(1g), which possesses an electron-withdrawing group at the
aromatic nucleus gave the corresponding 2ga in modest yield
(entries 9-11). Fortunately, this reaction was also effective for
heterocyclic compounds, and methyl nicotinoylacetate (1h)
afforded the corresponding tartronic ester 2h in good yield (entry
12). Furthermore, benzoylacetone (1i), without an ester group,
was reactive for this tandem reaction condition and gave the
mixed products 2ia and 2ib (entry 13).
Scheme 1
.
Plausible Path of Transformation of ꢀ-Ketoesters to
Tartronic Esters
The developed protocol was easily scaled up; the reaction
of 1a and 0.2 equiv of CaI2 in MeOH (150 mL) was
irradiated with a fluorescent lamp for 24 h in an oxygen
atmosphere on a 10 mmol scale, and dimethyl 2-butyl-2-
hydroxymalonate (2aa) was obtained in 92% yield (eq 2).
is postulated by considering all of the results mentioned
above, the change of the solution color to yellow, and
the necessity of continuous irradiation, catalytic amount
of CaI2, and molecular oxygen. At first, ꢀ-ketoester 1 is
transformed to radical species 6 through abstraction of
hydrogen by the iodo radical, which is formed from I- in
situ. The resulting species 6 traps molecular oxygen to
generate hydroperoxide 8 through peroxiradical 7, and this
hydroperoxide 7 is transformed to 3. The resulting 3 is
attacked by alcohol and rearranged to produce tartronic
In order to examine the mechanism of this reaction, we
studied the time-course of this transformation (Figure 1). The
(6) (a) Itoh, A.; Hashimoto, S.; Kodama, T.; Masaki, Y. Synlett 2005,
2107–2109. (b) Itoh, A.; Hashimoto, S.; Masaki, Y. Synlett 2005, 2639–
2640. (c) Hirashima, S.; Itoh, A. Synthesis 2006, 1757–1759. (d) Hirashima,
S.; Hashimoto, S.; Masaki, Y.; Itoh, A. Tetrahedron 2006, 62, 7887–7891.
(e) Hirashima, S.; Itoh, A. Photochem. Photobiol. Sci. 2007, 6, 521–524.
(f) Hirashima, S.; Itoh, A. Green Chem. 2007, 9, 318–320. (g) Hirashima,
S.; Itoh, A. J. Synth. Org. Chem. Jpn. 2008, 66, 748–756.
(7) Anastas, P. T.; Warnar, J. C. Green Chemistry, Theory and Practice;
Oxford University Press: Oxford, 1998.
(8) For selected examples of tandem reaction, see: (a) Porco, J. A., Jr.;
Schoenen, F. J.; Stout, T. J.; Clardy, J.; Schreiber, S. L. J. Am. Chem. Soc.
1990, 112, 7410–7411. (b) Denmark, S. E.; Thorarensen, A. Chem. ReV.
1996, 96, 137–166. (c) Molander, G. A.; Harris, C. R. J. Am. Chem. Soc.
1996, 118, 4059–4071. (d) Chen, C.; Layton, M. E.; Sheehan, S. M.; Shair,
M. D. J. Am. Chem. Soc. 2000, 122, 7424–7425. (e) Shi, F.; Li, X.; Xia,
Y.; Zhang, L.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 129, 15503–15504.
(9) A typical procedure follows: A dry methanol solution (5 mL) of
1a (0.3 mmol) and CaI2 (0.06 mmol) in a Pyrex test tube equipped with
an O2 balloon was irradiated under stirring conditions for 10 h with
four of 22 W fluorescent lamps, which was set from the test tube in the
distance of 80 mm. The reaction mixture was concentrated under the
reduced pressure, dissolved in ethyl acetate, and washed with sodium
thiosulfate and brine. The organic layer was dried over MgSO4 and
concentrated under reduced pressure. The pure product 2aa was obtained
by preparative TLC.
Figure 1. Time-course of transformation of ꢀ-ketoesters to tartronic
esters.
mixture of R,ꢀ-diketoester and its hydrated species 3a, which
we could obtain as an intermediate, increased for 2 h and
gradually decreased with increasing yield of 2aa (Table 1,
entry 9).10 In addition, 2aa was obtained in 90% yield when
3a was used as a substrate under the conditions mentioned
above.11
(10) Oxidation of ꢀ-dicarbonyl compounds to tricarbonyl compounds:
(a) Schank, K.; Leider, R.; Lick, C.; Glock, R. HelV. Chim. Acta 2004, 87,
869–924. (b) Carnell, A. J.; Johnstone, R. A. W.; Parsy, C. C.; Sanderson,
W. R. Tetrahedron Lett. 1999, 40, 8029–8032. (c) Batchelor, M. J.; Gillespie,
R. J.; Golec, J. M. C.; Hedgecock, C. J. R. Tetrahedron Lett. 1993, 34,
167–170. (d) Adam, W.; Prechtl, F. Chem. Ber. 1991, 124, 2369–2372. (e)
Wasserman, H. H.; Pickett, J. E. Tetrahedron 1985, 41, 2155–2162. (f)
Jung, M. E.; Shishido, K.; Davis, L. H. J. Org. Chem. 1982, 47, 891–892.
(g) Bigelow, L. A.; Hanslick, R. S. Org. Synth. 1933, 13, 38–40. (h) Muller,
R. Chem. Ber. 1933, 66B, 1668–1670. (i) Astin, S.; Newman, A. C. C.;
Riley, H. L. J. Chem. Soc. 1933, 391–394. (j) Dox, A. W. Org. Synth.
1925, 4, 27–29.
Furthermore, 13C-enriched substrate 4 produced 5 under
the same reaction conditions (eq 3).
(11) Benzilic acid rearrangement of R,ꢀ-diketoesters, see: (a) Dahn, H.;
Dao, L. H.; Hunma, R. HelV. Chim. Acta 1982, 65, 2458–2463. (b) Dahn,
H.; Gowal, H.; Schlunke, H. P. HelV. Chim. Acta 1970, 53, 1598–1605,
and references cited therein.
Scheme 1 shows a proposal for a reaction mechanism
for the conversion of ꢀ-ketoesters to tartronic esters, which
1950
Org. Lett., Vol. 12, No. 9, 2010