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Molbank ◽  
10.3390/m1317 ◽  
2022 ◽  
Vol 2022 (1) ◽  
pp. M1317
Author(s):  
Yuliya E. Ryzhkova ◽  
Varvara M. Kalashnikova ◽  
Fedor V. Ryzhkov ◽  
Michail N. Elinson

Michael addition–halogenation–intramolecular ring-closing (MHIRC) reactions are processes in which a halogen atom as a leaving group can attach to substrates or reactants during the reaction, which then undergoes intramolecular ring closure. In this communication the MHIRC transformation of 4-benzylidene-3-phenylisoxazol-5(4H)-one and 1,3-dimethylbarbituric acid in the presence of N-bromosuccinimide and sodium acetate in EtOH at room temperature was carefully investigated to give novel 1,3-dimethyl-3′,5-diphenyl-1,5-dihydro-2H,5′H-spiro[furo[2,3-d]pyrimi- dine-6,4′-isoxazole]-2,4,5′(3H)-trione in a good yield. The structure of the new compound was confirmed by the results of elemental analysis as well as mass, nuclear magnetic resonance, and infrared spectroscopy.


Author(s):  
Keyuan Zhang ◽  
Tianbing Liang ◽  
Yulong Wang ◽  
Chonglong He ◽  
Mingyou Hu ◽  
...  

A practical method for the synthesis of allylic thioacyanate from allylic alcohol was disclosed employing K2S2O8 as the oxidant and NH4SCN as the thiocyanate source. Without introducing a leaving group...


Nature ◽  
2021 ◽  
Vol 600 (7889) ◽  
pp. 444-449
Author(s):  
Da Zhao ◽  
Roland Petzold ◽  
Jiyao Yan ◽  
Dieter Muri ◽  
Tobias Ritter

AbstractTritium labelling is a critical tool for investigating the pharmacokinetic and pharmacodynamic properties of drugs, autoradiography, receptor binding and receptor occupancy studies1. Tritium gas is the preferred source of tritium for the preparation of labelled molecules because it is available in high isotopic purity2. The introduction of tritium labels from tritium gas is commonly achieved by heterogeneous transition-metal-catalysed tritiation of aryl (pseudo)halides. However, heterogeneous catalysts such as palladium supported on carbon operate through a reaction mechanism that also results in the reduction of other functional groups that are prominently featured in pharmaceuticals3. Homogeneous palladium catalysts can react chemoselectively with aryl (pseudo)halides but have not been used for hydrogenolysis reactions because, after required oxidative addition, they cannot split dihydrogen4. Here we report a homogenous hydrogenolysis reaction with a well defined, molecular palladium catalyst. We show how the thianthrene leaving group—which can be introduced selectively into pharmaceuticals by late-stage C–H functionalization5—differs in its coordinating ability to relevant palladium(II) catalysts from conventional leaving groups to enable the previously unrealized catalysis with dihydrogen. This distinct reactivity combined with the chemoselectivity of a well defined molecular palladium catalyst enables the tritiation of small-molecule pharmaceuticals that contain functionality that may otherwise not be tolerated by heterogeneous catalysts. The tritiation reaction does not require an inert atmosphere or dry conditions and is therefore practical and robust to execute, and could have an immediate impact in the discovery and development of pharmaceuticals.


2021 ◽  
Author(s):  
Taeho Kang ◽  
José Manuel González ◽  
Zi-Qi Li ◽  
Klement Foo ◽  
Peter Cheng ◽  
...  

A versatile method to access differentially substituted 1,3- and 1,4-diamines via a nickel-catalyzed three-component 1,2-carboamination of alkenyl amines with aryl/alkenylboronic ester nucleophiles and N–O electrophiles is reported. The reaction proceeds efficiently with free primary and secondary amines without needing a directing auxiliary or protecting group, and is enabled by fine-tuning the leaving group on the N–O reagent. The transformation is highly regioselective and compatible with a wide range of coupling partners and alkenyl amine substrates, all performed at room temperature. A series of kinetic studies support a mechanism in which alkene coordination to the nickel catalyst is turnover-limiting.


2021 ◽  
Author(s):  
Zi-Qi Li ◽  
Yilin Cao ◽  
Taeho Kang ◽  
Keary Engle

A multi-component approach to structurally complex organosulfur products is described via the nickel-catalyzed 1,2-carbosulfenylation of unactivated alkenes with organoboron nucleophiles and tailored organosulfur electrophiles. Key to the development of this transformation is the identification of a modular N-alkyl-N-(arylsulfenyl)arenesulfonamide family of sulfur electrophiles. Tuning the electronic and steric properties of the leaving group in these reagents controls pathway selectivity, favoring three-component coupling and suppressing side reactions, as examined via computational studies. The unique syn-stereoselectivity differs from traditional electrophilic sulfenyl transfer processes involving a thiiranium ion intermediate and arises from the directed arylnickel(I) migratory insertion mechanism, as elucidated through reaction kinetics and control experiments. Reactivity and regioselectivity are facilitated by a collection of monodentate, weakly coordinating native directing groups, including sulfonamides, alcohols, amines, amides, and azaheterocycles.


2021 ◽  
Author(s):  
◽  
Claire Alison Turner

<p>The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction.  Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles.  Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans.  An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.</p>


2021 ◽  
Author(s):  
◽  
Claire Alison Turner

<p>The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction.  Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles.  Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans.  An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.</p>


Synthesis ◽  
2021 ◽  
Author(s):  
Ivo Dias ◽  
Sara C. Silva-Reis ◽  
Beatriz L. Pires-Lima ◽  
Xavier C. Correia ◽  
Hugo F. Costa-Almeida

In this work, a convenient synthetic protocol for the unprecedented N-hydroxylation of proline residue in Melanostatin (MIF-1) neuropeptide is reported. This methodology is grounded on the incorporation of N-(cyanoethyl)prolyl residue followed by on-site oxidation by Cope elimination with m-chloroperbenzoic acid, exploring the unrecognized dual role of the cyanoethyl group as an effective N-protecting group under peptide synthesis conditions and as a suitable leaving group during the chemoselective on-site N-oxidation. Following this protocol N-hydroxy-MIF-1 is obtained with 78% global yield from N-(cyanoethyl)-L-proline. This synthetic approach opens a new avenue for access to N-hydroxylated Melanostatin analogs with direct application in neurochemistry and Parkinson’s research.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ye-Wei Chen ◽  
Yang Liu ◽  
Han-Yu Lu ◽  
Guo-Qiang Lin ◽  
Zhi-Tao He

AbstractTransition metal-catalyzed asymmetric allylic substitution with a suitably pre-stored leaving group in the substrate is widely used in organic synthesis. In contrast, the enantioselective allylic C(sp3)-H functionalization is more straightforward but far less explored. Here we report a catalytic protocol for the long-standing challenging enantioselective allylic C(sp3)-H functionalization. Through palladium hydride-catalyzed chain-walking and allylic substitution, allylic C-H functionalization of a wide range of acyclic nonconjugated dienes is achieved in high yields (up to 93% yield), high enantioselectivities (up to 98:2 er), and with 100% atom efficiency. Exploring the reactivity of substrates with varying pKa values uncovers a reasonable scope of nucleophiles and potential factors controlling the reaction. A set of efficient downstream transformations to enantiopure skeletons showcase the practical value of the methodology. Mechanistic experiments corroborate the PdH-catalyzed asymmetric migratory allylic substitution process.


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