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Organic Letters Feb 2020Hydrazones readily synthesized from -aminopyrroles or -aminoazoles and aldehydes undergo Rh(III)-catalyzed dual C-H activation and coupling with aryl- and...
Hydrazones readily synthesized from -aminopyrroles or -aminoazoles and aldehydes undergo Rh(III)-catalyzed dual C-H activation and coupling with aryl- and alkyl-substituted alkynes to give pyrrolopyridazines or azolopyridazines, respectively. This transformation represents a rare example of hydrazoyl C-H activation and proceeds without heteroatom functionality to direct C-H activation. Hydrazones derived from aromatic, alkenyl, and aliphatic aldehydes were effective inputs, and tethering the alkyne to the hydrazone enabled annulations to more complex, tricyclic products.
Topics: Alkynes; Azoles; Catalysis; Hydrazones; Molecular Structure; Organometallic Compounds; Pyridazines; Pyrroles; Rhodium; Stereoisomerism
PubMed: 31977232
DOI: 10.1021/acs.orglett.0c00186 -
Journal of the American Chemical Society Apr 2020The marine macrolide chagosensine is supposedly distinguished by a ()-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also...
The marine macrolide chagosensine is supposedly distinguished by a ()-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two -2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The "northern" THF ring and the -configured diol in the "southern" sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved. To meet the challenge, the preparation of the required building blocks was optimized, and a convergent strategy for their assembly was developed. A key role was played by the cobalt-catalyzed oxidative cyclization of alken-5-ol derivatives ("Mukaiyama cyclization"), which is shown to be exquisitely chemoselective for terminal alkenes, leaving even terminal alkynes (and other sites of unsaturation) untouched. Likewise, a palladium-catalyzed alkyne alkoxycarbonylation reaction with formation of an α-methylene-γ-lactone proved instrumental, which had not found application in natural product synthesis before. Further enabling steps were a nickel-catalyzed "Tamaru-type" homocrotylation, stereodivergent aldehyde homologations, radical hydroindation, and palladium-catalyzed alkyne-1,2-bis-stannation. The different building blocks were assembled in a serial fashion to give the idiosyncratic chlorodienes by an unprecedented site-selective Stille coupling followed by copper-mediated tin/chlorine exchange. The macrolactones were closed under forcing Yamaguchi conditions, and the resulting products were elaborated into the targeted compound library. Yet, only one of the eight diastereomers turned out to be stable in the solvent mixture that had been used to analyze the natural product; all other isomers were prone to ring opening and/or ring expansion. In addition to this stability issue, our self-consistent data set suggests that chagosensine has almost certainly little to do with the structure originally proposed by the isolation team.
Topics: Alkenes; Alkynes; Biological Products; Catalysis; Chemistry Techniques, Synthetic; Cobalt; Cyclization; Furans; Lactones; Macrolides; Oxidation-Reduction; Stereoisomerism
PubMed: 32142305
DOI: 10.1021/jacs.0c01700 -
Journal of Labelled Compounds &... Apr 2022Base catalysed exchange with sodium hydroxide, calcium oxide or N,N,N,N-tetramethylguanidine in deuterium oxide is a viable procedure for the preparation of terminally...
Base catalysed exchange with sodium hydroxide, calcium oxide or N,N,N,N-tetramethylguanidine in deuterium oxide is a viable procedure for the preparation of terminally deuterated alkynes for those alkynes stable to strong base. The use of silver perchlorate as a catalyst is an alternative practical option when labelling alkynes which are sensitive to base or contain functionalities which would lead to labelling elsewhere in the molecule. Labelling with this catalyst takes place smoothly at ambient temperature in a mixture of N,N-dimethylformamide and deuterium oxide.
Topics: Alkynes; Catalysis; Deuterium
PubMed: 35067956
DOI: 10.1002/jlcr.3963 -
Angewandte Chemie (International Ed. in... Sep 2020The discovery of safe, general, and practical procedures to prepare vinyl fluorides from readily available precursors remains a synthetic challenge. The metal-free...
The discovery of safe, general, and practical procedures to prepare vinyl fluorides from readily available precursors remains a synthetic challenge. The metal-free hydrofluorination of alkynes constitutes an attractive though elusive strategy for their preparation. Introduced here is an inexpensive and easily handled reagent that enables the development of simple and scalable protocols for the regioselective hydrofluorination of alkynes to access both the E and Z isomers of vinyl fluorides. These reaction conditions were suitable for a diverse collection of alkynes, including several highly functionalized pharmaceutical derivatives. Computational and experimental mechanistic studies support C-F bond formation through vinyl cation intermediates, with the E- and Z-hydrofluorination products forming under kinetic and thermodynamic control, respectively.
Topics: Alkynes; Borates; Halogenation; Molecular Structure; Stereoisomerism; Vinyl Compounds
PubMed: 32485005
DOI: 10.1002/anie.202006278 -
Molecules (Basel, Switzerland) Nov 2022The accurate and sensitive detection of biomolecules by surface-enhanced Raman spectroscopy (SERS) is possible, but remains challenging due to the interference from...
The accurate and sensitive detection of biomolecules by surface-enhanced Raman spectroscopy (SERS) is possible, but remains challenging due to the interference from biomolecules in complex samples. Herein, a new SERS sensor is developed for background-free detection of hydrogen peroxide (HO) with an ultralow detection limit (1 × 10 mol/L), using a Raman-silent strategy. The Au microparticles (Au-RSMPs) resembling rose-stones are devised as SERS substrates with a high enhancement effect, and 4-mercaptophenylboronic acid (4-MPBA) is selected as an HO-responsive Raman reporter. Upon the reaction with HO, the phenylboronic group of 4-MPBA was converted to a phenol group, which subsequently reacted with 4-diazonium-phenylalkyne (4-DP), an alkyne-carrying molecule via the azo reaction. The formed product exhibits an intense and sharp SERS signal in the Raman-silent region, avoiding interference of impurities and biomolecules. As a proof-of-concept demonstration, we show that this SERS sensor possesses significant merits towards the determination of HO in terms of broad linear range, low limit of detection, and high selectivity, showing promise for the quantitative analysis of HO in complicated biological samples.
Topics: Hydrogen Peroxide; Spectrum Analysis, Raman; Alkynes
PubMed: 36432018
DOI: 10.3390/molecules27227918 -
Molecules (Basel, Switzerland) Mar 2019The recent developments in asymmetric A³ (aldehyde⁻alkyne⁻amine) coupling has been summarized in this review. Several interesting modifications of the ligands... (Review)
Review
The recent developments in asymmetric A³ (aldehyde⁻alkyne⁻amine) coupling has been summarized in this review. Several interesting modifications of the ligands enabled the highly enantioselective synthesis of chiral propargylamines, which are further used in the construction of nitrogen-containing chiral building blocks.
Topics: Aldehydes; Alkynes; Amines; Catalysis; Pargyline; Propylamines; Stereoisomerism
PubMed: 30925732
DOI: 10.3390/molecules24071216 -
The Journal of Organic Chemistry Oct 2012The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a highly effective method for the selective incorporation of deuterium atom into the C-5 position of the...
The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a highly effective method for the selective incorporation of deuterium atom into the C-5 position of the 1,2,3-triazole structure. Reactions of alkynes and azides can be conveniently carried out in a biphasic medium of CH(2)Cl(2)/D(2)O, using the CuSO(4)/Na ascorbate system. The mildness of the method renders it applicable to substrates of relatively high complexity, such as nucleosides. Good yields and high levels of deuterium incorporation were observed. A reaction conducted in equimolar H(2)O and D(2)O showed 2.7 times greater incorporation of hydrogen atom as compared to deuterium. This is consistent with the H(+) and D(+) ion concentrations in H(2)O and D(2)O, respectively. With appropriately deuterated precursors, partially to fully deuterated triazoles were assembled where the final deuterium atom was incorporated in the triazole-forming step.
Topics: Alkynes; Azides; Catalysis; Copper; Cyclization; Molecular Structure; Triazoles
PubMed: 23016757
DOI: 10.1021/jo301146j -
Molecules (Basel, Switzerland) May 2022A modular platform for the synthesis of tunable aza-oxa-based macrocycles was established. Modulations in the backbone and the side-chain functional groups have been...
A modular platform for the synthesis of tunable aza-oxa-based macrocycles was established. Modulations in the backbone and the side-chain functional groups have been rendered to achieve the tunable property. These aza-oxa-based macrocycles can also differ in the number of heteroatoms in the backbone and the ring size of the macrocycles. For the proof of concept, a library of macrocycles was synthesized with various hanging functional groups, different combinations of heteroatoms, and ring sizes in the range of 17-27 atoms and was characterized by NMR and mass spectrometry. In light of the importance of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and the significance of triazole groups for various applications, we employed the click-reaction-based macrocyclization. The competence of the synthesized macrocycles in various biomedical applications was proven by studying the interactions with the serum albumin proteins; bovine serum albumin and human serum albumin. It was observed that some candidates, based on their hanging functional groups and specific backbone atoms, could interact well with the protein, thus improving the bioactive properties. On the whole, this work is a proof-of-concept to explore the backbone- and side-chain-tunable macrocycle for different properties and applications.
Topics: Alkynes; Azides; Catalysis; Click Chemistry; Copper; Humans; Serum Albumin, Bovine; Triazoles
PubMed: 35684347
DOI: 10.3390/molecules27113409 -
The Journal of Organic Chemistry Mar 2019Silyl triflate precursors to cyclic alkynes and allenes serve as valuable synthetic building blocks. We report a concise and scalable synthetic approach to prepare the...
Silyl triflate precursors to cyclic alkynes and allenes serve as valuable synthetic building blocks. We report a concise and scalable synthetic approach to prepare the silyl triflate precursors to cyclohexyne and 1,2-cyclohexadiene. The strategy involves a retro-Brook rearrangement of an easily accessible cyclohexanone derivative, followed by triflation protocols. This simple, yet controlled, method should enable the further study of strained alkynes and allenes in chemical synthesis.
Topics: Alkynes; Cyclohexenes; Molecular Structure; Organosilicon Compounds
PubMed: 30840455
DOI: 10.1021/acs.joc.8b03223 -
Molecules (Basel, Switzerland) Dec 2022The present review narrates several reports which deal with the synthesis of fused 1,2,3-triazole containing scaffolds following a sequential multicomponent reaction... (Review)
Review
The present review narrates several reports which deal with the synthesis of fused 1,2,3-triazole containing scaffolds following a sequential multicomponent reaction (MCR)-intramolecular azide-alkyne cycloaddition (IAAC) approach. The reviewed reactions were cleverly designed so as to incorporate azide and alkyne functionalities in the MCR product which was then subjected to IAAC. The review is divided into two sections based on the number of components in the multicomponent reaction. We have aimed at a critical discussion and also have highlighted either advantages or disadvantages of each methodology.
Topics: Cycloaddition Reaction; Azides; Alkynes; Triazoles; Catalysis; Molecular Structure
PubMed: 36615500
DOI: 10.3390/molecules28010308