On the Mechanism of the Nickel-Catalyzed Boron Insertion into the C−O Bond of Benzofuran

2019 ◽  
Author(s):  
Ana Mateo-Martínez ◽  
Hayate Saito ◽  
Hideki Yorimitsu ◽  
Carles Bo
Keyword(s):  
Reductive Elimination ◽  
Nucleophilic Attack ◽  
Dft Studies ◽  
Reaction Conditions ◽  
Elementary Steps

<p>The reaction of benzofurans with diboron reagents and Cs<sub>2</sub>CO<sub>3</sub>catalyzed by Ni(0) complexes results in the insertion of boron into the C-O bond. The reaction conditions mimic those reported by Martin and Hosoya for borylating aryl C-F bonds, but neither the role of the base nor the sequence of elementary steps is clear. Herein we report on the mechanism of such transformation on the basis of DFT studies, which suggest that the base activates the diboron reagent and generates a reactive boryl group, that Ni(II) is reduced back to Ni(0) during the boryl insertion into the Ni-O bond, and that the classical reductive elimination step is best viewed as a ring-contracting nucleophilic attack. </p>

On the Mechanism of the Nickel-Catalyzed Boron Insertion into the C−O Bond of Benzofuran

2019 ◽  
Author(s):  
Ana Mateo-Martínez ◽  
Hayate Saito ◽  
Hideki Yorimitsu ◽  
Carles Bo
Keyword(s):  
Reductive Elimination ◽  
Nucleophilic Attack ◽  
Dft Studies ◽  
Reaction Conditions ◽  
Elementary Steps

<p>The reaction of benzofurans with diboron reagents and Cs<sub>2</sub>CO<sub>3</sub>catalyzed by Ni(0) complexes results in the insertion of boron into the C-O bond. The reaction conditions mimic those reported by Martin and Hosoya for borylating aryl C-F bonds, but neither the role of the base nor the sequence of elementary steps is clear. Herein we report on the mechanism of such transformation on the basis of DFT studies, which suggest that the base activates the diboron reagent and generates a reactive boryl group, that Ni(II) is reduced back to Ni(0) during the boryl insertion into the Ni-O bond, and that the classical reductive elimination step is best viewed as a ring-contracting nucleophilic attack. </p>

scholarly journals The Mechanism of Rhodium Catalyzed Allylic C–H Amination

2019 ◽  
Author(s):  
Robert Harris ◽  
Jiyong Park ◽  
Taylor Nelson ◽  
Nafees Iqbal ◽  
Daniel Salgueiro ◽  
...  
Keyword(s):  
Acid Catalyst ◽  
Reductive Elimination ◽  
Quantum Mechanical ◽  
Allylic Amination ◽  
Reaction Conditions ◽  
Allyl Complex ◽  
Acetate Ligand ◽  
Amination Reaction ◽  
Lewis Acid Catalyst

The mechanism of catalytic allylic C–H amination reactions promoted by Cp*Rh complexes is reported. Reaction kinetics experiments, stoichiometric studies, and DFT calculations demonstrate that allylic C–H activation to generate a Cp*Rh(π-allyl) complex is viable under mild reaction conditions. The role of external oxidant in the catalytic cycle is elucidated. Quantum mechanical calculations, stoichiometric reactions, and cyclic voltammetry<b></b>experiments support an oxidatively induced reductive elimination process of the allyl fragment with an acetate ligand. Lastly, evidences supporting the amination of an allylic acetate intermediate is presented. Both nucleophilic substitution catalyzed by Ag<sup>+</sup>that behaves as a Lewis acid catalyst and an inner-sphere amination catalyzed by Cp*Rh are shown to be viable for the last step of the allylic amination reaction.

scholarly journals Mechanistic Studies of Pd-Catalyzed Fluorination of Cyclic Vinyl Triflates: Evidence for in situ Ligand Modification

2021 ◽  
Author(s):  
Yuxuan Ye ◽  
Seoung-Tae Kim ◽  
Ryan P. King ◽  
Mu-Hyun Baik ◽  
Stephen L. Buchwald
Keyword(s):  
Trans Isomer ◽  
Computational Study ◽  
Reductive Elimination ◽  
Nucleophilic Attack ◽  
Ligand Modification ◽  
Low Efficiency ◽  
Vinyl Triflates ◽  
Nucleophilic Fluorination

<div><div><div><p>Pd-catalyzed nucleophilic fluorination reactions are important methods for the synthesis of fluoroarenes and fluoroalkenes. However, these reactions can generate a mixture of regioisomeric products that are often difficult to separate. While investigating the Pd- catalyzed fluorination of cyclic vinyl triflates, we observed that the addition of a substoichiometric quantity of TESCF3 significantly improves both the efficiency and the regioselectivity of the fluorination process. Herein, we report a combined experimental and computational study on the mechanism of this transformation focused on the role of TESCF3. We found that in the absence of additives such as TESCF3, the transmetalation step produces predominantly the thermodynamically more stable trans isomer of the key LPd(vinyl)F complex (L = biaryl monophosphine ligand). This intermediate, rather than undergoing reductive elimination, preferentially reacts through an intramolecular β-deprotonation to form a Pd-cyclohexyne intermediate. This undesired reactivity is responsible for the low efficiency (11% yield) and poor regioselectivity (1.8:1) of the catalytic reaction. When TESCF3 is added to the reaction mixture, the cis-LPd(vinyl)F complex is instead formed, through a pathway involving an unusual dearomatization of the ligand by nucleophilic attack from a trifluoromethyl anion (CF3–). In contrast to the trans isomer, this cis-LPd(vinyl)F complex readily undergoes reductive elimination to provide the vinyl fluoride product with desired regioselectivity, without the generation of Pd-cyclohexyne intermediates.</p></div></div></div>

scholarly journals Mechanistic Studies of Pd-Catalyzed Fluorination of Cyclic Vinyl Triflates: Evidence for in situ Ligand Modification

2021 ◽  
Author(s):  
Yuxuan Ye ◽  
Seoung-Tae Kim ◽  
Ryan P. King ◽  
Mu-Hyun Baik ◽  
Stephen L. Buchwald
Keyword(s):  
Trans Isomer ◽  
Computational Study ◽  
Reductive Elimination ◽  
Nucleophilic Attack ◽  
Ligand Modification ◽  
Low Efficiency ◽  
Vinyl Triflates ◽  
Nucleophilic Fluorination

<div><div><div><p>Pd-catalyzed nucleophilic fluorination reactions are important methods for the synthesis of fluoroarenes and fluoroalkenes. However, these reactions can generate a mixture of regioisomeric products that are often difficult to separate. While investigating the Pd- catalyzed fluorination of cyclic vinyl triflates, we observed that the addition of a substoichiometric quantity of TESCF3 significantly improves both the efficiency and the regioselectivity of the fluorination process. Herein, we report a combined experimental and computational study on the mechanism of this transformation focused on the role of TESCF3. We found that in the absence of additives such as TESCF3, the transmetalation step produces predominantly the thermodynamically more stable trans isomer of the key LPd(vinyl)F complex (L = biaryl monophosphine ligand). This intermediate, rather than undergoing reductive elimination, preferentially reacts through an intramolecular β-deprotonation to form a Pd-cyclohexyne intermediate. This undesired reactivity is responsible for the low efficiency (11% yield) and poor regioselectivity (1.8:1) of the catalytic reaction. When TESCF3 is added to the reaction mixture, the cis-LPd(vinyl)F complex is instead formed, through a pathway involving an unusual dearomatization of the ligand by nucleophilic attack from a trifluoromethyl anion (CF3–). In contrast to the trans isomer, this cis-LPd(vinyl)F complex readily undergoes reductive elimination to provide the vinyl fluoride product with desired regioselectivity, without the generation of Pd-cyclohexyne intermediates.</p></div></div></div>

scholarly journals The Mechanism of Rhodium Catalyzed Allylic C–H Amination

2019 ◽  
Author(s):  
Robert Harris ◽  
Jiyong Park ◽  
Taylor Nelson ◽  
Nafees Iqbal ◽  
Daniel Salgueiro ◽  
...  
Keyword(s):  
Acid Catalyst ◽  
Reductive Elimination ◽  
Quantum Mechanical ◽  
Allylic Amination ◽  
Reaction Conditions ◽  
Allyl Complex ◽  
Acetate Ligand ◽  
Amination Reaction ◽  
Lewis Acid Catalyst

The mechanism of catalytic allylic C–H amination reactions promoted by Cp*Rh complexes is reported. Reaction kinetics experiments, stoichiometric studies, and DFT calculations demonstrate that allylic C–H activation to generate a Cp*Rh(π-allyl) complex is viable under mild reaction conditions. The role of external oxidant in the catalytic cycle is elucidated. Quantum mechanical calculations, stoichiometric reactions, and cyclic voltammetry<b></b>experiments support an oxidatively induced reductive elimination process of the allyl fragment with an acetate ligand. Lastly, evidences supporting the amination of an allylic acetate intermediate is presented. Both nucleophilic substitution catalyzed by Ag<sup>+</sup>that behaves as a Lewis acid catalyst and an inner-sphere amination catalyzed by Cp*Rh are shown to be viable for the last step of the allylic amination reaction.

Microbial Bioconversion: A Regio-specific Method for Novel Drug Design and Toxicological Study of Metabolites

2019 ◽  
Vol 20 (14) ◽  
pp. 1156-1162
Author(s):  
Maria Yousuf ◽  
Waqas Jamil ◽  
Khayala Mammadova
Keyword(s):  
Microbial Transformation ◽  
Specific Method ◽  
Reaction Conditions ◽  
Small Organic Molecules ◽  
Toxicological Studies ◽  
Drug Designing ◽  
Transformation Methods ◽  
Novel Drug

The methods of chemical structural alteration of small organic molecules by using microbes (fungi, bacteria, yeast, etc.) are gaining tremendous attention to obtain structurally novel and therapeutically potential leads. The regiospecific mild environmental friendly reaction conditions with the ability of novel chemical structural modification in compounds categorize this technique; a distinguished and unique way to obtain medicinally important drugs and their in vivo mimic metabolites with costeffective and timely manner. This review article shortly addresses the immense pharmaceutical importance of microbial transformation methods in drug designing and development as well as the role of CYP450 enzymes in fungi to obtain in vivo drug metabolites for toxicological studies.

TBAI Catalyzed Electrochemical C-H Bond Activation of 2-arylated-N-methoxyamides for the Synthesis of Phenanthridinones

Synlett ◽  
2021 ◽  
Author(s):  
Kripa Subramanian ◽  
Subhash L. Yedage ◽  
Kashish Sethi ◽  
Bhalchandra M. Bhanage
Keyword(s):  
Electrochemical Method ◽  
Bond Activation ◽  
Supporting Electrolyte ◽  
Bioactive Compound ◽  
Reaction Conditions ◽  
Redox Catalyst ◽  
Synthetic Utility ◽  
One Step ◽  
Constant Potential

An electrochemical method for the synthesis of phenanthridinones via constant potential electrolysis (CPE) mediated by <i>n</i>-Bu<sub>4</sub>NI (TBAI) has been reported. The protocol is metal and oxidant free and proceeds with 100% current efficiency. Here TBAI plays the dual role of the redox catalyst as well as supporting electrolyte. The intramolecular C-H activation proceeds under mild reaction conditions and short reaction time via electrochemically generated amidyl radicals. The reaction has been scaled up to gram level showing its practicability and the synthetic utility and applicability of the protocol has been demonstrated by the direct one-step synthesis of the bioactive compound Phenaglaydon.

N-Chlorinative Ring Contraction of 1,4-Dimethoxyphthalazines via a Bicyclization/Ring-Opening Mechanism

Synthesis ◽  
2020 ◽  
Author(s):  
Jeong Kyun Im ◽  
Ilju Jeong ◽  
Jun-Ho Choi ◽  
Won-jin Chung ◽  
ByeongDo Yang ◽  
...  
Keyword(s):  
Ring Opening ◽  
Reaction Conditions ◽  
Ring Contraction ◽  
Silyl Group ◽  
Favorskii Rearrangement ◽  
Mechanistic Analysis ◽  
Group A ◽  
Overall Efficiency ◽  
Trichloroisocyanuric Acid

AbstractAn unprecedented N-chlorinative ring contraction of 1,2-diazines was discovered and investigated with an electrophilic chlorinating reagent, trichloroisocyanuric acid (TCICA). Through optimization and mechanistic analysis, the assisting role of n-Bu4NCl as an exogenous nucleophile was identified, and the optimized reaction conditions were applied to a range of 1,4-dimethoxyphthalazine derivatives. Also, an improvement of overall efficiency was demonstrated by the use of a labile O-silyl group. A bicyclization/ring-opening mechanism, inspired by the Favorskii rearrangement, was proposed and supported by the DFT calculations. Furthermore, the efforts on scope expansion as well as the evaluation of other electrophilic promoters revealed that the newly developed ring contraction reactivity is a unique characteristic of 1,4-dimethoxyphthalazine scaffold and TCICA.

scholarly journals Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

2016 ◽  
Vol 12 ◽  
pp. 2588-2601 ◽  
Author(s):  
Vladimir A Stepchenko ◽  
Anatoly I Miroshnikov ◽  
Frank Seela ◽  
Igor A Mikhailopulo
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Reaction Conditions ◽  
E Coli ◽  
No Formation ◽  
Structural Peculiarities ◽  
Substrate Properties ◽  
Nucleoside Phosphorylases ◽  
Derivatives Of

The trans-2-deoxyribosylation of 4-thiouracil (4SUra) and 2-thiouracil (2SUra), as well as 6-azauracil, 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases. 4SUra revealed satisfactory substrate activity for UP and, unexpectedly, complete inertness for TP; no formation of 2’-deoxy-2-thiouridine (2SUd) was observed under analogous reaction conditions in the presence of UP and TP. On the contrary, 2SU, 2SUd, 4STd and 2STd are good substrates for both UP and TP; moreover, 2SU, 4STd and 2’-deoxy-5-azacytidine (Decitabine) are substrates for PNP and the phosphorolysis of the latter is reversible. Condensation of 2SUra and 5-azacytosine with dRib-1P (Ba salt) catalyzed by the accordant UP and PNP in Tris∙HCl buffer gave 2SUd and 2’-deoxy-5-azacytidine in 27% and 15% yields, respectively. 6-Azauracil and 6-azathymine showed good substrate properties for both TP and UP, whereas only TP recognizes 2-thio-6-azathymine as a substrate. 5-Phenyl and 5-tert-butyl derivatives of 6-azauracil and its 2-thioxo derivative were tested as substrates for UP and TP, and only 5-phenyl- and 5-tert-butyl-6-azauracils displayed very low substrate activity. The role of structural peculiarities and electronic properties in the substrate recognition by E. coli nucleoside phosphorylases is discussed.

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