanohydrins, hydrazones,
imines and oximes are less used because their removal is
often difficult [1,4]. In this paper we describe o-carbo-
rane as a novel protective group of aldehydes and
ketones, which is stable under aqueous protic acid and
Lewis acid conditions and is readily cleaved under basic
conditions.
It is widely accepted that acetals and ketals are very
useful as protective groups for aldehydes and ketones
[1,2]. The protective groups are introduced readily by
treating the carbonyl compounds with an alcohol or a
diol in the presence of acid, and are stable to aqueous
and nonaqueous bases, to nucleophiles including
organometallic reagents, and to hydride reduction.
However, acetals and ketals are readily cleaved by acid
hydrolysis and Lewis acid coordination. The latter
property is a drawback of these protective groups in the
case of a Lewis acid-mediated reaction, in which a
reactive functional group in the substrate is required to
react with a Lewis acid without affecting the protective
group [3]. Lewis acid-mediated or catalyzed reactions
are used frequently in modern organic synthesis. Cer-
2. Results and discussion
2.1. Clea6age reaction of o-carboranyl methanols
Aldehydes and ketones 1 undergo the addition reac-
tion with lithiocarborane 2, which is prepared by the
reaction of o-carborane with n-BuLi, to afford the
corresponding functionalized o-carboranyl methanols 3
[5]. As alternative methods, previously we developed
the addition reactions of stannyl- [6,7], silyl- [8,9], and
ꢀ This paper is dedicated to the late Professor Rokuro Ogawara.
* Corresponding author. Tel. +81-22-217-6581; fax: +81-22-217-
6784; e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp.
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(98)00922-X

108
H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
nonmetalated [10] carboranes to various electrophiles
including aldehydes and ketones, which proceeded un-
der palladium-catalyzed or tetrabutylammonium
fluoride-mediated conditions. Therefore, carboranyl
methanols are easily available from aldehydes and ke-
tones under various reaction conditions. If the cleavage
of the C–C bond between carbinol and o-carborane
takes place very readily, the o-carborane unit may
become a potentially useful protecting group to func-
tionalized carbonyl compounds. We found that o-car-
boranyl methanols 3 were very stable under aqueous
protic acid and Lewis acid conditions and were readily
cleaved under basic conditions to produce the corre-
sponding carbonyl compounds 1 and o-carborane (Eq.
(1)).
isolated yield in entry 4). It is known that o-carborane
(closo) is converted to nido-o-carborane by treatment
with bases. However, under the cleavage conditions, the
closo framework was stable to KOH. Accordingly, re-
cycling of o-carborane is possible. Another attractive
point of this protective group is that protected alde-
hydes and ketones 3 are readily crystallized and stable
to air, moisture, and acids.
Having established optimum conditions for the de-
carboranylation of 3a, we next applied this procedure
to various carboranyl methanols 3b–n (Table 2). The
carboranyl methanols 3 were prepared in essentially
quantitative yield by treating aldehydes and ketones 1
with lithiocarborane 2. The decarboranylation of 3b
proceeded smoothly to give benzaldehyde 1b in 84%
yield (entry 2). Other aromatic aldehyde derivatives
3c–g bearing either an electron-donating or an elec-
tron-withdrawing group gave the corresponding alde-
hydes in good yields (entries 3–7). Not only aromatic
aldehydes but also h,i-unsaturated aldehydes 1h and 1i
were obtained in good to high yields from the corre-
sponding carboranyl methanols 3h and 3i (entries 8 and
9). In the case of disubstituted carboranyl methanols
3j–n, which were prepared readily by the addition of
lithiocarborane 2 with the corresponding ketones, the
cleavage reaction proceeded smoothly to give the corre-
sponding ketones 1j–n in good to high yields (entries
10–14). The carboranyl methanols 3 were very stable
under strong acid or Lewis acid conditions. When
benzaldehyde dimethyl acetal was treated with TiCl4
(two equivalents) in dichloromethane, benzaldehyde 1b
was obtained in 82% yield. However, treatment of 3b
with aqueous HCl(1 N) or TiCl4 (two equivalents) for 2
days gave no benzaldehyde, but 3b was recovered
quantitatively.
(1)
Conditions used to cleave o-carborane from 1-carbo-
ranyl-2-naphthylmethanol 3a are shown in Table 1.
Several bases, such as NaOMe, pyridine, n-BuLi, and
t-BuOK, were examined and KOH was the most suit-
able for this cleavage. The use of excess (three equiva-
lents) and 1.1 equivalents of KOH in THF gave 1 in
fair to good yields (entries 1 and 2). It was found that
even a catalytic amount of KOH was enough to induce
the cleavage of o-carborane (entry 3). Small amounts of
2-naphthylmethanol were obtained as by-product in
entries 1–3. However, the presence of small amounts of
water in the THF prevented formation of the by-
product (entries 4 and 5) and the best result was
obtained by using 0.15 equivalents of KOH in THF/
H2O (100/1) as a solvent (entry 4). Under these condi-
tions, o-carborane was recovered in high yields (76%
Table 1
The decarboranylation of 1-carboranyl-2-naphthylmethanol 3a pro-
moted by KOH at room temperature
Entry Amount (equiva- Solvent
lents) of KOH
Yielda of 1 (%)
1
2
3
4
5
3.0
1.1
0.15
0.15
0.15
THF
THF
THF
38b
58b
57b
THF/H2O (100/1) 92
THF/H2O (10/1) 60
a Yields were determined by GC analysis using hexadecane as an
internal standard.
b Reduced product (2-naphthylmethanol) was also produced in 8%
(entry 1), 17% (entry 2), and 14% (entry 3) yield, respectively.

H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
109
Table 2
The decarboranylation of various o-carboranylmethanols 3 promoted by a catalytic amount of KOH in THF/H2O (100/1)
Entry
Aldehyde and ketone
1
Carboranylmethanol
3
Time (days)
Yielda (%)
(isolated yield)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
3a
3b
3c
3d
3e
3f
3g
3h
3I
3j
2
3
1
1
3
2
2
2
2
2
3
2
2
2
92c (85)
84c
88
74
70
75c
74
86 (74)
62
78
3k
3l
3m
3n
83 (66)
93
92d
97
a Yields were determined by 1H-NMR using p-xylene as an internal standard.
b In some cases, the products were isolated by using silica gel column chromatography and the isolated yields are shown in parenthesis.
c Yields were determined by GC analysis using hexadecane as an internal standard.
d NaOH (0.15 equivalents) was used instead of KOH.
It is known that decarboxylation of o-carboranyl
carboxylates is accomplished by sodium ethoxide [11],
n-butyllithium [12], or potassium hydroxide [13], giving
the parent o-carboranes (Eq. (2)) [14]. In the present
reaction, an ionic species 4 generated by treatment of 3
with KOH would undergo a facile cleavage reaction,
since o-carborane is a reasonably good leaving group
(as shown in Eq. (2)).
in 95% yield (Scheme 1). The adduct 3g was treated
with n-BuLi (three equivalents) at −78°C to give
dibutylated compound 5 in 74% yield; only the ester
group reacted with n-BuLi and the carboranylmethanol
group was stable to the reagent. The decarboranylation
of 5 proceeded very smoothly by treatment with KOH
(0.15 equivalents) in THF–H2O (100/1), giving the
corresponding aldehyde 6 in 80% yield. Here also,
o-carborane was recovered in an essentially quantitative
yield.
2.3. Selecti6e reduction of ester in the presence of
aldehyde
The protective group of 3g was also stable to hydride
reduction using lithium aluminum hydride. The reduc-
tion of 3g with lithium aluminum hydride in THF
under reflux gave the diol 7 in 95% yield (Scheme 2).
Removal of o-carborane from
7 proceeded very
smoothly under the usual reaction condition, giving the
corresponding aldehyde 8, in which the ester group of
1g was reduced chemoselectively to the alcohol, in 77%
yield.
(2)
2.2. Selecti6e alkylation of ester in the presence of
aldehyde
2.4. Selecti6e alkylation of ketone in the presence of
Next we examined representative reactions of bifunc-
tional molecules to demonstrate the synthetic utility of
o-carborane as a protective group. The addition of
lithiocarborane 2 to aldehyde 1a, which has an ester
and aldehyde functional group in the same molecule, at
−78°C gave carboranylmethanol 3g chemoselectively
aldehyde
Furthermore, chemoselective allylation of a ketone
group in the presence of an aldehyde group was exam-
ined by using bifunctional molecule 9 [15] (Scheme 3).
The chemoselective addition of o-carborane to the alde-

110
H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
Scheme 1.
hyde group of 9 was accomplished by the palladium
catalyzed reaction [6]; the reaction of 9 with o-carbo-
ranyltributylstannane in the presence of a catalytic
amount of Pd2dba3·CHCl3 (10 mol%)/dppe (20 mol%)
in THF under reflux gave the adduct 10 in 69% yield.
The reaction of lithiocarborane 2 with 9 gave a mixture
of products which arose from the addition to both a
ketone and aldehyde group. The reaction of the ketone
10 with n-BuLi (two equivalents) gave the alkylated
adduct 11. The decarboranylation of 11, which was
used without purlfication, proceeded very smoothly by
treatment with KOH, giving the corresponding alde-
hyde 12 in 80% yield in two steps from 10.
those protective groups which are stable to protic and
Lewis acid conditions have not been available for or-
ganic synthesis. o-Carborane can be readily introduced
to those carbonyl compounds chemoselectively under
the anionic condition or even under the mild condi-
tions, and the corresponding carboranyl carbinols are
stable to protic and Lewis acid conditions and cleaved
easily under base-catalyzed conditions. We believe that
this new protective methodology will be utilized widely
in modern organic synthesis.
4. Experimental section
2.5. Lewis acid-promoted selecti6e monoallylation of
dialdehyde
1H- and 13C-NMR spectra were recorded on a Jeol
GSX-270 spectrometer. The chemical shifts are re-
ported in l 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-HX11O. Most commercially
supplied chemicals were distilled and stored over molec-
ular sieves.
The o-carborane protective group was also stable to
Lewis acid-promoted allylation (Scheme 4). The TiCl4-
mediated reaction of allyltrimethylsilane with the alde-
hyde 14, which was prepared by the selective
monoaddition of 2 to 13 (four equivalents), gave ho-
moallylic alcohol 15. The decarboranylation of crude
product 15 proceeded smoothly by the treatment with
NaOH (0.15 equivalents) in THF-H2O (100/1), giving
the corresponding monoallylated aldehyde 16 in 67%
yield in two steps from 14. In this case, the use of
NaOH was more effective for the cleavage reaction
than that of KOH.
These results indicate that o-carborane moiety can
serve as a useful protective group for aldehydes and
that chemoselective protection of an aldehyde func-
tional group in the presence of a ketone and/or ester is
achieved using the o-carborane protective group.
4.1. A representati6e procedure of formation (1a“3a)
To a solution of o-carborane (720 mg, 5 mmol) in
dry THF (50 ml) at −78°C was added n-BuLi (3.1 ml,
1.6 M in hexane) dropwise with stirring. The mixture
was stirred for 30 min at −78°C and 1a (859 mg, 5.5
mmol) was added. The solution was stirred for 1 h and
then warmed to room temperature. After quenching
with water, the mixture was extracted with ether and
dried over anhydrous magnesium sulfate. Evaporation
of the solvents followed by purification using silica gel
column chromatography (hexane:ethyl acetate=5:1)
afforded 3a (1.29 g, 4.3 mmol, 86%). In no case was
disubstituted carborane obtained. The use of dilute
solutions of lithium carborane (ca. 0.1 M) is essential to
obtain selectively the mono-substituted carborane
derivatives. Furthermore, in the addition of 2 to alde-
3. Conclusion
Although acetals and ketals have been very popular
and useful protective groups for aldehydes and ketones,

H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
111
Scheme 2.
hyde 1g, which contains ester and aldehyde functional
groups in the same molecule, carboranylmethanol 3g
was obtained chemoselectively in 95% yield under the
same condition (entry 7).
4.1.5. 1-(o-Carboranyl)-p-methylbenzyl alcohol (3e)
Liquid: IR (CHCl3) 3600, 3500ꢀ3150, 3150ꢀ2800,
2570, 1730, 1650, 1610, 1095, 1010, 900 cm−1 1H-
.
NMR (CDCl3) l 7.20 (s, 4H), 5.23 (d, J=3.0 Hz, 1H),
3.77 (bs, 1H), 2.51 (d, J=3.0 Hz, 1H), 2.37 (s, 3 H).
MS (EI) m/z 264 (M+), 143 (carborane), 121 (M+
–
4.1.1. o-Carboranyl-2-naphthylmethanol (3a)
White solid: m.p. 147°C; IR (KBr) 3585, 3086, 2633,
carborane), 93 (MePh): HRMS (EI) Calc. for
C10H20OB10 m/z 266.2445. Found m/z 266.2448.
2603, 2580, 2552, 1356, 1315, 1247, 1184, 1166, 1083
1
cm−1. H-NMR (CDCl3) l 7.87 (m, 3H), 7.78 (s, 1H),
4.1.6. o-Carboranyl-p-trifluoromethylbenzyl alcohol (3f)
White solid: IR (KBr) 3674, 3553, 3444, 3087, 2970,
2937, 2900, 2582, 1622, 1419, 1384, 1325, 1247, 1168
7.54 (m, 2H), 7.45 (dd, J=9.0, 2.0 Hz, 1H), 5.44 (d,
J=3.5 Hz, 1H), 3.84 (s, 1H), 2.72 (d, J=3.5 Hz, 1H).
HRMS (FAB) Calc. for C13H20OB10: m/z 302.2445.
Found: m/z 302.2450. Anal. Calc. for C13H20OB10: C,
51.98, H, 6.71. Found: C, 51.70, H, 6.41%
1
cm−1. H-NMR (CDCl3) l 7.67 (d, J=8.0 Hz, 2H),
7.48 (d, J=8.0 Hz, 2H), 5.34 (d, J=3.0 Hz, 1H), 3.94
(s, 1H), 2.73 (d, J=3.0 Hz, 1H). HRMS (FAB) Calc.
for C10H17OB10F3: m/z 320.2162. Found: m/z 320.2152.
4.1.2. o-Carboranylbenzyl alcohol (3b)
Colorless solid: m.p. 70°C; IR (KBr) 3550, 3100,
4.1.7.
1
2550, 1490, 1460, 1100, 1040, 770, 710 cm−1. H-NMR
o-Carboranyl-(4-methexycarbonylphenyl)methanol (3g)
White solid: m.p. 152°C; IR (KBr) 3367, 3088, 2954,
2619, 1685, 1610, 1577, 1434, 1407,1317,1294,
(CDCl3) l 7.36 (m, 5H), 5.27 (d, J=3.5 Hz, 1H). 3.81
(bs, 1H), 2.56 (d, J=3.5 Hz, 1H) MS (EI) m/z 250
(M+), 233 (M+ –OH), 108 (M+ –carborane), 77 (Ar).
Anal. Calc. for C9H18OB10; C, 43.18 H, 7.25. Found: C,
42.98, H, 7.09%.
1
1188,1114, 1085, 1020 cm−1. HNMR (CDCl3) l 8.06
(d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 5.33 (d,
J=3.5 Hz, 1H), 3.93 (s, 3H), 3.89 (s, 1H), 2.70 (d,
J=3.5 Hz, 1H). HRMS (FAB) Calc. for C11H20O3B10:
m/z 310.2343. Found: m/z 310.2355. Anal. Calc. for
C11H20O3B10: C, 42.84; H, 6.54. Found: C, 42.76; H,
6.48%.
4.1.3. o-Carboranyl-p-methoxybenzyl alcohol (3c)
White crystal: m.p. 111°C; IR (CHCl3) 3600, 3500ꢀ
3150, 3150ꢀ2850, 2840, 2570, 1610, 1500, 1300, 1220,
1
1170, 1090, 1030 cm−1; H-NMR (CDCl3) l 7.25 (d,
J=9.0 Hz, 2H), 6.91 (d, J=9.0 Hz, 2H), 5.22 (d,
J=3.0 Hz, 1H), 3.83 (s, 3H), 3.78 (bs, 1H), 2.48 (d,
J=3.0 Hz, 1H). MS (EI) m/z 280 (M+), 264 (M+ –H),
121 (MeOPhC), 109 (MeOPh), 94 (OPh), 77 (Ph).
HRMS (EI): Calc. for C10H20O2B10 m/z 282.2394.
Found m/z 282.2395. Anal. Calc. for C10H20O2B10: C,
42.80, H, 7.19. Found: C, 42.20, H, 6.95%.
4.1.8. trans-1-(o-Carboranyl)-3-phenyl-2-propen-1-ol
(3h)
Liquid; IR (CCl4) 3590, 3500ꢀ3200, 3060, 2560,
1930, 1640, 1480, 1440, 1360, 1180, 1080, 1000, 950
1
cm−1; H-NMR (CDCl3) l 7.43ꢀ7.28 (m, SH), 6.63
(d, J=15.0 Hz, 1H), 6.09 (dd, J=15.0, 7.5 Hz, 1H),
4.77 (dd, J=7.5, 4.0 Hz, 1H), 4.07 (bs, 1H), 2.24 (d,
J=4.0 Hz, 1H). MS (EI) 276 (M+), 143 (carborane),
133 (M+ –carborane). HRMS (EI): Calc. for
C11H20OB10: m/z 278.2445. Found: m/z 278.2446.
4.1.4. o-Carboranyl-p-methylthiabenzyl alcohol (3d)
White solid: m.p. 117°C; IR (KBr) 3400, 3087, 2572,
1596, 1492, 1434, 1404, 1180, 1091, 1047, 1014 cm−1
.
1H-NMR (CDCl3) l 7.24 (s, 4H), 5.23 (d, J=3.0 Hz,
1H), 3.81 (s, 1H), 2.55 (d, J=3.0 Hz, 1H), 2.50 (s, 3H).
13C-NMR (CDCl3) l 140.76, 134.91, 127.02, 126.13,
78.56, 74.75, 59.26, 15.35. HRMS (FAB) Calc. for
C10H20OB10S: m/z 298.2166. Found: m/z 298.2170.
Anal. Calc. for C10H20OB10S: C, 40.52; H, 6.80; S,
10.82. Found: C, 40.52; H, 6.65; S, 11.10%.
4.1.9. 1-o-Carboranyl-2-octen-1-ol (3i)
Liquid: IR (CCl4) 3583, 3435, 3085, 2956, 2927, 2856,
1
1085, 1018 cm−1. H-NMR (CDCl3) l 5.77 (dt, J=
15.0, 7.5 Hz, 1H), 5.40 (dd, J=15.0, 8.0 Hz, 1H), 4.52
(dd, J=8.0, 4.0 Hz, 1H) 4.01 (s, 1H), 2.09 (m, 3H),
1.43ꢀ1.26 (m, 6H), 0.90 (t, J=6.5 Hz, 3H). 13C-NMR
(CDCl3) l 137.73, 127.56, 77.92, 73.77, 58.31, 31.93,

112
H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
Scheme 3.
31.3, 28.28, 22.37, 13.96. HRMS (FAB) Calc. for
C10H26OB10: m/z 272.2915. Found: m/z 272.2923. Anal.
Calc. for C10H26OB10: C, 44.42, H, 9.69. Found: C,
44.12, H, 9.42%.
4.1.13. 2-o-Carboranyloctan-2-ol (3m)
Colorless oil: IR (CDCl3) 3584, 3475, 3091, 2956,
1
2929, 2858, 2578, 914 cm−1. H-NMR (CDCl3) l 4.09
(s, 1H), 1.84 (s, 1H), 1.71 (t, J=8.0 Hz, 2H), 1.43 (s,
3H), 1.29 (m, 8H), 0.89 (t, J=7.0 Hz, 3H). 13C-NMR
(CDCl3) l 85.58, 73.46, 60.38, 43.05, 31.67, 29.46,
27.82, 24.42, 22.55, 13.96. Anal. Calc. for C10H28OB10:
C, 44.09; H, 10.36. Found: C,43.79; H, 10.09%.
4.1.10. 1-o-Carboranyl-1-phenylethanol (3j)
White solid: m.p. 118°C; IR (KBr) 3589, 3566, 3367,
3064, 2989, 2586, 1492, 1446, 1379, 1176, 1145, 1072,
1
914 cm−1. H-NMR (CDCl3) l 7.35ꢀ7.48 (m, SH),
3.43 (s, 1H), 2.47 (s, 1H), 1.94 (s, 3H). 13C-NMR
(CDCl3) l 142.63, 128.75, 128.40, 125.70, 74.75, 61.65,
32.19, 28.39. HRMS (FAB) Calc. for C10H20OB10: m/z
266.2445. Found: m/z 266.2448. Anal. Calc. for
C10H20OB10: C, 45.4, H, 7.63. Found: C, 44.8, H,
7.60%.
4.1.14. 5-o-Carboranylnonan-5-ol (3n)
Colorless oil: IR (KBr) 3589, 3475, 3089, 2960, 2933,
2873, 2578, 1465, 1380, 1342, 1257, 1124, 1080 cm−1
.
1H-NMR (CDCl3) l 4.09 (s, 1H), 1.89 (s, 1H), 1.69 (m,
4H), 1.32 (m, 8H), 0.93 (t, J=7.0 Hz, 6H). 13C-NMR
(CDCl3) l 85.58, 75.33, 60.44, 40.14, 26.52, 22.89,
13.88. HRMS (FAB) Calc. for C11H30OB10: m/z
288.3228. Found: m/z 288.3232.
4.1.11. 1-o-Carboranyl-1-(2-naphthyl)ethanol (3k)
White solid: m.p. 148°C IR (KBr) 3566, 3078, 3063,
2575, 1598, 1506, 1446, 1380, 1355, 1271, 1215, 1186,
1
1128, 1076, 1016 cm−1. H-NMR (CDCl3) l 7.94 (s,
4.2. A representati6e procedure of clea6age reaction
(3a“1a)
1H), 7.86 (m, 3H), 7.55 (m, 3H), 3.50 (s, 1H), 2.64 (s,
1H), 2.05 (s, 3H). 13C-NMR (CDCl3) l 140.0, 132.9,
132.6, 128.6, 128.1, 127.6, 127.0, 126.8, 125.0, 123.4,
84.1, 74.9, 61.74, 32.39. HRMS (FAB) Calc. for
C14H22OB10: m/z 316.2602. Found: m/z 316.2599. Anal.
Calc. for C14H22OB10: C, 53.48, H, 7.05. Found: C,
53.31, H, 6.88%.
To a THF/H2O (100/1, 9 ml) solution of 3a (274 mg,
0.91 mmol) was added KOH (7.7 mg, 0.136 mmol, 0.15
equivalents) at room temperature and the mixture was
stirred for 2 days. The reaction was quenched with
saturated aqueous ammonium chloride solution. The
mixture was extracted with ether, dried over anhydrous
magnesium sulfate, and concentrated. Purification by
silica gel column chromatography with hexane/ethyl
acetate (10:1) gave the corresponding aldehyde 1a (121
mg, 0.775 mmol, 85%, 92% by GC) first and then
o-carborane (100 mg, 0.69 mmol, 76%). 1h and 1k were
also obtained from 3h and 3k in the same manner in 74
and 66% isolated yields, respectively (entries 8 and 11).
In other cases, yields were determined by 1H-NMR
and/or GC analysis as shown in Table 2.
4.1.12. 2-o-Carboranyl-4-phenyl-3-buten-2-ol (31)
White solid: m.p. 137°C; IR (KBr) 3589, 3076, 3028,
2997, 2933, 2594, 2563, 1598, 1577, 1494, 1375, 1296,
1274, 1178, 1114, 1018 cm−1 1H-NMR (CDCl3) l
.
7.43–7.29 (m, SH), 6.70 (d, J=16.0 Hz, 1H), 6.23 (d,
J=16.0 Hz, 1H), 4.07 (s, 1H), 2.23 (s, 1H), 1.67 (s, 3H).
HRMS (FAB) Calc. for C12H22OB10: m/z 292.2602.
Found: m/z 292.2612. Anal. Calc. for C12H22OB10: C,
49.6; H, 7.64. Found: C, 49.5; H, 7.50%.

H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
113
Scheme 4.
4.3. Selecti6e alkylation of ester 1g
4.4. Selecti6e reduction of ester 1g
4.3.1. 5-[4-(o-Carboranylhydroxymethyl)
phenyl]nonan-5-ol (5)
4.4.1. o-Carboranyl-(4-hydroxymethyl
phenyl)methanol (7)
To a solution of compound 3g (100 mg, 0.32 mmol)
in dry THF (3 ml) at −78°C was added n-BuLi (0.6
ml, 1.63 M in hexane) dropwise with stirring. The
mixture was stirred for 30 min at −78°C and then
warmed to room temperature. After quenching with
saturated aqueous ammonium chloride solution, the
mixture was extracted with ether and dried over anhy-
drous magnesium sulfate. Evaporation of the solvents
followed by purification using silica gel column chro-
matography (hexane:ethyl acetate=10:1) afforded 5
(94 mg, 0.24 mmol, 74%) as a colorless liquid: IR (neat)
3361, 3089, 2956, 2933, 2582, 1465, 1411, 1342, 1299,
To a solution of 3g (163 mg, 0.53 mmol) in dry THF
(5 ml) at room temperature was added lithium alu-
minum hydride (139 ml, 3.70 mmol) with stirring. The
mixture was stirred for 4 h under reflux and cooled to
0°C. After quenching with saturated aqueous ammo-
nium chloride solution, the mixture was extracted with
ether and dried over anhydrous magnesium sulfate.
Evaporation of the solvents followed by purification
using silica gel column chromatography (hexane:ethyl
acetate=1:2) afforded 7 (141 mg, 0.50 mmol, 95%) as
a white solid: m.p. 132°C; IR (KBr) 3516, 3454, 3205,
3084, 3062, 2916, 2879, 2580, 1419, 1301, 1211, 1091,
1
1
1288, 1253, 1207 cm−1. H-NMR (CDCl3) l 7.40 (d,
1016 cm−1. H-NMR (CDCl3) l 7.40 (d, J=8.0 Hz,
J=8.0 Hz, 2H), 7.29 (d, J=8.0 Hz, 2H), 5.26 (d,
J=3.0 Hz, 1H), 3.84 (s, 1H), 2.57 (d, J=3.0 Hz, 1H),
1.82–1.75 (m, 4H), 1.60–1.56 (m, 8H), 0.82 (t, J=7.0
Hz, 6H). HRMS (FAB, M+ –H) Calc. for
C18H35O2B10: m/z 393.3568. Found: m/z 393.3567.
2H), 7.32 (d, J=8.0 Hz, 2H), 5.27 (d, J=3.0 Hz, 1H),
4.72 (s, 2H), 3.87 (s, 1H), 2.74 (s, 1H), 1.78 (s, 1H).
HRMS (FAB) Calc. for C10H20O2B10: m/z 282.2394.
Found: m/z 282.2405. Anal. Calc. for C10H20O2B10: C,
42.8; H, 7.19. Found: C, 42.5; H, 7.08.
4.3.2. 5-(4-Formylphenyl)nonan-5-ol (6)
4.4.2. 4-Hydroxymethylbenzaldehyde (8)
To a THF/H2O (100/1, 4 ml) solution of 5 (153 mg,
0.39 mmol) was added KOH (3.3 mg, 0.059 mmol, 0.15
equivalents) at room temperature and the mixture was
stirred for 1 day. The reaction was quenched with
saturated aqueous ammonium chloride solution. The
mixture was extracted with ether, dried over anhydrous
magnesium sulfate, and concentrated. Purification by
silica gel column chromatography with hexane/ethyl
acetate (10:1) gave the corresponding aldehyde 6 (77
mg, 0.31 mmol, 80%) as a yellow oil: 1H-NMR (CDCl3)
l 9.98 (s, 1H), 7.85 (d, J=8.0 Hz, 2H), 7.54 (d, J=8.0
Hz, 2H), 1.78 (m, 4H), 1.22 (m, 8H), 0.77 (t, J=7.0
Hz, 6H). HRMS (FAB) Calc. for C16H24O2: m/z
248.1776. Found: m/z 248.1764.
To a THF/H2O (100/1, 2 ml) solution of 7 (40 mg,
0.143 mmol) was added KOH (1.2 mg, 0.02 mmol, 0.15
equivalents) at room temperature and the mixture was
stirred for 2 days. The reaction was quenched with
saturated aqueous ammonium chloride solution. The
mixture was extracted with ether, dried over anhydrous
magnesium sulfate, and concentrated. Purification by
silica gel column chromatography with hexane/ethyl
acetate (1:1) gave the corresponding aldehyde 8 (15 mg,
0.11 mmol, 77%) as a white needle: IR (KBr) 3427,
1
2922, 2850, 1678, 1608 cm−1. H-NMR (CDCl3) l 9.99
(s, 1H), 7.87 (d, J=8.0 Hz, 2H), 7.52 (d, J=8.0 Hz,
2H), 4.80 (s, 2H), 2.08 (bs, 1H). HRMS (FAB) Calc.
for C8H8O2: m/z 136.0524. Found: m/z 136.0523.

114
H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
1
4.5. Selecti6e reduction of ketone 9
1566, 1215, 1166 cm−1. H-NMR (CDCl3) l 10.04, (s,
1H), 7.89 (d, J=8.0 Hz, 2H), 7.56 (d, J=8.0 Hz, 2H),
6.55 (m, 2H), 2.43 (m, 2H), 1.73 (m, 2H), 1.59 (m, 2H),
1.31 (s, 3H), 1.03 (t, J=7.0 Hz, 3H), 1.42 (m, 6H).
13C-NMR (CDCl3) l 191.7, 143.9, 135.2, 134.9, 130.1,
128.9, 126.3, 72.59, 41.81, 40.83, 27.76, 26.89, 26.12,
23.24, 14.05. HRMS (FAB) Calc. for C17H24O2: m/z
260.1776. Found: m/z 260.1765.
4.5.1. 4-(5-Oxo-l-hexenyl)benzaldehyde (9)
This was synthesized via Heck reaction of p-bro-
mobenzaldehyde and 5-hexer-2-one, which was pre-
pared by the literature procedure [15]. Colorless oil: IR
(KBr) 2922, 2841, 1691, 1600, 1566, 1366, 1164, 914,
1
742, cm−1. H-NMR (CDCl3) l 10.04 (s, 1H), 7.89 (d,
J=7.2 Hz, 2H), 7.56 (d, J=7.2 Hz, 2H), 6.52 (d,
J=15.0 Hz, 1H), 6.47 (dt, J=15.O, 5.5 Hz, 1H), 2.73
(t, J=6.0 Hz, 2H), 2.62 (dt, J=5.5, 6.0 Hz, 2H), 2.26
(s, 3H). 13C-NMR (CDCl3) l 207.08, 191.15, 143.12,
134.68, 132.72, 129.64, 129.38, 126.07, 42.16, 29.49,
26.69. HRMS (FAB) Calc. for C13H14O2: m/z 202.0994.
Found: m/z 202.0993.
4.6. Selecti6e monoallylation of dialdehyde 13
4.6.1. 3-(o-Carboranylhydroxymethyl)benzaldehyde (14)
To a solution of o-carborane (144 mg, 1.0 mmol) in
dry THF (100 ml) at −78°C was added n-BuLi (0.66
ml, 1.68 M in hexane) dropwise and the mixture was
stirred for 30 min at −78°C. This mixture was added
to a solution of 13 (522 mg, 3.9 mmol) in THF (10 ml)
dropwise at −78°C. The solution was stirred for 1 h
and then warmed to room temperature. After quench-
ing with saturated aqueous ammonium chloride solu-
tion, the mixture was extracted with ether and dried
over anhydrous magnesium sulfate. Evaporation of the
solvents followed by purification using silica gel column
chromatography (hexane:ethyl acetate=4:1) afforded
14 (144 g, 0.52 mmol, 52%) as a white solid: m.p.
147.5°C. IR (CCl4) 3392, 3090, 2579, 1685, 1604, 1230,
4.5.2. 6-[4-(o-Carboranylhydroxymethyl)phenyl]-
5-hexen-2-one (10)
A solution of 9 (161 mg, 0.80 mmol), tributylstannyl-
carborane (442 mg, 0.96 mmol), Pd2dba3·CHCl3 (167
mg, 0.16 mmol), and bisdiphenylphosphinoethane
(dppe) (126 mg, 0.32 mmol) in dry THF (5 ml) was
stirred under reflux for 4 h. Evaporation of the solvent
followed by purification using silica gel column chro-
matography (hexane:ethyl acetate=5:1) afforded 10
(191 mg, 0.55 mmol, 69%) as a yellow oil: IR (KBr)
3583, 3392, 3084, 303O, 2956, 2922, 2576, 1701, 1363,
1141, 1089, 1047, 1018 cm−1 1H-NMR (CDCl3) l
.
1
1087, 1047 cm−1. H-NMR (CDCl3) 7.44 (d, J=8.0
10.02, (s, 1H), 7.91–7.84 (m, 2H), 7.65–7.55 (m, 2H),
5.37 (d, J=3.6 Hz, 1H), 4.01 (s, 1H), 3.02 (d, J=3.6
Hz, 1H). 13C-NMR (CDCl3) l 191.6, 139.9, 136.6,
132.7, 130.9, 129.4, 127.3, 74.3, 58.9, 27.7. HRMS
(FAB) Calc. for C10H18O2B10: m/z 280.2238. Found:
m/z 280.2240.
Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 6.50 (d, J=16.0 Hz,
1H), 6.33 (dt, J=16.O, 6.5 Hz, 1H), 5.33 (d, J=3.0
Hz, 1H), 3.91 (s, 1H), 3.31 (d, J=3.0 Hz, 1H), 2.73 (t,
J=7.0 Hz, 2H), 2.58 (dt, J=7.0, 6.5 Hz, 2H), 2.27 (s,
3H). 13C-NMR (CDCl3) l 208.7, 138.5, 137.3, 130.1,
129.9, 126.8, 126.1, 78.76, 74.64, 59.23, 42.93, 29.95,
26.98.
4.6.2. 3-(1-Hydroxy-3-buteny)benzaldehyde (16)
To a solution of 14 (57 mg, 0.21 mmol) and al-
lyltrimethylsilane (36 ml, 0.22 mmol) in dry CH2Cl2 (1
ml) at −78°C was added TiCl4 (0.8 ml, 1.0 M in
CH2Cl2) dropwise and the mixture was stirred for 1 h at
−78°C. After quenching with saturated aqueous
sodium hydrogen carbonate solution, the mixture was
extracted with ether, dried over anhydrous magnesium
sulfate, and concentrated. The residue was dissolved in
a THF/H2O (100/1, 2 ml) solution and NaOH (1.2 mg,
0.03 mmol, 0.15 equivalents) was added. The mixture
was stirred at room temperature for 1 day. After
quenching with saturated aqueous ammonium chloride
solution, the mixture was extracted with ether, dried
over anhydrous magnesium sulfate, and concentrated.
Purification by silica gel column chromatography with
hexane/ethyl acetate (10:1) gave the corresponding alde-
hyde 16 (24 mg, 0.14 mmol, 67%) as a colorless oil: IR
(CCl4) 3408, 3076, 2956, 2927, 2856, 1693, 1641, 1602,
4.5.3. 4-(5-Hydroxy-5-methyl-1-nonenyl)benzaldehyde
(12)
To a solution of compound 10 (67 mg, 0.19 mmol) in
dry THF (2 ml) at −78°C was added n-BuLi (0.46 ml,
1.63 M in hexane) dropwise with stirring. The mixture
was stirred for 30 min at −78°C and then warmed to
room temperature. After quenching with saturated
aqueous ammonium chloride solution, the mixture was
extracted with ether, dried over anhydrous magnesium
sulfate, and concentrated. The residue was dissolved in
a THF/H2O (100/1, 2 ml) solution and KOH (1.6 mg,
0.03 mmol, 0.15 equivalents) was added. The mixture
was stirred at room temperature for 2 days. After
quenching with saturated aqueous ammonium chloride
solution, the mixture was extracted with ether, dried
over anhydrous magnesium sulfate, and concentrated.
Purification by silica gel column chromatography with
hexane/ethyl acetate (4:1) gave the corresponding alde-
hyde 12 (40 mg, 0.15 mmol, 80%) as a colorless oil: IR
(KBr) 3427, 3028, 2956, 2931, 286O, 2594, 1695, 1602,
1
1483, 1466, 1443, 1414, 1389 cm−1. H-NMR (CDCl3)
l 9.99, (s, 1H), 7.87 (t, J=1.7 Hz, 1H), 7.77 (dt,
J=7.5, 1.7 Hz, 1H), 7.63 (dt, J=7.5, 1.7 Hz, 1H), 7.50

H. Nakamura et al. / Journal of Organometallic Chemistry 574 (1999) 107–115
115
hensive Organic Synthesis, Pergamon Press, Oxford, vol. 1, 1991,
pp. 325–354.
[4] TMS-cyanohydrins are readily cleaved under aqueous acidic and
basic conditions and under Lewis acid conditions. Others are
generally stable to acidic conditions.
[5] It was reported that generation of monolithiocarborane 2 by
treating o-carborane with n-BuLi was accompanied by dilithio-
carborane formation due to the disproportionation reaction of 2
(see F.A. Gome, S.E. Johnson, M.F. Hawthorne, J. Am. Chem.
Soc. 113 (1991) 5915). However, we have found that the redistri-
bution reaction can be avoided by carrying out the lithiation of
o-carborane under controlled conditions and 2 is then generated
in essentially quantitative yield from o-carborane. Also, see Ref.
[8].
(t, J=7.5 Hz, 1H), 5.82–5.70 (m, 1H), 5.18 (m, 1H),
5.12 (m, 1H), 4.82 (t, J=6.0 Hz, 1H), 2.61–2.46 (m,
2H), 2.43 (s, 1H). 13C-NMR (CDCl3) l 192.3, 145.0,
136.5, 133.7, 131.9, 129.0, 128.9, 126.9, 118.9, 72.5,
43.8. HRMS (FAB) Calc. for C11H12O2: m/z 176.0837.
Found: m/z 176.0840.
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.