Marnix van der Kolk

Ligandless, telescoped, one-pot reductive Mizoroki-Heck reactions proceed smoothly and regioselectively in eco-friendly eutectic mixtures, and under aerobic conditions to yield 2-(hetero)aryl THF or THP derivatives in up to 95 % yield. Key intermediates have also been targeted in DES en route to pharmacologically relevant molecules.

Abstract

A Deep Eutectic Solvent, choline chloride/glycerol (1 : 2 mol mol⁻¹), proved to be an effective and sustainable reaction medium to promote telescoped, one-pot Mizoroki-Heck cross-coupling/reduction processes between 2,3-dihydrofuran or 3,4-dihydro-2H-pyran and several (hetero)aryl halides to easily access valuable 2-(hetero)aryl tetrahydrofuran (THF) or tetrahydropyran derivatives in up to 95 % yield. Notably, the whole transformation takes place under aerobic conditions, in the absence of additional ligands, and with a good substrate scope. The practicability of the method is also exemplified by the sustainable synthesis of two key THF derivatives, which are side chains of pharmacologically relevant inhibitors of Kv1.2 channel.

Abstract

Herein, a three component Catellani-type reaction catalyzed by the Palladium/Norbornene/CuI (Pd/NBE/CuI) cooperative system by using N-acylph-thalimides as acyl electrophiles is reported, which gives access to a series of aromatic ketones. The transformation is performable in the presence of water, albeit with decreased reaction yield. The additive CuI was crucial to facilitate the cleavage of C(O)−N bond of imide. This protocol showed broad substrate scope: both alkyl and aryl acyl groups could be installed at the ortho-position of aryl iodides; alkenes and boronic acids can be used as termination reagents.

Illustrated herein is a Pd(II) catalyzed one-pot direct difunc-tionalization of two distinct C(sp3)-H bonds [gem-ʹ-di-Me groups bearing aliphatic carboxylic acid] with bifunctional reagent (BFR) 2-iodo benzoic acid. The methyl 2-pyridyl sul-foximine (MPyS) bidentate directing group (DG), 2-chloro-5-trifluoromethyl ligand, and NaBrO3 co-oxidant combination helps the concerted metalation deprotonation (CMD) of inert C(sp3)-H bond as well reductive elimination steps; density functional theory (DFT) studies validate such insights. This process makes two [CC and CO] bonds of gem-ʹ-di-Me groups of DG-enabled aliphatic carboxylic acids in a single operation offering access to unusual benzo-fused peripheral substituted ω-membered lactones. This concept is uncovered for the first time. The transformation tolerates labile functional groups featuring broad scope with the construction of wide range of novel molecules of structural diversity. Ki-netic and control experiments study reveal the participation of monomeric-Pd-species on the catalytic cycle. Synthetic versatility of the complex molecular entities is also presented.

We report a Cu-catalysed oxidative coupling of aliphatic amines with alkylboronic esters to give high value alkyl amines, products found widely in applications from medicinal chemistry to materials science. This operationally simple reaction, which can be performed on gram scale, runs under mild conditions and exhibits excellent functional group tolerance. The terminal oxidant of the reaction is O2 from the air, avoiding the need for additional chemical oxidants. Investigation into the reaction mechanism suggests the intermediacy of an alkyl radical, generated from the boronic ester upon activation through an amino radical transfer process. To demonstrate its utility and potential for late-stage functionalization, we showcase the method as the final step in the total synthesis of a TRPV 1 antagonist.

Publication date: 2022

Source: Advances in Catalysis, Volume 70

Author(s): Arjan W. Kleij

Abstract

A coupling reaction of 2-iodobiphenyl with benzoisoxazole under the cooperative catalysis of Pd(CH₃CN)₂Cl₂ and P(4-F−Ph)₃ is disclosed. The reaction proceeds via intramolecular C−H activation/N−O cleavage/migratory insertion sequence to give an array of N-arylcarbazoles with an aldehyde or a ketone. The employment of benzoisoxazoles as an amination agent obviates the need for stoichiometric amount of oxidants.

Publication date: September 2022

Source: Journal of Catalysis, Volume 413

Author(s): Xingju Li, Siquan Feng, Xiangen Song, Qiao Yuan, Bin Li, Lili Ning, Weimiao Chen, Jingwei Li, Yunjie Ding

This Review summarizes the reported methods of direct C−H functionalization of furfurals without prior modification of the redox state of the aldehyde function. The aim is to illustrate the different approaches implemented for the functionalization of the C−H positions of the furan ring as well as of the aldehyde functional group.

Abstract

Furfural and related compounds are building blocks of industrial interest, obtained from raw biomass. Their use as precursors of basic and fine chemicals has gained increasing attention as a green alternative to petroleum-derived compounds. Several works have reported the functionalization of furfurals to obtain a wider range of chemicals, opening up new synthetic possibilities and applications, ranging from biofuels to pharmaceuticals. Among these works, processes based on C−H activation are the most attractive ones for their atom economy and the possibility to use non-activated substrates. This minireview summarizes the reported methods of direct C−H functionalization of furfurals without prior modification of the redox state of the aldehyde function. In particular, the transition metal catalyzed functionalization of each bond of the heteroaromatic nucleus of these molecules is systematically discussed, as well as examples of C−H transformations of the aldehyde function.

Abstract

A synthetic strategy for the installation of diversely functionalized quinones at the C4 position of indoles is developed via palladium-catalyzed C−H and double C−H functionalization. This synthetic protocol provides a rapid route to a variety of 4-quinonylindoles via the direct coupling of 3-formylindoles with quinones. Furthermore, this synthetic methodology also efficiently affords biologically interesting bis(indol-4-yl)quinones in good yields by direct one-pot double C−H activation of 3-formylindoles with the corresponding quinones.

Publication date: 1 March 2023

Source: Catalysis Today, Volumes 411–412

Author(s): Aliaksandr Karnitski, Jae-Wook Choi, Dong Jin Suh, Chun-Jae Yoo, Hyunjoo Lee, Kwang Ho Kim, Chang Soo Kim, Kyeongsu Kim, Jeong-Myeong Ha