780
J . Org. Chem. 1997, 62, 780 781
Ta ble 1. Th e Deca r bor a n yla tion of
1-Ca r bor a n yl-2-n a p h th ylm eth a n ol 3a P r om oted by KOH
a t Room Tem p er a tu r e
o-Ca r bor a n e a s a Novel P r otective Gr ou p
for Ald eh yd es a n d Keton es
amount (equiv)
Hiroyuki Nakamura, Kouichi Aoyagi, and
Yoshinori Yamamoto*
entry
of KOH
solvent
yielda of 1 (%)
1
2
3
4
5
3.0
1.1
0.15
0.15
0.15
THF
THF
THF
38b
58b
57b
92
Department of Chemistry, Graduate School of Science,
Tohoku University, Sendai 980-77, J apan
THF/H2O (100/1)
THF/H2O (10/1)
60
Received November 14, 1996
a
Yields were determined by GC analysis using hexadecane as
It is widely accepted that acetals and ketals are very
useful as protective groups for aldehydes and ketones.1,2
The protective groups are readily cleaved by acid hy-
drolysis and Lewis acid coordination. The latter property
is a drawback of these protective groups in the case of a
Lewis acid-mediated reaction.3 We wish to report that
the functionalized o-carboranyl methanols 3, which can
be prepared easily by the addition of lithiocarborane 2
to carbonyl compounds 1,4 are very stable under aqueous
protic acid and Lewis acid conditions and are readily
cleaved under basic conditions to produce the corre-
sponding carbonyl compounds 1 and o-carborane (eq 1).
b
an internal standard. Reduced product (2-naphthylmethanol)
was also produced in 8% (entry 1), 17% (entry 2), and 14% (entry
3) yield, respectively.
Ta ble 2. Th e Deca r bor a n yla tion of Va r iou s
o-Ca r bor a n ylm eth a n ols 3 P r om oted by a Ca ta lytic
Am ou n t of KOH in THF /H2O (100/1)
aldehyde
carboranylmethanol time
yielda (%)
(d) (isolated yield)b
entry and ketone 1
3
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
3k
3l
3m
3n
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
83 (66)
93
92d
97
a
Yields were determined by 1H NMR using p-xylene as an
b
internal standard. 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
d
using hexadecane as an internal standard. NaOH (0.15 equiv)
Conditions used to cleave o-carborane from 1-carbora-
nyl-2-naphthylmethanol 3a are shown in Table 1. We
examined several bases, such as NaOMe, pyridine, n-
BuLi, and t-BuOK, but we found that KOH was the most
suitable for this cleavage. The use of excess (3.0 equiv)
and 1.1 equiv 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-naphthyl-
methanol were obtained as byproduct in entries 1 3.
However, the presence of small amounts of water in the
THF prevented formation of the byproduct (entries 4 and
5), and the best result was obtained by using 0.15 equiv
of KOH in THF/H2O (100/1) as a solvent (entry 4). Under
these conditions, o-carborane was recovered in high yields
(76% isolated yield in entry 4).5 Accordingly, recycling
of o-carborane is possible.6
was used instead of KOH.
various carboranylmethanols 3b n (Table 2). The de-
carboranylation of 3b proceeded smoothly to give ben-
zaldehyde 1b in 84% yield (entry 2). Other aromatic
aldehyde derivatives 3c g bearing either an electron-
donating or an electron-withdrawing group gave the
corresponding aldehydes in good yields (entries 3 7). Not
only aromatic aldehydes but also ,â-unsaturated alde-
hydes 1h and 1i were obtained in good to high yields from
the corresponding carboranylmethanols 3h and 3i (en-
tries 8 and 9). In the case of di-substituted carboranyl-
methanols 3j n , the cleavage reaction proceeded smoothly
to give the corresponding ketones 1j n in good to high
yields (entries 10 14). The carboranylmethanols 3 were
very stable under strong acid or Lewis acid conditions.7
A representative procedure is as follows. A. F or m a -
tion (1a f 3a ). To a solution of o-carborane (720 mg, 5
Having established optimum conditions for the decar-
boranylation of 3a , we next applied this procedure to
(4) It was reported that generation of monolithiocarborane 2 by
treating o-carborane with n-BuLi was accompanied by dilithiocarbo-
rane formation due to the disproportionation reaction of 2 (see Gome,
F. A.; J ohnson, S. E.; Hawthorne, M. F. J . Am. Chem. Soc. 1991, 113,
5915). However, we have found that the redistribution reaction can
be avoided by carrying out the lithiation of o-carborane under controlled
conditions (see a representative example in text).
(5) o-Carborane (closo) is converted to nido-o-carborane by treatment
with bases. However, under the cleavage conditions, the closo frame-
work was stable to KOH.
(6) Other attractive points of this protective group are that protected
aldehydes and ketones 3 are readily crystallized and stable to air,
moisture, and acids.
(7) When benzaldehyde dimethyl acetal was treated with TiCl4 (2
equiv) in dichloromethane, benzaldehyde 1b was obtained in 82% yield.
However, treatment of 3b with aqueous HCl (1 N) or TiCl4 (2 equiv)
for 2 days gave no benzaldehyde, but 3b was recovered quantitatively.
(1) Protective Groups in Organic Synthesis; Greene, T. W., Wuts, P.
G. M., Ed.; J ohn Wiley: New York, 1991; pp 175 223.
(2) Stork, G.; Maldonado, L. J . Am. Chem. Soc. 1971, 93, 5286.
Evans, D. A.; Hoffman, J . M.; Truesdale, L. K. J . Am. Chem. Soc. 1973,
95, 5822. Hiyama, T.; Oishi, H.; Saimoto, H. Tetrahedron Lett. 1985,
26, 2459. Also see ref 1.
(3) On the other hand, the latter property can become an advantage
of the protecting group. Very high asymmetric induction is ac-
complished by the Lewis acid-mediated reactions of chiral acetals:
Mukaiyama, T. Angew. Chem., Int. Ed. Engl. 1977, 16, 817. J ohnson,
W. S.; Elliott, R.; Elliott, D. J . Am. Chem. Soc. 1983, 105, 2904.
J ohnson, W. S.; Edington, C.; Elliott, J . D.; Silverman, I. R. J . Am.
Chem. Soc. 1984, 106, 7588. Yamamoto, Y.; Nishii, S.; Yamada, J . J .
Am. Chem. Soc. 1986, 108, 7116. Also see the recent review: Com-
prehensive Organic Synthesis; Schreiber, S. L., Ed.; Pergamon Press:
Oxford, 1991; Vol. 1, pp 325 354.
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