Synthesis of 6H-Dibenzo[b,d]pyran-6-ones Using the Inverse Electron Demand Diels–Alder Reaction

Abstract

A set of coumarin-fused electron-deficient 1,3-dienes was synthesized, which differ in the nature of the electron-withdrawing group (EWG) at the terminus of the diene unit and (when EWG = CO(2)Me) the nature and position of substituents. These dienes reacted with the enamine derived from cyclopentanone and pyrrolidine to afford the corresponding cyclopenteno-fused 6H-dibenzo[b,d]pyran-6-ones, most likely via a domino inverse electron demand Diels-Alder (IEDDA)/elimination/transfer hydrogenation sequence. The parent diene (EWG = CO(2)Me, no substituents) was reacted with a range of electron-rich dienophiles (mostly enamines) to afford the corresponding 6H-dibenzo[b,d]pyran-6-ones or their nondehydrogenated precursors, which were aromatized upon treatment with a suitable oxidant. The enamines could either be synthesized prior to the reaction or generated in situ. The syntheses of 30 dibenzopyranones are reported.

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“…They led to the functionalized products dibenzopyranones 61 after aromatization by oxidation of the nondehydrogenated precursor intermediates which were due to be produced (Scheme 15). It is important to note, that the tested enamines 60 were chemically accessible by their generation before or in situ 101 .…”

“…We mention here a few examples of steroid hormone analogues, receptor agonists, growth factor inhibitors and flavonoid derivatives with protective properties against cardiovascular diseases and cancer [101][102][103][104][105] .…”

Synthesis of 6H-Dibenzo[b,d]pyran-6-one Derivatives via Coumarin-Fused Cyclohexa-1,3-diene Intermediates

“…The residue was purified by column chromatography (silica gel, EtOAchexane, 1:2 to 1:1) to afford 4a-q. 9, 168.8, 160.5, 154.1, 153.0, 148.2, 147.9, 147.2, 144.1, 141.7, 137.5, 128.3, 124.7, 124.0, 118.3, 117.7, 110.7, 61.9, 51.8, 39.4, 24.7, 21.1, 14 1, 160.9, 154.8, 145.7, 141.7, 125.6, 118.2, 113.3, 110.9, 109.8, 102.9, 61.1, 43.3, 24.0, 23.7, 14.4 2, 160.94, 160.90, 154.8, 143.8, 140.4, 125.8, 117.1, 116.1, 113.4, 109.8, 102.9, 61.0, 50.4, 29.4, 24.8, 17.6, 14.4 Ethyl 3-Hydroxy-9-methyl-6-oxo-7-phenyl-7,8-dihydro-6H-dibenzo [b,d] (d,J = 9.0 Hz,1 H),5 H),7.06 (d,J = 1.2 Hz,1 H),6.85 (dd,J = 8.4,2.1 Hz,1 H),6.76 (d,J = 2.1 Hz,1 H),4.63 (s,1 H),2 H), 3.48 (s, 1 H), 2.02 (s, 3 H), 1.14 (t, J = 7.2 Hz, 3 H). 13 C NMR (75 MHz, ): δ = 170.…”

“…Ethyl 3,9-Dihydroxy-9-methyl-6-oxo-7-phenyl-7,8,9,10-tetrahydro-6H-dibenzo [b,d] (d,J = 8.7 Hz,1 H),5 H),6.84 (dd,J = 8.7,2.1 Hz,1 H),6.75 (d,J = 2.1 Hz,1 H),4.57 (s,1 H),2 H), 3.44 (s, 1 H), 2.22 (s, 3 H), 2.02 (s, 3 H), 1.14 (t, J = 7.2 Hz, 3 H). 13 C NMR (75 MHz, ): δ = 170.…”

Green and Rapid Access to Benzocoumarins via Direct Benzene Construction through Base‐Mediated Formal [4+2] Reaction and Air Oxidation

“…Unfortunately,s uch approachesa re rarelys tudied likely because in organic synthesist he construction of an ew benzene ring is often avoided. In 2008, Deiters [14] developed an Rucatalyzed [2+ +2+ +2] trimerization method for the synthesis 3,4-benzocoumarins.In2010, Bodewell [15] developed an amine-catalyzed inverse electron demand [4+ +2] Diels-Alder reaction for access to these compounds. [16] Our laboratoriesa re interestedi nn ew strategies for the direct construction of aromatic rings that can provide unusuals horts ynthetic routes for functional molecules.W er ecently report the N-heterocyclic carbene-organic catalyst-mediated formal [3+ +3] reaction [17] ( Figure 1c) andu nsaturated aldehyde d-carbon activation [18] for the synthesiso ft he benzene unit.…”