Iridium-Catalyzed Transformations

SCHEME 5.27 Fe(ni)/Cu(I)-cocatalyzed exchange between Grignard reagents and alkynes. 

SCHEME 5.28 Possible mechanism for the Grignard exchange reaction. 

SCHEME 5.31 Ir-catalyzed synthesis of quinazolinones from primary alcohols and 

SCHEME 5.32 Ir-catalyzed three-component reaction of secondary amines, aldehydes, and alkynes. 

SCHEME 5.34 Ir-catalyzed cascade allylic vmylation/intramolecular allylic amination. 

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The iridium-catalyzed transformation between carboxyhc acid and vinyl acetate [28] or allyl acetate [30] was also promoted to afford vinyl or allyl carboxylates in good yields. 

In 2011, Hartwig and coworkers reported the total synthesis of taiwaniaquinol B (55, Scheme 11.9), a member of a family of diterpenoids that are derived from the abietane skeleton [36]. A key aspect of the Hartwig synthesis of taiwaniaquinol B was the use of the iridium-catalyzed borylation reaction to accomplish the C(5) functionalization of resorcinol derivative 53. This regioselectivity for the overall bromination is complementary to that which would be obtained using a standard electrophilic aromatic substitution (EAS) reaction. In the transformation of 53 to 54, a sterically controlled borylation was first accomplished, which was then followed by treatment of the boronic ester intermediate with cupric bromide to... 

Boronic esters have been used in a wide range of transformations. These useful reagents have been transformed into numerous functional groups and are essential reagents for several C-C bond-forming reactions. Transition metal-catalyzed hydroboration of olefins often leads to mixtures of branched and linear products. Several groups have reported asymmetric reductions of vinyl boronic esters [50-52] with chiral rhodium P,P complexes however, the first iridium-catalyzed reduction was reported by Paptchikhine et al (Scheme 10) [53]. 

The activation of alcohols by iridium-catalyzed borrowing hydrogen reactions has also been applied to the formation of C-C bonds [113]. Reactions proceed by temporary removal of hydrogen from an alcohol to give an aldehyde (or ketone), which is transformed into an alkene with subsequent return of the hydrogen to provide a new C-C bond. Ishii and coworkers have used [lr(cod)Cl]2 with... 

A novel hydrazepine formation is observed in the iridium-catalyzed reaction of alkynyl hydrazone 304 with Bu Me2SiH in excess under slightly forcing conditions (Equation (53))/ The transformation leading to 305 can be explained by continuous interaction of Bu MceSiH with a silylformylation product of 304 under the reaction conditions/ ... 

Direct arylations of arenes are, however, not restricted to palladium-catalyzed transformations, but were also accomplished with, inter alia, iridium complexes. Thus, the direct coupling of various aryl iodides with an excess of benzene in the presence of [Cp IrHCl]2 afforded the corresponding biaryl products, but usually in moderate yields only (Scheme 9.30) [69]. The reaction is believed to proceed via a radical-based mechanism with initial base-mediated reduction of iridium(III) followed by electron transfer from iridium(II) to the aryl iodide. Rather high catalyst loadings were required and the phenylation of toluene (90) under these reaction conditions provided a mixture of regioisomers 91, 92, and 93 in an overall low yield (Scheme 9.30) [69]. 

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. 

Thus, oxidation of the allylic alcohol 363 to the corresponding aldehyde in the presence of a large excess of manganese dioxide initiated the domino oxidation/Diels-Alder/hetero-Diels-Alder sequence. After formation of 366 via an endo-E-syn transition state, the terminal aldehyde 367 then gave the tetracycle 364 in the concluding hetero-Diels-Alder step in 28% yield after 2 days. Intermediate 364 was then further transformed into the natural product 365 in an additional 14 steps, featuring an intramolecular Heck reaction and an iridium-catalyzed isomerization. 

You et al. reported the iridium-catalyzed enantioselective functionalization of indoles and pyrroles. In the event, indole 181 is transformed, via an intramolecular allylic alkylation, into a spirocyclic intermediate at C3, which then undergoes selective methylene migration to form 182 with no loss of enantiopurity (up to 99% ee is obtained).The indole ring can tolerate substitution with various halogens or methoxy groups, while pyrroles can be substituted with alkyl or aryl groups (13JA8169). 

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. ... 

The use of NHCs as ancillary ligands in iridium-catalyzed Oppenauer-type oxidation of alcohols to carbonyls has led to some of the most active catalysts for this class of transformation. In 2005, Yamaguchi and co-workers reported the synthesis of a number of [(Cp )Ir] complexes featuring NHCs as the ancillary ligands.In addition to neutral complexes of the formula... 

The synthesis of chiral racemic atropisomeric pyridines by cobalt-catalyzed [2 + 2 + 2] cycloaddition between diynes and nitriles was reported in 2006 by Hrdina et al. using standard CpCo catalysts [CpCo(CO)2, CpCo(C2H4)2, CpCo(COD)] [34], On the other hand, chiral complexes of type II were used by Gutnov et al. in 2004 [35] and by Hapke et al. in 2010 [36] for the synthesis of enantiomerically enriched atropisomers of 2-arylpyridines (Scheme 1.18). This topic is described in detail in Chapter 9. It is noteworthy that the 2004 paper contains the first examples of asymmetric cobalt-catalyzed [2 - - 2 - - 2] cycloadditions. At that time, it had been preceded by only three articles dealing with asymmetric nickel-catalyzed transformations [37]. Then enantioselective metal-catalyzed [2 -i- 2 - - 2] cycloadditions gained popularity, mostly with iridium- and rhodium-based catalysts, as shown in Chapter 9. 

Numerous studies aimed at the understanding of the mechanism of these processes rapidly appeared. In this context, Murai examined the behavior of acyclic linear dienyne systems in order to trap any carbenoid intermediate by a pendant olefin (Scheme 82).302 A remarkable tetracyclic assembly took place and gave the unprecedented tetracyclo[6.4.0.0]-undecane derivatives as single diastereomer, such as 321 in Scheme 82. This transformation proved to be relatively general as shown by the variation of the starting materials. The reaction can be catalyzed by different organometallic complexes of the group 8-10 elements (ruthenium, rhodium, iridium, and platinum). Formally, this reaction involves two cyclopropanations as if both carbon atoms of the alkyne moiety have acted as carbenes, which results in the formation of four carbon-carbon bonds. 

Many metals including nickel,32,33 ruthenium,34 iridium,35 36 lanthanum,37,38 titanium,39 and zirconium40-42 have been employed in this transformation with varying degrees of success, but rhodium has remained the metal of choice for transition metal hydroboration. The mechanism of rhodium-catalyzed hydroboration (Scheme 4), is thought to depend on the nature of the substrate, the catalyst, the ligand used and the reaction conditions employed.43... 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [40]. 

I 14 Transformations of (Organo)siHcon Compounds Catalyzed by Iridium Complexes... 

When substituted silanes are used instead of hydrogen, the process is referred to as silylformylation or silylcarbonylation. Only rhodium complexes catalyze the transformation of unsaturated compounds to silylaldehydes via the silylformylation reaction. Iridium complexes also are able to catalyze the simultaneous incorporation of substituted silanes and CO into unsaturated compounds, although during the reaction other types of product are formed. In the presence of [ IrCl(C03) ] and [Ir4(CO)i2]) the alkenes react with trisubstituted silanes and CO to give enol silyl ethers of acyl silanes [58] according to Scheme 14.10. 

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