REGIOSELECTIVE LEWIS ACID-DIRECTED REACTIONS OF 2-ALKOXY-5-ALKYL-1,4-BENZOQUINONES WITH STYRENES - SYNTHESIS OF BURCHELLIN AND GUIANIN NEOLIGNANS

Reactions of 2-carbomethoxy-5-methoxy-1,4-benzoquinone with (E)-propen ylbenzenes promoted by Ti(IV) regio- and stereoselectively yield trans xy-7-methoxy-3-methyl-2,3-dihydro-5-benzofuranols. However, the produ cts found in Lewis acid-promoted reactions of 2-alkoxy-5-alkyl-1,4-ben zoquinones with (E)-propenylbenzenes depend on the nature of the Lewis acid. Low-temperature reactions with SnCl4 produce -7-aryl-8-methylbi cyclo[4.2.0]oct-5-ene-2,5-diones 21-23 and products derived from them. Allowing the reactions to warm to room temperature results in roxy-3- methyl-2,3,3a,6-tetrahydro-6-oxobenzofurans as mixtures of keto-enol t automers 26/27 and 28/ 29. With Ti(IV) as promoter, the reactions can be made to produce either 21-23 or the regioisomeric -8-aryl-7-methylb icyclo[4.2.0]oct-3-ene-2,5-diones 18-20. The ratio of the two depends upon the makeup of the Ti(IV) promoter and the substituents on the pro penylbenzene. A mechanistic rationale is presented involving regiosele ctive coordination of the different Lewis acids to the quinone. Thus, SnCl4 binds to the C-1 carbonyl and C-2 alkoxy oxygens, forming a comp lex possessing a 2-alkoxy-5-alkyl-4-oxa-2,5-cyclohexadienyl carbocatio n moiety (e.g. 30) which undergoes a thermally allowed 4 pi + 2 pi (5 + 2) cycloaddition with propenylbenzene to give a bicyclo[3.2.1]octeny l carbocation 31; this cation then rearranges to the observed products . On the other hand, the Ti(IV)-promoted reactions give either bicyclo [3.2.1]octenyl carbocation 31 or 34, depending upon reaction condition s, followed by rearrangement. Cyclobutanes 18-20 undergo protic acid r earrangement to give trans -alkyl-2-aryl-3-methyl-2,3-dihydro-5-benzof uranols 15-17, whereas cyclobutanes 21-23 yield hydroxy-6-methylbicycl o[3.2.1]oct-3-ene-2,8-diones 24/25. The reactions provide an efficient and stereoselective route to neolignans of the guianin and burchellin classes.