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:

<A NAME="RD30807ST-1A">1a</A> Tejedor D. Garcia-Tellado F. Org. Prep. Proced. Int.  2004,  36:  33 

<A NAME="RD30807ST-1B">1b</A> Zografos AL. Georgiadis D. Synthesis  2006,  3157 

<A NAME="RD30807ST-2A">2a</A> Gill M. Steglich W. Prog. Chem. Org. Nat. Prod.  1987,  51:  1 

<A NAME="RD30807ST-2B">2b</A> Rao YS. Chem. Rev.  1976,  76:  625 

For reviews on the Dieckmann condensation, see:

<A NAME="RD30807ST-3A">3a</A> Davis BR. Garrett PJ. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.806-829  

<A NAME="RD30807ST-3B">3b</A> Schaefer JP. Bloomfield JJ. Org. React.  1967,  15:  1 

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

<A NAME="RD30807ST-4A">4a</A> Pulvinones: Bernier D. Moser F. Brückner R. Synthesis  2007,  2240 

<A NAME="RD30807ST-4B">4b</A> See also: Bernier D. Brückner R. Synthesis  2007,  2249 

<A NAME="RD30807ST-4C">4c</A> Retipolide E, ornatipolide: Ingerl A. Justus K. Hellwig V. Steglich W. Tetrahedron  2007,  63:  6548 

<A NAME="RD30807ST-4D">4d</A> Abyssomicin C, atrop-abyssomicin C, and abyssomicin D: Nicolaou KC. Harrison ST. J. Am. Chem. Soc.  2007,  129:  429 

<A NAME="RD30807ST-4E">4e</A> (+)-Tetronolide: Boeckman RK. Shao P. Wrobleski ST. Boehmler DJ. Heintzelman GR. Barbosa AJ. J. Am. Chem. Soc.  2006,  128:  10572 

<A NAME="RD30807ST-4F">4f</A> Quartromicins: Trullinger TK. Qi J. Roush WR. J. Org. Chem.  2006,  71:  6915 

<A NAME="RD30807ST-4G">4g</A> Secretase inhibitors: Larbig G. Schmidt B. J. Comb. Chem.  2006,  8:  480 

<A NAME="RD30807ST-5">5</A> Bretschneider T. Benet-Buchholtz J. Fischer R. Nauen R. Chimia  2003,  57:  697 ; and references therein

<A NAME="RD30807ST-6">6</A> 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:

<A NAME="RD30807ST-7A">7a</A> Desage-El Murr M. Nowaczyk S. Le Gall T. Mioskowski C. Amekraz B. Moulin C. Angew. Chem. Int. Ed.  2003,  42:  1289 

<A NAME="RD30807ST-7B">7b</A> Heurtaux B. Lion C. Le Gall T. Mioskowski C. J. Org. Chem.  2005,  70:  1474 

<A NAME="RD30807ST-7C">7c</A> Desage-El Murr M. Nowaczyk S. Le Gall T. Mioskowski C. Eur. J. Org. Chem.  2006,  1489 

<A NAME="RD30807ST-7D">7d</A> Willis C. Bodio E. Bourdreux Y. Billaud C. Le Gall T. Mioskowski C. Tetrahedron Lett.  2007,  48:  6421 

<A NAME="RD30807ST-8">8</A> Lloyd-Jones GC. Angew. Chem. Int. Ed.  2002,  41:  953 ; and references therein

<A NAME="RD30807ST-9">9</A> Campbell AC. Maidment MS. Pick JH. Stevenson DFM. J. Chem. Soc., Perkin Trans. 1  1985,  1567 

<A NAME="RD30807ST-10">10</A>

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]⁺.