7 research outputs found
Microwave Heated Continuous Flow Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones
A protocol
for Pd(II)-catalyzed desulfitative synthesis of aryl
ketones from sodium aryl sulfinates and nitriles in continuous flow
has been developed. The reactions proceed with microwave heating using
microwave transparent tube reactors, affording the desired aryl ketones
in fair to good yields. Microwave transparent aluminum oxide reactors
were identified as a safe and thermostable alternative to borosilicate
glass reactors
Continuous Flow Synthesis under High-Temperature/High-Pressure Conditions Using a Resistively Heated Flow Reactor
A cheap,
easy-to-build, and effective resistively heated reactor
for continuous flow synthesis at high temperature and pressure is
herein presented. The reactor is rapidly heated directly using an
electric current and is capable of rapidly delivering temperatures
and pressures up to 400 °C and 200 bar, respectively. High-temperature
and high-pressure applications of this reactor were safely performed
and demonstrated by selected transformations such as esterifications,
transesterifications, and direct carboxylic acid to nitrile reactions
using supercritical ethanol, methanol, and acetonitrile. Reaction
temperatures were between 300 and 400 °C with excellent conversions
and good to excellent isolated product yields. Examples of Diels–Alder
reactions were also carried out at temperatures up to 300 °C
in high yield. No additives or catalysts were used in the reactions
Direct Palladium(II)-Catalyzed Synthesis of Arylamidines from Aryltrifluoroborates
A fast and convenient synthesis of arylamidines starting from readily available potassium aryltrifluoroborates and cyanamides is reported. The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O<sub>2</sub>CCF<sub>3</sub>), 6-methyl-2,2′-bipyridyl, TFA, and MeOH, providing the corresponding arylamidines in moderate to excellent yields
Microwave Promoted Transcarbamylation Reaction of Sulfonylcarbamates under Continuous-Flow Conditions
Successful conditions for the transcarbamylation/transesterification
reaction of sulfonylcarbamates with alcohols by microwave heating
under continuous-flow conditions were developed. After optimization
of the processes, two series of <i>O</i>-alkylsulfonylcarbamates
were obtained in high yields and purities using microwave transparent
borosilicate tube reactors. In order to also illustrate the usefulness
of the protocol in a medicinal chemistry context, the methodology
was used for the synthesis of three angiotensin II type 2 receptor
ligands
Selective Synthesis of Spirooxindoles by an Intramolecular Heck–Mizoroki Reaction
We report a highly diastereoselective
synthesis of cyclopentene–spirooxindole
derivatives via an intramolecular Heck–Mizoroki reaction using
aryl bromides as precursors. The reactions were performed under dry
conditions or in a DMF–water system. This protocol can be useful
to introduce several functionalities to the aromatic nucleus of the
spirooxindoles. DFT calculations were performed to rationalize the
high antiselectivity. A functionalized spiroproduct was transformed
into a cyclic amino acid derivative
Theoretical and Experimental Investigation of Palladium(II)-Catalyzed Decarboxylative Addition of Arenecarboxylic Acid to Nitrile
The reaction mechanism of palladium(II)-catalyzed decarboxylative
addition of 2,6-dimethoxybenzoic acid to acetonitrile was investigated
by means of density functional theory (DFT) calculations. Calculations
of the free energy profile for decarboxylation and carbopalladation
indicated carbopalladation as the rate-determining step of the reaction.
Investigation of the free energy profile for a series of experimentally
evaluated nitrogen-based bidentate palladium ligands revealed that
higher energy is required for decarboxylation and carbopalladation
employing the experimentally least efficient ligand. The DFT investigation
also showed that the relative free energies of the transition states
were lowered in polar solvent, and preparative experiments confirmed
that a nonoptimal ligand could be greatly improved by addition of
water to the reaction system
Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones from Sodium Arylsulfinates and Nitriles: Scope, Limitations, and Mechanistic Studies
A fast
and efficient protocol for the palladium(II)-catalyzed production
of aryl ketones from sodium arylsulfinates and various organic nitriles
under controlled microwave irradiation has been developed. The wide
scope of the reaction has been demonstrated by combining 14 sodium
arylsulfinates and 21 nitriles to give 55 examples of aryl ketones.
One additional example illustrated that, through the choice of the
nitrile reactant, benzofurans are also accessible. The reaction mechanism
was investigated by electrospray ionization mass spectrometry and
DFT calculations. The desulfitative synthesis of aryl ketones from
nitriles was also compared to the corresponding transformation starting
from benzoic acids. Comparison of the energy profiles indicates that
the free energy requirement for decarboxylation of 2,6-dimethoxybenzoic
acid and especially benzoic acid is higher than the corresponding
desulfitative process for generating the key aryl palladium intermediate.
The palladium(II) intermediates detected by ESI-MS and the DFT calculations
provide a detailed understanding of the catalytic cycle