7502
Y. Ryu, A. I. Scott / Tetrahedron Letters 44 (2003) 7499–7502
MAHO to produce the corresponding 1,3-acetonedicar-
boxylic acid diester. No divalent metal chelator is
required and a tertiary amine is sufficient for successful
condensation.
tion, dried over MgSO4 and evaporated in vacuo to
provide a crude mixture.The pure product was obtained
by a silica gel column chromatography.
13. 1,3-Acetonedicarboxylic acid diesters have been exten-
sively used as building blocks for more extended carbo-
cyclic structures such as polyquinenes and steroid
skeletons by the Weiss reaction or other condensation
reactions. For examples, see: (a) Gupta, A. K.; Fu, X.;
Snyder, J. P.; Cook, J. M. Tetrahedron 1991, 23, 3665; (b)
Danishefsky, S.; Crawley, L. S.; Solomon, D. M.; Heggs,
P. J. Am. Chem. Soc. 1971, 93, 2356
Acknowledgements
We would like to thank the Robert A. Welch Founda-
tion for financial support.
1
14. Data for compound 2c: H NMR (500 MHz, CDCl3) l
7.70 (s, 1H, Ph), 7.03 (s, 1H, Ph), 5.56 (s, 2H, benzylic
CH2), 3.98, 3.94 (2s, 3H each, 2 OCH3) and 3.76 (s, 2H,
CH2); 13C NMR (125 MHz, CDCl3) l 195.5 (CO),
166.12 (COO), 153.9, 148.6, 139.9, 126.4, 110.6, 108.3 (6
Ph), 64.5 (benzylic CH2), 56.8, 55.6 (2 OCH3), and 49.2
(CH2).
References
1. Heath, R. J.; Rock, C. O. Nat. Prod. Rep. 2002, 19, 581.
2. For catechol mediated Claisen condensation, see: Scott,
A. I.; Wiesner, C. J.; Yoo, S.; Chung, S.-K. J. Am. Chem.
Soc. 1975, 97, 6277.
3. For glycouril mediated Claisen condensation, see: Chen,
H.; Harrison, P. H. M. Can. J. Chem. 2002, 80, 601 and
references cited therein.
4. Kokube, Y.; Yoshida, J. Tetrahedron Lett. 1978, 19, 367.
5. Brooks, D. W.; Lu, L. D.-L.; Masamune, S. Angew.
Chem., Int. Ed. Engl. 1979, 18, 72.
6. Sakai, N.; Sorde, N.; Matile, S. Molecules 2001, 6, 845.
7. Wong, S. S. Chemistry of Protein Conjugation and Cross-
Linking; CRC Press: Boca Raton, 1993.
1
15. Data for compound 2e: H NMR (500 MHz, CDCl3) l
5.33 (t, J=6.9 Hz, 1H, vinylic), 5.07 (t, J=6.4 Hz, 1H,
vinylic), 4.65 (d, J=6.9 Hz, 2H, CH2O), 3.60 (s, 2H,
CH2CO2), 2.10–2.02 (m, 4H, CH2), 1.70, 1.67, and 1.59
(3s, 3H each, 3 CH3); 13C NMR (125 MHz, CDCl3) l
195.6 (CO), 166.9 (COO), 143.4, 132.0 (2 quaternary
vinylic), 123.8, 117.7 (2 vinylic CH), 62.5 (CH2O), 49.1
(CH2CO), 39.7, 26.4 (2 CH2), 25.8, 17.8, and 16.6 (3
CH3); HRMS (ESI) calculated for C25H37O5 (M−H)−:
−
417.2646; found: 417.2620.
8. SDPP was prepared by the literature procedure: Ogura,
H.; Nagai, S.; Takeda, K. Tetrahedron Lett. 1980, 21,
1467.
9. Bannwarth, W.; Knorr, R. Tetrahedron Lett. 1991, 32,
1157.
1
16. Data for compound 2f: H NMR (500 MHz, CDCl3) l
5.26 (t, J=7.0 Hz, 1H, terminal vinylic), 5.02 (m, 2H, 2
internal vinylic), 4.59 (t, J=7.0 Hz, 2H, CH2O), 3.53 (s,
2H, CH2CO2), 2.04–1.88 (m, 8H, CH2), 1.63, 1.60 (2s, 3H
each, 2 CH3), 1.52 (s, 6H, 2 CH3); 13C NMR (125 MHz,
CDCl3) l 195.7 (CO), 167.0 (COO), 143.5, 135.7, 131.5
(3 quaternary vinylic C), 124.5, 123.8, 117.7 (3 vinylic
CH), 62.6 (CH2O), 49.1 (CH2CO), 39.9, 39.7, 26.9, 26.4
(4 CH2), 25.9, 17.9, 16.7 and 16.2 (4 CH3); HRMS (ESI)
10. For a review of Meldrum’s acid in organic synthesis, see:
Chen, B.-C. Heterocycles 1991, 32, 529.
11. 2,2-Dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) was
heated with an equivalent of an alcohol in refluxing
toluene for 4 h. Upon cooling 1c was precipitated and
collected by filtration. Other MAHOs were simply
purified by subsequent extraction with saturated aqueous
sodium bicarbonate followed by 1N-HCl solution. The
calculated for C35H53O5 (M−H)−: 553.3898; found:
−
553.3831.
17. For reviews of reactions in aqueous amphiphilic self-
assembling systems, see: (a) Lindstrom, U. M. Chem.
Rev. 2002, 102, 2751; (b) Engberts, J. B. F. N.; Blan-
damer, M. J. Chem. Commun. 2001, 1701–1708.
18. It is likely that the final product was already formed
during the reaction rather than work-up according to a
time course study by silica gel thin layer chromatographic
analysis.
19. As we could expect from the suggested mechanism, a
cross-condensation between two different MAHOs
yielded one cross-condensation product and two self-con-
densation products in almost equal distribution. For
instance, a reaction of 1a and 1h with TSTU and DPEA
in DMF provided 1,3-acetonedicarboxylic acid benzyl
tert-butyl ester in 34% yield along with 2a and 2h in 25
and 26% yield, respectively. A slightly higher yield of the
cross-condensation product is probably due to a slight
difference in reactivities of two NHS intermediates gener-
ated from their corresponding MAHOs.
1
structure of each MAHO prepared was confirmed by H,
13C NMR spectroscopy and ESI-MS spectrometry. For
the new compound 1f: 1H NMR (500 MHz, CDCl3) l
7.70 (br, 1H, COOH), 5.35 (t, J=7.2 Hz, 1H, vinyl), 5.08
(m, 2H, vinyl), 4.69 (d, J=7.2 Hz, 2H, CH2O), 3.43 (s,
2H, malonyl CH2), 2.13–1.96 (m, 8H, 4 CH2), 1.72, 1.68
(2s, 3H each, 2 CH3), and 1.60 (s, 6H, 2 CH3); 13C NMR
(125 MHz, CDCl3) l 171.2 (COOH), 167.3 (COO),
143.7, 135.7, 131.5 (3 quaternary vinylic C), 124.5, 123.7,
117.5 (3 vinylic CH), 63.0 (CH2O), 40.9, 39.9, 39.7 (2
CH2 and malonyl CH2), 26.9, 26.3 (2 CH2), 25.9, 17.9,
16.7 and 16.2 (4 CH3); HRMS (ESI) calculated for
C18H27O4 (M−H)−: 307.1915; found: 307.1904.
−
12. The general procedure for self-condensation of MAHO is
as follows: a solution of a MAHO (1 mmol), TSTU (1.2
mmol) and DPEA (3 mmol) in DMF (2 mL) was stirred
for 30 min and evaporated in vacuo. The residue was
dissolved in chloroform and washed with 1N-HCl solu-