T. Yakura et al. / Tetrahedron Letters 43 (2002) 6925–6927
6927
ous. Such a process, however, is not required in our
method. Although we have not experienced any acci-
dents, we recommend that for safety a small volume of
solvent should be left during the evaporation process
and then the remaining mixture is allowed to solidify by
spontaneous evaporation of the solvent in a flask or on
a large plate.
New York, 1993; Vol. 43, pp. 251–798; (b) Krow, G. R.
In Comprehensive Organic Synthesis; Trost, B. M., Flem-
ing, I.; Ley, S. V., Ed.; Pergamon Press: Oxford, 1991;
Vol. 7, pp. 671–688; (c) Strukul, G. Angew. Chem., Int.
Ed. Engl. 1998, 37, 1198–1209; (d) Renz, M.; Meunier, B.
Eur. J. Org. Chem. 1999, 737–750.
2. (a) Chida, N. J. Synth. Org. Chem. Jpn. 2000, 58, 642–
653; (b) Beauhaire, J.; Ducrot, P.-H. Bioorg. Med. Chem.
1996, 4, 413–418; (c) Cook, G. R.; Beholz, L. G.; Stille, J.
R. J. Org. Chem. 1994, 59, 3575–3584; (d) de Mattos, M.
C. S.; Kover, W. B. Synth. Commun. 1993, 23, 2895–
2907; (e) Liu, Z.-Y.; He, L.; Zheng, H. Synlett 1993,
191–192.
This method is quite general and effective for Baeyer–
Villiger reactions of hindered ketones. Some additional
examples under these new conditions as well as the
reactions carried out in CH2Cl2 are shown in Table 2.8
The crystalline a-substituted cyclopentanone (3a)
reacted with m-CPBA in the presence of NaHCO3
under the new solvent-free conditions for only 10 min
to give 4a in quantitative yield, whereas a similar
reaction of 3a in CH2Cl2 for 10 min gave 28% of 4a
along with 72% of unreacted 3a (entry 1).13 A similar
reaction of the a,a-disubstituted cyclopentanone (3b)
was completed within 4 h by the new procedure and
afforded 4b in 93% yield, while the oxidation of 3b in
CH2Cl2 for the same reaction time was not completed
and gave only 13% of 4b and 85% of unreacted 3b
(entry 2). The oily cyclopentanone (3c) having an elec-
tron-withdrawing ester group at the a-position, for
which the Baeyer–Villiger reaction in CH2Cl2 in the
presence of NaHCO3 required 5 days,5a was also oxi-
dized under the new conditions within 3 h to produce
lactone (4c) in 96%. The Baeyer–Villiger reaction of
cyclohexanone (3d), which is a key step of the efficient
synthesis of 4,4-disubstituted g-butyrolactones,6 was
accelerated by using our new procedure (entry 4). An
acyclic ketone (3e) having quaternary carbon at the
a-position was allowed to react under the new condi-
tions for 24 h to give 99% of the corresponding ester
(4e) exclusively (entry 5). A similar acceleration was
observed in the case of the reaction of the aromatic
ketone (3f) (entry 6).
3. (a) Hagiwara, H.; Nagatomo, H.; Kazayama, S.; Sakai,
H.; Hoshi, T.; Suzuki, T.; Ando, M. J. Chem. Soc.,
Perkin Trans.
1 1999, 457–459; (b) Hagiwara, H.;
Nagatomo, H.; Yoshii, F.; Hoshi, T.; Suzuki, T.; Ando,
M. J. Chem. Soc., Perkin Trans. 1 2000, 2645–2648.
4. Corey, E. J.; Kim, S.; Yoo, S.; Nicolaou, K. C.; Melvin,
L. S., Jr.; Brunelle, D. J.; Falck, J. R.; Trybulski, E. J.;
Lett, R.; Sheldrake, P. W. J. Am. Chem. Soc. 1978, 100,
4620–4622.
5. (a) Nishimura, Y.; Mori, K. Eur. J. Org. Chem. 1998,
233–236; (b) Solladie´, G.; Boeffel, D.; Maignan, J. Tetra-
hedron 1996, 52, 2065–2074.
6. Pinheiro, S.; de Farias, F. M. C.; Saraiva, A. S.; Campos,
M. P. A. Tetrahedron: Asymmetry 1998, 9, 2031–2034.
7. Compound 1 was easily prepared from (2S,3S,4R)-4-tert-
butyldimethylsilyloxy - 2 - methoxycarbonyl - 3 - methyl - 2-
cyclopentanone14 in 95% yield in three steps: (i) reduction
with lithium aluminum hydride; (ii) monosilylation with
TBDMSCl and imidazole; (iii) oxidation with tetra-
propylammonium perruthenate.
8. All new compounds reported herein exhibited satisfactory
spectral data.
9. Sodium bicarbonate is known to promote the Baeyer–Vil-
liger reaction, see: Whitesell, J. K.; Matthews, R. S.;
Helbling, A. M. J. Org. Chem. 1978, 43, 784–786.
10. Toda, F.; Yagi, M.; Kiyoshige, K. J. Chem. Soc., Chem.
Commun. 1988, 958–959 and also see Ref. 3.
In conclusion, an inorganic base, NaHCO3, accelerated
the solvent-free Baeyer–Villiger reaction of ketones
with bulky substituents to give the corresponding esters
and lactones in excellent yields. Repetition of a dissolu-
tion and evaporation technique every 3 h is extremely
effective for shortening the reaction time.
11. For a review of solvent-free reactions, see: Tanaka, K.;
Toda, F. Chem. Rev. 2000, 100, 1025–1074.
12. Typical procedure is as follows: to a solution of ketone (1
mmol) and m-CPBA (2 mmol) in CH2Cl2 (3–5 ml) was
added finely ground NaHCO3 (1–2 mmol) and then the
suspension was concentrated to be a solid residue. When
the reaction was not completed after 3 h, a small volume
of CH2Cl2 was added to the mixture and the whole
mixture was concentrated to a solid. This process (a
dissolution and evaporation) was repeated every 3 h.
13. Taylor et al. reported that the similar reaction in CH2Cl2
in the presence of NaHCO3 at rt for 3.75 h gave the
lactone in 100% yield, see: Taylor, R. J. K.; Wiggins, K.;
Robinson, D. H. Synthesis 1990, 589–590.
Acknowledgements
The authors wish to thank Miss Reiko Hirabayashi for
her technical support and also thank Professor Yoshi-
hiko Ito for helpful discussions.
References
14. Yakura, T.; Tanaka, K.; Kitano, T.; Uenishi, J.; Ikeda,
M. Tetrahedron 2000, 56, 7715–7721.
1. For recent reviews, see: (a) Krow, G. R. In Organic
Reactions; Paquette, L. A., Ed.; John Wiley & Sons, Inc: