Benzo[ a ]heptalenes from Heptaleno[1,2‐ c ]furans. Part I

It is shown that heptaleno[1,2‐ c ]furans 1 , which are available in two steps from heptalene‐4,5‐dicarboxylates by reduction and oxidative dehydrogenation of the corresponding vicinal dimethanols 2 with MnO 2 or IBX ( Scheme 4 ), react thermally in a Diels–Alder ‐type [4+2] cycloaddition at the furan ring with a number of electron‐deficient dipolarophiles to yield the corresponding 1,4‐epoxybenzo[ d ]heptalenes ( cf. Schemes 6, 15, 17 , and 19 ). The thermal reaction between dimethyl acetylenedicarboxylate (ADM) and 1 leads, kinetically controlled, via a sterically less‐congested transition state ( Fig. 4 ) to the formation of the ( M* )‐configured 1,4‐dihydro‐1,4‐epoxybenzo[ a ]heptalenes, which undergo a cyclic double‐bond shift to the energetically more‐relaxed benzo[ d ]heptalenes 4 ( Schemes 6 and 7 ). Most of the latter ones exhibit under thermal conditions epimerization at the axis of chirality, so that the ( M* )‐ and ( P* )‐stereoisomers are found in reaction mixtures. The ( P* )‐configured forms of 4 are favored in thermal equilibration experiments, in agreement with AM1 calculations ( Table 1 ). The relative ( P* ,1 S* ,4 R* )‐ and ( M* ,1 S* ,4 R *)‐configuration of the crystalline main stereoisomers of the benzo[ d ]heptalene‐2,3‐dicarboxylates 4a and 4f , respectively, was unequivocally established by an X‐ray crystal‐structure determination ( Figs. 1 and 2 ). Acid‐induced rearrangement of 4 led to the formation of the corresponding 4‐hydroxybenzo[ a ]heptalene‐2,3‐dicarboxylates 5 in moderate‐to‐good yields ( Schemes 8, 13 , and 14 ). When the aromatization reaction is performed in the presence of trifluoroacetic acid (TFA), trifluoroacetates of type 6 and 13 ( Schemes 8, 12 , and 13 ) are also formed via deprotonation of the intermediate tropylium ions of type 7 ( Scheme 11 ). Thermal reaction of 1 with dimethyl maleate gave the 2,3‐ exo ‐ and 2,3‐ endo ‐configured dicarboxylates 14 as mixtures of their ( P* )‐ and ( M* )‐epimers ( Scheme 15 ). Treatment of these forms with lithium di(isopropyl)amide (LDA) at −70° gave the expected benzo[ a ]heptalene‐2,3‐dicarboxylates 15 in good yields ( Scheme 16 ). Fumaronitrile reacted thermally also with 1 to the corresponding 2‐ exo ,3‐ endo ‐ and 2‐ endo ,3‐ exo ‐configured adducts 17 , again as mixtures of their ( P* )‐ and ( M* )‐epimers ( Scheme 17 ), which smoothly rearranged on heating in dimethoxyethane (DME) in the presence of Cs 2 CO 3 to the benzo[ a ]heptalene‐2,3‐dicarbonitriles 18 ( Scheme 18 ). Some cursory experiments demonstrated that hex‐3‐yne‐2,5‐dione and ( E )/( Z )‐hexa‐3‐ene‐2,5‐dione undergo also the Diels–Alder ‐type cycloaddition reaction with 1 ( Scheme 19 ). The mixtures of the stereoisomers of the 2,3‐diacetyl‐1,4‐epoxytetrahydrobenzo[ d ]heptalenes 22 gave, on treatment with Cs 2 CO 3 in DME at 80°, only mixtures of the regioisomeric inner aldol products 24 and 25 of the intermediately formed benzo[ a ]heptalenes 23 ( Scheme 20 ).