Showing papers in "Organic chemistry frontiers in 2014"
TL;DR: This review focuses specifically on the use of monodentate nitrogen-based directing groups published during the past two years, with the aim of covering a body of literature that is complementary to existing reviews.
Abstract: The use of directing groups has proven to be a successful strategy to enhance reactivity and control selectivity in C–H functionalization reactions. In the past decade, a multitude of new transformations and new directing groups have been explored, and several recent reviews have discussed directing group approaches for C–H functionalization. This review focuses specifically on the use of monodentate nitrogen-based directing groups published during the past two years, with the aim of covering a body of literature that is complementary to existing reviews.
480 citations
TL;DR: In this paper, a class of conformationally flexible ligands composed of a tertiary amino oxide-amide backbone and a straight-chain alkyl spacer was developed, which act as neutral tetradentate ligands to bind a wide variety of metal ions.
Abstract: A class of conformationally flexible ligands composed of a tertiary amino oxide–amide backbone and a straight-chain alkyl spacer was developed. These C2-symmetric chiral N,N′-dioxide ligands could be straightforwardly synthesized from readily available amino acids and amines. They act as neutral tetradentate ligands to bind a wide variety of metal ions. Non-planar cis-α M(N,N′-dioxide) complexes enable an intriguing and easily fine-tuned chiral platform for a number of asymmetric reactions. Privileged N,N′-dioxide ligands frequently show wide substrate generality and exceptional levels of stereocontrol for a specific catalytic reaction. We describe approaches to the ligand design and synthesis, structure and bonding in coordination complexes, and the recent developments in asymmetric catalysis.
298 citations
TL;DR: In this paper, the authors focus on C-H bond cleavage in oxidative transformation via iron catalysis, as well as applications in synthetic chemistry, and present a review of the state of the art at the frontiers of chemistry.
Abstract: It has been a long time since C–H bond oxidations first attracted chemists’ attention. In the last several decades, C–H bond oxidation has been extensively investigated and applied in chemistry. Transition-metal catalyzed C–H bond oxidative transformations presents one of the state-of-arts at the frontiers of chemistry. Iron, as a cheap, readily accessible metal, has already shown its unique utility. This review attempts to focus on C–H bond cleavage in oxidative transformation via iron catalysis, as well as applications in synthetic chemistry.
231 citations
TL;DR: This review provides a concise account of enantioselective syntheses of axially chiral allenes with a selection of published protocols.
Abstract: While one-carbon central chirality of organic molecules has been recognized and extensively studied for more than a century, far less attention has been paid to three-carbon axial chirality of allenes, although they exist in nature with interesting biological activity and have been demonstrated with great synthetic potentials. However, remarkable progress has been made in this field in recent years, giving rise to axially chiral allenes with a wide range of functionalities with practical enantioselectivity. This review provides a concise account of enantioselective syntheses of axially chiral allenes with a selection of published protocols.
203 citations
TL;DR: While the field of C-C activation of relatively unstrained systems is underdeveloped, it is expected that this review will provide insight into new developments and pave the path for robust, practical applications.
Abstract: New modes of chemical reactivity are of high value to synthetic organic chemistry. In this vein, carbon–carbon (C–C) activation is an emerging field that offers new possibilities for synthesizing valuable complex molecules. This review discusses the pioneering stoichiometric discoveries in this field up to the most recent synthetic applications that apply catalytic transformations. Specifically, the review focuses on C–C activation in relatively unstrained systems, including stoichiometric reactions, chelation-directed and chelation-free catalytic reactions. While the field of C–C activation of relatively unstrained systems is underdeveloped, we expect that this review will provide insight into new developments and pave the path for robust, practical applications.
202 citations
TL;DR: In particular, catalytic asymmetric allylation of carbonyl compounds and imines with organoboronates has seen rapid development in the past decade and is the focus of this review.
Abstract: Enantioselective allylation is a highly used organic reaction to prepare chiral homoallylic alcohols and amines, which serve as important building blocks in the synthesis of a variety of natural products and pharmaceuticals. In particular, catalytic asymmetric allylation of carbonyl compounds and imines with organoboronates has seen rapid development in the past decade and is the focus of this review.
149 citations
TL;DR: In this article, the authors focus on selected applications of Sonogashira coupling and subsequent transformations as key steps in the total synthesis of natural products, including conjugated enynes or enediynes.
Abstract: This review will focus on selected applications of Sonogashira coupling and subsequent transformations as key steps in the total synthesis of natural products. A brief introduction to the history and development of Sonogashira coupling will be presented. The organization of the synthetic applications is based on the structure of target molecules and the transformations followed by the Sonogashira coupling, which includes (1) preparation of natural products containing conjugated enynes or enediynes; (2) Sonogashira coupling followed by stereoselective reduction and (3) Sonogashira coupling followed by regioselective annulations.
133 citations
TL;DR: A convenient copper-mediated direct difluoromethylation of electron-deficient aryl iodides, as well as heteroaryl and β-styryl iodine compounds, using TMSCF2H has been developed, affording various diffluorometHylated products in moderate to excellent yields.
Abstract: A convenient copper-mediated direct difluoromethylation of electron-deficient aryl iodides, as well as heteroaryl and β-styryl iodides, using TMSCF2H has been developed. This one-step protocol proceeded at room temperature, affording various difluoromethylated products in moderate to excellent yields.
131 citations
TL;DR: In this paper, a 3-etherified azaspiro[4.5]trienones from N-arylpropiolamides and ethers is presented using TBHP oxidant.
Abstract: Cu-catalyzed synthesis of 3-etherified azaspiro[4.5]trienones from N-arylpropiolamides and ethers is presented using TBHP oxidant. This is achieved through C(sp3)–H functionalization, ipso-carbocyclization and dearomatization, and this method represents a new example of alkyne oxidative 1,2-difunctionalization with an ipso-aromatic carbon and a C(sp3)–H bond by simultaneously forming two new carbon–carbon bonds.
112 citations
TL;DR: Chiral iminopyridine oxazoline (IPO) ligands were designed, synthesized and utilized for the first cobalt-catalyzed highly regio-and enantioselective anti-Markovnikov hydroboration of 1,1-disubstituted aryl alkenes.
Abstract: Chiral iminopyridine oxazoline (IPO) ligands were designed, synthesized and utilized for the first cobalt-catalyzed highly regio- and enantioselective anti-Markovnikov hydroboration of 1,1-disubstituted aryl alkenes. These novel IPO ligands will likely be of high value for asymmetric transformations with first-row transition metals.
110 citations
TL;DR: Multicomponent reaction technology is now widely recognized for its impact on drug discovery projects and is strongly endorsed by industry as well as academia, however, still relatively few products based on MCRs are marketed or under development.
Abstract: Multicomponent reaction (MCR) technology is now widely recognized for its impact on drug discovery projects and is strongly endorsed by industry as well as academia. However, still relatively few products based on MCRs are marketed or under development. This provides tremendous opportunities for organic chemists to shorten synthetic pathways, thus reducing the cost-of-goods considerably. A recent example of the HCV drug Telaprevir is highlighted where introduction of two MCRs could lead to a shortening of the synthesis route by more than 50%.
TL;DR: Reaction of this reagent with a variety of aryl and vinyl boronic acids in the presence of a copper catalyst generated the trifluoromethylthiolated arenes and alkenes in good to excellent yields.
Abstract: A new high yielding method for the preparation of a shelf-stable electrophilic trifluoromethylthiolating reagent, N-(trifluoromethylthio)phthalimide, is described. Reaction of this reagent with a variety of aryl and vinyl boronic acids in the presence of a copper catalyst generated the trifluoromethylthiolated arenes and alkenes in good to excellent yields.
TL;DR: In this article, a review highlights the recent applications of titanocene(III) complexes in the field of natural product synthesis from the seminal precedents to the development of modern catalytic methods.
Abstract: This review highlights the recent applications of titanocene(III) complexes in the field of natural product synthesis from the seminal precedents to the development of modern catalytic methods. The power of the titanocene(III)-based approaches is demonstrated by the straightforward syntheses of many natural products from readily available starting materials.
TL;DR: A cyclic C-bromo-iminium bromide reacts with lithium trimethylsilyl acetylide to afford the title compound 2+˙ in 40% yield as discussed by the authors.
Abstract: A cyclic C-bromo-iminium bromide reacts with lithium trimethylsilyl acetylide to afford the title compound 2+˙ in 40% yield. In contrast to other organic mixed valence compounds, this radical cation can be stored in air. Oxidation and reduction of 2+˙ afford the corresponding dication 2++ and neutral cumulene 2, respectively, in good yields.
TL;DR: In this paper, the transition-metal-free azidofluorination of unactivated alkenes is reported. But the synthesis of β-fluorinated alkyl azides with excellent functional group compatibility and good stereoselectivity is not considered.
Abstract: We report herein the transition-metal-free azidofluorination of unactivated alkenes. Thus, the condensation of various alkenes with TMSN3 and Selectfluor in aqueous CH3CN at RT led to the efficient and regioselective synthesis of β-fluorinated alkyl azides with excellent functional group compatibility and good stereoselectivity. A single electron transfer mechanism involving the oxidative generation of azidyl radicals is proposed.
TL;DR: Vanadium(III) oxide catalyzes the direct fluorination of C(sp3)-H groups with Selectfluor and a fluorine atom can be introduced to the tertiary position of 1,4-cineole and L-menthone selectively.
Abstract: Vanadium(III) oxide catalyzes the direct fluorination of C(sp3)–H groups with Selectfluor. This reaction is operationally simple. The catalyst and the reaction by-product can be removed easily by filtration. Using this method, a fluorine atom can be introduced to the tertiary position of 1,4-cineole and L-menthone selectively.
TL;DR: In this article, two distinct modes of reactivity within this class: the thermal pericyclic or hetero-Diels Alder (hDA) reaction and the transition metal-catalysed formal [4 + 2] cycloaddition reaction are discussed.
Abstract: Cycloaddition reactions are powerful tools in synthetic chemistry. Incorporation of a nitrogen-containing component via cycloaddition represents an attractive strategy for assembling aza-heterocycles. One approach takes advantage of [4 + 2] cycloaddition reactions of 1-azadiene derivatives and 2-carbon π-components to access pyridines, a particularly significant subset of aza-heterocycles. This highlight discusses two distinct modes of reactivity within this class: the thermal pericyclic or hetero-Diels Alder (hDA) reaction and the transition metal-catalysed formal [4 + 2] cycloaddition reaction.
TL;DR: Progress in C–H fluorination is highlighted, which is arguably the most efficient approach to incorporate fluorine since it obviates the need of pre-functionalization of organic compounds.
Abstract: Incorporation of fluorine atom(s) into organic compounds is often desirable in the discovery of new pharmaceuticals, agrochemicals, and materials. However, development of transformations to incorporate fluorine is challenging because of its highly electronegative nature. Recent advances in C–H functionalization have allowed new approaches to C–F bonds. Herein we highlight progress in C–H fluorination, which is arguably the most efficient approach to incorporate fluorine since it obviates the need of pre-functionalization of organic compounds.
TL;DR: This Highlight details the recent emergence of a new type of A3 reaction (three-component condensation of an amine, an aldehyde and an alkyne) that incorporates an iminium isomerization step and leads to amine α-alkynylation.
Abstract: This highlight details the recent emergence of a new type of A3 reaction (three-component condensation of an amine, an aldehyde and an alkyne). In contrast to the classic A3 coupling process, the redox-A3 reaction incorporates an iminium isomerization step and leads to amine α-alkynylation. The overall transformation is redox-neutral by virtue of a combined reductive N-alkylation/oxidative C–H bond functionalization.
TL;DR: This method achieves selective scission of the C(sp3)–H bond adjacent to halide atoms leading to a halo-substituted alkyl radical, and provides a new synthetic utilization of aryl halides toward polyhalo- substituted oxindoles in good to excellent yields.
Abstract: We describe here a new visible light facilitated radical strategy for 1,2-alkylarylation of activated alkenes with a C(sp2)–H bond of arenes and a C(sp3)–H bond of alkyl halides. This method achieves selective scission of the C(sp3)–H bond adjacent to halide atoms leading to a halo-substituted alkyl radical, and provides a new synthetic utilization of aryl halides toward polyhalo-substituted oxindoles in good to excellent yields. Moreover, the concise transformation of the products, polyhalo-substituted oxindoles, into vinyl halides and alkynyl halides was also illustrated.
TL;DR: In this article, the first organocatalytic activation of monofluorinated silyl enol ethers was reported, by nucleophilic tertiary amine catalysis, to develop asymmetric reactions for the construction of chiral carbons featuring a C-F bond.
Abstract: We report the first organocatalytic activation of monofluorinated silyl enol ethers 1, by nucleophilic tertiary amine catalysis, to develop asymmetric reactions for the construction of fully substituted chiral carbons featuring a C–F bond. Accordingly, a highly stereoselective Mukaiyama-aldol reaction of isatins to furnish hydroxyoxindoles bearing two adjacent tetrasubstituted carbon stereocenters is developed.
TL;DR: In this paper, the first examples of carbofluorination of unactivated alkenes were reported, and the reaction was efficient and highly regioselective, and enjoyed a broad substrate scope and wide functional group compatibility.
Abstract: In this article, we report the first examples of carbofluorination of unactivated alkenes. Under catalysis by AgNO3, the reactions of unactivated alkenes with Selectfluor reagent and active methylene compounds such as acetoacetates or 1,3-dicarbonyls in CH2Cl2–H2O–HOAc solution afforded the corresponding three-component condensation products under mild conditions. Furthermore, with the promotion of NaOAc, the AgOAc-catalyzed carbofluorination of various unactivated alkenes with Selectfluor and acetone proceeded smoothly in aqueous solution at 50 °C. The carbofluorination was efficient and highly regioselective, and enjoyed a broad substrate scope and wide functional group compatibility. These formal fluorine atom transfer radical addition reactions provide a convenient entry to structurally divergent, polyfunctional organofluorine compounds as versatile synthetic intermediates.
TL;DR: In this article, the authors discuss the most recent findings in the field of catalytic transformation of C(sp3)−H bonds into C (sp3)-F bonds.
Abstract: Organofluorine compounds have found widespread applications in the pharmaceutical and agrochemical industries. Efficient construction of organofluorine molecules is highly desirable. Catalytic transformation of C(sp3)–H bonds into C(sp3)–F bonds provides the simplest and most straightforward way to organofluorine compounds. This Highlight discusses the most recent findings in the field.
TL;DR: In this paper, an efficient NBS-promoted method for the synthesis of (E)-β-halo vinylsulfones has been developed, which went through an environmentally friendly metal-free process to achieve the halosulfonylation of terminal alkynes with high selectivity.
Abstract: An efficient NBS-promoted method for the synthesis of (E)-β-halo vinylsulfones has been developed. The present protocol went through an environmentally friendly metal-free process to achieve the halosulfonylation of terminal alkynes with high selectivity.
TL;DR: Using an oxidizing directing group, a mild RuII-catalyzed direct coupling of N-phenoxypivalamide with internal alkynes was developed, generating the benzofurans in moderate to high yields.
Abstract: Using an oxidizing directing group, a mild RuII-catalyzed direct coupling of N-phenoxypivalamide with internal alkynes was developed, generating the benzofurans in moderate to high yields.
TL;DR: In this paper, a simple and versatile fluorescent dye NPS based on 1,8-naphthalimide was successfully designed and prepared, which exhibited excellent selectivity for Hg2+ over many other metal ions including Zn2+, Mn2+, Ba2+, Ni2+, Cu2+, Co2+, Pb2+, Mg2+, Cd2+, Fe2+, Al3+, Ag+, Na+, and Li+.
Abstract: A simple and versatile fluorescent dye NPS based on 1,8-naphthalimide was successfully designed and prepared. It was found that NPS exhibited excellent selectivity for Hg2+ over many other metal ions including Zn2+, Mn2+, Ba2+, Ni2+, Cu2+, Co2+, Pb2+, Mg2+, Cd2+, Fe2+, Al3+, Ag+, Na+, and Li+. In particular, NPS displayed a significant fluorescence “turn-on” to Hg2+ in aqueous solution and living cells, which could be potentially used for quantification of Hg2+. Moreover, two model compounds were rationally designed and synthesized, from which further insight into the sensing mechanism and binding mode of NPS with Hg2+ was obtained. Surprisingly, NPS exhibited interesting twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) behaviours in aqueous solution.
TL;DR: Copper(I)-catalyzed enantioselective hydroboration of 3-aryl substitutedcyclopropene-3-carboxylate is described, providing chiral cyclopropylboronates with excellent enantiOSElectivities and the chiral boronates could be conveniently converted into chiral 1,2-diaryl substituted Cyclopropane derivatives.
Abstract: Copper(I)-catalyzed enantioselective hydroboration of 3-aryl substituted cyclopropene-3-carboxylate is described, providing chiral cyclopropylboronates with excellent enantioselectivities (89–95% ee) in moderate to high yields (55–86%). The non-directing effect of the ester group was observed, and the reaction proceeded with solely trans-selectivity. The chiral boronates could be conveniently converted into chiral 1,2-diaryl substituted cyclopropane derivatives.
TL;DR: A palladium-catalyzed base-accelerated ortho-selective C–H alkenylation of phenols to synthesize bioactive coumarin derivatives was developed and several coumarins with bioactive properties were synthesized.
Abstract: A palladium-catalyzed base-accelerated ortho-selective C–H alkenylation of phenols to synthesize bioactive coumarin derivatives was developed. The reaction condition was mild and the substrate scope was broad with both electron-neutral and electron-deficient phenols, which is complementary to the previous methods to synthesize electron-rich coumarins. Several bioactive molecules were functionalized and several coumarins with bioactive properties were synthesized. Mechanistic studies showed that this reaction underwent C–H bond activation via direct metallation rather than the Friedel–Crafts pathway.
TL;DR: Bicyclic/tricyclic functionalized cyclopropyl ketones are formed in mostly good yields in three steps from readily available enones/enals, which compares favorably with related strategies based on the diazo approach in terms of step economy and operational safety.
Abstract: What a trade: diazo ketones for alkynes? By utilizing a conformationally rigid P,N-bidentate ligand, highly efficient intramolecular cyclopropanation reactions using flexible and electronically neutral terminal alkyne substrates are realized via a sterically shielded tri-coordinated gold carbene intermediate. Bicyclic/tricyclic functionalized cyclopropyl ketones are formed in mostly good yields in three steps from readily available enones/enals, which compares favorably with related strategies based on the diazo approach in terms of step economy and operational safety. With this chemistry, we have expanded alkynes as surrogates of α-diazo ketones to cyclopropanation reactions.
TL;DR: Highly stereoselective 1,4-addition of alkylphenylphosphines to α,β-unsaturated carbonyl compounds catalyzed by PCP or NCN pincer–Pd complexes is described to synthesize chiral phosphorus compounds bearing both P- and C-stereogenic centers with good to excellent enantioselectivity.
Abstract: Highly stereoselective 1,4-addition of alkylphenylphosphines to α,β-unsaturated carbonyl compounds catalyzed by PCP or NCN pincer–Pd complexes is described to synthesize chiral phosphorus compounds bearing both P- and C-stereogenic centers with good to excellent enantioselectivity (up to 99.6% ee).