Sulfur(IV)‐Mediated Unsymmetrical Heterocycle Cross‐Couplings

Abstract

Despite the tremendous utilities of metal‐mediated cross‐couplings in modern organic chemistry, coupling reactions involving nitrogenous heteroarenes remain a challenging undertaking – coordination of Lewis basic atoms into metal centers often necessitate elevated temperature, high catalyst loading, etc. Herein, we report a sulfur (IV) mediated cross‐coupling amendable for the efficient synthesis of heteroaromatic substrates. Addition of heteroaryl nucleophiles to a simple, readily‐accessible alkyl sulfinyl (IV) chloride allows formation of a trigonal bipyramidal sulfurane intermediate. Reductive elimination therefrom provides bis‐heteroaryl products in a practical and efficient fashion.

Zirconium-redox-shuttled cross-electrophile coupling of aromatic and heteroaromatic halides

“…1,2 Therefore, a significant effort has been devoted toward the development of efficient methods for the synthesis of heteroaromatic arenes. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] These efforts gave rise to a number of transition metal-catalyzed cross-coupling reactions, including those that led to the 2010 Nobel Prize in Chemistry. 18 In general, cross-coupling reactions produce a carbon-carbon bond through the coupling of an organometallic fragment and an (heteroaryl) aryl halide or pseudohalide (Scheme 1A).…”

“…In order to overcome this limitation, several issues must be addressed, including the incompatibility of the heteroaromatic compounds with the organometallic coupling reagents and stoichiometric reducing agents, while maintaining selectivity for cross-coupling. 16,31 Nevertheless, encouraged by the great value of heteroaromatic compounds, we sought an alternative platform for catalysis of both homo-electrophile coupling and XEC of readily available aromatic and heteroaromatic halides. In previously reported systems, selective in situ formation of one organometallic reagent under reductive coupling conditions requires that two electrophilic coupling partners have significantly different reactivities.…”