Synthesis of Spirocyclic 1,2-Diamines by Dearomatising Intramolecular Diamination of Phenols

Abstract

The stereocontrolled synthesis of complex spirotricyclic systems containing an embedded syn-1,2-diaminocyclohexane unit is reported, based upon a dearomatising oxidation of phenols bearing pendant ureas capable of acting as double nucleophiles. This complexity-generating transformation yields products with rich functionality suitable for application in the synthesis of potentially bioactive compounds.

Scaffold Remodelling of Diazaspirotricycles Enables Synthesis of Diverse sp3‐Rich Compounds With Distinct Phenotypic Effects

“…We designed spirotricyclic ureas 2a-c bearing structurally and electronically-diverse N-urea substituents as our basic building blocks for scaffold elaboration (note: throughout, the suffixes a, b and c refer to structures bearing 2-propyl, 4-methoxyphenyl and p-toluenesulfonyl substituents respectively). The requisite ureas were prepared using our previously-developed oxidative dearomatisation [14] using the corresponding hydroxyphenyl ureas 1a-c (see Supporting Information), Scheme 1. Although the oxidative dearomatisation reactions were moderate yielding, the short nature of the synthetic route allowed ready supply of material for further study.…”

“…[13] We have recently developed an oxidative dearomatisation reaction that generates spirotricyclic diamines in a single step from readily-available (hydroxyphenyl)propyl ureas. [14] The resulting products contain rich functionality which we believed would be ideal for exploitation in a top-down approach to the generation of diverse scaffolds (Figure 1). Herein we describe the successful realisation of this approach, and the generation of a small screening library based upon the scaffolds generated.…”