Mechanistic Studies on the Alkylation of Amines with Alcohols Catalyzed by a Bifunctional Iridium Complex

Abstract

The mechanism of the N-alkylation of amines with alcohols catalyzed by an iridium complex containing an Nheterocyclic carbene (NHC) ligand with a tethered alcohol/alkoxide functionality was investigated by a combination of experimental and computational methods. The catalyst resting state is an iridium−hydride species containing the amine substrate as a ligand, and decoordination of the amine, followed by coordination of the imine intermediate to the iridium center, constitute the rate-determining step (rds) of the catalytic process. The alcohol/alkoxide that is tethered to the NHC participates in every step of the catalytic cycle by accepting or releasing protons and forming hydrogen bonds with the reacting species. Thus, the iridium complex with the alcohol/alkoxide tethered to the N-heterocyclic carbene ligand acts as a bifunctional catalyst.

Nonclassical Mechanism in the Cyclodehydration of Diols Catalyzed by a Bifunctional Iridium Complex

“…In fact, excluding cyclic ether 3 b , which is obviously formed by a different mechanism (c.f., KIE), the opposite reactivity trend was observed, as the data fit well to standard Hammett σ values (Figure a) with a negative ρ value of −1.7. This is very similar to what we reported before for a rate‐limiting Ir‐catalyzed hydrogen transfer from benzylic alcohols …”

“…We have previously investigated the activity of Ir III complexes that bear functionalized NHC ligands ( 1 ) in C−N bond‐forming reactions with anilines and alcohols. Mechanistic investigations indicated that the oxygen functionality on the NHC ligand was involved in proton transfer steps, which enables reactions to be performed under base‐free conditions . The binfunctional nature of the NHC–Ir complexes ( 1 ) was also explored in the acceptorless dehydrogenation of alcohols (Scheme , top).…”

Homogeneous Water Oxidation by Half‐Sandwich Iridium(III) N‐Heterocyclic Carbene Complexes with Pendant Hydroxy and Amino Groups

“…Whether the observed lag time for water oxidation catalyzed by 1 – 3 is caused by initial de‐coordination of the chloride ligands was investigated in experiments in which the chlorides were chemically removed to afford [IrCp*(NHC)(MeCN)](BF 4 ) 2 ( 5 ) ,. Upon addition of CAN to a solution of 5 , a lag time for oxygen evolution similar to that of 1 is observed (Figure S4), illustrating that the lag time is not associated with the dissociation of chloride ligands from the Ir center.…”

“…Crabtree and co‐workers have reported that IrCp* complexes with bidentate chelates ligands such as 2,2′‐bipyridine, 2‐phenylpyridine, or 2‐(2′‐pyridyl)‐2‐propanoate are resistant towards nanoparticle formation, whereas monodentate chelate compounds are prone to degrade to IrO x nanoparticles even in presence of a milder oxidant such as NaIO 4 . Complexes 1 and 2 have monodentate NHC ligands in the solid state, but both these ligands can potentially act as bidentate ligands, which could help in stabilizing the catalysts, in particular when in higher oxidation states. One possibility for stabilizing a high‐valent Ir species has been demonstrated by using the bidentate pyridine alkoxide ligand 2‐(2′‐pyridyl)‐2‐propanoate, where μ‐oxo‐bridged Ir IV dimers can be produced and characterized …”

Nickel‐Catalyzed N‐Alkylation of Acylhydrazines and Arylamines Using Alcohols and Enantioselective Examples

“…[8] At ypical process involves dehydrogenation of an alcohol to form ak etone by am etal catalyst, in situ condensation to ak etimine,a nd subsequent addition of the metal hydride catalyst. [9][10][11][12] No prior chemical activation of alcohols is needed and ideally water is the only byproduct. Furthermore, only acatalytic amount of ametal hydride complex is present at anytime,a nd allows better compatibility of polar groups.…”