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Origins of Enantioselectivity during Allylic Substitution Reactions Catalyzed by Metallacyclic Iridium Complexes
journal contribution
posted on 2012-05-16, 00:00 authored by Sherzod
T. Madrahimov, John F. HartwigIn depth mechanistic studies of iridium catalyzed regioselective
and enantioselective allylic substitution reactions are presented.
A series of cyclometalated allyliridium complexes that are kinetically
and chemically competent to be intermediates in the allylic substitution
reactions was prepared and characterized by 1D and 2D NMR spectroscopies
and single-crystal X-ray difraction. The rates of epimerization of
the less thermodynamically stable diastereomeric allyliridium complexes
to the thermodynamically more stable allyliridium stereoisomers were
measured. The rates of nucleophilic attack by aniline and by N-methylaniline on the isolated allyliridium complexes were
also measured. Attack on the thermodynamically less stable allyliridium
complex was found to be orders of magnitude faster than attack on
the thermodynamically more stable complex, yet the major enantiomer
of the catalytic reaction is formed from the more stable diastereomer.
Comparison of the rates of nucleophilic attack to the rates of epimerization
of the diastereomeric allyliridium complexes containing a weakly coordinating
counterion showed that nucleophilic attack on the less stable allyliridium
species is much faster than conversion of the less stable isomer to
the more stable isomer. These observations imply that Curtin–Hammett
conditions are not met during iridium catalyzed allylic substitution
reactions by η3-η1-η3 interconversion. Rather, these data imply that when these conditions
exist for this reaction, they are created by reversible oxidative
addition, and the high selectivity of this oxidative addition step
to form the more stable diastereomeric allyl complex leads to the
high enantioselectivity. The stereochemical outcome of the individual
steps of allylic substitution was assessed by reactions of deuterium-labeled
substrates. The allylic substitution was shown to occur by oxidative
addition with inversion of configuration, followed by an outer sphere
nucleophilic attack that leads to a second inversion of configuration.
This result contrasts the changes in configuration that occur during
reactions of molybdenum complexes studied with these substrates previously.
In short, these studies show that the factors that control the enantioselectivity
of iridium-catalyzed allylic substitution are distinct from those
that control enantioselectivity during allylic substitution catalyzed
by palladium or molybdenum complexes and lead to the unique combination
of high regioselectivity, enantioselectivity, and scope of reactive
nucleophile.
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Keywords
enantioselectivitynucleophilic attackMetallacyclic Iridium ComplexesIn depthdiastereomeric allyliridium complexesmolybdenum complexessphere nucleophilic attackconfigurationenantioselective allylic substitution reactionsallylic substitution reactionsallylic substitution2 D NMR spectroscopiesoxidative addition stepcyclometalated allyliridium complexesoxidative additionAllylic Substitution Reactions Catalyzed
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