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26 pages, 10153 KiB

Open AccessArticle

Ring Expansion of Alkylidenecarbenes Derived from Lactams, Lactones, and Thiolactones into Strained Heterocyclic Alkynes: A Theoretical Study

by Nguyen Nhat Thu Le, Josefine Just, Jonathan M. Pankauski, Paul R. Rablen and Dasan M. Thamattoor

Molecules 2019, 24(3), 593; https://doi.org/10.3390/molecules24030593 - 7 Feb 2019

Cited by 3 | Viewed by 3606

Abstract

Strained cycloalkynes are of considerable interest to theoreticians and experimentalists, and possess much synthetic value as well. Herein, a series of cyclic alkylidenecarbenes—formally obtained by replacing the carbonyl oxygen of four-, five-, and six-membered lactams, lactones, and thiolactones with a divalent carbon—were modeled [...] Read more.

Strained cycloalkynes are of considerable interest to theoreticians and experimentalists, and possess much synthetic value as well. Herein, a series of cyclic alkylidenecarbenes—formally obtained by replacing the carbonyl oxygen of four-, five-, and six-membered lactams, lactones, and thiolactones with a divalent carbon—were modeled at the CCSD(T)/cc-pVTZ//B3LYP/6-311+G** and CCSD(T)/cc-pVTZ//CCSD/6-311+G** levels of theory. The singlet carbenes were found to be more stable than the triplets. The strained heterocyclic alkynes formed by ring expansion of these singlet carbenes were also modeled. Interestingly, the C≡C bonds in the five-membered heterocycles, obtained from the rearrangement of β-lactam- and β-lactone-derived alkylidenecarbenes, displayed lengths intermediate between formal double and triple bonds. Furthermore, 2-(1-azacyclobutylidene)carbene was found to be nearly isoenergetic with its ring-expanded isomer, and 1-oxacyclopent-2-yne was notably higher in energy than its precursor carbene. In all other cases, the cycloalkynes were lower in energy than the corresponding carbenes. The transition states for ring-expansion were always lower for the 1,2-carbon shifts than for 1,2-nitrogen or oxygen shifts, but higher than for the 1,2-sulfur shifts. These predictions should be verifiable using carbenes bearing appropriate isotopic labels. Computed vibrational spectra for the carbenes, and their ring-expanded isomers, are presented and could be of value to matrix isolation experiments. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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21 pages, 33303 KiB

Open AccessArticle

TfOH-Promoted Reaction of 2,4-Diaryl-1,1,1-Trifluorobut-3-yn-2-oles with Arenes: Synthesis of 1,3-Diaryl-1-CF₃-Indenes and Versatility of the Reaction Mechanisms

by Aleksey V. Zerov, Anna N. Kazakova, Irina A. Boyarskaya, Taras L. Panikorovskii, Vitalii V. Suslonov, Olesya V. Khoroshilova and Aleksander V. Vasilyev

Molecules 2018, 23(12), 3079; https://doi.org/10.3390/molecules23123079 - 25 Nov 2018

Cited by 11 | Viewed by 4610

Abstract

The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF₃-substituted diaryl propargyl alcohols) with arenes in CH₂Cl₂ afford 1,3-diaryl-1-CF₃-indenes in yields up to 84%. This new process for synthesis of such CF₃-indenes is complete at room temperature within [...] Read more.

The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF₃-substituted diaryl propargyl alcohols) with arenes in CH₂Cl₂ afford 1,3-diaryl-1-CF₃-indenes in yields up to 84%. This new process for synthesis of such CF₃-indenes is complete at room temperature within one hour. The synthetic potential, scope, and limitations of this reaction were illustrated by more than 70 examples. The proposed reaction mechanism invokes the formation of highly reactive CF₃-propargyl cation intermediates that can be trapped at the two mesomeric positions by the intermolecular nucleophilic attack of an arene partner with a subsequent intramolecular ring closure. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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12 pages, 2832 KiB

Open AccessArticle

Synthesis of Carvone-Derived 1,2,3-Triazoles Study of Their Antioxidant Properties and Interaction with Bovine Serum Albumin

by Armen S. Galstyan, Armen I. Martiryan, Karine R. Grigoryan, Armine G. Ghazaryan, Melanya A. Samvelyan, Tariel V. Ghochikyan and Valentine G. Nenajdenko

Molecules 2018, 23(11), 2991; https://doi.org/10.3390/molecules23112991 - 16 Nov 2018

Cited by 18 | Viewed by 4438

Abstract

Natural L-carvone was utilized as a starting material for an efficient synthesis of some terpenyl-derived 1,2,3-triazoles. Chlorination of carvone, followed by nucleophilic substitution with sodium azide resulted in the preparation of 10-azidocarvone. Subsequent CuAAC click reaction with propargylated derivatives provided an efficient synthetic [...] Read more.

Natural L-carvone was utilized as a starting material for an efficient synthesis of some terpenyl-derived 1,2,3-triazoles. Chlorination of carvone, followed by nucleophilic substitution with sodium azide resulted in the preparation of 10-azidocarvone. Subsequent CuAAC click reaction with propargylated derivatives provided an efficient synthetic route to a set of terpenyl-derived conjugates with increased solubility in water. All investigated compounds exhibit high antioxidant activity, which is comparable with that of vitamin C. It was also found that serum albumin and the terpenyl-1,2,3-triazoles hybrids spontaneously undergo reversible binding driven by hydrophobic interactions, suggesting that serum albumin can transport the target triazoles. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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7 pages, 654 KiB

Open AccessArticle

Synthesis of Acridines through Alkyne Addition to Diarylamines

by Kristen E. Berger, Grant M. McCormick, Joseph A. Jaye, Christina M. Rozeske and Eric H. Fort

Molecules 2018, 23(11), 2867; https://doi.org/10.3390/molecules23112867 - 3 Nov 2018

Cited by 8 | Viewed by 4363

Abstract

A new synthesis of substituted acridines is achieved by palladium-catalyzed addition of terminal acetylenes between the aryl rings of bis(2-bromophenyl)amine. By including a diamine base and elevating the temperature, the reaction pathway favors the formation of acridine over a double Sonogashira reaction to [...] Read more.

A new synthesis of substituted acridines is achieved by palladium-catalyzed addition of terminal acetylenes between the aryl rings of bis(2-bromophenyl)amine. By including a diamine base and elevating the temperature, the reaction pathway favors the formation of acridine over a double Sonogashira reaction to form bis(tolan)amine. This method is demonstrated with several aryl-alkynes and alkyl-alkynes. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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7 pages, 1277 KiB

Open AccessCommunication

Highly Efficient Recyclable Sol Gel Polymer Catalyzed One Pot Difunctionalization of Alkynes

by Justin Domena, Carlos Chong, Qiaxian R. Johnson, Bhanu P. S. Chauhan and Yalan Xing

Molecules 2018, 23(8), 1879; https://doi.org/10.3390/molecules23081879 - 27 Jul 2018

Cited by 2 | Viewed by 3928

Abstract

Amino-bridged gel polymer P1 was discovered to catalyze alkyne halo-functionalization in excellent yields, regioselectivity, functional group compatibility, and recyclability. We have observed that both aromatic and aliphatic alkynes can be converted to α,α-dihalogenated ketones in the presence of polymer P1 under metal-free conditions [...] Read more.

Amino-bridged gel polymer P1 was discovered to catalyze alkyne halo-functionalization in excellent yields, regioselectivity, functional group compatibility, and recyclability. We have observed that both aromatic and aliphatic alkynes can be converted to α,α-dihalogenated ketones in the presence of polymer P1 under metal-free conditions at room temperature within a short reaction time. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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11 pages, 1804 KiB

Open AccessArticle

Vinylation of a Secondary Amine Core with Calcium Carbide for Efficient Post-Modification and Access to Polymeric Materials

by Konstantin S. Rodygin, Alexander S. Bogachenkov and Valentine P. Ananikov

Molecules 2018, 23(3), 648; https://doi.org/10.3390/molecules23030648 - 13 Mar 2018

Cited by 35 | Viewed by 8030

Abstract

We developed a simple and efficient strategy to access N-vinyl secondary amines of various naturally occurring materials using readily available solid acetylene reagents (calcium carbide, KF, and KOH). Pyrrole, pyrazole, indoles, carbazoles, and diarylamines were successfully vinylated in good yields. Cross-linked and [...] Read more.

We developed a simple and efficient strategy to access N-vinyl secondary amines of various naturally occurring materials using readily available solid acetylene reagents (calcium carbide, KF, and KOH). Pyrrole, pyrazole, indoles, carbazoles, and diarylamines were successfully vinylated in good yields. Cross-linked and linear polymers were synthesized from N-vinyl carbazoles through free radical and cationic polymerization. Post-modification of olanzapine (an antipsychotic drug substance) was successfully performed. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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Review

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36 pages, 10545 KiB

Open AccessReview

Alkynes as Synthetic Equivalents of Ketones and Aldehydes: A Hidden Entry into Carbonyl Chemistry

by Igor V. Alabugin, Edgar Gonzalez-Rodriguez, Rahul Kisan Kawade, Aleksandr A. Stepanov and Sergei F. Vasilevsky

Molecules 2019, 24(6), 1036; https://doi.org/10.3390/molecules24061036 - 15 Mar 2019

Cited by 53 | Viewed by 10325

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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56 pages, 13754 KiB

Open AccessReview

Preparation and Utility of N-Alkynyl Azoles in Synthesis

by Brandon Reinus and Sean M. Kerwin

Molecules 2019, 24(3), 422; https://doi.org/10.3390/molecules24030422 - 24 Jan 2019

Cited by 8 | Viewed by 6379

Abstract

Heteroatom-substituted alkynes have attracted a significant amount of interest in the synthetic community due to the polarized nature of these alkynes and their utility in a wide range of reactions. One specific class of heteroatom-substituted alkynes combines this utility with the presence of [...] Read more.

Heteroatom-substituted alkynes have attracted a significant amount of interest in the synthetic community due to the polarized nature of these alkynes and their utility in a wide range of reactions. One specific class of heteroatom-substituted alkynes combines this utility with the presence of an azole moiety. These N-alkynyl azoles have been known for nearly 50 years, but recently there has been a tremendous increase in the number of reports detailing the synthesis and utility of this class of compound. While much of the chemistry of N-alkynyl azoles mirrors that of the more extensively studied N-alkynyl amides (ynamides), there are notable exceptions. In addition, as azoles are extremely common in natural products and pharmaceuticals, these N-alkynyl azoles have high potential for accessing biologically important compounds. In this review, the literature reports of N-alkynyl azole synthesis, reactions, and uses have been assembled. Collectively, these reports demonstrate the growth in this area and the promise of exploiting N-alkynyl azoles in synthesis. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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22 pages, 4754 KiB

Open AccessReview

Nanographene and Graphene Nanoribbon Synthesis via Alkyne Benzannulations

by Amber D. Senese and Wesley A. Chalifoux

Molecules 2019, 24(1), 118; https://doi.org/10.3390/molecules24010118 - 30 Dec 2018

Cited by 59 | Viewed by 9368

Abstract

The extension of π-conjugation of polycyclic aromatic hydrocarbons (PAHs) via alkyne benzannulation reactions has become an increasingly utilized tool over the past few years. This short review will highlight recent work of alkyne benzannulations in the context of large nanographene as well as [...] Read more.

The extension of π-conjugation of polycyclic aromatic hydrocarbons (PAHs) via alkyne benzannulation reactions has become an increasingly utilized tool over the past few years. This short review will highlight recent work of alkyne benzannulations in the context of large nanographene as well as graphene nanoribbon synthesis along with a brief discussion of the interesting physical properties these molecules display. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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16 pages, 5505 KiB

Open AccessReview

Recent Synthesis Developments of Organoboron Compounds via Metal-Free Catalytic Borylation of Alkynes and Alkenes

by Yanmei Wen, Chunmei Deng, Jianying Xie and Xinhuang Kang

Molecules 2019, 24(1), 101; https://doi.org/10.3390/molecules24010101 - 28 Dec 2018

Cited by 48 | Viewed by 9542

Abstract

Diboron reagents have been traditionally regarded as “Lewis acids”, which can react with simple Lewis base to create a significant nucleophilic character in one of boryl moieties. In particular, bis(pinacolato)diboron (B₂pin₂) reacts with simple Lewis bases, such as N [...] Read more.

Diboron reagents have been traditionally regarded as “Lewis acids”, which can react with simple Lewis base to create a significant nucleophilic character in one of boryl moieties. In particular, bis(pinacolato)diboron (B₂pin₂) reacts with simple Lewis bases, such as N-heterocyclic carbenes (NHCs), phosphines and alkoxides. This review focuses on the application of trivalent nucleophilic boryl synthon in the selective preparation of organoboron compounds, mainly through metal-free catalytic diboration and the β-boration reactions of alkynes and alkenes. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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84 pages, 68329 KiB

Open AccessReview

Acetylene in Organic Synthesis: Recent Progress and New Uses

by Vladimir V. Voronin, Maria S. Ledovskaya, Alexander S. Bogachenkov, Konstantin S. Rodygin and Valentine P. Ananikov

Molecules 2018, 23(10), 2442; https://doi.org/10.3390/molecules23102442 - 24 Sep 2018

Cited by 134 | Viewed by 17298

Abstract

Recent progress in the leading synthetic applications of acetylene is discussed from the prospect of rapid development and novel opportunities. A diversity of reactions involving the acetylene molecule to carry out vinylation processes, cross-coupling reactions, synthesis of substituted alkynes, preparation of heterocycles and [...] Read more.

Recent progress in the leading synthetic applications of acetylene is discussed from the prospect of rapid development and novel opportunities. A diversity of reactions involving the acetylene molecule to carry out vinylation processes, cross-coupling reactions, synthesis of substituted alkynes, preparation of heterocycles and the construction of a number of functionalized molecules with different levels of molecular complexity were recently studied. Of particular importance is the utilization of acetylene in the synthesis of pharmaceutical substances and drugs. The increasing interest in acetylene and its involvement in organic transformations highlights a fascinating renaissance of this simplest alkyne molecule. Full article

(This article belongs to the Special Issue Alkynes: From Reaction Design to Applications in Organic Synthesis)

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