Regioselective Lewis acid-directed reactions of 2-alkoxy-5-alkyl-1,4-benzoquinones with styrenes: Synthesis of burchellin and guianin neolignans

Article abstract of DOI:10.1021/jo00101a017

Reactions of 2-carbomethoxy-5-methoxy-1,4-benzoquinone with (E)-propenylbenzenes promoted by Ti(IV) regio- and stereoselectively yield trans 2-aryl-4-carbomethoxy-7-methoxy-3-methyl-2,3-dihydro-5-benzofuranols. However, the products found in Lewis acid-promoted reactions of 2-alkoxy-5-alkyl-1,4-benzoquinones with (E)-propenylbenzenes depend on the nature of the Lewis acid. Low-temperature reactions with SnCl₄ produce rel-(1R,6S,7S,8R)-4-alkoxy-1-alkyl-7-aryl-8-methylbicyclo[4.2.0]oct-3- ene-2,5-diones 21-23 and products derived from them. Allowing the reactions to warm to room temperature results in rel-(2S,3S,3aR)-3a-alkyl-2-aryl-5-hydroxy-3-methyl-2,3,3a,6-tetrahydro -6-oxobenzofurans as mixtures of keto-enol tautomers 26/27 and 28/29. With Ti(IV) as promoter, the reactions can be made to produce either 21-23 or the regioisomeric rel-(1S,6R,7R,8S)-4-alkoxy-1-alkyl-8-aryl-7-methylbicyclo[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 propenylbenzene. A mechanistic rationale is presented involving regioselective coordination of the different Lewis acids to the quinone. Thus, SnCl₄ binds to the C-1 carbonyl and C-2 alkoxy oxygens, forming a complex possessing a 2-alkoxy-5-alkyl-4-oxo-2,5-cyclohexadienyl carbocation moiety (e.g. 30) which undergoes a thermally allowed 4π + 2π (5 + 2) cycloaddition with propenylbenzene to give a bicyclo[3.2.1]octenyl 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 conditions, followed by rearrangement. Cyclobutanes 18-20 undergo protic acid rearrangement to give trans 7-alkoxy-4-alkyl-2-aryl-3-methyl-2,3-dihydro-5-benzofuranols 15-17, whereas cyclobutanes 21-23 yield 5-alkyl-7-aryl-3-hydroxy-6-methylbicyclo[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.