Iridium -catalyzed heterocyclization

There have been many reports of the use of iridium-catalyzed transfer hydrogenation of carbonyl compounds, and this section focuses on more recent examples where the control of enantioselectivity is not considered. In particular, recent interest has been in the use of iridium A -heterocyclic carbene complexes as active catalysts for transfer hydrogenation. However, alternative iridium complexes are effective catalysts [1, 2] and the air-stable complex 1 has been shown to be exceptionally active for the transfer hydrogenation of ketones [3]. For example, acetophenone 2 was converted into the corresponding alcohol 3 using only 0.001 mol% of this... 

The iridium-catalyzed reaction of primary amines with diols gave cyclic amines. The reaction of amine 109 with diol 110 in the presence of [Cp lrCl2]/NaHC03 catalyst gave heterocyclization product 111 (Equation 10.26) [50]. 

Although not fitting exactly into the scope of this book, the iridium catalyzed borylation of five membered heterocycles through C-H bond activation also deserves mentioning. A recent report by Miyaura disclosed the reaction of bis(pinacolato)diboron with heteroaromatic systems, where thiophene, fiirane and pyrrole were converted to their 2-boryl derivatives with good selectivity (6.86.), The yields presented refer to the diboron compound since the heterocycles were used in excess in all cases. Indole, benzofurane and benzothiophene were monoborylated with similar efficiency.116... 

Suzuki T, Morita K, Ikemiyagi H, Watanabe K, Hiroi K, Katoh T (2006) Synthesis of the hemiacetal pheromone of the spined citrus bug biprorulus bibax utilizing an iridium catalyzed oxidative lactonization. Heterocycles 69 457-461... 

The iridium-catalyzed borylation of C—H bonds has established itself as a reliable method for heteroaromatic functionalization. The borylation of pyrrole tends to occur at the most acidic C—H bond treatment of l f-pyrrole (1) with B2pin2 (pin = Me4C202) occurs at the C2 position to afford heteroarylboronate 26 in 80% yield (Scheme 10.7). Traditional cross-coupling methods can then be used to convert the C—B bond into a C—C bond. A one-pot, two-step process for this transformation was realized in 2008 by Miyaura and co-workers 26 could be prepared in situ from reaction of 177-pyrrole (1) and an alkoxyborane (either B2pin2 or HBpin), and subsequently trapped with 2-bromothiophene to allow access to bis-heterocycle 27 in 93% yield. ... 

Driver and coworkers reported on iridium-catalyzed Af-heterocyclization by benzylic C-H bond activation [154]. In this case, treatment of an ort/ro-substituted aryl azide with a catalytic amount of [lr(OMe)(cod)]2 (2mol%) at 25 C gave a mixture of the corresponding aniline, indole, and indoline in 19, 13, and 58% yield, respectively, for a total yield of 90% (Scheme 11.6). The introduction of the electron-withdrawing CF3 group on the aryl substituent led to indoline derivatives in high yield with high selectivity. 

In conclusion, this chapter described some representative examples of the iridium-catalyzed synthesis of heterocycles involving C-H bond activation. The reactions include oxidative ort/ro-aryl C-H, benzyl, and sp -CH activation... 

Tejel C, Ciriano MA (2007) Catalysis and Organometallic Chemistry of Rhodium and Iridium in the Oxidation of Organic Substrates. 22 97-124 Tekavec TN, Louie J (2006) Transition Metal-Catalyzed Reactions Using N-Heterocyclic Carbene Ligands (Besides Pd- and Ru-Catalyzed Reactions). 21 159-192 Tesevic V, see Gladysz JA (2008) 23 67-89... 

In contrast, reactions catalyzed by la were typically conducted with added [Ir (C0D)C1]2 to trap the K -phosphoramidite ligand after dissociation, and thereby, to leave the unsaturated active catalyst. Under these conductions, as much as half of the iridium in the system is present in an inactive acyclic species. In contrast, when ethylene adduct lb is used as the catalyst, all of the iridium belongs to the active metalacyclic species. Hartwig and coworkers have recently taken advantage of the increased availability of the active catalyst generated from lb to develop new allylic substitution reactions. These new processes include the reactions of carbamates, nitrogen heterocycles, and ammonia. 

Intensive studies also showed that many transition metal complexes are able to catalyze aromatic C-H borylation of various arenes (Scheme 7), e.g., Cp Ir(H)(Bpin)(PMe3) [64,65], Cp Rh(Ti4-C6Me6) [65,66], ( 75-Ind)Ir(COD) [67], (776-mesitylene)Ir(Bpin)3 [67], [IrX(COD)]2/bpy (X = Cl, OH, OMe, OPh) [68-70]. A very recent study by Marder and his coworkers showed that [Ir(OMe)(COD)]2 can also catalyze borylation of C-H bonds in N-containing heterocycles [71]. For the Ir-catalyzed borylation reactions, it is now believed that tris(boryl)iridium(III) complexes [67,69], 40c, [72] are likely the reactive intermediates and a mechanism involving an Ir(III)-Ir(V) catalytic cycle is operative [67,69]. A recent theoretical study [73] provided further support for this hypothesis. A mechanism, shown in Scheme 8, was proposed. Interestingly, there are no cr-borane complexes involved in the Ir-catalyzed reactions. The very electropositive boryl and hydride ligands may play important roles in stabilizing the iridium(V) intermediates. 

Progress on the addition of aromatic C-H bonds to olefins has been made by Periana with iridium catalysts - - and Gunnoe with ruthenium catalysts. - Both systems illustrate that the anti-Markovnikov addition products can be generated in larger quantities than the Markovnikov products, although mixtures of regioisomers are still observed. Intramolecular additions of the C-H bonds of electron-rich heterocycles to electron-deficient alkenes have also been reported (Equation 18.65). Most recently, Tilley has reported the addition of the C-H bond of methane across an olefin catalyzed by scandocene complexes. This reaction occurs, albeit slowly, with Markovnikov regiochemistry. 

Alternatively, they were also found to be good racemization catalysts. Iridium complexes, but also rhodium compounds, catalyzed the racemization step in the enzymatic dynamic kinetic resolution of secondary alcohols, and excellent results were reported for alkyl-aryl as well as dialkyl secondary alcohols. Finally, picolyl and pyridine functionalized N-heterocyclic carbene iridium complexes [(C N)Ir(Cp )Cl]Cl were moderately active catalysts for the polymerization of norbomene in the presence of methylaluminoxane as cocatalyst. ... 

While major advances in the area of C-H functionalization have been made with catalysts based on rare and expensive transition metals such as rhodium, palladium, ruthenium, and iridium [7], increasing interest in the sustainability aspect of catalysis has stimulated researchers toward the development of alternative catalysts based on naturally abundant first-row transition metals including cobalt [8]. As such, a growing number of cobalt-catalyzed C-H functionalization reactions, including those for heterocycle synthesis, have been reported over the last several years to date (early 2015) [9]. The purpose of this chapter is to provide an overview of such recent advancements with classification according to the nature of the catalytically active cobalt species involved in the C-H activation event. Besides inner-sphere C-H activation reactions catalyzed by low-valent and high-valent cobalt complexes, nitrene and carbene C-H insertion reactions promoted by cobalt(II)-porphyrin metalloradical catalysts are also discussed. 

Ishii and coworkers reported that the JV-heterocyclization of naphthylamines with diols can be achieved with an iridium catalyst. In a typical example, the reaction of 1-naphthylamine with 1,3-propanediol was carried out with a catalytic amount of IrClg (5 mol%), r c-2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) (10 mol%), and the corresponding 7,8-benzoquinoline was obtained in 96% yield (Scheme 11.11) [159]. The proposed reaction mechanism indicates that the imine intermediate is formed by the reaction of the amine and aldehyde by Ir-catalyzed dehydrogenation. Subsequent hydrogenation by the in situ generated Ir hydride leads to an aminoalcohol followed by cyclization to the desired quinoline products. 

Kuo H-Y, Liu Y-H, Peng S-M, Liu S-T. N,N -Dialkylation catalyzed by bimetallic iridium complexes containing a saturated bis-N-heterocyclic carbene (NHC) ligand. Organometallics. 2012 31 7248-7255. 

Palladium remains the most widely recognized transition metal to effect stereoselective allylic alkylation reactions. Consequently, diastereoselective and enantioselective Pd-catalyzed processes are extensively discussed in Sections 14.2 and 14.3. More recent advances in the field of metal-catalyzed al-lylation reactions include the use of chiral iridium complexes, dealt with in Section 14.4 [33, 34]. Section 14.5 describes selected stereoselective copper-catalyzed SN2 -allylation reactions [33, 35-37], while a brief presentation of allylation reactions with other transition metals including Mo and Rh is given in Section 14.6 [8, 13, 33, 38, 39]. The closing Section 14.7 deals with selected methods for asymmetric ring-opening reactions of unsaturated heterocycles [38, 40, 41]. 

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