Showing papers in "Organic and Biomolecular Chemistry in 2018"
TL;DR: This review will focus on the sudden outburst of literature regarding the use of small organic molecules as photocatalysts after 2013, and focuses on acridinium salts, benzophenones, pyrylium salt, thioxanthone derivatives, phenylglyoxylic acid, BODIPYs, flavin derivatives, and classes of organic molecule as catalysts for the photoc atalytic generation of C-C and C-X bonds.
Abstract: Photocatalysis, the use of light to promote organic transformations, is a field of catalysis that has received limited attention despite existing for over 100 years. With the revolution of photoredox catalysis in 2008, the rebirth or awakening of the field of photoorganocatalysis has brought new ideas and reactions to organic synthesis. This review will focus on the sudden outburst of literature regarding the use of small organic molecules as photocatalysts after 2013. In particular, it will focus on acridinium salts, benzophenones, pyrylium salts, thioxanthone derivatives, phenylglyoxylic acid, BODIPYs, flavin derivatives, and classes of organic molecules as catalysts for the photocatalytic generation of C-C and C-X bonds.
182 citations
TL;DR: The main topic of the present review is the synthesis of 'polyheterocycles' via a direct MCR or via a one-pot process involving MCRs coupled to further cyclizations (via ionic, metal-catalyzed, pericyclic, or free-radical-mediated cyclizations).
Abstract: Polyheterocycles are one of the most desired synthetic targets due to their numerous and valuable applications in various fields. Multicomponent reactions (MCRs) are highly convergent one-pot processes, in which three or more reagents are combined sequentially to construct complex products, with almost all the atoms coming from the starting reagents. In this context, the syntheses of 'heterocycles' via MCR-based processes have been reviewed a number of times. However, there is not a single review (recent or otherwise) covering the synthesis of 'polyheterocycles' via a direct MCR or via a one-pot process involving MCRs coupled to further cyclizations (via ionic, metal-catalyzed, pericyclic, or free-radical-mediated cyclizations). This issue is consequently the main topic of the present review, which considers work from the last decade. The work is categorized according to the key processes involved in the syntheses of polyheterocycles, aiming to give readers an easy understanding of this MCR-based chemistry and to provide insights for further investigations. The reaction mechanisms providing novel elements to these MCR-based methods for the synthesis of polyheterocycles are also discussed.
159 citations
TL;DR: This review mainly focuses on the recent advances in the synthesis of cyclopropanes classified by the type of catalytic system, including regio-, diastereo-, and enantio-selective reactions.
Abstract: Cyclopropanes, one of the most important strained rings, have gained much attention for more than a century because of their interesting and unique reactivity They not only exist in many natural products, but have also been widely used in the fields of organic synthesis, medicinal chemistry and materials science as versatile building blocks Based on the sustainable development in this area, this review mainly focuses on the recent advances in the synthesis of cyclopropanes classified by the type of catalytic system, including regio-, diastereo-, and enantio-selective reactions
135 citations
TL;DR: This review will discuss the recent major developments in the catalytic enantioselective synthesis of chiral spiropyrrolidine derivatives since 2009.
Abstract: Spirocyclic pyrrolidines are structural motifs frequently found in a wide variety of natural products, pharmaceuticals and biologically significant compounds. In the past few years, catalytic asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides have shown to be one of the most straightforward methods for the stereoselective preparation of diverse biologically important spiropyrrolidine heterocycles in high yields with excellent enantioselectivities under mild reaction conditions. In this review, we will discuss the recent major developments in the catalytic enantioselective synthesis of chiral spiropyrrolidine derivatives since 2009.
134 citations
TL;DR: Recently, gem-diborylalkanes have attracted much attention as versatile building blocks and fundamental intermediates in organic synthesis, because they enable multiple C-C bond construction and further transformation at C-B bonds.
Abstract: Recently, gem-diborylalkanes have attracted much attention as versatile building blocks and fundamental intermediates in organic synthesis, because they enable multiple C-C bond construction and further transformation at C-B bonds. Importantly, gem-diborylalkanes can be utilised as bisnucleophilic partners in a variety of chemo-selective C-C bond-forming reactions. This review describes recent developments in synthesising gem-diborylalkanes in complex molecules along with their chemical transformation. In the first part of the review the different synthetic approaches used to synthesise gem-diborylalkanes are described. In the second part, an overview of the chemoselective transformation of gem-diborylalkanes into various functionalized materials is discussed along with one-carbon homologation of diborylmethane via a selective uni- and bidirectional method.
133 citations
TL;DR: Chiral spiro phosphoric acids as chiral proton-transfer shuttle (CPTS) catalysts are proven to be efficient catalysts for the proton transfer of active intermediates in carbene insertion reactions, and upon combining with achiral dirhodium catalysts, the CPTS catalysts accomplish highly enantioselective insertions of N-h, S-H, and C-H bonds.
Abstract: Transition metal-catalyzed carbene insertion into X-H bonds (X = N, O, S, and C) represents a typical carbene transfer reaction and has been widely used in organic synthesis. The enantioselectivity-determining step in some of these insertion reactions is the proton transfer of active intermediates such as ylides, metal enolates, or free enols. Since most of the traditional chiral transition metal catalysts tend to dissociate from these active intermediates and cannot be involved in the proton-transfer step, enantiocontrol of these insertion reactions has long been a challenging task. Since 2011, we have developed chiral spiro phosphoric acids as chiral proton-transfer shuttle (CPTS) catalysts, which have been proven to be efficient catalysts for the proton transfer of active intermediates in carbene insertion reactions. Upon combining with achiral dirhodium catalysts, the CPTS catalysts accomplish highly enantioselective insertions of N-H, S-H, and C-H bonds. Herein, a number of important chiral building blocks, including α-amino acid derivatives, α-amino ketones, α-thioesters, and α,α-diaryl acetates, were prepared with high yields and high enantioselectivities through these insertion reactions.
130 citations
TL;DR: Recent advances and key developments in the field of decarbonylative cross-coupling reactions of amides are presented as well as future challenges and potential applications for this exciting field are discussed.
Abstract: Cross-coupling reactions are among the most powerful C–C and C–X bond forming tools in organic chemistry. Traditionally, cross-coupling methods rely on the use of aryl halides or pseudohalides as electrophiles. In the past three years, decarbonylative cross-couplings of amides have emerged as an attractive method for the construction of a wide variety of carbon–carbon and carbon–heteroatom bonds, allowing for the synthetically-valuable functional group inter-conversion of the amide bond. These previously elusive reactions hinge upon selective activation of the N–C(O) acyl amide bond, followed by CO extrusion, in a formal double N–C/C–C bond activation, to generate a versatile aryl–metal intermediate as an attractive alternative to traditional cross-couplings of aryl halides and pseudohalides. In this perspective review, we present recent advances and key developments in the field of decarbonylative cross-coupling reactions of amides as well as discuss future challenges and potential applications for this exciting field.
116 citations
TL;DR: An overview of the recent development of iodine mediated electrochemical oxidative coupling reactions with use of iodine as a mediator to achieve indirect electrochemical reactions has been given.
Abstract: Electrochemical oxidative cross-coupling with hydrogen evolution has become an environmentally friendly and efficient way to form new bonds. Direct electrosynthesis by anodic oxidation has been developed for the synthesis of complex molecules. However, in some cases, redox catalysts were needed to avoid over-oxidation and to achieve better reaction selectivity. Recently, the use of iodine as a mediator to achieve indirect electrochemical reactions has drawn increasing attention. This review article gives an overview of the recent development of iodine mediated electrochemical oxidative coupling reactions.
113 citations
TL;DR: This review updates the rapidly developing field of transient directing groups for C-H functionalisation on sp2 and sp3 carbon centres, to form new C-C and C-X bonds.
Abstract: C–H functionalisation promises a paradigm shift in synthetic planning. However, the additional steps often required to install and remove directing groups currently detract from the efficiency. The strategy of reversible installation of a directing group via an imine linkage has recently emerged, with the imine formed and hydrolysed in situ. Such transient directing groups can promote transition metal catalysed functionalisation of unactivated C–H bonds of aldehydes, ketones and amines. This approach removes additional steps usually required for covalent directing groups and can use catalytic quantities of the imine forming component. This review updates the rapidly developing field of transient directing groups for C–H functionalisation on sp2 and sp3 carbon centres, to form new C–C and C–X bonds. We focus on the structures of the transient directing groups as mono or bidentate coordinating groups for various metal catalysts.
106 citations
TL;DR: A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes has been developed under metal-free conditions and proceeded efficiently under mild conditions over a broad range of substrates and with functional group tolerance.
Abstract: A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes has been developed under metal-free conditions. This method provided a convenient and efficient approach to various 3-acylated quinoxalin-2(1H)-ones from readily available starting materials with excellent regioselectivity. This reaction proceeded efficiently under mild conditions over a broad range of substrates and with functional group tolerance.
102 citations
TL;DR: This review covers the synthetic methods and the application of chiral spirocyclic phosphoric acids in asymmetric catalysis.
Abstract: The development of suitable chiral catalysts, which represent powerful, economically feasible tools for the preparation of optically active organic molecules, is a fundamental endeavour in synthetic chemistry. Chiral phosphoric acids derived from axially chiral 1,1'-bi-2-naphthol (BINOL) are a widely used class of strong Bronsted acid catalysts and have been applied successfully in many asymmetric catalyzed reactions. Accordingly, the development and application of chiral spirocyclic phosphoric acids derived from axially chiral 1,1'-spirobiindane-7,7'-diol (SPINOL) have received increasing attention in the last eight years. This review covers the synthetic methods and the application of chiral spirocyclic phosphoric acids in asymmetric catalysis.
TL;DR: New findings in the study of triplet photosensitizers are useful for photovoltaics, photodynamic therapy and photocatalysis, as well as in fundamental photochemistry studies.
Abstract: In this review, recent progress in heavy atom-free triplet photosensitizers was summarized. The general approaches include attaining S1/Tn states sharing similar energy levels or proper molecular geometry to satisfy the angular momentum reservation in intersystem crossing (ISC). ISC via the higher singlet excited state (Sn, n > 1) → Tm (m > 1), which is a rarely reported phenomenon, was also discussed. The ISC of some Bodipy dimers was proposed to be via the 'doubly excited state', but recent studies show that the ISC mechanism of these Bodipy dimers is charge separation/recombination. These new findings in the study of triplet photosensitizers are useful for photovoltaics, photodynamic therapy and photocatalysis, as well as in fundamental photochemistry studies.
TL;DR: The highly efficient Rose Bengal-catalysed C(sp2)-H selenylation of indoles, imidazoles and arenes was achieved using a half molar equiv.
Abstract: In this report, the highly efficient Rose Bengal-catalysed C(sp2)-H selenylation of indoles, imidazoles and arenes was achieved using a half molar equiv. of diorganoyl diselenides. This metal-free, photo-induced protocol resulted in selenylated products in good to excellent yields. The reaction features are high yields, an atom-economic, gram-scalable and metal-free approach, and applicability to different biologically relevant (hetero)arenes.
TL;DR: A simple and practical method through stereoselective difunctionalization of alkynes with NaSCN or KSeCN at room temperature for the synthesis of alkenyl dithiocyanates andAlkenyl diselenocyanate could be efficiently and conveniently obtained in moderate to good yields.
Abstract: A simple and practical method for the synthesis of alkenyl dithiocyanates and alkenyl diselenocyanates has been developed via stereoselective difunctionalization of alkynes with NaSCN or KSeCN at room temperature. Through this methodology, a series of alkenyl dithiocyanates and alkenyl diselenocyanates could be efficiently and conveniently obtained in moderate to good yields under mild and metal-free conditions by the simple use of oxone and PhI(OAc)2 as the oxidants.
TL;DR: This review summarizes the recent advances in the development of the chemical tools of 1O2 and introduces chemical methods for ground-state generation of 1 O2 and discloses molecular probes of1O2.
Abstract: Growing evidence indicates intermediacy of singlet dioxygen (1O2) in a variety of pathophysiological processes. 1O2 has also found great utility of destructive actions for clinical and environmental applications. However, many details of the molecular mechanisms mediated by 1O2 remain insufficiently understood. Efforts to elucidate the 1O2 chemistry have been hampered by the lack of chemical tools capable of generation and detection of 1O2. In this review, I summarize the recent advances in the development of the chemical tools of 1O2. This article focuses on two topics. The first part introduces chemical methods for ground-state generation of 1O2. Designs of the molecular carriers of 1O2 are also explained. The second part discloses molecular probes of 1O2. The probes are categorized into three groups, depending on signaling modalities: absorption-based probes, photoluminescent probes, and chemiluminescent probes. Focus is on the molecular design to maximize the signaling actions. Disadvantages of using the probes are also discussed to motivate the future research. I hope that this review will serve as helpful guidance to the exploitation and development of the chemical tools of 1O2.
TL;DR: Some of the most recent advances in the construction of cyclic compounds from the annulation of Morita-Baylis-Hillman (MBH) adducts are summarized, which have demonstrated their importance by possessing diverse functional groups.
Abstract: In this review, we summarize some of the most recent advances in the construction of cyclic compounds from the annulation of Morita-Baylis-Hillman (MBH) adducts, which have demonstrated their importance by possessing diverse functional groups. Significant examples including [3 + 2], [3 + 3], [3 + 4] and other cyclizations described herein with MBH adducts were proven to be efficient approaches for the preparation of diverse cyclic structure motifs. However, most of the reported strategies are based on the use of non-chiral catalysts/ligands, whilst stereoselective reactions remain largely unexplored. This area is still in its infancy and future research on MBH adducts will definitely benefit the organic chemistry community, especially for the synthesis of drug candidates and other molecules that might draw attention to materials sciences.
TL;DR: This review introduces methods for β-lactam synthesis and presents newly developed reactions, and approaches the synthesis of β- lactams according to different retro synthesis strategies.
Abstract: During the past century, β-lactams have been identified as the core of penicillin and since then several strategies have been developed for their synthesis Traditional methods for β-lactam synthesis usually involved amide bond formation and the Staudinger reaction In recent years, by the advancement of photo- and transition metal-catalysis, several new methods have been reported for β-lactam synthesis For instance: ligand assisted metal catalyzed C-H activation/intermolecular oxidative amidation draws attention for β-lactam synthesis In this review we introduce methods for β-lactam synthesis and present newly developed reactions We approach the synthesis of β-lactams according to different retro synthesis strategies
TL;DR: This review highlights the C-glycosylation methods that have been practised in the total synthesis of natural products and pharmaceuticals in the past decade.
Abstract: Chemical C-glycosylation has been well developed to improve stereoselectivity in recent years. Due to its high efficiency to build C-glycosides or O-cyclic compounds, C-glycosylation has found widespread use in the synthesis of biologically active molecules. This review highlights the C-glycosylation methods that have been practised in the total synthesis of natural products and pharmaceuticals in the past decade.
TL;DR: This mini review focuses on the recent progress of total synthesis of complex alkaloids based on the nucleophilic additions to N-alkoxyamides, tertiary amides and secondary amides.
Abstract: Nucleophilic addition to amides has been recognized as a promising transformation for total synthesis of complex alkaloids. Amides can accept two different organometallic reagents through the nucleophilic addition, which enables it to serve as a stable surrogate of multi-substituted amines. However, the nucleophilic addition has been overlooked for a long time due to three main reasons: low electrophilicity of amide carbonyls, potential hydrolysis of the reaction intermediate and excess addition of an organometallic reagent. This mini review focuses on the recent progress of total synthesis of complex alkaloids based on the nucleophilic additions to N-alkoxyamides, tertiary amides and secondary amides.
TL;DR: This review provides an overview of the recent achievements in classical Piancatelli reactions, discussing reaction conditions and catalytic systems, and focuses on the variants recently developed, including the use of new nucleophiles in the process.
Abstract: The Piancatelli reaction, also called the Piancatelli rearrangement, consists in the direct conversion of furfuryl alcohols to cyclopentenone derivatives through a furan ring opening-electrocyclization process. Discovered in the late 70's, this reaction has been scarcely used for more than 40 years but recently has been the focus of particular interest from the scientific community and an increasing number of publications on the topic have emerged in the last few years. The first part of this review provides an overview of the recent achievements in classical Piancatelli reactions, discussing reaction conditions and catalytic systems, whereas the second part focuses on the variants recently developed, including the use of new nucleophiles in the process. Finally, the third part of this review deals with the recent application of this transformation to the production of commodity chemicals from renewable carbon feedstocks based on sugar-derived furanic platforms.
TL;DR: A summary and analysis of recent advances towards the development of catalytic Mitsunobu reactions that employ innocuous terminal oxidants and reductants to achieve recycling is provided.
Abstract: The Mitsunobu reaction is widely regarded as the pre-eminent method for performing nucleophilic substitutions of alcohols with inversion of configuration. However, its applicability to large-scale synthesis is undermined by the fact that alcohol activation occurs at the expense of two stoichiometric reagents – a phosphine and an azodicarboxylate. The ideal Mitsunobu reaction would be sub-stoichiometric in the phosphine and azodicarboxylate species and employ innocuous terminal oxidants and reductants to achieve recycling. This Review article provides a summary and analysis of recent advances towards the development of such catalytic Mitsunobu reactions.
TL;DR: In this review, recent progress in the development of azobenzene-based molecular photoswitches and their applications in the photocontrol of protein structure and function are summarized.
Abstract: Molecular photoswitches are a class of chemical structures that can readily isomerize between distinct geometries upon irradiation with light. Molecular photoswitches are utilized to control protein structure and function with temporal and spatial precision. In this review, we summarize the recent progress in the development of azobenzene-based molecular photoswitches and their applications in the photocontrol of protein structure and function. For clarity of discussion, we divide the known photoswitchable proteins into different categories: protein motifs, ion channels, receptors, and enzymes. Basic approaches and considerations for the structure-guided design of photoswitchable ligands are discussed. The applications and limitations of current photoswitches are also discussed.
TL;DR: A general, efficient and environmentally benign, one-step synthesis of substituted quinoline derivatives was achieved by acceptorless dehydrogenative coupling of o-aminobenzylalcohols with ketones and secondary alcohols catalyzed by a cheap, earth abundant and easy to prepare nickel catalyst.
Abstract: A general, efficient and environmentally benign, one-step synthesis of substituted quinoline derivatives was achieved by acceptorless dehydrogenative coupling of o-aminobenzylalcohols with ketones and secondary alcohols catalyzed by a cheap, earth abundant and easy to prepare nickel catalyst [Ni(MeTAA)], featuring a tetraaza macrocyclic ligand (tetramethyltetraaza[14]annulene (MeTAA)). A wide variety of substituted quinolines were synthesized in high yields starting from readily available o-aminobenzylalcohols and ketones or secondary alcohols. A few controlled reactions were carried out to establish the acceptorless dehydrogenative nature of the reactions.
TL;DR: This review will summarize the recent advances in catalytic carbene/alkyne metathesis with readily available and stable materials, such as α-carbonyl diazo compounds, and be divided by the type of the terminating carbene reactions.
Abstract: Metal carbene, as a reactive intermediate, has shown versatile applications in modern organic synthesis. One of the priorities in this area is exploration of stable carbene precursors with structural diversity. Catalytic carbene/alkyne metathesis (CAM) with readily available and stable materials, such as α-carbonyl diazo compounds, provides an effective approach for the in situ generation of vinyl carbene intermediates, which is difficult to directly access with other carbene precursors. Thus, novel cascade transformations involving the CAM process for the straightforward construction of polycyclic frameworks have been well documented. Challenges including side reaction control and asymmetric catalysis in this area need to be explored. This review will summarize the recent advances in this field and be divided by the type of the terminating carbene reactions.
TL;DR: The goal of this review is to cover the different chiral iodine compound-catalyzed oxidative transformations including α-functionalization of carbonyl compounds, dearomatization of phenol derivatives and difunctionalization of alkenes which should demonstrate that iodine catalysis has now found its place in the realm of asymmetric organocatalysis.
Abstract: The implementation of chiral iodine catalysis has tremendously been developed in the field of asymmetric synthesis over the past decade. It enables the stereoselective creation of C–O as well as C–C, C–N and C–X (X = halogen) bonds through oxidative transformations. Thanks to the low toxicity and ease of handling of iodine compounds, this strategy offers many advantages over classical metal-catalyzed oxidations with chiral ligands. The approaches rely on iodine(I/III) or (−I/+I) catalysis by using a chiral aryliodine or ammonium iodide respectively in combination with a suitable terminal oxidant. As such, the design of iodine compounds with central, axial or even planar chirality has allowed us to achieve high enantioselectivities. The goal of this review is to cover the different chiral iodine compound-catalyzed oxidative transformations including α-functionalization of carbonyl compounds, dearomatization of phenol derivatives and difunctionalization of alkenes which should demonstrate that iodine catalysis has now found its place in the realm of asymmetric organocatalysis.
TL;DR: Mechanistic studies, chemical methodologies and reagents for the synthesis of isocyanates from carboxylic acids, the conversion of isOCyanates to amines and amine derivatives, and their applications in the synthesisation of bioactive natural products and their congeners are presented.
Abstract: The Curtius rearrangement is a versatile reaction in which a carboxylic acid can be converted to an isocyanate through an acyl azide intermediate under mild conditions. The resulting stable isocyanate can then be readily transformed into a variety of amines and amine derivatives including urethanes and ureas. There have been wide-ranging applications of the Curtius rearrangement in the synthesis of natural products and their derivatives. Also, this reaction has been extensively utilized in the synthesis and application of a variety of biomolecules. In this review, we present mechanistic studies, chemical methodologies and reagents for the synthesis of isocyanates from carboxylic acids, the conversion of isocyanates to amines and amine derivatives, and their applications in the synthesis of bioactive natural products and their congeners.
TL;DR: A visible-light-induced cascade Meerwein addition/cyclization of alkenes involving C-F bond cleavage was developed, allowing for the incorporation of various aromatic moieties originating from aryldiazonium salts.
Abstract: A visible-light-induced cascade Meerwein addition/cyclization of alkenes involving C–F bond cleavage was developed. This method offers a rapid access to azaspirocyclic cyclohexadienones from N-benzylacrylamides via C–F bond cleavage applying H2O as an external oxygen source, allowing for the incorporation of various aromatic moieties originating from aryldiazonium salts.
TL;DR: Advances in the metal-catalyzed 1,3-dipolar cycloaddition reactions of nitrile oxides, mainly in the last decade, will be presented and discussed.
Abstract: In the present review advances in the metal-catalyzed 1,3-dipolar cycloaddition reactions of nitrile oxides, mainly in the last decade, will be presented and discussed. An overview on the structure, preparation, dimerization and related reactions as well as the relevant aspects in the cycloaddition chemistry of nitrile oxides (including mechanistic aspects) have also been considered.
TL;DR: A convenient and efficient indium-catalyzed approach to synthesize alkenyl iodides has been developed through direct iodoalkylation of alkynes with alcohols and aqueous HI under mild conditions.
Abstract: A convenient and efficient indium-catalyzed approach to synthesize alkenyl iodides has been developed through direct iodoalkylation of alkynes with alcohols and aqueous HI under mild conditions. This catalytic protocol offers an attractive approach for the synthesis of a diverse range of alkenyl iodides in good to excellent yields.
TL;DR: A variety of thiocarbamates were easily synthesized through this methodology, which has the advantages of simple operation, eco-friendly conditions, good functional group tolerance, and readily accessible raw materials.
Abstract: A simple and practical molecular iodine-mediated method for the efficient construction of thiocarbamates from isocyanides, thiols and water under metal-free and mild conditions has been developed. A variety of thiocarbamates were easily synthesized through this methodology, which has the advantages of simple operation, eco-friendly conditions, good functional group tolerance, and readily accessible raw materials.