scispace - formally typeset
Search or ask a question
Journal ArticleDOI

C-H Activation: Toward Sustainability and Applications.

02 Feb 2021-ACS central science (American Chemical Society (ACS))-Vol. 7, Iss: 2, pp 245-261
TL;DR: In this article, the authors highlight the research areas seeking to overcome the sustainability challenges of C-H activation: the pursuit of abundant metal catalysts, the avoidance of static directing groups, the replacement of metal oxidants, and the introduction of bioderived solvents.
Abstract: Since the definition of the "12 Principles of Green Chemistry" more than 20 years ago, chemists have become increasingly mindful of the need to conserve natural resources and protect the environment through the judicious choice of synthetic routes and materials. The direct activation and functionalization of C-H bonds, bypassing intermediate functional group installation is, in abstracto, step and atom economic, but numerous factors still hinder the sustainability of large-scale applications. In this Outlook, we highlight the research areas seeking to overcome the sustainability challenges of C-H activation: the pursuit of abundant metal catalysts, the avoidance of static directing groups, the replacement of metal oxidants, and the introduction of bioderived solvents. We close by examining the progress made in the subfield of aryl C-H borylation from its origins, through highly efficient but precious Ir-based systems, to emerging 3d metal catalysts. The future growth of this field will depend on industrial uptake, and thus we urge researchers to strive toward sustainable C-H activation.
Citations
More filters
Journal ArticleDOI
TL;DR: The unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation of C-H through the concomitant induction of the chiral information is reported, furnishing rare atropoisomeric C2-arylated indoles.
Abstract: Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is the most obvious disconnection to construct such compounds, the direct enantioselective C-H arylation through the concomitant induction of the chiral information remains extremely challenging and uncommon. Herein, the unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation is reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies and DFT computation revealed an uncommon mechanism for this asymmetric transformation, with the oxidative addition being the rate- and enantio-determining step. Excellent stereoselectivities were reached (up to 96% ee), while using an unusual N-heterocyclic carbene ligand bearing an essential remote substituent. Attractive dispersion interactions along with positive C-H---π interactions exerted by the ligand were identified as key factors to guarantee the excellent enantioselection.

46 citations

Journal ArticleDOI
TL;DR: This review summarises deuteration methods of various organic motifs containing C(sp2)-H and C( sp3)-H bonds utilizing C-H bond functionalisation as a key step along with a variety of catalysts, and exemplifies their biological relevance.
Abstract: C-H deuteration has been intricately developed to satisfy the urgent need for site-selectively deuterated organic frameworks. Deuteration has been primarily used to study kinetic isotope effects of reactions but recently its significance in pharmaceutical chemistry has been discovered. Deuterium labelled compounds have stolen the limelight since the inception of the first FDA-approved deuterated drug, for the treatment of chorea-associated Huntington's disease, and their pharmacological importance was realised by chemists, although surprisingly very late. Various approaches were developed to carry out site-selective deuteration. However, the most common and efficient method is hydrogen isotope exchange (HIE). This review summarises deuteration methods of various organic motifs containing C(sp2)-H and C(sp3)-H bonds utilizing C-H bond functionalisation as a key step along with a variety of catalysts, and exemplifies their biological relevance.

43 citations

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the advent and recent emerging strategies to improve the sustainability and environmentally benign nature of C-H activation manifolds, and discuss how to achieve high levels of resource economy in molecular syntheses.
Abstract: Transition metal catalyzed C–H activation has surfaced as a powerful tool to improve the efficacy of molecular synthesis. Last two decades have witnessed a considerable progress in the activation of otherwise inert C–H bonds. However, during recent years, focus has shifted to address rising concerns to achieve high levels of resource economy in molecular syntheses. Herein, we discuss the advent and recent emerging strategies to improve the sustainability and environmentally benign nature of C–H activation manifolds.

39 citations

Journal ArticleDOI
14 Oct 2021-Chem
TL;DR: A review of modern strategies for the C-H functionalization of heteroarenes with these alternative coupling partners can be found in this paper, where some non-catalytic strategies involving new reagents and techniques are also introduced.

37 citations

References
More filters
Journal ArticleDOI
06 Dec 1991-Science
TL;DR: Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal.
Abstract: Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.

3,830 citations

Journal ArticleDOI
TL;DR: The concepts of design and the scientific philosophy of Green Chemistry are covered with a set of illustrative examples and the challenge of using the Principles as a cohesive design system is discussed.
Abstract: Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).

2,942 citations

Journal ArticleDOI
TL;DR: The ability of transition metal complexes to preorganize π-electron systems serves as the basis both of simple additions usually accompanied by subsequent hydrogen shifts and of cycloadditions as mentioned in this paper.
Abstract: Enhancing the efficiency of the synthesis of complex organic products constitutes one of the most exciting challenges to the synthetic chemist. Increasing the catalogue of reactions that are simple additions or that minimize waste production is the necessary first step. Transition metal complexes, which can be tunable both electronically and sterically by varying the metal and/or ligands, are a focal point for such invention. Except for catalytic hydrogenation, such methods have been rare in complex synthesis and virtually unknown for CC bond formation until the advent of cross-coupling reactions. These complexes may orchestrate a variety of CC bond-forming processes, important for creation of the basic skeleton of the organic structure. Their ability to insert into CH bonds primes a number of different types of additions to relatively nonpolar π-electron systems. Besides imparting selectivity, they make feasible reactions that uncatalyzed were previously unknown. The ability of these complexes to preorganize π-electron systems serves as the basis both of simple additions usually accompanied by subsequent hydrogen shifts and of cycloadditions. The ability to generate “reactive” intermediates under mild conditions also provides prospects for new types of CC bond-forming reactions. While the examples reveal a diverse array of successes, the opportunities for new invention are vast and largely untapped.

2,223 citations

Journal ArticleDOI
TL;DR: This critical review summarizes and discusses endeavours towards the development of mild C-H activation methods and wishes to trigger more research towards this goal.
Abstract: Functionalizing traditionally inert carbon–hydrogen bonds represents a powerful transformation in organic synthesis, providing new entries to valuable structural motifs and improving the overall synthetic efficiency. C–H bond activation, however, often necessitates harsh reaction conditions that result in functional group incompatibilities and limited substrate scope. An understanding of the reaction mechanism and rational design of experimental conditions have led to significant improvement in both selectivity and applicability. This critical review summarizes and discusses endeavours towards the development of mild C–H activation methods and wishes to trigger more research towards this goal. In addition, we examine select examples in complex natural product synthesis to demonstrate the synthetic utility of mild C–H functionalization (84 references).

2,137 citations

Journal ArticleDOI
TL;DR: This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry, and are more atom- and step-economical than previous methods.
Abstract: The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry.

1,838 citations