Cycloheptaindoles represent a unique class of 6,5,7-tricyclic indole fused seven-membered ring compounds that appear in a wide variety of natural products and biologically active pharmaceuticals. The extensive biological profiles exhibited by the homologues of this skeleton inspired the development of efficient methods that produce highly functionalized and unsymmetrically substituted cycloheptaindoles. Herein we discuss the development of a formal [5+2] cycloaddition toward functionalized cycloheptaindole derivatives. The transformation proceeds through a Ca(II)-catalyzed reaction of C-acylated indolyl alkylidene b-keto-esters with substituted olefins. The approach described provides efficient access to cycloheptaindole derivatives in up to 98% yield with mono- and di-substituted aryl alkenes. Interestingly with phenyl vinyl ether and sulfide, a unique cycloheptaindole bicyclic structure is formed which suggests an alterative novel [5+2] cycloaddition pathway. The practicality of this methodology is highlighted in the functional group tolerance, mild reaction conditions, easy scale-up, and versatile derivatization.

Calcium-catalyzed formal [5+2] cycloaddition of alkylidene β-ketoesters with substituted olefins: Chemodivergent synthesis of highly functionalized cycloheptaindoles

2019 Fall National Meeting

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