P-Stereogenic Ir-MaxPHOX: A Step toward Privileged Catalysts for Asymmetric Hydrogenation of Nonchelating Olefins

Biosca, Maria; Cruz-Sánchez, Pol de la; Faiges, Jorge; Margalef, Jèssica; Salomó, Ernest; Riéra, Antoni; Ferré, Joan; Maseras, Feliu; Besora, María; Pàmies, Òscar; Diéguez, Montserrat

doi:10.1021/acscatal.2c05579

Cited by 15 publications

(19 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In such case, the calculated barrier from the QM/MM scanning is over 25 kcal/mol (Figure S5). Notably, DFT methods have proven to be reliable to reproduce the small differences in describing selectivity. ,− Thus, our calculations support the fact that the nucleophilic attack by the substrate N1 site, during which the π electrons from the CN1 site was shifted to the σ* orbital of the O–O moiety, is the most favorable pathway. For comparison, we also tested the first electrophilic attack step using two additional snapshots (Figure S12), which indeed yield similar reaction energy profiles as the one in the main text (Figure ).…”

Section: Resultssupporting

confidence: 68%

Peroxo-Diiron(III/III) as the Reactive Intermediate for N-Hydroxylation Reactions in the Multidomain Metalloenzyme SznF: Evidence from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations

et al. 2023

View full text Add to dashboard Cite

Upon oxygen activation, the non-heme diiron enzymes can generate various active species for oxidative transformations. In this work, the catalytic mechanism of the diiron active site (heme-oxygenase-like diiron oxidase (HDO) domain) in SznF has been comprehensively studied by molecular docking, classical molecular dynamics (MD) and quantum mechanical/molecular mechanical (QM/MM) MD simulations, and hybrid QM/MM calculations. The HDO domain of SznF catalyzes the selective hydroxylation of Nω-methyl-l-arginine (l-NMA) to generate Nδ-hydroxy-Nω-methyl-l-Arg (l-HMA) and Nδ,Nω-dihydroxy-Nω,-methyl-l-Arg (l-DHMA), which is a key step in the synthesis of the nitrosourea pharmacophore of the pancreatic cancer drug streptozotocin (SZN). Our study shows that the peroxo-diiron(III/III) intermediate in Sznf maintains a butterfly-like conformation, while the further protonation of the diiron(III/III) intermediate is found to be inaccessible and unfavorable thermodynamically. Among various mechanisms, we found that the most favorable mechanism involves the nucleophilic attack of the guanidium group onto the peroxo group of P1, which drives the heterolytic cleavage of the O–O bond. Moreover, the selectivity of N-hydroxylation by the peroxo-diiron(III/III) intermediate can be fully supported by MD simulations, suggesting that the peroxo-diiron(III/III) is the reactive intermediate for N-hydroxylation in SznF. The present study expands our understanding on the O2 activation and N-hydroxylation by the non-heme diiron enzymes.

show abstract

Section: Resultssupporting

confidence: 68%

Peroxo-Diiron(III/III) as the Reactive Intermediate for N-Hydroxylation Reactions in the Multidomain Metalloenzyme SznF: Evidence from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The first set was based on previously known Rh‐diphosphine catalysts (Rh/ L1 – L6 , see Supporting Information) selected among the best candidates for the AH of functionalized olefins (including the previously mentioned Rh‐Josiphos type catalysts, see Supporting Information) [2c,11b] . The second set was a selection of Ir−P,N catalysts that had successfully hydrogenated trisubstituted α,β‐unsaturated ketones (Ir/ L7 – L10 and L14 ) [10a,d,e,i,n] and tetrasubstituted non‐chelating cyclic and acylic olefins (Ir/ L11 – L17 ) [10i,n,12] . The initially tested conditions were those reported to be optimal for other types of tetrasubstituted olefins, and depended on the employed metal (see Supporting Information for details).…”

Section: Resultsmentioning

confidence: 99%

Unlocking the Asymmetric Hydrogenation of Tetrasubstituted Acyclic Enones

Faiges,

Biosca,

Pericàs

et al. 2023

Angew Chem Int Ed

Self Cite

View full text Add to dashboard Cite

Asymmetric hydrogenation (AH) of tetrasubstituted olefins generating two stereocenters is still an open topic. There are only a few reports on the AH of tetrasubstituted olefins with conjugated functional groups, while this process can create useful intermediates for the subsequent elaboration of relevant end products. Most of the tetrasubstituted olefins successfully submitted to AH belong to a small number of functional classes; remarkably, the AH of tetrasubstituted acyclic enones still represents an unsolved challenge. Herein, we disclose a class of air‐stable Ir−P,N catalysts, prepared in three steps from commercially available amino alcohols, that can hydrogenate, in minutes, a wide range of electronically and sterically diverse acyclic tetrasubstituted enones (including exocyclic ones) with high yields and high enantioselectivities. The factors responsible for the excellent selectivities were elucidated by combining deuterogenation experiments and theoretical calculations. The calculations indicated that the reduction follows an IrI/IrIII mechanism, in which enantioselectivity is controlled in the first migratory insertion of the hydride to the most electrophilic olefinic Cβ and the formation of the hydrogenated product via reductive elimination takes place prior to the coordination of dihydrogen and the subsequent oxidative addition. The potential of the new catalytic systems is demonstrated by the derivatization of hydrogenation products.

show abstract

“…Overview of different MaxPHOXÀ Ir(I)-complexes being able to catalyze various hydrogenation reactions. [72] Scheme 27. MaxPHOXÀ Ir(I)-catalyzed asymmetric hydrogenation of N-aryl imine 156 (BArF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate).…”

Section: Discussionmentioning

confidence: 99%

A Powerful P−N Connection: Preparative Approaches, Reactivity, and Applications of P‐Stereogenic Aminophosphines

Huber,

Bauer

2024

Chemistry A European J

View full text Add to dashboard Cite

For more than five decades, P‐stereogenic aminophosphine chalcogenides and boranes have attracted scientific attention and are still in the focus of ongoing research. In the last years, novel transition metal‐based synthesis methods have been discovered, in addition to the long‐known use of chiral auxiliaries. Enantiomerically pure compounds with N–P+–X‐ (X = O, S, BH3) motifs served as valuable reactive building blocks to provide new classes of organophosphorus derivatives, thereby preserving the stereochemical information at the phosphorus atom. Over the years, intriguing applications in organocatalysis and transition metal catalysis have been reported for some representatives. Asymmetric reductions of C═C, C═N, and C═O double bonds were feasible with selected P‐stereogenic aminophosphine oxides in the presence of hydrogen transfer reagents. P‐stereogenic aminophosphine boranes could be easily deprotected and used as ligands for various transition metals to enable catalytic asymmetric hydrogenations of olefins and imines. This review traces the emergence of a synthetically and catalytically powerful functional compound class with phosphorus‐centered chirality in its main lines, starting from classical approaches to modern synthesis methods to current applications.

show abstract

P-Stereogenic Ir-MaxPHOX: A Step toward Privileged Catalysts for Asymmetric Hydrogenation of Nonchelating Olefins

Cited by 15 publications

References 118 publications

Peroxo-Diiron(III/III) as the Reactive Intermediate for N-Hydroxylation Reactions in the Multidomain Metalloenzyme SznF: Evidence from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations

Peroxo-Diiron(III/III) as the Reactive Intermediate for N-Hydroxylation Reactions in the Multidomain Metalloenzyme SznF: Evidence from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations

Unlocking the Asymmetric Hydrogenation of Tetrasubstituted Acyclic Enones

A Powerful P−N Connection: Preparative Approaches, Reactivity, and Applications of P‐Stereogenic Aminophosphines

Contact Info

Product

Resources

About