Palladium-Catalyzed Regioselective Carbonylation of 2-Trifluoromethyl-1,3-enynes to Multisubstituted Conjugated Dienes

A novel and efficient palladium‐catalyzed regioselective and stereodivergent ring‐closing reaction of aminoenynes with aldehydes and boronic acids or hydrosilane is developed. This three‐component reaction allows for the modular synthesis of a series of exocyclic 1,3‐dienes bearing 5‐ to 8‐membered saturated N‐heterocycles. The reactions utilize a simple Pd‐catalyst and work with broad range of aminoenynes, aldehydes and organometallic reagents under mild reaction conditions. The products represent useful intermediates for chemical synthesis due to the versatility of the conjugated diene. Preliminary mechanistic details of the method are also revealed.

Palladium‐Catalyzed Aminoalkylative Cyclization Enables Modular Synthesis of Exocyclic 1,3‐Dienes

Zou,

Zhao,

Huang

2023

Palladium‐Catalyzed Carbonylative Multicomponent Fluoroalkylation of 1,3‐Enynes: Concise Construction of Diverse Cyclic Compounds

Kuai,

Teng,

2024

Self Cite

Multicomponent reactions, particularly those entailing four or more reagents, have presented a longstanding challenge due to the inherent complexities associated with balancing reactivity, selectivity, and compatibility. In this study, we describe a palladium‐catalyzed multi‐component fluoroalkylative carbonylation of 1,3‐enynes. A series of products featuring three active functional groups‐allene, fluoroalkyl, and carboxyl, were efficiently and selectively integrated in a single chemical operation. Furthermore, more intricate fluoroalkyl‐substituted pyrimidinones can be constructed by simply altering the 1,3‐bisnucleophilic reagent. This approach also provides a valuable strategy for the late‐stage modification of naturally occurring molecules and concise construction of diverse cyclic compounds.

Modular and Diverse Synthesis of Acrylamides by Palladium‐Catalyzed Hydroaminocarbonylation of Acetylene

Cao,

Wang,

Neumann

et al. 2024

The development of all kinds of covalent drugs had a major impact on the improvement of the human health system. Covalent binding to target proteins is achieved by so‐called electrophilic warheads, which are incorporated in the respective drug molecule. In the last decade, specifically acrylamides emerged as attractive warheads in covalent drug design. Herein, a straightforward palladium‐catalyzed hydroaminocarbonylation of acetylene has been developed, allowing a modular and diverse synthesis of bio‐active acrylamides. This general protocol features high atom efficiency, wide functional group compatibility, high chemoselectivity and proceeds additive free under mild reaction conditions. The synthetic utility of this protocol is showcased in the synthesis of ibrutinib, osimertinib, and other bio‐active compound derivatives.