S. Mattsson et al. / Tetrahedron Letters 48 (2007) 2497–2499
2499
Li+
Although the fastest rates in general were observed
O
when esters incorporating an a-heteroatom were reacted
(e.g., esters 1, 15 and 17) the method can also be applied
to esters incorporating a b-heteroatom (e.g., esters 7 and
13). Unless not activated (as in the case of ester 9), those
esters lacking a heteroatom in both these positions
reacted very slowly (e.g., ester 11). This selectivity can
be an advantage in some cases. For example, diester
19 gave only monoacid 20 (structure confirmed by
HMQC) and no hydrolysis occurred at the other ester
moiety. We also wanted to investigate if this method
was suitable for the cleavage of chiral auxiliary deriva-
tives such as oxazolidinones and camphorsultams. Thus,
in two separate experiments the method described above
was applied on acetylated camphorsultam 21 and
acetylated oxazolidinone 23, respectively (Scheme 2).
Whereas the cleavage of the oxazolidinone derivative
partly failed due to the formation of byproduct 25, cam-
phorsultam 22 was successfully isolated from amide 21
in 90% yield after 5 h of stirring at room temperature.
X
O
R
n
OH-
Figure 2. Proposed reaction intermediate for the lithium-mediated
hydrolyses. X = heteroatom, n = 1 or 2.
amine bases can be used. Preliminary results also indi-
cate that the method is useful for the cleavage of chiral
auxiliary derivatives (e.g., camphorsultam amides).
Acknowledgements
We thank Clas Landersjo¨ for performing the HMQC
experiments and Johan Gottfries for computer assisted
elucidation of the experiments.
Supplementary data
The explanation for the rate-increase in the lithium-
mediated hydrolyses might be due to the coordination
of lithium to the ester carbonyl group and to the hetero-
atom at the a or b position, resulting in a five- or six-
membered chelate, respectively (Fig. 2). Such a coordi-
nation would make the ester carbonyl group more reac-
tive towards the attack of the hydroxide ion. This would
explain why esters lacking heteroatoms in the a or b
positions with respect to the ester carbonyl group, react
more slowly.
Additional experiments where the effect of using differ-
ent lithium salts, amines and solvents in the hydrolysis
of esters 1 and 17 are investigated. Detailed experimen-
tal procedures and full characterization of all new com-
pounds. Supplementary data associated with this article
References and notes
In conclusion, a mild, simple and selective hydrolysis
method has been developed that can be applied to esters,
which either are activated (e.g., phenyl esters) or incor-
porate an a- or b-heteroatom with respect to the ester
carbonyl group. Provided that the reaction is run in
either aqueous CH3CN or THF and depending on the
sensitivity of the substrate, various lithium salts and
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H
H
LiBr, Et N
3
NH
CH CN/H O
N
3
2
O
S
S
O
O
5 h
O
O
21
22
5. See for example: (a) Tsuzuki, K.; Nakajima, Y.; Watanabe,
T.; Yanagiya, M.; Matsumoto, T. Tetrahedron Lett. 1978,
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McKinstry, L.; Kopecky, D. J.; Gleason, J. L. J. Am.
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Seebach, D. Helv. Chim. Acta 1994, 77, 1124–1165; (c)
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90% yield
O
O
O
O
LiBr, Et N
O
N
3
HO
O
NH
HN
+
CH CN/H O
3
2
15 min
23
25
46%
24
54%
Scheme 2. Hydrolysis of acetylated camphorsultam 21 and acetylated
(S)-4-benzyl-2-oxazolidinone 23.