Copper Complexes as Functional Models for Dopamine β-Hydroxylase - Mechanistic Study of Oxygen Atom Transfer from Cu/O Species to Benzylic C−H Bonds

Blain, Ingrid; Giorgi, Michel; Riggi, Innocenzo De; Réglier, Marius

doi:10.1002/1099-0682(20011)2001:1<205::aid-ejic205>3.0.co;2-u

Cited by 34 publications

(10 citation statements)

References 21 publications

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“…15 Recently, the group of Réglier 16 reported outstanding comparative studies on the activities of DBH and biomimetic models for the benzylic hydroxylation of 2-aminoindane derivatives (Scheme 4). The two equivalent benzylic positions in 2-aminoindane can be differentiated by benzylic monosubstitution with a deuterium atom.…”

Section: Dopamine B-hydroxylase (Dbh)mentioning

confidence: 99%

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et al. 2001

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Section: Dopamine B-hydroxylase (Dbh)mentioning

confidence: 99%

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et al. 2001

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“…While numerous model systems for the aromatic hydroxylation function of tyrosinase exist, fewer studies on aliphatic hydroxylations have been reported . For the latter, prominent examples were put forth by the groups of Itoh and Réglier (Scheme ) –. After treating copper complexes of chelating N‐donor ligands with molecular oxygen, the intramolecular hydroxylation of the benzylic C−H ligand position was observed with high regio‐ and even stereoselectivity (Scheme , top and middle).…”

Section: Introductionmentioning

confidence: 99%

“… Regioselective benzylic C−H bond hydroxylation reported by Itoh (top) ,. Regio‐ and stereoselective benzylic C−H bond hydroxylation reported by Réglier using tetralin substituted ligands (middle); competing hydroxylation of benzylic and non‐activated aliphatic C−H bonds reported by Réglier using cyclopentyl substituted ligands (bottom) …”

Section: Introductionmentioning

confidence: 99%

Copper‐Mediated Selective Hydroxylation of a Non‐activated C−H Bond in Steroids: A DFT Study of Schönecker's Reaction

Gupta

Diefenbach

Holthausen

et al. 2016

Chemistry A European J

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The regio- and stereoselective copper-mediated hydroxylation of a non-activated aliphatic C-H bond in steroids by dioxygen, initially reported by Schönecker et al. (Angew. Chem. Int. Ed. 2003, 42, 3240-3244), has recently evolved into a valuable synthetic tool. In the present work, a detailed mechanistic density functional theory (DFT) study addressing the origin of the remarkable selectivity of Schönecker's reaction is reported. The applied BLYP-D3/def2-TZVP(SDD) level of DFT is benchmarked against experimental and coupled-cluster reference data. The resulting mechanistic scenario involves formation of a bis-μ-oxo dicopper complex as key intermediate. In this complex three C-H bonds of the pendant steroid ligand are predisposed towards intramolecular activation by the bis-μ-oxo dicopper core. The lowest activation barrier (12.0 kcal mol ) is computed for β-hydroxylation at the C12 position, in agreement with the experimental observations. Natural bond orbital (NBO) analysis reveals stabilizing orbital interactions that favor the β-hydroxylation pathway over competing reaction channels.

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“…Hydroxylations of aromatic or benzylic C-H bonds using simpler nitrogen-containing ligands have been quite successful [34][35][36][37][38][39][40]. Normally, the ligands themselves are hydroxylated in the reaction.…”

Section: B-hydroxylations With Aminoalkyl-2-pyridino Ligandsmentioning

confidence: 99%