Palladium-Catalyzed α-Arylation of Cycloalkanones with Sterically Hindered Bromoazines under Neat Conditions

Abstract

The palladium-catalyzed cross-coupling of cycloalkanones with a range of heteroaryl bromides is described herein. The transformation proceeds best with third-generation tris-tBu-phosphine Pd pre-catalyst in neat cycloalkanones. Careful screening of the reaction conditions revealed K₃PO₄ as an effective weak and mild base thereby tolerating base-sensitive functional groups such as acetals or nitrogen protecting groups. Moderate to good yields were achieved for a series of 29 examples with various degrees of structural complexity. Importantly, these optimized conditions allow the α-(hetero)aryl cross-coupling of ortho-substituted (hetero)aryl bromide substrates with different cyclo­alkanones that typically failed to react efficiently under previously reported conditions.

Key words

palladium catalysis - α-arylation - cycloalkanones - bromoazines - third-generation tris-tBu-phosphine Pd pre-catalyst - neat conditions

Publication History

Received: 03 September 2024

Accepted: 19 September 2024

Article published online:
22 October 2024

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