Fine Feathers Make Fine Birds: The Heck Reaction in Modern Garb

TLDR

The palladium‑catalyzed Heck reaction, discovered in the late 1960s, has become a cornerstone of modern synthesis, enabling diverse, convergent routes to complex molecules and is rapidly expanding into industrial applications. Careful substrate selection and tailored conditions allow Heck sequences that proceed consecutively or in a single operation, generating multiple C–C bonds. Recent advances demonstrate that Heck reactions tolerate heteroatoms, enable chemoselective and regioselective monocouplings, construct cascades forming up to eight new C–C bonds, and achieve enantioselective synthesis of complex natural products with quaternary stereocenters.

Abstract

Abstract The palladium‐catalyzed coupling of haloarenes and haloalkenes with alkenes, which was discovered by Richard F. Heck in the late sixties, has been a topic of fluctuating interest; however, in the last six years activity in this area has flourished. Careful choice of substrates and skillful tailoring of reaction conditions lead to impressive sequences consisting of even different reaction types that occur not only in a consecutive mode, but also in a single operation. The wellestablished Heck reaction, together with other mechanistically related palladiumcatalyzed transformations with arene, alkene, and alkyne derivatives, opens the door to a tremendous variety of elegant and highly convergent routes to structurally complex molecules. The reaction is not disturbed by heteroatoms such as oxygen and nitrogen (nor by sulfur and phosphorus with some limitations). The spectrum of recent achievements starts with a range of chemoselective and regioselective monocouplings of highly functionalized substrates with unsymmetrical and multisubstituted reaction partners. Other advances include cascade reactions in which three, four, five, and even eight new CC bonds are formed to yield oligofunctional and oligocyclic products with impressive molecular complexity. Even the enantioselective construction of complex natural products with quaternary stereocenters has been achieved with Heck reactions in key steps, as exemplified by the synthesis of crinan, picrotoxinin, and morphine. Today, the Heck reaction is indispensible in the arsenal of synthetic methods available to organic chemists. Certainly it is only a matter of time before the Heck reaction is applied in industrial syntheses.