Heterogeneous Metal Catalysis for the Environmentally Benign Synthesis of Medicinally Important Scaffolds, Intermediates, and Building Blocks

2021 ◽  
Vol 25 ◽  
Author(s):  
Maysa Ilamanova ◽  
Maxim Mastyugin ◽  
Christian Schäfer ◽  
Anne Kokel ◽  
Béla Török

: This account provides a broad overview of the application of solid metal catalysts in synthetic chemistry with a focus on the synthesis of medicinally important scaffolds or building blocks. Heterogeneous catalysis is a fundamental contributor to green or sustainable synthesis. Despite this, many synthetic chemists overwhelmingly focus on homogeneous methods, and due to their unfamiliarity with solid catalysts, many would not consider using them. The primary purpose of this work is to bring solid catalysts and their application possibilities to the attention of synthetic chemists in a format that focuses on reactions, thus building a bridge between the two sides for the benefit of sustainable applications and, eventually, the whole society. The two major parts of this account describe the common types of solid metal catalysts and the applications of these catalysts in sustainable synthesis. The first part gives an overview of the major types of solid metal catalysts, including common hydrogenation catalysts to metal nanoparticles. The second and more extensive part illustrates the use of these catalysts in a thematic order based on reaction types, including hydrogenation, hydrogenolysis, oxidation, metathesis, cross-coupling reactions, and hydroformylation.

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1349 ◽  
Author(s):  
Arnar Guðmundsson ◽  
Jan-E. Bäckvall

Transition metal catalysis in modern organic synthesis has largely focused on noble transition metals like palladium, platinum and ruthenium. The toxicity and low abundance of these metals, however, has led to a rising focus on the development of the more sustainable base metals like iron, copper and nickel for use in catalysis. Iron is a particularly good candidate for this purpose due to its abundance, wide redox potential range, and the ease with which its properties can be tuned through the exploitation of its multiple oxidation states, electron spin states and redox potential. This is a fact made clear by all life on Earth, where iron is used as a cornerstone in the chemistry of living processes. In this mini review, we report on the general advancements in the field of iron catalysis in organic chemistry covering addition reactions, C-H activation, cross-coupling reactions, cycloadditions, isomerization and redox reactions.


2008 ◽  
Vol 80 (3) ◽  
pp. 621-637 ◽  
Author(s):  
Rik R. Tykwinski ◽  
Mojtaba Gholami ◽  
Sara Eisler ◽  
Yuming Zhao ◽  
Frederic Melin ◽  
...  

During the past two decades, shape-persistent conjugated macrocycles with a broad spectrum of attributes and topologies have been synthesized. This includes macrocycles with remarkable electronic, optical, and supramolecular properties, as well as intriguing frameworks. Expanded radialenes are a class of conjugated shape-persistent macrocycles that arise from the formal insertion of acetylene units into a radialene framework. A related class of macrocycles, the expanded radiaannulenes, contains both endo- and exocyclic vinylene and vinylidene segments, respectively, and accordingly exhibits properties intermediate between radialenes and annulenes. Enyne building blocks have been developed that are suitable for forming a macrocyclic framework through a step-wise sequence of Pd-catalyzed cross-coupling reactions. This "building-block" approach allows us to explore a range of molecular architectures that will ultimately provide for an understanding of π-delocalization in these compounds. The synthesis and structural characterization of the first members of this new class of expanded radialenes and radiaannulenes are described.


2013 ◽  
Vol 85 (2) ◽  
pp. 377-384 ◽  
Author(s):  
Jeffrey S. Quesnel ◽  
Bruce A. Arndtsen

Multicomponent coupling reactions provide a method to combine several substrates in a single reaction. When coupled with transition-metal catalysis, these reactions can be used to both activate and control the assembly of multiple simple building blocks directly into useful products. This account will describe our work in this area, with a focus on the use of palladium catalysis as a tool to couple imines and CO with other substrates into a range of heterocyclic derivatives in one-step reactions.


2021 ◽  
Author(s):  
Lara Zetzsche ◽  
Jessica Yazarians ◽  
Suman Chakrabarty ◽  
Meagan Hinze ◽  
April Lukowski ◽  
...  

Despite their varied purposes, many indispensable molecules in medicine, materials, and asymmetric catalysis share a biaryl core. The necessity of joining arene building blocks to access these valuable compounds has inspired multiple approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task. Oxidative coupling of two C–H bonds offers an efficient strategy for the formation of a biaryl C–C bond, however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to small molecule- mediated methods by providing a paradigm with catalyst-controlled selectivity. In this article, we disclose a strategy for biocatalytic cross-coupling through oxidative C–C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyze cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site- selectivity, and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.


2019 ◽  
Vol 15 ◽  
pp. 1416-1424
Author(s):  
Ruben Pomar Fuentespina ◽  
José Angel Garcia de la Cruz ◽  
Gabriel Durin ◽  
Victor Mamane ◽  
Jean-Marc Weibel ◽  
...  

1,3-Enynes are important building blocks in organic synthesis and also constitute the key motif in various bioactive natural products and functional materials. However, synthetic approaches to stereodefined substituted 1,3-enynes remain a challenge, as they are limited to Wittig and cross-coupling reactions. Herein, stereodefined 1,3-enynes, including tetrasubstituted ones, were straightforwardly synthesized from cis or trans-alkynylated oxiranes in good to excellent yields by a one-pot cascade process. The procedure relies on oxirane deprotonation, borylation and a stereospecific rearrangement of the so-formed alkynyloxiranyl borates. This stereospecific process overall transfers the cis or trans-stereochemistry of the starting alkynyloxiranes to the resulting 1,3-enynes.


Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5427
Author(s):  
Larisa V. Politanskaya ◽  
Pavel A. Fedyushin ◽  
Tatyana V. Rybalova ◽  
Artem S. Bogomyakov ◽  
Nargiz B. Asanbaeva ◽  
...  

New stable polyfluorinated nitroxide radicals for use in cross-coupling reactions, namely, N-tert-butyl-N-oxyamino-2,3,5,6-tetrafluoro-4-iodobenzene and N-tert-butyl-N-oxyamino-2,3,5,6-tetrafluoro-4-ethynylbenzene, were prepared from perfluoroiodobenzene. The reaction of the polyfluoro derivative with tert-butylamine under autoclaving conditions leading to the formation of N-tert-butyl-2,3,5,6-tetrafluoro-4-iodoaniline proved to be the key stage of the whole process. The fluorinated tert-butyl iodophenyl nitroxide was found to form in a solid state via N–O···I halogen bonds, a one-dimensional assembly of the radicals. The acceptor role of the nitroxide group in the halogen bonding changes to a donor role when the nitroxide reacts with Cu(hfac)2. In the last case, zero-dimensional assembly prevails, giving a three-spin complex with axial coordinated nitroxide groups and, as a consequence, causing ferromagnetic intramolecular exchange interactions between Cu(II) and radical spins.


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