Photochemically Enabled Total Syntheses of Stemoamide Alkaloids

Abstract

Photochemical transformations continue to serve as powerful synthetic tools for rapid chemical synthesis and diversification. Recent developments in photoredox and photochemical reactivity have captured the attention of researchers in a wide array of disciplines, where many new applications of these reactions have been reported. We disclose the use of photochemical synthetic strategies as a modern approach to natural product synthesis that leverages the inherent reactivity of radicals as a platform for constructing complex scaffolds. We demonstrate this in an iterative photochemical synthesis, offering novel synthetic tactics, mild conditions, and operationally simple synthetic procedures to construct three stemoamide alkaloids in the shortest sequences to date. The key disconnection involves the use of both the oxidative and reductive capabilities of an acridinium photoredox catalyst to forge the densely functionalized tetrahydrofuran ring via a polar radical crossover cycloaddition. The resultant butyrolactone serves as a handle for a radical polar crossover cycloaddition to construct a unique oxaspirocyclic butenolide. Finally, a late-stage heteroarene transmutation provides a linchpin intermediate used to access three stemoamide alkaloids. The efficiency of these syntheses exemplifies the power of this approach while also demonstrating a departure from traditional disconnections and shedding light on a new type of synthetic art.