Divergent Palladium‐Catalyzed Cross‐Coupling of Nitropyrazoles with Terminal Alkynes

Abstract

Facile homo‐coupling of terminal alkynes, which generates conjugated diynes, is an undesired pathway in the development of transition‐metal‐catalyzed oxidative C–H functionalization of (hetero)arenes with terminal alkynes. By incorporating this process into a catalytic cycle, we achieved regio‐ and stereoselective hydroarylation of nitropyrazoles with the resulting 1,3‐diynes. A simple change in the stoichiometry and oxidant allowed direct C–H alkynylation of nitropyrazoles, producing the corresponding alkynyl pyrazoles.

Cross‐Dehydrogenative Alkynylation: A Powerful Tool for the Synthesis of Internal Alkynes

“…Catalyzed by 5 mol % of Pd(PPh 3 ) 4 , various azoles (3 equiv) were directly alkynylated by terminal alkynes at 100 °C in toluene with the aid of 4 equivalents of t ‐BuOLi under an air atmosphere, generating the corresponding products in 31 %–88 % yields. Very recently, the C−H alkynylation of nitropyrazoles was also realized in one pot through palladium catalysis with use of Ag 2 CO 3 as an oxidant …”

Catalytic Hydrofunctionalization Reactions of 1,3-Diynes

“…The second example, consisting in a tandem homocoupling/hydroarylation of terminal alkynes with nitropyrazoles to afford the functionalized enynes 27, is depicted in Scheme 14 [34]. As in the precedent case, the hydroarylation of the 1,3-diyne intermediates proceeded in a syn manner, with the internal carbon of the diyne participating now in the formation of the new C-C bond.…”

Joy and Challenges of Alkynylation of Arenes and Heteroarenes through Double C−H Functionalizations

“…Very recently Joo et al described an elegant direct oxidative CÀ H alkynylation of pyrazoles containing electron withdrawing groups with alkynes which give the desired alkynylated products in good yields (Scheme 21). [28] In this procedure Pd (OAc) 2 used as a catalyst, PPh 3 as a ligand, isobutyric acid as an additive,Ag 2 CO 3 as activator and Cs 2 CO 3 as the base, where one equivalent of terminal alkyne was employed. Interestingly, when three equivalents of terminal alkynes were used, a regio- and stereoselective hydroarylation of nitropyrazoles was furnished as a major product.…”