title: 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 CpXligands 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-η3ligand 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.
authors.affiliation: Department of Chemistry, Columbia University , New York, New York 10027, United States.|Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Piou
authors.affiliation: Department of Chemistry, Columbia University , New York, New York 10027, United States.|Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Fedor
authors.initials: F
authors.lastname: Romanov-Michailidis
authors.affiliation: Department of Biochemistry, University of Geneva , 1211 Geneva 4, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Romanova-Michaelides
authors.affiliation: Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Kelvin E
authors.initials: KE
authors.lastname: Jackson
authors.affiliation: Department of Chemistry, Columbia University , New York, New York 10027, United States.|Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Natthawat
authors.initials: N
authors.lastname: Semakul
authors.affiliation: Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Taggart
authors.affiliation: Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Newell
authors.affiliation: Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Rithner
authors.affiliation: Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Robert S
authors.identifier: 0000-0002-0104-4166
authors.initials: RS
authors.lastname: Paton
authors.affiliation: Department of Chemistry, Columbia University , New York, New York 10027, United States.|Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.
authors.forename: Tomislav
authors.identifier: 0000-0001-6287-8669
authors.initials: T
authors.lastname: Rovis
mesh_terms: D000465:Algorithms; D002384:Catalysis; D003517:Cyclopentanes / Q000737:chemistry*; D008024:Ligands; D016014:Linear Models; D009942:Organometallic Compounds / Q000737:chemistry*; D011789:Quantum Theory; D012238:Rhodium / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D003517:Cyclopentanes; D008024:Ligands; D009942:Organometallic Compounds; D012238:Rhodium