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Molecules (Basel, Switzerland) Mar 2019The high energy packed in alkyne functional group makes alkyne reactions highly thermodynamically favorable and generally irreversible. Furthermore, the presence of two... (Review)
Review
The high energy packed in alkyne functional group makes alkyne reactions highly thermodynamically favorable and generally irreversible. Furthermore, the presence of two orthogonal π-bonds that can be manipulated separately enables flexible synthetic cascades stemming from alkynes. Behind these "obvious" traits, there are other more subtle, often concealed aspects of this functional group's appeal. This review is focused on yet another interesting but underappreciated alkyne feature: the fact that the CC alkyne unit has the same oxidation state as the -CH2C(O)- unit of a typical carbonyl compound. Thus, "classic carbonyl chemistry" can be accessed through alkynes, and new transformations can be engineered by unmasking the hidden carbonyl nature of alkynes. The goal of this review is to illustrate the advantages of using alkynes as an entry point to carbonyl reactions while highlighting reports from the literature where, sometimes without full appreciation, the concept of using alkynes as a hidden entry into carbonyl chemistry has been applied.
Topics: Aldehydes; Alkynes; Catalysis; Cyclization; Ketones; Molecular Structure; Stereoisomerism
PubMed: 30875972
DOI: 10.3390/molecules24061036 -
Nature Reviews. Chemistry Jun 2023One of the simplest organic functional groups, the alkyne, offers a broad canvas for the design of cascade transformations in which up to three new bonds can be added to... (Review)
Review
One of the simplest organic functional groups, the alkyne, offers a broad canvas for the design of cascade transformations in which up to three new bonds can be added to each of the two sterically unencumbered, energy-rich carbon atoms. However, kinetic protection provided by strong π-orbital overlap makes the design of new alkyne transformations a stereoelectronic puzzle, especially on multifunctional substrates. This Review describes the electronic properties contributing to the unique utility of alkynes in radical cascades. We describe how to control the selectivity of alkyne activation by various methods, from dynamic covalent chemistry with kinetic self-sorting to disappearing directing groups. Additionally, we demonstrate how the selection of reactive intermediates directly influences the propagation and termination of the cascade. Diverging from a common departure point, a carefully planned reaction route can allow access to a variety of products.
Topics: Alkynes; Carbon; Kinetics
PubMed: 37117812
DOI: 10.1038/s41570-023-00479-w -
Nature Communications Jun 2023The alkyne unit is a versatile building block in organic synthesis and the development of selective multifunctionalization of alkynes is an important object of research...
The alkyne unit is a versatile building block in organic synthesis and the development of selective multifunctionalization of alkynes is an important object of research in this field. Herein, we report an interesting gold-catalyzed, four-component reaction that achieves the oxo-arylfluorination or oxo-arylalkenylation of internal aromatic or aliphatic alkynes, efficiently breaking a carbon-carbon triple bond and forming four new chemical bonds. The reaction divergence can be controlled by site-directing functional groups in the alkynes; the presence of a phosphonate unit favors the oxo-arylfluorination, while the carboxylate motif benefits oxo-arylalkenylation. This reaction is enabled by an Au(I)/Au(III) redox coupling process using Selectfluor as both an oxidant and a fluorinating reagent. A wide range of structurally diverse α,α-disubstituted ketones, and tri- or tetra-substituted unsaturated ketones have been prepared in synthetically valuable yields and with excellent chemo-, regio- and stereoselectivity. The gram-scale preparation and late-stage application of complex alkynes have further enhanced their synthetic value.
Topics: Gold; Alkynes; Catalysis; Ketones; Carbon
PubMed: 37322071
DOI: 10.1038/s41467-023-39243-5 -
Molecules (Basel, Switzerland) Dec 2020Popular and readily available alkenes and alkynes are good substrates for the preparation of functionalized molecules through radical and/or ionic addition reactions.... (Review)
Review
Popular and readily available alkenes and alkynes are good substrates for the preparation of functionalized molecules through radical and/or ionic addition reactions. Difunctionalization is a topic of current interest due to its high efficiency, substrate versatility, and operational simplicity. Presented in this article are radical addition followed by oxidation and nucleophilic addition reactions for difunctionalization of alkenes or alkynes. The difunctionalization could be accomplished through 1,2-addition (vicinal) and 1,n-addition (distal or remote) if H-atom or group-transfer is involved in the reaction process. A wide range of moieties, such as alkyl (R), perfluoroalkyl (R), aryl (Ar), hydroxy (OH), alkoxy (OR), acetatic (OCR), halogenic (X), amino (NR), azido (N), cyano (CN), as well as sulfur- and phosphorous-containing groups can be incorporated through the difunctionalization reactions. Radicals generated from peroxides or single electron transfer (SET) agents, under photoredox or electrochemical reactions are employed for the reactions.
Topics: Alkenes; Alkynes; Free Radicals; Oxidation-Reduction; Peroxides
PubMed: 33379397
DOI: 10.3390/molecules26010105 -
Angewandte Chemie (International Ed. in... Jul 2021A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in...
A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in activating alkynes, and we show that electronic effects, when competing stereoelectronic and inductive factors are properly balanced, sufficiently activate a linear alkyne in the uncatalyzed conjugative retro-Cope elimination reaction while adequately protecting it against cellular nucleophiles. This design preserves the low steric profile of an alkyne and pairs it with a comparably unobtrusive hydroxylamine. The kinetics are on par with those of the fastest strain-promoted azide-alkyne cycloaddition reactions, the products regioselectively formed, the components sufficiently stable and easily installed, and the reaction suitable for cellular labeling.
Topics: Alkynes; Amination; Azides; Cycloaddition Reaction; Molecular Structure
PubMed: 34019705
DOI: 10.1002/anie.202104863 -
Chemistry (Weinheim An Der Bergstrasse,... May 2015In the last few years, the development of versatile methodologies to incorporate trifluoromethyl groups into organic molecules has attracted significant attention in... (Review)
Review
In the last few years, the development of versatile methodologies to incorporate trifluoromethyl groups into organic molecules has attracted significant attention in synthetic chemistry. This review gives an overview over the development on the trifluoromethylation of alkynes, which have not been solely discussed before. Formation of diverse C(sp, sp(2) , sp(3) )-CF3 bonds are all covered in this review.
Topics: Alkynes; Chemistry Techniques, Synthetic; Halogenation; Hydrocarbons, Fluorinated; Methylation
PubMed: 25737368
DOI: 10.1002/chem.201406432 -
ACS Macro Letters Jul 2022Terminal alkynes display high reactivity toward Ru-carbene metathesis catalysts. However, the formation of a less reactive bulky carbene hinders their...
Terminal alkynes display high reactivity toward Ru-carbene metathesis catalysts. However, the formation of a less reactive bulky carbene hinders their homopolymerization. Simultaneously, the higher reactivity of alkynes does not allow efficient cross propagation with sterically less-hindered cycloalkene monomers, resulting in inefficient copolymerization. Nonetheless, terminal alkynes undergo rapid cross-metathesis with vinyl ethers. Therefore, an efficient cross propagation can be achieved with terminal alkynes and cyclic enol ether monomers. Here, we show that terminal alkyne derivatives can be copolymerized in an alternating fashion with 2,3-dihydrofuran using Grubbs' third generation catalyst (). A linear relationship of the number-average molecular weight versus monomer to initiator ratio and block copolymer synthesis confirmed a controlled copolymerization. The SEC and NMR analyses of the synthesized copolymers confirmed the excellent control over molecular weight and exclusive alternating nature of the copolymer. The regioselective chain transfer of to vinyl ether and the high reactivity of the Fischer-type Ru carbene toward terminal alkynes was also exploited for polymer conjugation. Finally, the presence of an acid labile backbone functionality in the synthesized alternating copolymers allowed complete degradation of the copolymer within a short time interval which was confirmed by SEC analyses.
Topics: Alkynes; Catalysis; Polymerization; Polymers
PubMed: 35736023
DOI: 10.1021/acsmacrolett.2c00258 -
Chemical Society Reviews Mar 2014Transition-metal (TM)-catalyzed hydroarylation reactions of alkynes have received much attention, because they enable the net insertion of alkyne C-C triple bonds into... (Review)
Review
Transition-metal (TM)-catalyzed hydroarylation reactions of alkynes have received much attention, because they enable the net insertion of alkyne C-C triple bonds into C-H bonds of aromatic precursors, resulting in regio- and stereo-selective formation of synthetically useful arylalkenes. Taking advantage of this feature, TM-catalyzed alkyne hydroarylations have been successfully used for the synthesis of heterocycles. TM-catalyzed alkyne hydroarylations can be classified into three major categories depending on the type of reaction and precursors involved: (1) palladium-catalyzed reductive Heck reactions of alkynes with aryl halides, (2) TM-catalyzed conjugate arylation reactions of activated alkynes with arylboronic acids, and (3) TM-catalyzed aromatic C-H alkenylations with alkynes. This review surveys heterocycle synthesis via TM-catalyzed hydroarylation of alkynes according to the above classification, with an emphasis on the scope and limitations, as well as the underlying mechanisms.
Topics: Alkynes; Boronic Acids; Catalysis; Heterocyclic Compounds; Palladium; Transition Elements
PubMed: 24336638
DOI: 10.1039/c3cs60369e -
Chemical Society Reviews Feb 2014Cyclization reactions of alkynes, especially the double carbometallation of alkynes, have drawn much interest from organic chemists because of their high efficiency in... (Review)
Review
Cyclization reactions of alkynes, especially the double carbometallation of alkynes, have drawn much interest from organic chemists because of their high efficiency in the construction of polycycles. Utilizing different nucleophiles or catalytic systems, various efficient strategies to access challenging skeletons have been extensively explored in recent years. In this review, achievements in this field are presented in three major parts (the syn-syn, anti-anti, and syn-anti addition reactions of diynes or two alkyne molecules). Cyclization reactions of diynes initiated by nucleophiles, [2+2+n] cycloaddition, or other processes and reactions, involving two identical or different alkynes are described, which provide facile and reliable approaches to various π systems, medium-sized rings, and even macrocycles.
Topics: Alkynes; Amines; Cyclization; Cycloaddition Reaction; Furans; Metals; Nitriles
PubMed: 24280731
DOI: 10.1039/c3cs60313j -
Organic Letters Dec 2022A copper-catalyzed electrophilic enamidation starting from alkynes is reported. Hydrozirconation of an alkyne with the Schwartz reagent forms a vinyl zirconium...
A copper-catalyzed electrophilic enamidation starting from alkynes is reported. Hydrozirconation of an alkyne with the Schwartz reagent forms a vinyl zirconium intermediate, which directly undergoes a copper-catalyzed electrophilic enamidation with dioxazolones. High functional group tolerance of hydrozirconation enables the use of functionalized alkynes including esters. The developed conditions are successfully applied to syntheses of partial structures found in biologically active natural products.
Topics: Alkynes; Copper; Catalysis; Zirconium
PubMed: 36384002
DOI: 10.1021/acs.orglett.2c03497