Efficient and Atom-Economic
Synthesis of α-Substituted β-Chromonyl-α,β-unsaturated
Carbonyls through Molecular Rearrangement

Vivek Khedkar; Wei Liu; Heiko Dückert; Kamal Kumar

doi:10.1055/s-0029-1219176

LETTER

Efficient and Atom-Economic Synthesis of α-Substituted β-Chromonyl-α,β-unsaturated Carbonyls through Molecular Rearrangement

Vivek Khedkar^a, Wei Liu^a,b, Heiko Dückert^a,b, Kamal Kumar*^a
^a Max Planck Institut für Molekulare Physiologie, Otto-Hahn Str. 11, 44227 Dortmund, Germany
Fax: +49(231)1332496; e-Mail: Kamal.Kumar@mpi-dortmund.mpg.de;
^b Technische Universität Dortmund, Fachbereich Chemie, 44221 Dortmund, Germany

Abstract

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Abstract

Under mild acidic conditions [4+2] cycloadducts of 3-formylchromones and acetylenecarboxylates rearrange to yield α-substituted-β-chromonyl-α,β-unsaturated carbonyl compounds in excellent yields.

Key words

benzopyrones - rearrangements - cascade reactions - acetylenecarboxylates

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References

References and Notes

<A NAME="RG31909ST-1A">1a</A> Veitch NG. Grayer RJ. Nat. Prod. Rep. 2008, 25: 555

<A NAME="RG31909ST-1B">1b</A> Harborne JB. Williams CA. Nat. Prod. Rep. 1995, 12: 639

<A NAME="RG31909ST-1C">1c</A> Harborne JB. Williams CA. Nat. Prod. Rep. 1998, 15: 631

<A NAME="RG31909ST-1D">1d</A> Harborne JB. Williams CA. Nat. Prod. Rep. 2001, 18: 310

<A NAME="RG31909ST-1E">1e</A> Williams CA. Grayer RJ. Nat. Prod. Rep. 2004, 21: 539

<A NAME="RG31909ST-1F">1f</A> Ferreira D. Slade D. Marais JPJ. In Flavonoids: Chemistry, Biochemistry and Applications Andersen OM. Markham KR. CRC Press; Boca Raton: 2006. p.553-616

<A NAME="RG31909ST-1G">1g</A> Veitch NC. Nat. Prod. Rep. 2007, 24: 417

<A NAME="RG31909ST-1H">1h</A> Reynaud J. Guilet D. Terreux R. Lussignol M. Walchshofer N. Nat. Prod. Rep. 2005, 22: 504

<A NAME="RG31909ST-1I">1i</A> Mackova Z. Koblovska R. Lapcik O. Phytochemistry 2006, 67: 849

<A NAME="RG31909ST-1J">1j</A> Flavonoids: Chemistry, Biochemistry and Applications Andersen OM. Markham KR. CRC Press; Boca Raton: 2006.

<A NAME="RG31909ST-1K">1k</A> The Flavonoids: Advances in Research since 1986 Harborne JB. Chapman and Hall; London: 1994.

<A NAME="RG31909ST-1L">1l</A> The Science of Flavonoids Grotewold E. Springer; New York / London: 2006.

<A NAME="RG31909ST-1M">1m</A> Maurya R. Yadav PP. Nat. Prod. Rep. 2005, 22: 400

Selected reports:

<A NAME="RG31909ST-2A">2a</A> Dahlen K. Wallen EAA. Grotli M. Luthman K. J. Org. Chem. 2006, 71: 6863

<A NAME="RG31909ST-2B">2b</A> Bhat AS. Whetstone JL. Brueggemeier RW. J. Comb. Chem. 2000, 2: 597

<A NAME="RG31909ST-2C">2c</A> Patil NT. Huo Z. Yamamoto Y. Tetrahedron 2007, 63: 5954

<A NAME="RG31909ST-3A">3a</A> Sabitha G. Aldrichimica Acta 1996, 29: 15

<A NAME="RG31909ST-3B">3b</A> Ghosh CK. Patra A. J. Heterocycl. Chem. 2008, 45: 1529

<A NAME="RG31909ST-4A">4a</A> Khan KM. Ambreen N. Hussain S. Perveen SI. Choudhary M. Bioorg. Med. Chem. 2009, 17: 2983

<A NAME="RG31909ST-4B">4b</A> Sersen F. Loos D. Mezesova L. Lacova M. Med. Chem. 2008, 4: 355

<A NAME="RG31909ST-4C">4c</A> Shihara M. Sakagami H. Anticancer Res. 2008, 28: 277

<A NAME="RG31909ST-4D">4d</A> Dang A. Miller DO. Dawe LN. Bodwell GJ. Org. Lett. 2008, 10: 233

<A NAME="RG31909ST-4E">4e</A> Kawase M. Tanaka T. Kan H. Tani S. Nakashima H. Sakagami H. In Vivo 2007, 21: 829

<A NAME="RG31909ST-4F">4f</A> Barath Z. Radics R. Spengler G. Ocsovszki I. Kawase M. Motohashi N. Shirataki Y. Shah A. Molnar J. In Vivo 2006, 20: 645

<A NAME="RG31909ST-5A">5a</A> Waldmann H. Khedkar V. Dückert H. Schürmann M. Oppel IM. Kumar K. Angew. Chem. Int. Ed. 2008, 47: 6869

<A NAME="RG31909ST-5B">5b</A> Terzidis MA. Dimitriadou E. Tsoleridis CA. Stephanidou-Stephanatou J. Tetrahedron Lett. 2009, 50: 2174

General Procedure for the Rearrangement of the Adducts 3 to 4
TFA (1 mL in 5 mL CH₂Cl₂) was added slowly dropwise to the CH₂Cl₂ solution (5 mL) of the tricyclic benzopyrones 3 (1 mmol). The reaction mixture was stirred at r.t. for 30 min under argon. The reaction was monitored by TLC using cyclohexane-EtOAc (7:3) as eluent. After evaporation of the solvent, the crude product was purified by column chroma-tography on silica gel with cyclohexane-EtOAc as the eluent.

Spectroscopic Data for the Ketoester 4a Yellow solid; mp 177-178 ˚C; R _f = 0.33 (cyclohexane-EtOAc, 6:4). ^¹H NMR (400 MHz, CDCl₃): δ = 8.32 (d, J = 0.7 Hz, 1 H), 8.21-8.19 (dd, J = 1.6, 8.0 Hz, 1 H), 7.63 (td, J = 1.6, 7.8 Hz, 1 H), 7.50 (d, J = 0.7 Hz, 1 H), 7.49-7.47 (dd, J = 1.0, 7.4 Hz, 1 H), 7.43 (td, J = 1.0, 7.4 Hz, 1 H), 3.98 (s, 3 H), 3.82 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 180.8, 174.0, 164.8, 161.1, 159.6, 155.7, 134.6, 132.9, 131.6, 126.7, 126.2, 123.3, 118.3, 118.0, 53.1, 52.6. ESI-HRMS: m/z calcd for C₁₆H₁₃O₇ [M + H⁺]: 317.06558; found: 317.06568.

Spectroscopic Data for the Aldehyde 4h
Yellow solid; mp 120-122 ˚C; R _f = 0.39 (cyclohexane-EtOAc, 6:4). ^¹H NMR (400 MHz, CDCl₃): δ = 9.71 (s, 1 H, CHO), 8.66 (d, J = 0.8 Hz, 1 H), 8.28-8.24 (m, 2 H), 7.73 (d, J = 0.8 Hz, 1 H), 7.52-7.44 (m, 2 H), 3.89 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 189.3, 174.8, 165.6, 158.4, 155.8, 140.8, 134.5, 133.8, 126.4, 126.3, 123.6, 118.4, 118.3, 52.6. ESI-HRMS: m/z calcd for C₁₄H₁₁O₅ [M + H⁺]: 259.06010; found: 259.06017.

Spectroscopic Data for the Phenyl Ketone 4o
Yellow solid; mp 171-173 ˚C; R _f = 0.45 (cyclohexane-EtOAc, 6:4). ^¹H NMR (400 MHz, CDCl₃): δ = 8.18-8.16 (dd, J = 1.3, 8.4 Hz, 1 H), 8.15 (d, J = 1.0 Hz, 1 H), 8.05 (d, J = 1.0 Hz, 1 H), 7.93-7.91 (dd, J = 1.3, 8.4 Hz, 1 H), 7.63 (td, J = 7.8 Hz, 1 H), 7.55-7.35 (m, 5 H), 7.28-7.25 (m, 1 H), 4.25-4.19 (q, J = 7.1 Hz, 2 H), 1.17 (t, J = 7.1 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 194.5, 175.2, 164.3, 156.2, 155.8, 140.6, 136.1, 134.1, 133.8, 132.9, 129.8, 129.0, 128.7, 128.5, 126.1, 125,7, 123.5, 119.0, 118.1, 61.5, 13.9. ESI-HRMS: m/z calcd for C₂₁H₁₇O₅ [M + H⁺]: 349.10705; found: 349.10719.

<A NAME="RG31909ST-10A">10a</A> Ishar MPS. Kumar K. Singh R. Tetrahedron Lett. 1998, 39: 6547

<A NAME="RG31909ST-10B">10b</A> Ishar MPS. Singh G. Kumar K. Singh R. Tetrahedron 2000, 56: 7817

The authors appreciate the comments from one of the referees regarding the mechanistic postulations.

<A NAME="RG31909ST-12">12</A> Neo AG. Carrillo RM. Barriga S. Momán E. Marcaccini S. Marcos CF. Synlett 2007, 327

An alternative synthesis of 4 by a Wittig olefination of 3-formylchromone would require the corresponding ketoester or aldehydic phosphoranes which are not commercially available and require multistep synthesis and also remain susceptible to self-olefination and polymerization reaction. The same is true for the alternative aldol condensation strategy to provide 4 by reacting chromone aldehydes with ketoester 7. Using our previously reported methodology^¹4 to condense 1,3-dicarbonyls with 3-formylchromone, we could observe self-condensation products of 7 but not any formation of 4a (Scheme [4] ).

Scheme 4

<A NAME="RG31909ST-14">14</A> Waldmann H. Kühn M. Liu W. Kumar K. Chem. Commun. 2008, 1211