70(P-55) Enatiocontrolled Syntheses of Natural Products Utilizing γ-Substituted Butenolides
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Enantiocontrolled syntheses of γ-substituted butenolides (1), bearing with alkyl, alkenyl and aryl substituents, were established from a chiral tricyclic lactone (3) via continuous diastereoselective nucleophilic addition, followed by retro-Diels-Alder reaction as key steps. Both enantiomers of lactone (3) were prepared from known chiral alcohol (4) in large scale. Continuous nuceleophilic addition to lactone (3) proceeded diastereoselectively to construct chiral secondary and tertiary alcohol moieties and to furnish diol (10). Some of the newly generated asymmetric centers were controlled by the order in which the nucleophilic reagents were added. After oxidation of 10 to lactone (13), a retro-Diels-Alder reaction of 13 in refluxing diphenyl ether yielded corresponding γ-substituted butenolides (1). The synthetic butenolides (1) were utilized for the formal and total syntheses of natural products, such as (+)- and (-)-trans-quercus lactones (14), (-)-ngainone [(-)-16], (+)-ipomeamarone [(+)-16], and a constituent in lavender (Lavandura vera D. C.) oil (1e). During this research, we also found a new type of retro-Diels-Alder-ene (RDAE) reaction of lactone (17), bearing with homoprenyl and homocrotyl substituents at their γ-position, to yield bicyclic lactone (19). In the case of homocrotyl substituent, RDAE reaction afforded a single lactone (19b) with the corresponding butenolide (18b, 18c) in spite of their geometry of the alkene moiety. This result showed that RDAE reaction proceeded through the exo transition state in the case of (Z)-alkene and through the endo one in the case of (E)-alkene. The RDAE reaction was strongly accelerated by the introduction of trimethylsilyl (TMS) group on a crotyl unit to yield a single lactone (19c) without the butenolide (18c). The lactone (19c) was transformed to known bicyclic lactone (22) via oxidation of vinyl silane and following acidic ring opening of the epoxide as key steps. From 22, total synthesis of (+)-methyl jasmonate (24), which was isolated from jasmine and was an important compound in plant growth regulation, was achieved in 7 steps via 6-epi-cucurbate (23). In conclusion, we established new enatiocontrolled, partially enantiodivergent, syntheses of γ-substituted butenolides, bearing with versatile γ-substituents, from a chiral tricyclic lactone (3). We also achieved total synthesis of some natural products utilizing the synthetic γ-substituted butenolides (1) as key intermediates.
