Studies on development of new synthetic method of 1,3-Diyl and application to organic synthesis

Abstract

Cycloaddition reaction of alkylidene carbenes generated from alkynyliodonium salts has been studied. Intramolecular cycloaddition of alkylidene carbene to an olefin affords 1,3-diyl by homolytic cleavage of adduct. This 1,3-diyl is trapped by the other olefin, diylophile in a proper position to produce triquinane, and moreover preparation of the tetraquinane framework of Crinipellin with proper stereochemistry has been achieved. In case of triquinane synthesis, isocapnellenone, X-ray crystallography showed the unexpectedly trans, syn, cis-fused ring junction triquinane since the reaction utilizing with intramolecular diyl trapping reaction via alkylidene carbene was affected severely by steric influence. Therefore, with a very careful design, it will be possible to prepare the product with a mixed ring junction stereochemistry. This method provides a good synthetic strategy to construct polyquinane skeletons, but it exhibits the several disadvantages such as functional group transformations and relatively low product yields. Therefore, alternative generation method of 1,3-diyl was needed to apply for synthesis of natural product. A new efficient way to generate TMM diyls was developed with allenes and N-aziridinylimines and successfully utilized in [2+3] cycloaddition reaction with olefins. The novel one pot sequential transformation of thermally labile pyrazoles obtained through [2+3] cycloaddition reaction of diazoalkanes with allenes produced TMM diyls and the generated diyls were trapped by olefin to form polyquinanes. Total synthesis of (±)-ceratopicanol, linear triquinane natural product, was successful through 11 steps from pentynal. Triquinane core structure was assembled by thermolysis of allenyl aziridinylimine. And also, the preparation of the tetraquinane framework of Crinipellin with proper stereochemistry was succeeded with new methodology to generate TMM diyl from allene and N-aziridinylimine.