86618-05-5Relevant academic research and scientific papers
Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide-Functionalized Phosphine Ligands
Hu, Zhiyong,Wei, Xiao-Jing,Handelmann, Jens,Seitz, Ann-Katrin,Rodstein, Ilja,Gessner, Viktoria H.,Goo?en, Lukas J.
supporting information, p. 6778 - 6783 (2021/02/01)
The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
MIDA boronate allylation-synthesis of ibuprofen
Brodie, Glen,France, David J.,Memarzadeh, Sarah,Phillips, David,Tang, Gi Lum
, p. 30624 - 30630 (2020/09/11)
MIDA boronates are among the most useful reagents for the Suzuki-Miyaura reaction. This chemistry typically generates new bonds between two aromatic rings, thereby restricting access to important areas of chemical space. Here we demonstrate the coupling of MIDA boronates to allylic electrophiles, including a new synthesis of the well-known COX inhibitor ibuprofen. This journal is
A chemoselective Reformatsky-Negishi approach to α-haloaryl esters
Wong, Brian,Linghu, Xin,Crawford, James J.,Drobnick, Joy,Lee, Wendy,Zhang, Haiming
, p. 1508 - 1515 (2014/02/14)
A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)2 and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.
Use of a robust dehydrogenase from an archael hyperthermophile in asymmetric catalysis-dynamic reductive kinetic resolution entry into (s)-profens
Friest, Jacob A.,Maezato, Yukari,Broussy, Sylvain,Blum, Paul,Berkowitz, David B.
supporting information; experimental part, p. 5930 - 5931 (2010/07/05)
Described is an efficient heterologous expression system for Sulfolobus solfataricus ADH-10 (Alcohol Dehydrogenase isozyme 10) and its use in the dynamic reductive kinetic resolution (DYRKR) of 2-arylpropanal (Profen-type) substrates. Importantly, among the 12 aldehydes tested, a general preference for the (S)-antipode was observed, with high ee's for substrates corresponding to the NSAIDs (nonsteroidal anti-inflammatory drugs) naproxen, ibuprofen, flurbiprofen, ketoprofen, and fenoprofen. To our knowledge, this is the first application of a dehydrogenase from this Sulfolobus hyperthermophile to asymmetric synthesis and the first example of a DYRKR with such an enzyme. The requisite aldehydes are generated by Buchwald-Hartwig-type Pd(0)-mediated α-arylation of tert-butyl propionate. This is followed by reduction to the aldehyde in one [lithium diisobutyl tert-butoxyaluminum hydride (LDBBA)] or two steps [LAH/Dess-Martin periodinane]. Treatment of the profenal substrates with SsADH in 5% EtOH/phosphate buffer, pH 9, with catalytic NADH at 80 °C leads to efficient DYRKR, with ee's exceeding 90% for 9 aryl side chains, including those of the aforementioned NSAIDs. An in silico model, consistent with the observed broad side chain tolerance, is presented. Importantly, the SsADH-10 enzyme could be conveniently recycled by exploiting the differential solubility of the organic substrate/product at 80 °C and at rt. Pleasingly, SsADH-10 could be taken through several thermal cycles, without erosion of ee, suggesting this as a generalizable approach to enzyme recycling for hyperthermophilic enzymes. Moreover, the robustness of this hyperthermophilic DH, in terms of both catalytic activity and stereochemical fidelity, speaks for greater examination of such archaeal enzymes in asymmetric synthesis.
Effect of group substitution on the physiochemical properties of ibuprofen prodrugs
Bansal,Khar,Dubey,Sharma
, p. 422 - 424 (2007/10/02)
A series of alkyl ester prodrugs of ibuprofen was synthesized and studied for its physicochemical properties like aqueous solubility, octanol-water partition coefficient and hydrolysis kinetics in aqueous buffer and human plasma. These physicochemical parameters have a forebearing on the overall activity profile of these prodrugs. Mathematical relationships have been derived to characterize these properties.
A simple one-pot synthesis of 2-aryl-propionic t-butyl esters by carbonylation
Prasad, Chalasani S N,Adapa, Srinivas R
, p. 1067 - 1068 (2007/10/02)
A mild and convenient, one-pot synthetic laboratory procedure for t-butoxycarbonylation of arylhalogenoethyl derivatives is described.
A new mild method for the synthesis of esters and benzenethiol esters by activation of pyridine-2-thiol or benzothiazol-2-thiol esters by methyl iodide
Ravi,Mereyala
, p. 6089 - 6090 (2007/10/02)
Activation of in-situ generated pyridine-2-thiol or benzothiazol-2-thiol esters by methyl iodide at room temperature in presence of alcohols and benzenethiol yields the corresponding esters and thiol esters.
