MechanisticStudies on Iridium Catalyzed Allylic Substitution

Mechanistic Studies on Iridium Catalyzed Allylic Substitution
Sherzod T. Madrahimov Final Seminar May 18, 2012
High regio- and stereocontrol will always be an essential part of developing useful
reactions. A reaction that has a perfect regio- and stereocontrol is less likely to require extensive
purification to obtain the product in high levels of purity. Existing reactions can be optimized in
terms of selectivity by studying the factors that influence the selectivity. Thus, mechanistic
studies on the origins of regio- and enantioselectivity are an integral part of developing useful
reactions.
Iridium catalyzed allylic substitution has become a powerful method for the enantioselective
formation of both carbon–heteroatom and carbon–carbon bonds since its discovery in 1997. 1-2
The first report on iridium catalyzed allylic substitution described the reactions of stabilized
carbon nucleophiles with monosubstituted allylic electrophiles. 3 The method was extended to
amine nucleophiles in a later report. 4 Iridium catalyzed allylic substitution reaction formed the
product of allylic substitution at the branched allylic terminus. This selectivity contrasts the
selectivity of palladium catalyzed allylic substitution reactions which form linear organic
products. 5-6
Scheme 1. Allylic substitution reactions catalyzed by cyclometalated iridium phosphoramidite
complexes.
Formation of branched chiral products from linear monosubstituted allylic electrophiles
allows development of stereoselective versions of allylic substitution reactions. Several
complexes of iridium containing chiral enantioenriched ligands catalyze enantioselective
reactions between monosubstituted allylic electrophiles with limited success. Iridium complexes
containing chiral phosphoramidite ligands emerged as the catalysts of choice for the allylic
substitution reactions of monosubstituted allylic electrophiles. 1

Mechanistic studies on iridium catalyzed allylic substitution reactions catalyzed by iridium
phosphoramidite complexes revealed that the active catalyst is generated through a base assisted
cyclometalation of the phosphoramidite to form five-membered iridacycle. 7 A mechanism for the
reaction was proposed based on a series of kinetic experiments. According to this mechanism the
product bound cyclometalated complex is the resting state of the catalyst. 8
First examples of allyliridium complexes containing cyclometalated phosphoramidite ligand
were prepared. A series of stoichiometric experiments showed that these allyliridium complexes
were chemically and kinetically competent to be intermediates in iridium catalyzed allylic
substitution reactions. 9 Double inversion mechanism for the iridium catalyzed allylic substitution
reaction was also shown through a combination of catalytic and stoichiometric reactions of
cyclometalated iridium complexes. A series of kinetic studies also showed that oxidative
addition was the enantiodetermining step in iridium catalyzed allylic substitution. 10
Scheme 2. Origins of enantioselectivity in iridium catalyzed allylic substitution.
Finally, allyliridium complexes containing cyclometalated triphenylphosphite ligand were
prepared. These complexes were competent to be intermediates in non-stereoselective allylic
substitution reactions catalyzed by iridium triphenylphosphite complexes. A series of kinetic
experiments showed that regioselectivity of iridium catalyzed allylic substitution is likely
controlled by a larger binding affinity of terminal alkenes to iridium center over internal
disubstituted alkenes.
References
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(2) Hartwig, J. F.; Stanley, L. M. Acc. Chem. Res. Mechanistically Driven Development of
Iridium Catalysts for Asymmetric Allylic Substitution 2010, 43, 1461-1475.

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