An improved method for transforming certain cournarins to 2,2-dimethylchro~i~cnes has been dcvelopctl. Umbelliferone (111) was efficiently converted to precocene 1 (20) (73%) by etherification to herniarin (It.) with tetratnethylorthocarbon;~tc, followed by reaction with methyllithium and eyelization of the resulting phenolic alcohol on silica gel.
GEORGE M. STRUNZ, DENIS BRILLON et PIEKRE G[GU€RE.Can. J . Chem. 61, I963 (1983). On a amCliorC la mcthode de la conversion de quelques eoumarines au dimithylcs-2.2-chrornknes. L'umbcllif6ronc ( l b ) dtait transform6 efficaeement en pr6eoccnc I (2b) (73%) par preparation de I'dthcr methyliquc herniarin (It.), utilisant le tctramCthylorthocarbonate, suivi de la rdaction avec le methyllithium et cyclisation de I'alcool phenolique risultant avec le gel de silice.The methoxy-2,2-dimethylchromenes 2b and 2c (1) were observed by Bowers to exhibit antiallatotropic activity in several hemimetabolous insect species (2), i.e. they disrupt juvenile hormone production, and cause precocious metamorphosis and sterility when administered to these insects. The compounds, designated precocenes I and 2 respectively (2), appear to be metabolized to the cytotoxic 3,4-epoxides in the corpus allatum, accounting for their selective effects against this endocrine organ (3).The precocenes have been synthesized via 4-chromanones produced by condensation of appropriately substituted phenols or phenol derivatives with dimethylacrylic acid or its chloride (2, 4).An alternative approach, which has been employed with variable success in the synthesis of substituted 2,2-dimethylchromenes, involves reaction of appropriate coumarins with methyl magnesium halides and cyclization of the product by acid treatment and/or distillation (5).W e have confirmed the previous observation (5d) that application of the Grignard procedure to 7-methoxycoumarin (herniarin) ( l c ) (prepared, vide itfin, by methylation of umbelliferone ( l b ) ) gives, at best, modest yields of the corresponding work-up, cyclization of the phenolic alcohol product under mild conditions on silica gel.The initial step, methylation of the phenolic hydroxyl group of umbelliferone, was executed virtually quantitatively by refluxing the latter with tetramethylorthocarbonate (6) in the presence of a catalytic amount of~p-toluenesulfonic acid.The methyllithium -silica gel procedure applied to coumarin itself afforded 2,2-dimethylchromene in 83% yield (cf. 59% by the Grignard method (50)).
ExperimentalCommercial umbelliferone (95+%) was purified prior to use by elution with acetone successively through columns of silica gel and of neutral alumina. The crystalline material obtained on removal of solvent melted at 234-237°C (hot-stage apparatus, uncorrected) (lit. (7) mp 230-23 1°C).
7-Methos~lco~rtnnrirz (hernicirin) (I c)A solution of umbelliferone ( l b ) (925 mg, 5.70 mmol; purified as above) in anhydrous tetrahydrofuran (12.0 mL) and tetramethylorthocarbonate ( I I .O mL) containing p-toluenesulfonic acid (3 me), was heated under reflux f...