Ir-catalyzed C-H activation

More recently, a protocol was elucidated by Malezcka and Smith to produce aryl borate esters directly without first producing aryl halides.144 The reaction involves an Ir-catalyzed C-H activation (Section 7-2-1) to yield the aryl borate, which can then be used directly in Suzuki cross-coupling (equation 12.71). This new development adds another green aspect to Suzuki cross-coupling, which is already a relatively green synthesis tool. 

Piericidin-related natural products were prepared and their absolute configurations established. The synthesis involved an Ir-catalyzed C-H activation to provide the hydroxypyridine, a Mukaiyama aldol reaction, and a Negishi coupling (13OL670). 

Iridium has been found to be a very robust late transition metal which can mediate or catalyze C—H bond activation reactions very efficiently. However, the highly enantioselective Ir-catalyzed C—H bond functionalization via a transient C—Ir species for the construction of C—C or C—X bonds only emerged recently. Mechanistically, the catalytic cycle starts with oxidative addition of the Ii catalyst to the inert C—H bonds (such as aromatic, olefinic, or aliphatic C—H bonds), which are usually assisted with an ortho directing group. Subsequently, the formed C—Ir species inserts into an unsaturated functionality such as alkene, alkyne, or imine, delivering a new C—Ir speeies. Finally, the reductive elimination releases the products and regenerates the Ir catalyst. 

Much of the insight gained from computational and mechanistic studies into heteroatom-assisted C-H activation at Pd(ll) metal centers has proven to be apphcable to Ru(ll), Rh(lll), and Ir(III) systems. Therefore, only a brief overview of the most relevant computational studies of these processes will be presented. Computational studies of Ru-, Rh-, and Ir-catalyzed C-H functionalization reactions will then be described. Most of these target the synthesis or deriva-tization of heterocycle systems and also include a treatment of the initial C-H activation step. 

Oxidative carbonylation can also be achieved by metal-assisted C - H activation. The Pd(II)-promoted oxidative carbonylation of arenes to give aromatic acids has been reported to occur under stoichiometric [127,128] as well as catalytic [129-138] conditions (Eqs. 28-30). In the case of alkylben-zenes, the Pd-catalyzed reaction shows only a moderate selectivity towards the para position. Better p-selectivilics have however been attained by employing Rh(III) or Ir(III) catalysts [139-146]. 

A sigruficant observation concerning the mechaiHsm of the Ir-catalyzed allyhc subsHtution was made when the preparahon of an (allyl)(P(OPh)3)Ir-mtermediate was attempted [6b]. Mixing [Ir(COD)Cl]2 and 2 equiv. of P(OPh)3 yields the complex Kl, which is a coordinatively unsaturated d -tf complex [16 valence electrons (VE)s] surprisingly, this did not react with typical aUylic substrates (Scheme 9.4) rather, a reacHon was started upon the addition of NaCH(C02Me)2. The nucleophile also acts as base, with C—H activation affording an Ir complex, which ehminates HCl to produce a 16-VE Ir complex. The subsequent addition of... 

Attention to catalyst preparation and reaction conditions is of crucial importance for the success of an Ir-catalyzed allylic substitution, because many ligands are altered by C—H activation at aryl (see above) or CH3 groups. For most reactions, tetrahydrofuran (THF) is the preferred solvent it is important that dry THF (<35gg H20mr THF, Karl Fischer titration) is used for catalyst preparation because this step is very sensitive to water. The following procedures have been appHed. 

Ir(CH3)(Py)(trop-0,0)2] (trop=0,0-K -0,0-tropolonato) is also active catalyst for the C—H activation of arenes [58]. Mechanistic investigations for the Ir-catalyzed reaction have been studied [59]. 

An Ir(l)-catalyzed asymmetric intermolecular hydroarylation of norbornene with benzamide was reported in good to excellent enantiomeric excess, albeit in low yields, via the aryl C—H activation (Scheme 5.14). In some cases, the hydroami-nation products of norbornene were also formed in high enantioselectivities. 

An iridium(l) complex, generated from l/2[Ir(OMe)(COD)]2 and 4,4 -di-/-butyl-2,2 -bipyridine (dtbpy), catalyzed the direct borylation of 2-substituted pyrroles in stoichiometric amounts relative to 2,2 -bi-l,3,2-dioxaborolane 785 in hexane at room temperature (Equation 188) <2003ASC1103>. The pyrrolylborates 786 from regioselective C-H activation at the 5-position were formed in high yields. Similar borylation of unsubstituted pyrrole with an equimolar amount of borolane 785 regioselectively provided 2,5-bis(boryl)pyrrole 787 (Equation 189). 

In 2000, Periana reported an Ir(iil)(acac)3 complex that could activate benzene and catalyze anti-Markovnikov additions of olefins to the aryl C-H bond. An iridium-phenyl complex was shown to be an intermediate. This complex was converted to an Ir(lll) derivative containing an iridium-methyl bond, a species which underwent alkane C-H activation (Equation (18)). ... 

Nishimura et al. achieved an enantioselective [3 + 2] annulation via Ir/chi-ral diene-catalyzed C—H bond activation between in situ formed cyclic Af-acyl... 

Over the last few years, the Ir-catalyzed allylic substitution has been investigated in several laboratories and was found to be well suited for applications in organic synthesis. Using this reaction, branched chiral allylic derivatives can be prepared with high selectivity from simple achiral monosubstituted allylic substrates (Scheme 11.1). The reaction has been carried out with C, N, O, and S nucleophiles. The very broad range of nucleophiles is impressive. Several reviews have appeared on the subject [1]. At present, the best catalysts are prepared from [Ir(cod)Cl]2 (cod, cycloocta-1,5-diene) [2, 3] or [Ir(dbcot)Cl]2 (dbcot, dibenzocyclooctatetraene) [4] and a chiral phosphoramidite by base-induced C-H activation. Reliable experimental procedures have been developed for the reaction [5]. 

Conclusion. [Ir(OMe)(cod)]2 is a very useful catalyst for C-H activation. With 4,4 -di-rm-butyl-2,2 -bipyridine as ligand, it can catalyze arene borylation to form arylboronates. The borylated arene can then be further converted to other products such as phenols, aryl halides, aryl silanes, arylboronic acids and aryl trifluo-roborates, in a single pot. 

Iridium complex-catalyzed cyclization of an Af-arylcarbamoyl chloride with an alkyne has been reported by Tsuji and coworkers [153]. In a typical example, Af-methyl-Af-phenylcarbamoyl was reacted with 5-decyne and a catalytic amount of [IrCl(cod)]2 (2.5mol%) and additional cod (30mol%) in refluxing o-xylene for 20 h to give 3,4-dimethyl-l-methyl-2-quinolone in 92% yield (Scheme 11.5). During this reaction, no indole product formed by decarbonylation was observed. This reaction is proposed to proceed by oxidative addition of Af-arylcarbamoyl chloride to Ir(I), giving a carbamoyl chloroiridium(III) species. Subsequently, the formation of a five-membered iridacycle by ortho-aryl C-H activation followed by insertion of the alkene and reductive elimination produces the 2-quinolone derivative. 

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