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Redox Relay Heck Reaction
Margaret Hilton
Sigman Lab
University of Utah
Heck Reaction
Since Heck’s seminal publication in 1968,
the Heck reaction has been a powerful
synthetic tool for the functionalization of
olefins with aryl groups.
General Mechanism*
Heck’s Conditions:
Heck, along with Negishi and Suzuki,
won the Chemistry Nobel Prize in
2010 for their work in cross coupling.
*Note: this reaction may also proceed through an oxidative mechanism, where
a PdII precatalyst , a transmetallating aryl reagent, and a terminal oxidant are
used, such as with Heck’s conditions shown.
Review: Chem. Rev. 2000, 100, 3009.
Other Examples and Applications: Overman JACS 1993, 115, 11028 , Sarpong JACS 2008, 130, 7222, Shibasaki JOC 1996, 61, 4876, Sigman JACS
2010, 132, 13981, Sigman JACS 2011, 133, 9692. 2010 Nobel Prize
Chain-Walking
After the initial migratory insertion,
which forms a C-C bond, a βhydride elimination will occur,
producing a Pd-H intermediate. If
the alkene remains coordinated to
palladium
and
the
hydride
reinserts at the opposite carbon,
the palladium catalyst is now
positioned one more carbon down
the alkyl chain. This is called a
“relay” or “chain walking” and
produces alkene isomers.
Hayashi JACS 1991, 113, 1417
Curran, JACS 2007, 129, 494
Examples of Relay via Palladium Catalysis
Can chain-walking be controlled?
Redox-Relay Heck Reaction
Sigman and coworkers have developed a redox-relay Heck reaction, where the
relay by palladium is controlled by a thermodynamic sink (an alcohol) on the
substrate. The unsaturation of the alkene is transferred to the alcohol to form
aldehydes or ketones.
Classical Variant
Oxidative Variant
Sigman Science 2012, 338, 1455
Sigman JACS, 2013, 135, 6830
Problems
1. Keay, JOC, 2007, 72, 7253