Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

Abstract

CpXRh(III)-catalyzed C-H functionalization reactions are a proven method for the efficient assembly of small molecules. However, rationalization of the effects of cyclopentadienyl (CpX) ligand structure on reaction rate and selectivity has been viewed as a black box, and a truly systematic study is lacking. Consequently, predicting the outcomes of these reactions is challenging because subtle variations in ligand structure can cause notable changes in reaction behavior. A predictive tool is, nonetheless, of considerable value to the community as it would greatly accelerate reaction development. Designing a data set in which the steric and electronic properties of the CpXRh(III) catalysts were systematically varied allowed us to apply multivariate linear regression algorithms to establish correlations between these catalyst-based descriptors and the regio-, diastereoselectivity, and rate of model reactions. This, in turn, led to the development of quantitative predictive models that describe catalyst performance. Our newly-described cone angles and Sterimol parameters for CpX ligands served as highly correlative steric descriptors in the regression models. Through rational design of training and validation sets, key diastereoselectivity outliers were identified. Computations reveal the origins of the outstanding stereoinduction displayed by these outliers. The results are consistent with partial η5−η3 ligand slippage that occurs in the transition state of the selectivity-determining step. In addition to the instructive value of our study, we believe that the insights gained are transposable to other Group 9 transition metals and pave the way toward rational design of C-H functionalization catalysts.

Rhodium(III) Complex with a Bulky Cyclopentadienyl Ligand as a Catalyst for Regioselective Synthesis of Dihydroisoquinolones through C−H Activation of Arylhydroxamic Acids

“…In order to put our catalyst on the scale proposed by Paton and Rovis et al . we synthesized the P(OEt) 3 adduct of 5 , namely the complex (C 5 H 2 t Bu 2 CH 2 t Bu)RhCl 2 ‐P(OEt) 3 ( 9 ), and measured its 31 P NMR spectrum.…”

“…This methodology is particularly useful for directed search for drugs candidates and other biologically active molecules . However, the control of chemo‐ and regioselectivity of the CH‐activation reactions is often challenging . For example, the reaction of O ‐pivaloyl derivative of phenylhydroxamic acid 1 with terminal alkenes 2 in the presence of rhodium catalyst can give two isomeric dihydroisoquinolones 3 and 4 (Scheme ).…”

A Planar‐Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones

“…[1][2][3] They have opened new ways to synthesize and explore an umber of valuable molecules,s uch as drugs [4] and fluorophores. [7][8][9][10][11] In this field, the development of chiral catalysts is the most challenging. [7][8][9][10][11] In this field, the development of chiral catalysts is the most challenging.…”

A new polypyridyl‐based Ru (II) complex as a highly efficient electrocatalyst for CO2 reduction

“…In recent years, computational study of the catalytic reactions has drawn significant attention from the researchers to confirm the experimental results, and to find a good relationship between the structures and properties of catalysts . Therefore, the theoretical calculations were performed to confirm the proposed electrocatalytic cycle for the CO 2 reduction to CO in the presence of cis ‐[Ru (Me 4 phen) 2 (CH 3 CN) 2 ](PF 6 ) 2 .…”