Mechanism of the Asymmetric Hydrogenation of Exocyclic α,β‐Unsaturated Carbonyl Compounds with an Iridium/BiphPhox Catalyst: NMR and DFT Studies

Abstract

The mechanism of the asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds with the (aS)-Ir/iPr-BiphPhox catalyst was studied by NMR experiments and DFT computational analyses. Computed optical yields of the asymmetric hydrogenation proceeding by an iridium(I)/iridium(III) mechanism involving a transition state stabilized through two intramolecular hydrogen bonds are in good accordance with the experimental ee values.

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

“…[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.…”

“…By employing Ir/P,Ntype structuresa nd ethylene as the model system, four previously proposed mechanisms of iridium-catalyzed olefin hydrogenationa re illustrated in Figure 2. [23][24][25][26][27][28] In these two mechanisms, labeled as I/III-MI-Solv and I/III-MI,t he hydrogenating iridium(III) dihydride species is first formed through the oxidative addition (OA) of the iridium(I) dihydrogen complex. [23][24][25][26][27][28] In these two mechanisms, labeled as I/III-MI-Solv and I/III-MI,t he hydrogenating iridium(III) dihydride species is first formed through the oxidative addition (OA) of the iridium(I) dihydrogen complex.…”

“…Then am igratory insertion (MI) of the bound olefin substratei nto am etalÀhydrideb ond occurs, as the first-Hh ydrogenation step, to generate an alkyl iridium(III) hydride intermediate. [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. [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.…”

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

“…Hydrogenation conditions were screened as listed in Ta ble 1. We commenced our investigations by using 1a as the model substrate with 1.0 mol %o f( a S)-Ir/iPr-BiphPHOX ([Ir(L1)cod]-BAr F ) [11] (Biph = biphenyl, cod = 1,5-cyclooctadiene,B Ar F = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) as catalysti nd ifferent solvents under 40 bar of hydrogen. The reactions were performeda tr oom temperature for 24 h( Table 1, entries 1-6).…”

Recent Experimental and Computational Studies of the Mechanisms of Enantioselection in Asymmetric Catalytic Reactions

“…18 Experimental studies showed that the precatalyst 54 is rapidly transformed into isomeric pentahydrides 55a,b which equilibrate in solution via the tetrahydride dimer 56 and monomeric dihydrides 57a d (Scheme 14).…”