A Divergent Asymmetric Total Synthesis of Coprophilin and Four Trichodermic Acids via a [1,5]-Hydride Shift–Aldol Cascade

TL;DR

The paper describes a new method to synthesize coprophilin and trichodermic acids using a novel cascade reaction and other key chemical steps.

Contribution

A new [1,5]-hydride shift–aldol cascade reaction is introduced for efficient synthesis of complex natural products.

Findings

An aluminum-promoted [1,5]-hydride shift–aldol cascade was used to build the bicyclic core of the natural products.

The method allows divergent functionalization of the core structure for multiple target syntheses.

Key transformations include exo-selective Diels–Alder and Fleming–Tamao oxidation for late-stage modifications.

Abstract

The asymmetric syntheses
of coprophilin and four members
of the
trichodermic acid family of natural products are disclosed. Our work
employs a number of key transformations, including an aluminum-promoted
[1,5]-hydride shift–aldol cascade reaction, an exo-selective Diels–Alder cycloaddition, and a late-stage Fleming–Tamao
oxidation. These key steps efficiently construct the bicyclic core
of the natural products, which can then be readily functionalized
in a divergent manner, allowing the synthesis of a wide range of natural
product targets.

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