Mechanistic Studies of Pd-Catalyzed Regioselective Aryl CH Bond Functionalization with Strained Alkenes: Origin of Regioselectivity

2011 ◽  
Vol 17 (29) ◽  
pp. 8175-8188 ◽  
Author(s):  
David I. Chai ◽  
Praew Thansandote ◽  
Mark Lautens
Keyword(s):  
Mechanistic Studies ◽  
Bond Functionalization ◽  
Strained Alkenes

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.

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.

Unactivated C(sp3)–H Bond Functionalization of Alkyl Nitriles with Vinylarenes and Mechanistic Studies

2016 ◽  
Vol 18 (23) ◽  
pp. 5986-5989 ◽  
Author(s):  
Xing-Wang Lan ◽  
Nai-Xing Wang ◽  
Cui-Bing Bai ◽  
Cui-Lan Lan ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Mechanistic Studies ◽  
Bond Functionalization

scholarly journals Mechanistic Studies on Gold-Catalyzed Direct Arene C–H Bond Functionalization by Carbene Insertion: The Coinage-Metal Effect

2016 ◽  
Vol 36 (1) ◽  
pp. 172-179 ◽  
Author(s):  
Manuel R. Fructos ◽  
Maria Besora ◽  
Ataualpa A. C Braga ◽  
M. Mar Díaz-Requejo ◽  
Feliu Maseras ◽  
...  
Keyword(s):  
Mechanistic Studies ◽  
Coinage Metal ◽  
Bond Functionalization ◽  
Carbene Insertion ◽  
Metal Effect

scholarly journals Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhe Chang ◽  
Jialin Huang ◽  
Si Wang ◽  
Geshuyi Chen ◽  
Heng Zhao ◽  
...  
Keyword(s):  
Natural Products ◽  
Chemical Synthesis ◽  
Late Stage ◽  
Nitrogen Heterocycles ◽  
Pharmaceutical Chemistry ◽  
Nitrogen Heterocycle ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Bond Functionalization ◽  
Modern Chemical

AbstractNitrogen heterocycle represents a ubiquitous skeleton in natural products and drugs. Late-stage C(sp3)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of particular significance to modern chemical synthesis and pharmaceutical chemistry. Here, we demonstrate copper-catalysed late-stage C(sp3)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions. We have investigated 8 types of N-heterocycles which are usually found as medicinally important skeletons. The scope and utility of this approach are demonstrated by late-stage C(sp3)-H modification of these heterocycles including a number of pharmaceuticals with a broad range of nucleophiles, e.g. methylation, arylation, azidination, mono-deuteration and glycoconjugation etc. Preliminary mechanistic studies reveal that the reaction undergoes a C-H fluorination process which is followed by a nucleophilic substitution.

Temporal and mechanistic studies on the resistance of glioma cells to temozolomide

2016 ◽  
Vol 228 (06/07) ◽  
Author(s):  
WP Roos ◽  
M Eich ◽  
S Quiros ◽  
AV Knizhnik ◽  
T Nikolova ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Mechanistic Studies

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>

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