scholarly journals Direct α-C–H bond functionalization of unprotected cyclic amines

2017 ◽  
Vol 10 (2) ◽  
pp. 165-169 ◽  
Author(s):  
Weijie Chen ◽  
Longle Ma ◽  
Anirudra Paul ◽  
Daniel Seidel
Keyword(s):  
Bond Functionalization ◽  
Cyclic Amines

Molecular Basis of Iterative C–H Oxidation by TamI, a Multifunctional P450 Monooxygenase from the Tirandamycin Biosynthetic Pathway

2020 ◽  
Author(s):  
Sean A. Newmister ◽  
Kinshuk Raj Srivastava ◽  
Rosa V. Espinoza ◽  
Kersti Caddell Haatveit ◽  
Yogan Khatri ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular Basis ◽  
Hydrophobic Interactions ◽  
Cytochromes P450 ◽  
Targeted Mutagenesis ◽  
P450 Monooxygenase ◽  
Bond Functionalization ◽  
Dynamics Simulations

Biocatalysis offers an expanding and powerful strategy to construct and diversify complex molecules by C-H bond functionalization. Due to their high selectivity, enzymes have become an essential tool for C-H bond functionalization and offer complementary reactivity to small-molecule catalysts. Hemoproteins, particularly cytochromes P450, have proven effective for selective oxidation of unactivated C-H bonds. Previously, we reported the in vitro characterization of an oxidative tailoring cascade in which TamI, a multifunctional P450 functions co-dependently with the TamL flavoprotein to catalyze regio- and stereoselective hydroxylations and epoxidation to yield tirandamycin A and tirandamycin B. TamI follows a defined order including 1) C10 hydroxylation, 2) C11/C12 epoxidation, and 3) C18 hydroxylation. Here we present a structural, biochemical, and computational investigation of TamI to understand the molecular basis of its substrate binding, diverse reactivity, and specific reaction sequence. The crystal structure of TamI in complex with tirandamycin C together with molecular dynamics simulations and targeted mutagenesis suggest that hydrophobic interactions with the polyene chain of its natural substrate are critical for molecular recognition. QM/MM calculations and molecular dynamics simulations of TamI with variant substrates provided detailed information on the molecular basis of sequential reactivity, and pattern of regio- and stereo-selectivity in catalyzing the three-step oxidative cascade.<br>

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

2017 ◽  
Author(s):  
Haibo Ge ◽  
Lei Pan ◽  
Piaoping Tang ◽  
Ke Yang ◽  
Mian Wang ◽  
...  
Keyword(s):  
Bond Activation ◽  
Theoretical Calculations ◽  
Experimental Studies ◽  
Bond Functionalization ◽  
Aliphatic Ketones ◽  
Site Selectivity ◽  
Mechanistic Investigation ◽  
Palladium Catalyzed ◽  
Metal Catalyzed ◽  
Site Selective

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp<sup>3</sup> carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>

Connecting Remote C–H Bond Functionalization and Decarboxylative Coupling Using Simple Amines

2019 ◽  
Author(s):  
Francisco de Azambuja ◽  
Ming-Hsiu Yang ◽  
Alexander Bruecker ◽  
Paul Cheong ◽  
Ryan Altman
Keyword(s):  
Organic Molecules ◽  
Mechanistic Studies ◽  
Bond Functionalization ◽  
Bond Forming ◽  
Decarboxylative Coupling

The manuscript describes a Pd-catalyzed reaction of benzylic electrophiles that gives para-substituted arene products. Mechanistic studies suggest a mechanism involving a dearomative C–C bond-forming step, followed by base-mediated rearomatization. This mechanism is uncommon and underappreciated in Pd-catalysis and further exploitation of this mechanism should enable access to other organic molecules.

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