Pyranoside Phosphite–Oxazoline Ligands for the Highly Versatile and Enantioselective Ir-Catalyzed Hydrogenation of Minimally Functionalized Olefins. A Combined Theoretical and Experimental Study

Abstract

A modular set of phosphite-oxazoline (P,N) ligands has been applied to the title reaction. Excellent ligands have been identified for a range of substrates, including previously challenging terminally disubstituted olefins, where we now have reached enantioselectivities of 99% for a range of substrates. The selectivity is best for minimally functionalized substrates with at least a moderate size difference between geminal groups. A DFT study has allowed identification of the preferred pathway. Computational prediction of enantioselectivities gave very good accuracy.

Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights

“…482,483 Their calculations revealed an Ir(III)/Ir(V) catalytic cycle in which migratory insertion of a hydride is selectivity determining. The effect of both ligand modification as well as enantioselectivity could be rationalized using a quadrant model.…”

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.…”

P,S-ligands for Ir-catalyzed Asymmetric Hydrogenation of Minimally Functionalized Olefins – A Theoretical Study

“…Inspired by the work on Ir-catalyzed hydrogenation using carbohydrate-derived P,N-ligands, 3 the abovementioned P,S-ligands have been used successfully to hydrogenate the minimally functionalized olefin 6 (Table 1), and similar substrates.…”