Asymmetric Hydrogenation with Iridium C,N and N,P Ligand Complexes: Characterization of Dihydride Intermediates with a Coordinated Alkene

Abstract

Previously elusive iridium dihydride alkene complexes have been identified and characterized by NMR spectroscopy in solution. Reactivity studies demonstrated that these complexes are catalytically competent intermediates. Additional H2 is required to convert the catalyst-bound alkene into the hydrogenation product, supporting an Ir(III) /Ir(V) cycle via an [Ir(III) (H)2 (alkene)(H2 )(L)](+) intermediate, as originally proposed based on DFT calculations. NMR analyses indicate a reaction pathway proceeding through rapidly equilibrating isomeric dihydride alkene intermediates with a subsequent slow enantioselectivity-determining step. As in the classical example of asymmetric hydrogenation with rhodium diphosphine catalysts, it is a minor, less stable intermediate that is converted into the major product enantiomer.

DFT Methods to Study the Reaction Mechanism of Iridium‐Catalyzed Hydrogenation of Olefins: Which Functional Should be Chosen?

“…[5,7] The difference between the I/III-MI-Solv and I/III-MI mechanisms lies in the fact that the latter involves no solvent molecule (dichloromethane for example) coordinated to the metal center, evidence for which comesf rom am ass spectroscopic study of Ir(PHOX)mediated hydrogenationo fs tyrene in the gas phase. [35] One Ir III /Ir V pathway, III/V-MI, ( Figure 2C)w as suggested according to DFT studies using the B3LYP functional on the truncated achiral modelo ft he Ir(PHOX) system and af ull model of ac hiral thiazoled erivative of the Ir(PHOX) complex. [26] In contrast, mechanisms involving Ir III and Ir V intermediates have been proposed and advocated by the groups of Andersson, Burgess, Hall, mainly based on DFT calculations on hydro-To enablet he selection of more accurate computational methods for the future theoretical exploration of the reactionm echanism of Ir-catalyzed olefin hydrogenation, we compared highlevel ab initio coupled clustera nd DFT calculations with as implified model of Pfaltz's Ir/P,N-type catalyst for all four previously proposed Ir I /Ir III and Ir III /Ir V mechanisms.…”

“…[12][13][14] Initiated by this groundbreaking discovery, hundreds of chiral iridium-based catalystsh ave been developed and tested for variousalkene hydrogenations. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In this regard, theoretical computation and modeling could potentially contribute to solving this conundrum, due to the lack of much relevant experimentald ata. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In this regard, theoretical computation and modeling could potentially contribute to solving this conundrum, due to the lack of much relevant experimentald ata.…”

Iridium‐Catalyzed Asymmetric Hydrogenation of Unfunctionalized Exocyclic C=C Bonds

“…Prompted by these groundbreaking discoveries, hundreds of chirali ridium-based catalysts were developeda nd applied to the reductiono fn umerous unfunctionalized alkenes. [1,7] However,a lthough ac onsiderable number of reportsw ere published pertaining to the reduction of unfunctionalized acyclic di-, tri-, and tetrasubstitutedo lefins as well as endocyclic olefins, [1,7,8] no general and efficient catalysts ystem was devel-oped for the asymmetric hydrogenation of unfunctionalized exocyclicolefins. [9] Owing to the large number of chiral benzofused five-membered rings present in pharmaceuticaln atural products and intermediates of key bioactived rugs (Scheme 1), [10] synthetic protocols for the straightforward and efficient construction of such skeletons are highly desired.…”

“…With the optimized reactionc onditions in hand, the asymmetric hydrogenation of substituted (E)-1-benzylidene-2,3-dihydro-1H-indenew as conducted at room temperature using the complex iridium-L4 ((aS)-Ir/In-BiphPHOX, 1mol %) in o-xylene (2 mL), under 60 bar of H 2 for 24 h( Ta ble 2). Various substrates 1 bearing unfunctionalized exocyclic doubleb onds could be easily converted into chiral substituted 1-benzyl-2,3-dihydro-1H-indenes 2.T he R 1 electron-withdrawing and electron-donating groups had no effect on the conversion (Table 2, entries [1][2][3][4][5][6][7][8][9][10][11][12]. Reductiono fs ubstrates bearing4 -Cl or 6-CH 3 groups pro- , AcOH (10 mL; 5 mLmL À1 ); [e] the absolute configuration of 2k was determined by X-ray crystallographic analysis.…”

Die selektive Arenhydrierung bietet einen direkten Zugang zu gesättigten Carbo‐ und Heterocyclen

“…Halogenid-verbrückte Iridium(III)-Dimere,d ie von der Mashima-Gruppe untersucht wurden, [31] stellen einen alternativen Präkatalysator mit einer ähnlichen aktiven Spezies dar. [32] Im Unterschied zu der (nucleophileren) aktiven Iridium(III)-Monohydridspezies des Präkatalysators I [28e] handelt es sich bei den aktiven Spezies des Iridium-PHOX-Katalysatorsystems II um einen sauren Iridium(III)-Dihydrid-Komplex, [33] der zur Hydrierung von elektronenarmen und -reichen N-und O-Heteroarenen genutzt werden kann. Außer chiralen Bisphosphinen wurden auch chirale P, N-Liganden wie Phosphinoxazoline (PHOX) in Kombination mit Iridium von den Charette- [28d] und Pfaltz-Gruppen eingesetzt (II).…”