Benzodioxan derivatives

Reaction of pyroc techol with epichlorohydrin in the presence of base affords the benzodioxan derivative, 136, (The reaction may well involve initial displacement of halogen by phenoxide followed by opening of the oxirane by the anion from the second phenolic group.) Treatment of the alcohol with thio-nyl chloride gives the corresponding chloro compound (137). Displacement of halogen by means of diethylamine affords piper-oxan (138), a compound with a-sympathetic blocking activity. 

The aprotic diazotisation of tetrachloroanthranilic acid in the presence of benzaldehyde or />-methoxybenzaldehyde results in the formation of the 1,3-benzodioxan derivatives (131, R = Ph) and (131, R = >-C gH 4-OMe) respectively 155). The absence of products analogous to (129) in these reactions suggests that the formation of the compounds (131) do involve tetrachlorobenzyne. Some indication of the mechanism of these reactions was given by the fact that no analogous adduct has been isolated in attempted reactions of tetrachlorobenzyne with p-nitrobenzaldehyde. However, in the presence of acetone we obtained a low yield of the compound (132). 

Treatment of the (—)-menthone-derived 2/7-1,3-benzoxazin-4(3//)-one 202 with triflic anhydride gave the triflate 203 in quantitative yield. Palladium-catalyzed cross-coupling of 203 with 2-pyridylzinc halide resulted in formation of an approximately 3 1 mixture of the 4-(2-pyridyl)-2//-l,3-benzoxazine 204 and a 4-imino-l,3-benzodioxane derivative 205 (Scheme 36). Compound 205 was formed by the isomerization of 203, which occurred with complete retention of stereochemistry. The 4-(2-pyridyl)-l,3-benzoxazine derivative 204 was applied in enantioselective allylic alkylations of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate as a chiral ligand inducing a 62% ee in the product <2005JOM(690)2027>. 

Cyclizations of o-(a -haloalk oxy)phenols have been widely studied and were used to afford an expedient synthesis of 5-alkyl-2,3-dihydro-l,4-benzodioxins <2004SC2487>. This approach via a nucleophilic substitution was used for the synthesis of 8-substituted-2-hydroxymethyl-l,4-benzodioxane derivatives 164 in an enantiopure form. Use of CsF instead of more basic conditions allowed higher yields and enantiomeric excess (Equation 28) <2001ASC95>. Dry tetrabutylammonium fluoride (TBAF) in THF was required and was basic enough to initiate an intramolecular Sn substitution from the protected phenol 165 to the fluoro-l,4-benzodioxane 166 <1996T6187>. 

A tandem palladium-catalyzed reaction can effect a similar transformation to produce 2-vinyl-substituted heterocyclic systems as in Eq. 8E.11. By varying the amino acid moiety of the ligand, 83% ee could be obtained from the use of the glycine-derived ligand 129 [161]. A maximum enantioselectivity of 65% ee has been recorded for this type of reaction in an earlier study with BINAP as ligand [ 162]. Because both ( )- and (Z)-isomers gave the same enantioselectivity, attack on the rapidly interconverting 7t-allyl intermediates seems to determine the selectivity. Modest enantioselectivities have been reported for the related asymmetric preparation of 2-vinylpiperazine and 1,4-benzodioxane derivatives [163,164],... 

Biologically active 2-substituted 1,4-benzodioxane derivatives 88KFZ925. 

Dihydroxy-N-methylindole 142 readily reacts with DHA in aqueous solution at room temperature (64CJC1401 65JCS4728) (Scheme 34). The two hydroxy groups of the indole interact with the a-diketone function of DHA to form the 1,4-benzodioxane 144. This type of reaction appears to be general since similar interactions occur between other o-diphenols and a-diketones. The mechanism by which the 1,4-benzodioxane derivative is obtained when adrenochrome 141 is reduced with ascorbic acid to give 142 via 143 was studied. 

Benzodioxane derivatives continue to be studied for this activity. Two compounds, SAS-506 (XVI) and MPB (XVII) were reported to be worthy of continued study. 

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