One‐step preparation of some 2‐isopropenyl‐2,3‐dihydronaphtho‐[2,3‐b]furan‐4,9‐diones

Abstract

Some 2-isopropenyl-2,3-dihydronaphtho [2,3-b]furan-4,9-diones 1a-f,b',f' were prepared by one-step cyclizations of 2-hydroxy-1,4-naphthoquinones 2a-f with 1,4-dibromo-2-methyl-2-butene (3).J. Heterocyclic Chem., 38, 511 (2001).Our recent interests were focused on the effective preparation of natural 2-isopropenyl-2,3-dihydrobenzofuran derivatives [1]. Some dehydroiso-α-lapachones 1a,b,b',f, having a 2-isopropenyl-2,3-dihydronaphtho- [2,3-b]furan-4,9-dione structure, were isolated from Cresentia cujete, and showed interesting mutagenic activities [2]. In this paper, one-step preparation of 2-isopropenyl-2,3-dihydronaphtho [2,3-b]furan-4,9-diones 1 are described.Nickl reported the first one-step preparation of 2-isopropenyl-2,3-dihydrobenzofuran derivatives; cyclization of 2',4',6'-trihydroxyacetophenone with 1,4-dibromo-2-methyl-2-butene 3 effectively gave 7-acetyl-2-isopropenyl-2,3-dihydrobenzofuran-4,6-diol in ethanol/sodium ethoxide solution [3]. But, the similar cyclization of general phenols with 3 generates only O-alkylation products in ethanol/sodium ethoxide solution. We found that the cyclization of general phenols with 3 was effective in non-polar solvents, such as ether or toluene with sodium metal or sodium hydride [1], and the cyclization of 1,3-diketones with 3 was effective in acetone with potassium carbonate [4].For the preparation of 1, a one-step cyclization of 2-hydroxy-1,4-naphthoquinones 2 with 3 was planned. The one-step cyclization was studied under several conditions using commercially available 2-hydroxy-1,4-naphthoquinone (2a), and the results are summarized in table 1. Cyclization of 2a with 3 gives none of the cyclized product in polar conditions, such as ethanol/sodium ethoxide or acetone/potassium carbonate, but gives the desired cyclized product 1a under non-polar conditions. Cyclizations using sodium hydride (2 equivalents) in refluxing ether or tetrahydrofuran, calcium hydride (2 equivalents) in refluxing toluene, and n-butyl lithium (1 equivalent) in refluxing toluene, show low yields (<4%). But, cyclization using sodium hydride (2 equivalents) in refluxing toluene shows the best yield of 16% after 24 hours. Use of equal (1 equivalent) or excess ( 3 equivalents) amounts of sodium hydride decreases the yields (1 equivalent gives 0%, 3 equivalents give 1%), and longer reaction time also decreases the yield (48 hours gives < 1%).For a preparation of the corresponding 2-hydroxy-1,4-naphthoquinones 1b-f, five methoxy-substituted 2-hydroxy-1,4-naphthoquinones 2b-f were prepared according to reported procedures [5a-e]. Four methoxysubstituted 2-hydroxy-1,4-naphthoquinones (2b-e) and