Decarboxylative cross-couplings of 2-aminopyrimidine-5-carboxylic acids

Electrophilic alkylation of arenes with 5-bromopyrimidine en route to 4-aryl-5-alkynylpyrimidines

“…10,11 Alternatively, a decarboxylative cross-coupling of alkynyl halides with hetarylcarboxylic acids can be employed. 12 Although the synthetic route involving 2 as an electrophilic component in the Sonogashira reaction seems very straightforward, access to these starting materials typically relies on another transition metal-catalyzed cross-coupling step, usually chemoselective Suzuki reaction between arylboronic acid 3 and hetaryl dihalide 4 (Scheme 1). [13][14][15][16][17][18] Since this conventional approach lacks any atom-economy appeal, we wondered, if an alternative synthetic strategy could be designed, utilizing a formal oxidative functionalization of two C-H bonds in arene 5 and pyrimidine 6 (Scheme 1).…”

Facile Conversion of Molecularly Complex (Hetero)aryl Carboxylic Acids into Alkynes for Accelerated SAR Exploration

“…[9] The direct transformation of carboxylic acids into the corresponding alkynes is also described in the literature. [10][11][12] However, the reported transformations suffer from a highly limited substrate scope, likely because of the harsh reaction conditions and temperatures (far above the boiling point of the corresponding solvents), significantly limiting their applicability and scalability. Therefore, we envisioned to develop an alternative method for converting an available (hetero)aryl carboxylic acid, originally designed for the formation of a given amide, into the corresponding alkyne derivative.…”