Heck redox relay
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Transcript of Heck redox relay
Organic Pedagogical Electronic Network
Redox Relay Heck Reaction
Margaret HiltonSigman Lab
University of Utah2014
ROH
n
RO
n
R'
[Pd]
ArX
Heck Reaction
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
*Note: this reaction may also proceed through an oxidative mechanism, where a Pd II
precatalyst , a transmetallating aryl reagent, and a terminal oxidant are used, such as with Heck’s conditions shown.
Since Heck’s seminal publication in 1968, the Heck reaction has been a powerful synthetic tool for the functionalization of olefins with aryl groups.
Heck’s Conditions:
HgCl
Li2PdCl4+MeOH, CuCl2
2 h, rt
O
O O
O57% yield
Heck, along with Negishi and Suzuki, won the Chemistry Nobel Prize in 2010 for their work in cross coupling.
General Mechanism*
Chain-Walking
Examples of Relay via Palladium Catalysis
Hayashi JACS 1991, 113, 1417Curran, JACS 2007, 129, 494
After the initial migratory insertion, which forms a C-C bond, a β-hydride 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.
O
ArOTf
Pd(OAc)2(R)-BINAP
i-Pr2NEtbenzene
+O Ar O Ar
+
Can chain-walking be controlled?
NMe
O
I Me Me
NMe
OPd2dba3•CHCl3(R)-BINAP
piperidineDMA, 100 °C
Redox-Relay Heck Reaction
Sigman Science 2012, 338, 1455Sigman JACS, 2013, 135, 6830
B(OH)2
ROH
n
RO
n
R'N N
O
t-BuF3C
Pd(CH3CN)2(OTs)2, DMFCu(OTf)2, O2, 3 Å MS
+
R'n = 0-5up to 99:1 er
N2PF6
ROH
n
RO
n
R'N N
O
t-BuF3C
Pd2dba3, DMF+
R'n = 0-2up to 99:1 er
Classical Variant
Oxidative Variant
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.
Problems
1. Keay, JOC, 2007, 72, 7253
O D O
D
O
D D
ODD
2. The four deuterium-labelled substrates A-D were used to determine theextent of chain-walking under palladium catalysis. Show all the possible productsthat could result from A-D after the initial migratory insertion of an aryl group.
A B C D
OPhOTf +
[Pd]
O Ph O Ph+
1. Draw a general catalytic cycle for the Heck reaction.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Contributed by: Margaret HiltonSigman LabUniversity of Utah2014