Cascade cyclization of 1,2,7,8-tetraones and total synthesis of (±)-nesteretal A

For the short synthesis of highly oxidized complex molecules, the regioselectivity and stereoselectivity of intramolecular domino aldol cyclization/acetalizations of 1,2,7,8-tetraones were investigated by using catalytic amounts of Bronsted bases, Bronsted acids, and Lewis acids. Good enantioselectivities (up to 76% ee) were observed in direct catalytic asymmetric cyclization of a 1,2,7,8-tetraone with chiral organocatalysts. The total synthesis of (+/-)-nesteretal A, a highly oxidized cage molecule, was accomplished in 7 steps by using TiCl4-promoted anti-selective aldol cyclization of a symmetrical 1,2,7,8-tetraone as a key reaction.

Automated summary

In this study, the regioselectivity and stereoselectivity of intramolecular domino aldol cyclization/acetalizations of 1,2,7,8-tetraones were investigated using various catalytic agents. Good enantioselectivities were observed in the direct catalytic asymmetric cyclization of a 1,2,7,8-tetraone with chiral organocatalysts. Furthermore, the total synthesis of (+/-)-nesteretal A, a highly oxidized cage molecule, was accomplished using TiCl4-promoted anti-selective aldol cyclization of a symmetrical 1,2,7,8-tetraone as the key reaction.