Iridium-Catalyzed Coupling Reactions

Yasutaka Ishii, Yasushi Obora and Satoshi Sakaguchi 

This chapter reviews an overview of the iridium-complex-catalyzed crosscoupling reachons to form carbon-carbon and carbon-heteroatom bonds [12], 

The dimerization of alkynes is a useful method for forming compounds such as enynes from simple alkynes [13]. The iridium-catalyzed dimerizahon of 1-alkyries was first reported by Crabtree, and afforded (Zj-head-to-head enynes using [Ir(biph)(PMe3)Cl] (biph = biphenyl-2,2 -diyl) as a catalyst [14]. Thereafter, an iridium complex generated in situ from [Ir(cod)Cl]2 and a phosphine ligand catalyzed the dimerizahon of 1-alkynes 1 to give (Tj-head-to-head enyne 2, fZj-head-to-head enyne 3, or 1,2,3-butatriene derivatives 4 in the presence of hiethylamine 

Iridium Complexes in Organic Synthesis. Edited by Luis A. Oro and Carmen Claver Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim T RN- 978H. 27.HQQfi.1 

The cross-dimerization of various electron-rich 1-alkynes 5 with electron-deficient internal alkynes such as methyl phenylpropiolate 6 was promoted by an [lrCl(cod)]2 combined with bidentate phosphine ligands such as (racj-BlNAP (Equation 10.2) [16]. This reaction produces a 1 1 adduct 7 in high regioselectivity and stereoselectivity. 

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Interestingly, the alkenylation of sp3 C-H bond is observed in the iridium-catalyzed coupling reaction of aldehydes, amines, and alkynes (Equation (56)).62... 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

In contrast to the above reactions of donor-acceptor cyclopropanes involving electrophrhc n-allyl intermediates, umpolung of cyclopropanes was observed in iridium-catalyzed coupling of VCP and alcohols (Scheme 2.59) [87]. In the reaction, nucleophilic 3t-allyliridium species were used to achieve diastereo- and enan-tioselective carbonyl allylation. 

Examples of catalytic formation of C-C bonds from sp C-H bonds are even more scarce than from sp C-H bonds and, in general, are limited to C-H bonds adjacent to heteroatoms. A remarkable iridium-catalyzed example was reported by the group of Lin [116] the intermolecular oxidative coupling of methyl ethers with TBE to form olefin complexes in the presence of (P Pr3)2lrH5 (29). In their proposed mechanism, the reactive 14e species 38 undergoes oxidative addition of the methyl C-H bond in methyl ethers followed by olefin insertion to generate the intermediate 39. p-hydride elimination affords 35, which can isomerize to products 36 and 37 (Scheme 10). The reaction proceeds under mild condition (50°C) but suffers from poor selectivity as well as low yield (TON of 12 after 24 h). 

Iridium-Catalyzed, Three-Component Coupling Reactions of Aldehydes,... 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

Iridium-catalyzed reductive coupling of acrylates and imines provides trans-P-lactams 22 bearing aromatic, alkenyl, and alkynyl side-chains, with high diastereoselection <02OL2537>. This reaction appears to proceed through a reductive Mannich addition-cyclization mechanism. 

Takagi, J., Sato, K., Hartwig, J. F., Ishiyama, T., Miyaura, N. Iridium-catalyzed C-H coupling reaction of heteroaromatic compounds with bis(pinacolato)diboron regioselective synthesis of heteroarylboronates. Tetrahedron Lett. 2002,43, 5649-5651. 

A related rhodium catalyzed enantioselective reductive coupling of acetylene to N arylsulfonyl imines leads to the formation of (Z) dienyl allylic amines (Scheme 1.28) [105]. The scope of the reaction is comparable to that demonstrated for the analogous iridium catalyzed process. The reaction between the acetylene and rhodium leads to the oxidative dimerization of acetylene to form a cationic rhoda cyclopentadiene that then reacts with the imine to generate the product after the protolytic cleavage and reductive elimination. 

Shibata et al. reported that, in the presence of an iridium catalyst, the carbonylative alkyne—alkyne coupling reaction of the diyne 102 with carbon monoxide gave the tetrahydrofuran-fused cyclopen-tadienone 103 (Scheme 35).114 The rhodium-catalyzed alkyne—alkyne coupling reaction of 102 with the isocyanide 104 produced the iminocyclopentadiene 105 (Scheme 36).114b These reactions proceed through formation of the metallacyclopentadiene intermediate 106, which undergoes insertion either of CO or of the isocyanide 104. 

Retrosynthetically, spiroketal precursor 8 would be accessed via a diaster-eoselective aldol reaction between chiral aldehyde 9 and a-chiral (3-arylated methyl ketone 10 (Scheme 3). Aldehyde 9 would be readily accessible from commercially available ethyl (S)-hydroxybutyrate, while methyl ketone 10 would be constmcted by the Suzuki cross-coupling of trifluoroboratoamide 11 and rotationally symmetric aryl halides 12/13. The use of Br or I in place of Cl in halides 12/13 was intended to increase the reactivity of 12/13 toward oxidative insertion and overcome the steric hindrance imparted by the ortho-disubstituted aromatic framework. The required functionalization of the aromatic ring to install the phthalide motif was envisioned to be possible via iridium-catalyzed CH-borylation either before or after formation of the spiroketal core. Our group already had experience with this remarkable transformation in the context of naphthalene chemistry. 

As already mentioned, the C-H/C-X coupling between simple arenes and aryl halides to form biphenyl derivatives is difficult in terms of reactivity and regiose-lectivity without directing group. In 2004, Fujita and Yamaguchi [28] reported the iridium-catalyzed direct arylation of benzene with aryl iodides. For example, when the reaction was carried out in the presence of the [Cp IrHCl]2 catalyst (5mol%) and KOt-Bu (3.3 equiv.) at 80°C, 4-methoxybiphenyl 34 was obtained in 66% yield. However, when substituted arenes were used instead of benzene, several... 

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. ... 

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