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

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

References and Notes

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6

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.

7

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.

8

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.

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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.

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

13

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