Iridium-Catalyzed Cycloadditions

Lewis acid-catalyzed cycloaddihon is also a powerful synthehc method, and various types of cycloaddihon have been reported. In parhcular, enantioselective variants using chiral Lewis acids have been comprehensively studied some of these were used as key reactions for natural product syntheses [5]. However, they generally require one or more heteroatoms in the substrates, such as enones or enoates, to which (chiral) Lewis acids can coordinate. In conhast, in the case of transition-metal-catalyzed cycloadditions, the metals coordinate direchy to the tt-electron and activate unsaturated motifs, which means that the heteroatom(s) are unnecessary. Moreover, the direct coordinahon to the reachon site can realize highly enantioselechve reachon using chiral transihon-metal complexes. 

In fact, a variety of hansihon metals have been used as efficient catalysts in a range of cycloaddihon reachons. Among these, the Co, Ni, Ru, Rh and Pd complexes have been the major players, whilst the Ir complexes have played only a minor role. Nonetheless, several Ir-catalyzed cycloadditions have been recently reported, which cannot be realized by other metal complexes. This chapter summarizes Ir complex-catalyzed cycloadditions, which include several types of cycloi-somerizahon and cycUzahon. 

Iridium Complexes in Organic Synthesis. Edited by Luis A. Oro and Carmen Claver Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim T RN- 978.V 7,7- 199E-1 

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Takeuchi and coworkers reported an iridium-catalyzed cycloaddition of a,o -diynes and nitriles to give pyridines in 2012 [57]. With [Ir (cod)Cl]2/DPPF or BINAP as the catalytic system, pyridines were formed effectively (Scheme 3.24). A wide range of nitriles (aliphatic and aromatic nitriles) can be applied and reacted smoothly with Q ,a -diynes to give the pyridines. In the case of unsymmetrical diyne bearing two different internal alkyne moieties, high regioselectivity can be achieved which can be explained by the different reactivities of the a-position in iridacyclopentadiene. Terpyridine and quinquepyridine were prepared as well. [Ir(cod)Cl]2/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic... 

In this chapter, the details of several types of Ir-complex-catalyzed cycloadditions have been summarized. Although, compared to other late transihon-metal com-plexes-such as those of Pd, Ni, Ru and Rh-the examples are few in number, some notable Ir-catalyzed cyclizations have recently been reported which cannot be achieved when uhlizing other metal catalysts. Until now it has not yet been possible to identify any dishnct explanation for the unique reachvity of iridium, and in parhcular its different reachvity compared to rhodium, which is located just above iridium in the Periodic Table of the elements. Nonetheless, many further developments of efficient and prachcal Ir-catalyzed cycloadditions are to be expected in the near future. 

Scheme 5 Synthesis of dibenzosilole using iridium-catalyzed [2 + 2 + 2] cycloaddition [43]. Reagents and conditions (a) [IrCl(COD)]2 2.5 mol%, PPh3 10mol%, Bu20, 110 °C, 24 h...

Bis(propargyl) ethers were converted to dihydrobenzo[c]furans through either a palladium-catalyzed tandem reaction with arylboronic acids <04CEJ5338> or an iridium-catalyzed <04JA8382> [2+2+21 cycloaddition reaction with alkynes. 

The practical and convenient solvent-free iridium-catalyzed [2 + 2 + 2] cycloaddition of a,(D-diynes and alkynes was explored as an efficient route for the synthesis of isoindolines, dihydrobenzo[c]frirans, and indanes (13S2003).The asymmetric synthesis of C2-symmetric axially chiral biaryls was achieved by the cationic rhodium(I)/l,3-bis(diphenylphosphino)pro-pane (dppp)-catalyzed diastereoselective double [2 + 2 + 2] cycloaddition of (R)-3-butyn-2-ol-derived tetraynes with functionalized monoynes (13EJOC6774). 

In 2005, Yamamoto et al. reported the synthesis of polycyclic pyrrole-2-carboxylates 76 via a CuBr -catalyzed three-component coupling of A-benzylallylamine, ethyl gly-oxalate, and terminal alkynes, and subsequent ttansforma-tion of the glycine-tethered 1,6-enynes 75 thus obtained through a cycloisomerization/Diels-Alder cycloaddition/ dehydrogenation sequence under iridium-catalyzed conditions (Scheme 3.43) [108]. 

In 2014, Ding et al. [70] reported an iridium-catalyzed azide-alkyne cycloaddition reaction (IrAAC) of electron-rich internal alkynes (Scheme 9.27). The reaction is highly regioselective in favor of the 1,5-isomer. 

Related allenylcyclopropanes can also participate in the [5-t-l] cycloaddition. For example, Iwasawa and co-workers found that allenylcyclopropanols reacted with stoichiometric Co2(CO)g, giving hydroquinone derivatives in moderate to good yields (see (4)) [12,13]. Murakami reported an example of iridium-catalyzed [5-t-l] cycloaddition of multisubstituted allenylcyclopropanes with carbon monoxide for synthesis of methylenecyclohexenones (see (5)) [ 14]. It was found that the presence of one, or preferably two, substiments at the allenic terminus was necessary. 

Collman et al. first prepared iridacyclopentadiene 1 by the reaction of IrCl(N2 )(PPh3)2 with dimethyl acetylenedicarboxylate (DMAD) in 1968 [6] (Scheme 5.1). They found that iridacyclopentadiene was a catalyst for the [2 + 2 + 2] cycloaddition of DMAD. The reaction of DMAD in the presence of 7 mol % tetracar-bomethoxyiridacyclopentadiene 1 under refluxing toluene for 16 h gave hex-acarbomethoxybenzene in 80% yield. However, the substrate was limited to DMAD. Iridium-catalyzed [2 + 2 + 2] cycloaddition of alkynes remained unexplored until 2001. 

In 2004, Shibata et al. reported on the atrop-selective biaryl synthesis by iridium-catalyzed [2 + 2 + 2] cycloaddition [8], They developed the synthesis of axially chiral 1,4-teraryls 16 with two atropisomeric chiralities by the neutral iridium(I)/Me-Duphos complex-catalyzed enantio- and diastereoselectivitive [2 + 2 + 2] cycloaddition of a,w-diynes 14, possessing ortho-substituted aryl groups at alkyne termini, with functionalized internal monoynes 15 in high yields with excellent enantio- and diastereoselectivity (Scheme 9.6) [8,9],... 

Axially chiral substituted pentacene 2.64 was first synthesized by the iridium-catalyzed [222] cycloaddition of anthracene derivatives 2.63 with 2-butyne-l,4-diol 2.60f (Scheme 2.23) [61, 63]. 

Scheme2.52 Synthesis of silafluorenes by iridium-catalyzed [24-2-1-2] cycloaddition of silicon-bridged diynes with alkynes.

Shibata, T., Arai, Y., Takami, K. et al. (2006) Iridium-catalyzed enantioselective [24-24-2] cycloaddition of diynes and monoalkynes for the generation of axial chiralities. Advanced Synthesis Catalysis, 348(16-17), 2475-2483. 

Matsuda, T., Kadowaki, Sh., Goya, V. and Murakami, M. (2007) Synthesis of silafluorenes by iridium-catalyzed [24-24-2] cycloaddition of silicon-bridged diynes with alkynes. Organic Letters, 9(1), 133-136. 

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