Alkynyl Thioethers in Gold-Catalyzed Annulations To Form Oxazoles.

Raju Jannapu Reddy,Paul W Davies,Matthew P Ball‐Jones

doi:10.1002/anie.201706850

Raju Jannapu Reddy, Paul W Davies + Show 1 more

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https://doi.org/10.1002/anie.201706850

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Abstract

Non‐oxidative, regioselective, and convergent access to densely functionalized oxazoles is realized in a functional‐group tolerant manner using alkynyl thioethers. Sulfur‐terminated alkynes provide access to reactivity previously requiring strong donor‐substituted alkynes such as ynamides. Sulfur does not act in an analogous donor fashion in this gold‐catalyzed reaction, thus leading to complementary regioselective outcomes and addressing the limitations of using ynamides.

Highlights

Sulfur does not act in an analogous donor fashion in this gold-catalyzed reaction, leading to complementary regioselective outcomes and addressing the limitations of using ynamides
Compared to other heteroatom-substituted alkynes, alkynyl thioethers are remarkably little explored in intermolecular late-transition-metal catalysis, despite being readily accessed and robust.[1,2]
In contrast, are privileged substrates: in p-acid catalysis their donor nature aids metal– alkyne coordination and affords highly polarized electrophiles, providing the high chemo- and regioselectivity required for the discovery of efficient intermolecular reactions (Scheme 1 a).[3,4]

Summary

Introduction

Ynamides enabled the discovery of formal [3+2] dipolar cycloadditions with nucleophilic nitrenoids,[7] allowing intermolecular access to a-imino gold carbene-type reactivity for heterocycle synthesis (Scheme 1 b).[8,9] Such reactions, which do not depend on ynamides, are scarce.[8b,h] A strong donor alkyne substituent proved critical in the formation of oxazoles using N-acyl pyridinium N-aminides, as electron-rich alkynes such as anisole derivatives did not react (Scheme 1 b, inset).[8a,b] Oxazoles are valuable synthetic intermediates[10,11] and structural components in bioactive natural products,[12] agrochemicals,[13] ligands,[14] and functional materials.[15]. Abstract: Non-oxidative, regioselective, and convergent access to densely functionalized oxazoles is realized in a functionalgroup tolerant manner using alkynyl thioethers. Sulfur-terminated alkynes provide access to reactivity previously requiring strong donor-substituted alkynes such as ynamides.

Results

Conclusion