Mechanistic Insights into Iridium‐Catalyzed Asymmetric Hydrogenation of Dienes

Abstract

Hydrogenation of 2,3-diphenylbutadiene (1) with the chiral carbene-oxazoline-iridium complex C has been studied by means of a combined experimental and computational approach. A detailed kinetic profile of the reaction was obtained with respect to consumption of the substrate and formation of the intermediate half-reduction products, 2,3-diphenylbut-1-ene (2) and the final product, 2,3-diphenylbutane (3). The data generated from these analyses, and from NMR experiments, revealed several facets of the reaction. After a brief induction period (presumably involving reduction of the cyclooctadiene ligand on C), the diene concentration declines in a zero-order process primarily to give monoene intermediates. When all the diene is consumed, the reaction accelerates and compound 3 begins to accumulate. Interestingly, the prevalent enantiomer of the monoene intermediate 2 is converted mostly to meso-3 so the enantioselectivity of the reaction appears to reverse. The reaction seems to be first-order with respect to the catalyst when the catalyst concentration is less than 0.0075 M; diffusion of hydrogen across the gas-liquid interface complicates the analysis at higher catalyst concentrations. Similarly, these diffusion effects complicated measurements of reaction rate versus applied pressure of dihydrogen; other factors like stir speed and flask geometry come into play under some, but not all, the conditions examined. Density functional theory (DFT) calculations, using the PBE method, were used to probe the reaction. These studies indicate a transoid-eta(4)-diene-dihydride complex forms in the first stages of the catalytic cycle. Further reaction requires dissociation of one alkene ligand to give a eta(2)-diene-dihydride-dihydrogen intermediate. A catalytic cycle that features Ir(3+)/Ir(5+) seems to be involved thereafter.

Asymmetric Hydrogenation Routes to Deoxypolyketide Chirons

“…[18,[22][23][24][25] Detailed theoretical studies from these laboratories have led us to conclude that hydrogenation of stilbene and styrene derivatives by catalyst 1 proceeds by a cycle involving a dihydride-dihydrogen iridium complex and cycling between Ir III and Ir V oxidation states. [26] These observations were broadly similar to those calculated by Brandt, Andersson and coworkers for a simplified phosphine-oxazoline iridium complex mediating hydrogenation of ethene.…”

“…In response, we have begun to study dienes and polyenes. [17][18][19] Then, very recently, Pfaltz et al reported reduction of a 1,5,9-triene to give (R,R,R)-toScheme 1. a) Internal deoxypolypropionate chirons and b) the asymmetric hydrogenation approaches to these chirons that are investigated here. P = protecting group, FG = CH 2 OH, CH 2 OR, or CO 2 R. Scheme 2.…”

Ligand Design for Catalytic Asymmetric Reduction

“…A chiral carbene-oxazoline ligand L5 is also useful for this purpose. 59 The mechanism of this reaction is to be elucidated by experimental [60][61][62][63] and theoretical 64,65 studies. Chiral titanocene catalysts also show high enantioselectivity for hydrogenation of simple olefins.…”

Donor‐Functionalised N‐Heterocyclic Carbene Complexes of Group 9 and 10 Metals in Catalysis: Trends and Directions

“…Electronic effects drive the alkene substrate trans to the NHC, enabling steric effects (mainly adamantane/alkene interaction) to efficiently control enantioface discrimination. [170] The application of 101 to the hydrogenation of more complex functionalised dienes has also been described, [171,172] whilst a pyrimidine analogue was recently described. [173] In direct line with the work of Burgess, Pfaltz has reported a library approach to 2-and 4-oxazoline-NHC cationic Ir I complexes (Scheme 21).…”