Allyl and prop-2-ynyl ethers in the phloroglucinol series and their thermal rearrangements. An alternative synthesis of deoxyhumulone and its analogues

Abstract

Treatment of phloroacetophenone (2′,4′,6′-trihydroxyacetophenone) with prop-2-ynyl bromide and potassium carbonate gave 2′-hydroxy-4′,6′-bis(prop-2-ynyloxy)acetophenone (3; R = H), 2′,4′-dihydroxy-6′-(prop-2-ynyloxy)acetophenone (4; R¹= CH₂C⋮CH, R²= H), 8-acetyl-2,3,5,6-tetrahydro-2,5-dimethylenebenzo-[1,2-b:3,4-b′]difuran-7-ol (5), and other minor products including 6′-hydroxy-5′-(prop-2-ynyl)-2′,4′-bis(prop-2-ynyloxy)acetophenone (9).

Hydrogenation of (3; R = H) with quinoline–sulphur-poisoned palladium was only partially selective giving 2′,4′-bis(allyloxy)-6′-hydroxyacetophenone (2; R¹= Me, R²= H) as the predominant product. Thermal rearrangement of (2; R¹= Me, R²= H) in refluxing N-methylpiperazine under nitrogen gave 3′-allyl-4′-allyloxy-2′,6′-dihydroxyacetophenone (12) in 55% yield whilst rearrangement in refluxing NN-diethylaniline gave the deoxyhumulone analogue, 3′,5′-diallyl-2′,4′,6′-trihydroxyacetophenone (1; R¹= Me, R²= H) in 85% yield.

Attempted etherification of phloroacetophenone with 1,1-dimethylprop-2-ynyl chloride in dry acetone gave no reaction but in the presence of water the major product was 8-acetyl-2,2-dimethylchromen-5,7-diol (13; R = H). Amongst other products were 7-acetyl-2,3-dihydro-3,3-dimethyl-2-methylenebenzo[b]furan-4,6-diol (14; R = H), which was transformed by dilute acid to 7-acetyl-2,3-dihydro-2,3,3-trimethylbenzo[b]furan-2,4,6-triol (18), 6-acetyl-2,2,8,8-tetramethyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-5-ol (7), and 8-acetyl-5-(1,1-dimethylprop-2-ynyloxy)-2,2-dimethylchromen-7-ol (20). Similar attempts to etherify 3′,5′-diacetylphloroacetophenone gave 6,8-diacetyl-2,2-dimethylchromen-5,7-diol (13; R = Ac) and 5,7-diacetyl-2,3-dihydro-3,3-dimethyl-2-methylenebenzo[b]furan-4,6-diol (14; R = Ac).

Thermal rearrangement of 2-isovaleryl-4,4-bis-(3-methylbut-2-enyl)cyclohexane-1,3,5-trione (26; R = Me₂CHCH₂) gave a complex mixture including 2,4,6-trihydroxy-3,5-bis-(3-methylbut-2-enyl)isovalerophenone (deoxyhumulone)(1; R¹= Me₂CHCH₂, R²= Me)(10%) and 8-isovaleryl-2,2-dimethyl-6-(3-methylbut-2-enyl)chroman-5,7-diol (30).