One-Pot Synthesis of Tetronic Acids from Esters

Abstract

Tetronic acids substituted by various groups were synthesized in one pot from the corresponding aryl- or heteroarylacetic acid esters and hydroxyacetic acid esters, by a tandem process involving a transesterification and a subsequent Dieckmann cyclization.

cyclizations - esters - heterocycles - lactones - ring closure

References and Notes

Reviews:

1a Tejedor D. Garcia-Tellado F. Org. Prep. Proced. Int.  2004,  36:  33 

1b Zografos AL. Georgiadis D. Synthesis  2006,  3157 

2a Gill M. Steglich W. Prog. Chem. Org. Nat. Prod.  1987,  51:  1 

2b Rao YS. Chem. Rev.  1976,  76:  625 

For reviews on the Dieckmann condensation, see:

3a Davis BR. Garrett PJ. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.806-829  

3b Schaefer JP. Bloomfield JJ. Org. React.  1967,  15:  1 

For recent syntheses of tetronic acids via Dieckmann condensation, see:

4a Pulvinones: Bernier D. Moser F. Brückner R. Synthesis  2007,  2240 

4b See also: Bernier D. Brückner R. Synthesis  2007,  2249 

4c Retipolide E, ornatipolide: Ingerl A. Justus K. Hellwig V. Steglich W. Tetrahedron  2007,  63:  6548 

4d Abyssomicin C, atrop-abyssomicin C, and abyssomicin D: Nicolaou KC. Harrison ST. J. Am. Chem. Soc.  2007,  129:  429 

4e (+)-Tetronolide: Boeckman RK. Shao P. Wrobleski ST. Boehmler DJ. Heintzelman GR. Barbosa AJ. J. Am. Chem. Soc.  2006,  128:  10572 

4f Quartromicins: Trullinger TK. Qi J. Roush WR. J. Org. Chem.  2006,  71:  6915 

4g Secretase inhibitors: Larbig G. Schmidt B. J. Comb. Chem.  2006,  8:  480 

5 Bretschneider T. Benet-Buchholtz J. Fischer R. Nauen R. Chimia  2003,  57:  697 ; and references therein

6 Weber V. Rubat C. Duroux E. Lartigue C. Madesclaire M. Coudert P. Bioorg. Med. Chem.  2005,  13:  4552 

For previous studies on the synthesis of pulvinic derivatives in our laboratory, see:

7a Desage-El Murr M. Nowaczyk S. Le Gall T. Mioskowski C. Amekraz B. Moulin C. Angew. Chem. Int. Ed.  2003,  42:  1289 

7b Heurtaux B. Lion C. Le Gall T. Mioskowski C. J. Org. Chem.  2005,  70:  1474 

7c Desage-El Murr M. Nowaczyk S. Le Gall T. Mioskowski C. Eur. J. Org. Chem.  2006,  1489 

7d Willis C. Bodio E. Bourdreux Y. Billaud C. Le Gall T. Mioskowski C. Tetrahedron Lett.  2007,  48:  6421 

8 Lloyd-Jones GC. Angew. Chem. Int. Ed.  2002,  41:  953 ; and references therein

9 Campbell AC. Maidment MS. Pick JH. Stevenson DFM. J. Chem. Soc., Perkin Trans. 1  1985,  1567 

10

Typical Experimental Procedures for Compound 3a In DMF: To a solution of methyl 4-methoxyphenylacetate (0.318 mL, 2.0 mmol) and methyl glycolate (0.170 g, 2.2 mmol) in DMF (10 mL) was added a 1 M solution of KOt-Bu in THF (4.4 mL, 4.4 mmol). The solution was stirred under argon at r.t. for 2 h. The reaction mixture was then poured into cooled 1 N HCl (15 mL). The aqueous phase was extracted with EtOAc (3 × 10 mL), the combined organic layers were washed several times with brine, dried over Na₂SO₄. After filtration and concentration in vacuo, the residue was purified by column chromatography [silica gel, 200:1, then CH₂Cl₂-MeOH (95:5) containing 0.2% AcOH], to give compound 3a as a white solid (0.370 g, 90%).In THF: To a solution of methyl 4-methoxyphenylacetate (0.318 mL, 2.0 mmol) and methyl glycolate (0.170 g, 2.2 mmol) in anhyd, degassed THF (10 mL) was added a 1 M solution of KOt-Bu in THF (4.4 mL, 4.4 mmol). The suspension obtained was refluxed under argon for 16 h. After cooling to r.t., the reaction mixture was poured into 1 N HCl (15 mL). Treatment and purification as above afforded compound 3a as a white solid (0.350 g, 85%). Compound 3a: mp 228 °C (lit. 9: 228-229 °C). IR (neat): 2955, 1695, 1641, 1610, 1514, 1426, 1398, 1351, 1297, 1256, 1169, 1053, 1030, 1022, 960, 836, 736 cm^-1. ¹H NMR (400 MHz, acetone-d ₆): δ = 3.81 (s, 3 H, OCH₃), 4.76 (s, 2 H, CH₂), 6.95 (d, J = 9.0 Hz, 2 H, CH), 7.94 (d, J = 9.0 Hz, 2 H, CH), 10.94 (br s, 1 H, OH). ¹³C NMR (100 MHz, acetone-d ₆): δ = 55.5 (OCH₃), 66.6 (C₅), 100.3 (C₃), 114.3 (C_{3 ′}), 123.8 (C_{1 ′}), 129.2 (C_{2 ′}), 159.4 (C_{4 ′}), 172.1, 173.5 (C₂, C₄). MS (ESI-TOF): m/z = 207 [M + H]⁺.