K. Mikami et al. / Tetrahedron Letters 45 (2004) 3681–3683
3683
77, 27; (e) Sato, K.; Hibara, A.; Tokeshi, M.; Hisamoto,
H.; Kitamori, T. Adv. Drug Deliver. Rev. 2003, 55, 379; (f)
Sato, K.; Hibara, A.; Tokeshi, M.; Hisamoto, H.; Kita-
mori, T. Anal. Sci. 2003, 19, 15.
Sc
H
O
O
Sc[N(SO2C8F17)2]3
R
O
path b
path a
Sc
4. Usual flow rate in the recent micropumping systems are in
the range of 10–500 lL/min, see: (a) Ehrfeld, W.; Hessel,
V.; Lehr, H. Top. Curr. Chem. 1998, 194, 233; (b) Jensen,
K. F. Chem. Eng. Sci. 2001, 56, 293; (c) Ehrfeld, W.;
H2O
H
H
H
O
O
O
O
O
O
O
€
Hessel, V.; Lowe, H. Microreactors: New Technology for
or
H
H
Sc
Sc
Sc
Modern Chemistry; Wiley-VCH: Weinheim, Germany,
2000; (d) Haswell, S. J.; Middleton, R. J.; O’Sullivan, B.;
Skelton, V.; Watts, P.; Styring, P. Chem. Commun. 2001,
391; (e) Fletcher, P. D. I.; Haswell, S. J.; Pombo-Villar, E.;
Warrington, B. H.; Watts, P.; Wong, S. Y. F.; Zhang, X.
Tetrahedron 2002, 58, 4735.
H2O2
O
O
R
R
R
Sc-OH
Sc
H2O
Sc
H2O
R
O
O
O
O
O
O
5. DiNaS can be now supplied from KYA TECH Corp. as a
high pressure (up to 20.0 MPa) syringe delivery system
controlling the tunable flow of solution from 1 to
200,000 nL/min.
R
R
Scheme 2. The mechanism of the metal peroxo formation followed by
the regioselective oxygen atom insertion.
6. Our primary communication of the aldol reaction in
DiNaS; Mikami, K.; Yamanaka, M.; Islam, M. N.; Kudo,
K.; Seino, N.; Shinoda, M. Tetrahedron Lett. 2003, 44,
7545.
can be illustrated in terms of efficient metal peroxo
formation in the nanoflow system as shown in Scheme 2.
It is crucial step either the complexation of the Sc cat-
alyst with H2O2 affording more nucleophilic Sc peroxo
species (path b) or the coordination of the Sc catalyst on
the ketone (path a). In path b, the intramolecular
nucleophilic attack of the hydroperoxy moiety on the
Sc-coordinated ketone can strictly control the direction
of O–O bond anti to the migratory carbon bearing R
group to afford highly regioselective product in contrast
to path a, where the intermolecular H2O2 attack should
be occurred. In the nanoflow system, the faster disper-
sion of aqueous H2O2 into BTF phase can predomi-
nantly re-form the Sc peroxo species by the
complexation of the Sc hydroxide with H2O2.
7. Reviews on lanthanide complexes: (a) Kagan, H. B.;
Namy, J. L. Tetrahedron 1986, 42, 6573; (b) Imamoto, T.
In Comprehensive Organic Synthesis; Trost, B. M., Flem-
ing, I., Eds.; Pergamon, 1991; p 231; (c) Molander, G. A.
Chem. Rev. p 29; (d) Imamoto, T. Lanthanide in Organic
Synthesis; Academic: London, 1994; 92; (e) Molander, G.
A.; Harris, C. R. Chem. Rev. 1996, 96, 307; (f) Lantha-
nides, Chemistry and Use in Organic Synthesis; Kobayashi,
S., Ed.; Springer: Berlin, 1999; (g) Mikami, K.; Terada,
M.; Matsuzawa, H. Angew. Chem., Int. Ed. Engl. 2002, 41,
3554.
8. Kotsuki, H. and co-workers have reported the use of
Sc(OTf)3 in the Baeyer–Villiger oxidation of methylcyclo-
hexanone by commercial grade m-CPBA provided high
regioselectivity (96:4) for 12 min: Synlett 1999, 462.
9. (a) Mikami, K.; Mikami, Y.; Matsuzawa, H.; Matsumoto,
Y.; Nishikido, J.; Yamamoto, F.; Nakajima, H. Tetrahe-
dron 2002, 58, 4015; (b) Barret, A. G. M.; Bouloc, N.;
Braddock, D. C.; Catterick, D.; Chadwick, D.; White, A.
J. P.; Williams, D. J. Tetrahedron 2002, 58, 3835.
10. (a) Maul, J. J.; Ostrowske, P. J.; Ublackes, G. A.; Linclan,
B.; Curran, D. P. Top. Curr. Chem. 1999, 206, 80; (b)
Ogawa, A.; Curran, D. P. J. Org. Chem. 1997, 62, 450; (c)
Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem.
Soc. 1974, 96, 7503.
In summary, we have envisioned that the Sc amide-
catalyzed B–V reaction is significantly increased in the
regioselectivity as well as the reaction rate by nanoflow
system even in the low concentration of the catalyst
(ꢀ0.1 mol %). Further investigations to develop asym-
metric Baeyer–Villiger reactions in nanoflow system are
now under progress.
References and notes
11. (a) B–V reaction catalyzed by other metal peroxo species
generated from H2O2, and references therein. Pt: Todesco,
M. D.; Pinna, F.; Strukul, G. Organometallics 1993, 12,
148; (b) Strukul, G.; Varagnolo, A.; Pinna, F. J. Mol.
Catal. A 1997, 117, 413; (c) Roberta, G.; Maurizio, C.;
Francesco, P.; Strukul, G. Organometallics 1998, 17, 661;
Re: (d) Herrmann, W. A.; Fischer, R. W. J. Mol. Catal.
1994, 94, 213; (e) Huston, P.; Espenson, J. H.; Bakac, A.
Inorg. Chem. 1993, 32, 4517; (f) Yamazaki, S. Chem. Lett.
1995, 127; Mo: (g) Jacobson, S. E.; Tang, R.; Mares, F. J.
Chem. Soc., Chem. Commun. 1978, 888; (h) Jacobson, S.
E.; Tang, R.; Mares, F. Inorg. Chem. 1978, 17, 3055.
12. The mechanistic issue of the B–V reaction in terms of the
metal peroxo formation has been studied in details,
particularly in the transition metal–H2O2 systems based
on Pt, by the kinetic study under various conditions. See
Refs. 11a–c.
1. Comprehensive reviews: (a) Renz, M.; Meunier, B. Eur. J.
Org. Chem. 1999, 737; (b) Strukul, G. Angew. Chem., Int.
Ed. 1998, 37, 1198; (c) Krow, G. R. Org. React. 1993, 43,
251; (d) Krow, G. R. In Comprehensive Organic Synthesis;
Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7, p 671;
(e) Vogel, P. Chimie Organique; De Boek-Universit: Paris,
Bruxelles, 1997.
2. Silbert, L. S.; Siegel, E.; Swern, D. J. Org. Chem. 1962, 27,
1336, and references cited therein.
3. (a) Ache, H.-J. In Micro Total Analytical Systems; van den
Berg, A., Bergveld, P., Eds.; Kluwer: Dordrecht, 1995; (b)
Microsystem Technology in Chemistry and Life Sciences;
Manz, A., Becker, H., Eds.; Springer: Berlin, 1998; (c)
Manz, A.; Graber, N.; Widmer, H. M. Sens. Actuators B
1990, 1, 244; (d) Freemantle, M. Chem. Eng. News 1999,