Synthesis of Conjugated Triynes via Alkyne Metathesis

2019 ◽  
Author(s):  
Idriss Curbet ◽  
Sophie Colombel-Rouen ◽  
Romane Manguin ◽  
Anthony Clermont ◽  
Alexandre Quelhas ◽  
...  
Keyword(s):  
Steric Hindrance ◽  
High Selectivity ◽  
Alkyne Metathesis ◽  
Cross Metathesis ◽  
Synthetic Strategy ◽  
Sterically Hindered ◽  
Site Selective

<div> <div> <div> <div> <p>The synthesis of conjugated triynes by molybdenum-catalyzed alkyne metathesis is reported. Strategic to the success of this approach is the utilization of sterically-hindered diynes that allowed for the site- selective alkyne metathesis to produce the desired con- jugated triyne products. The steric hindrance of alkyne moiety was found to be crucial in preventing the for- mation of diyne byproducts. This novel synthetic strategy was amenable to self- and cross-metathesis providing straightforward access to the corresponding symmetrical and dissymmetrical triynes with high selectivity. </p> </div> </div> </div> </div>

Synthesis of Conjugated Triynes via Alkyne Metathesis

2019 ◽  
Author(s):  
Idriss Curbet ◽  
Sophie Colombel-Rouen ◽  
Romane Manguin ◽  
Anthony Clermont ◽  
Alexandre Quelhas ◽  
...  
Keyword(s):  
Steric Hindrance ◽  
High Selectivity ◽  
Alkyne Metathesis ◽  
Cross Metathesis ◽  
Synthetic Strategy ◽  
Sterically Hindered ◽  
Site Selective

<div> <div> <div> <div> <p>The synthesis of conjugated triynes by molybdenum-catalyzed alkyne metathesis is reported. Strategic to the success of this approach is the utilization of sterically-hindered diynes that allowed for the site- selective alkyne metathesis to produce the desired con- jugated triyne products. The steric hindrance of alkyne moiety was found to be crucial in preventing the for- mation of diyne byproducts. This novel synthetic strategy was amenable to self- and cross-metathesis providing straightforward access to the corresponding symmetrical and dissymmetrical triynes with high selectivity. </p> </div> </div> </div> </div>

Synthesis of Conjugated Triynes via Alkyne Metathesis

2019 ◽  
Author(s):  
Romane Manguin ◽  
Idriss Curbet ◽  
Anthony Clermont ◽  
Alexandre Quelhas ◽  
Daniel S. Müller ◽  
...  
Keyword(s):  
Steric Hindrance ◽  
High Selectivity ◽  
Alkyne Metathesis ◽  
Cross Metathesis ◽  
Synthetic Strategy ◽  
Sterically Hindered ◽  
Site Selective

The synthesis of conjugated triynes by molybdenum-catalyzed alkyne metathesis is reported. Strategic to the success of this approach is the utilization of sterically-hindered diynes that allowed the site-selective alkyne metathesis to produce the desired conjugated triyne products. The steric hindrance of alkyne moiety was found to be crucial in preventing the formation of diyne byproducts. This novel synthetic strategy was amenable to self- and cross-metathesis providing straightforward access to the corresponding symmetrical and dissymmetrical triynes with high selectivity (up to 98%).

Alkene and Alkyne Metathesis: Navenone B (Cossy), (+)-Asperpentyn (Daesung Lee), (-)-Amphidinolide K (Eun Lee), Norhalichondrin B (Phillips)

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Allylic Alcohol ◽  
Alkyne Metathesis ◽  
University Of Illinois ◽  
Cross Metathesis ◽  
Synthetic Strategy ◽  
University Of Colorado ◽  
National University ◽  
The Cross ◽  
Seoul National University ◽  
The University

A variety of antibiotics and immune-suppressive agents contain extended arrays of all- ( E )-polyenes. Samir Bouzbouz of CNS Rouen and Janine Cossy of ESPCI ParisTech devised ( Synlett 2009, 803) a simple iterative route to polyacetates such as 1 and demonstrated that after cross-metathesis, elimination, in this case to give Navenone B 3, was facile. Both ketones and esters can promote the elimination. Daesung Lee of the University of Illinois at Chicago designed (Organic Lett. 2009, 11 , 571) a clever chain-walking ring-closing ene-yne metathesis, cyclizing 4 to 5. Deprotection led to (+)-asperpentyn 6. This should be a general entry to such polyoxygenated cyclohexenes. For the structures of H2 and G2, see Organic Highlights, September 13, 2004. One of the challenges in the synthesis of (-)-amphidinoloide K 10 is the assembly of the complex conjugated diene. Eun Lee of Seoul National University found (Angew. Chem. Int. Ed. 2009, 48, 2364) a solution to this problem in the Ru-catalyzed cross-metathesis between the alkyne 7 and the alkene 8. Note that the cross-metathesis proceeded with high regioselectivity and with substantial (7.5:1) control of the product alkene geometry. For the construction of complex natural products such as norhalichondrin B 14, it is important to employ a convergent synthetic strategy. For this to be successful, efficient methods for convergent coupling are required. In the course of a synthesis of 14, Andrew J. Phillips of the University of Colorado showed (Angew. Chem. Int. Ed. 2009, 48, 2346) that Ru-mediated cross-metathesis could be used to couple the enone 11 with the alkene 12. A less congested version of H2, designed by Robert H. Grubbs of Caltech, was used for the coupling. The electron-deficient alkene of 11 and the more electron-rich alkene of 12 made a matched set, promoting the cross-coupling. Note again, in this context, the desirability of leaving the allylic alcohol of 12 unprotected to facilitate Ru-catalyzed alkene cross-metathesis.

Remote C–H Functionalizations by Ruthenium Catalysis

Synthesis ◽  
2021 ◽  
Author(s):  
Korkit Korvorapun ◽  
Ramesh C. Samanta ◽  
Torben Rogge ◽  
Lutz Ackermann
Keyword(s):  
Steric Hindrance ◽  
Late Stage ◽  
Crop Protection ◽  
Full Control ◽  
Site Selectivity ◽  
Important Approach ◽  
Distinct Character ◽  
Ruthenium Catalysis ◽  
Material Sciences ◽  
Site Selective

Synthetic transformations of otherwise inert C–H bonds have emerged as a powerful tool for molecular modifications during the last decades, with broad applications towards pharmaceuticals, material sciences and crop protection. Consistently, a key challenge in C–H activation chemistry is the full control of site-selectivity. In addition to substrate control through steric hindrance or kinetic acidity of C–H bonds, one important approach for the site-selective C–H transformation of arenes is the use of chelation-assistance through directing groups, therefore leading to proximity-induced ortho-C–H metalation. In contrast, more challenging remote C–H activations at the meta- or para-positions continue to be scarce. Within this review, we demonstrate the distinct character of ruthenium catalysis for remote C–H activations until March 2021, highlighting among others late-stage modifications of bio-relevant molecules. Moreover, we highlight important mechanistic insights by experiments and computation, highlighting the key importance of carboxylate-assisted C–H activation with ruthenium(II) complexes.

The effect of steric hindrance on the SRN1 reaction of some α-Alkyl-p-nitrobenzyl chlorides

1976 ◽  
Vol 29 (12) ◽  
pp. 2621 ◽  
Author(s):  
RK Norris ◽  
D Randles
Keyword(s):  
Oxygen Atom ◽  
Steric Hindrance ◽  
Lithium Salt ◽  
Dimethyl Sulphoxide ◽  
Sterically Hindered ◽  
Srn1 Reaction

The reactions of a series of α-substituted p-nitrobenzyl chlorides, p- NO2C6H4CH(Cl)R (R = Me, Et, Prt, But), with the lithium salt of 2- nitropropane in dimethyl sulphoxide and dimethylformamide have been studied. When R = Me or Et, competing SRN1 and SN2 processes take place, giving C- and O-alkylated products respectively. In the more sterically hindered cases where R = Pri or But, the only reaction taking place has been shown to be an SRN1 reaction with exclusive O-alkylation. These observations indicate that the SRN1 reaction is prone to steric hindrance, and that radical alkylation of the ambident nitronate ion occurs on the more accessible oxygen atom in sterically hindered situations.

Advances in Alkene and Alkyne Metathesis

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Acetic Acid ◽  
Diels Alder ◽  
Alkyne Metathesis ◽  
Santa Barbara ◽  
Ring Closing Metathesis ◽  
Enol Ethers ◽  
Cross Metathesis ◽  
Simple Filtration ◽  
The University ◽  
Academy Of Sciences

As alkene metathesis is extended to more and more challenging substrates, improved catalysts and solvents are required. Robert H. Grubbs of Caltech developed (Organic Lett. 2008, 10, 441) the diisopropyl complex 1, that efficiently formed the trisubstituted alkene 6 by cross metathesis of 4 with 5. Hervé Clavier and Stephen P. Nolan of ICIQ, Tarragona, and Marc Mauduit of ENSC Rennes found (J. Org. Chem. 2008, 73, 4225) that after cyclization of 7 with the complex 2b, simple filtration of the reaction mixture through silica gel delivered the product 8 containing only 5.5 ppm Ru. The merit of CH2Cl2 as a solvent for alkene metathesis is that the catalysts (e.g. 1 - 3) are very stable. Claire S. Adjiman of Imperial College and Paul C. Taylor of the University of Warwick established (Chem. Commun. 2008, 2806) that although the second generation Grubbs catalyst 3 is not as stable in acetic acid, for the cyclization of 9 to 10 it is a much more active catalyst in acetic acid than in CH2Cl2 . Bruce H. Lipshutz of the University of California, Santa Barbara observed (Adv. Synth. Cat . 2008, 350, 953) that even water could serve as the reaction solvent for the challenging cyclization of 11 to 12, so long as the solubility- enhancing amphiphile PTS was included. Ernesto G. Mata of the Universidad Nacional de Rosario explored (J. Org. Chem. 2008, 73, 2024) resin isolation to optimize cross-metathesis, finding that the acrylate 13 worked particularly well. Karol Grela of the Polish Academy of Sciences, Warsaw optimized (Chem. Commun. 2008, 2468) cross-metathesis with a halogenated alkene 16. Jean-Marc Campagne of ENSC Montpellier extended (J. Am. Chem. Soc. 2008, 130, 1562) ring-closing metathesis to enynes such as 19. The product diene 20 was a reactive Diels-Alder dienophile. István E. Markó of the Université Catholique de Louvain applied (Tetrahedron Lett. 2008, 49, 1523) the known (OHL 20070122) ring-closing metathesis of enol ethers to the cyclization of the Tebbe product from 23. The ether 24 was oxidized directly to the lactone 25.

scholarly journals Etomidate and Etomidate Analog Binding and Positive Modulation of γ-Aminobutyric Acid Type A Receptors

2018 ◽  
Vol 129 (5) ◽  
pp. 959-969 ◽  
Author(s):  
Megan McGrath ◽  
Zhiyi Yu ◽  
Selwyn S. Jayakar ◽  
Celena Ma ◽  
Mansi Tolia ◽  
...  
Keyword(s):  
Steric Hindrance ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
Phenyl Ring ◽  
Type A ◽  
Binding Pocket ◽  
Aminobutyric Acid ◽  
Substituent Group ◽  
Acid Type ◽  
Site Selective

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Naphthalene-etomidate, an etomidate analog containing a bulky phenyl ring substituent group, possesses very low γ-aminobutyric acid type A (GABAA) receptor efficacy and acts as an anesthetic-selective competitive antagonist. Using etomidate analogs containing phenyl ring substituents groups that range in volume, we tested the hypothesis that this unusual pharmacology is caused by steric hindrance that reduces binding to the receptor’s open state. Methods The positive modulatory potencies and efficacies of etomidate and phenyl ring–substituted etomidate analogs were electrophysiology defined in oocyte-expressed α1β3γ2L GABAA receptors. Their binding affinities to the GABAA receptor’s two classes of transmembrane anesthetic binding sites were assessed from their abilities to inhibit receptor labeling by the site-selective photolabels 3[H]azi-etomidate and tritiated R-5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid. Results The positive modulatory activities of etomidate and phenyl ring–substituted etomidate analogs progressively decreased with substituent group volume, reflecting significant decreases in both potency (P = 0.005) and efficacy (P &lt; 0.0001). Affinity for the GABAA receptor’s two β+ − α– anesthetic binding sites similarly decreased with substituent group volume (P = 0.003), whereas affinity for the receptor’s α+ – β–/γ+ – β– sites did not (P = 0.804). Introduction of the N265M mutation, which is located at the β+ − α– binding sites and renders GABAA receptors etomidate-insensitive, completely abolished positive modulation by naphthalene-etomidate. Conclusions Steric hindrance selectively reduces phenyl ring–substituted etomidate analog binding affinity to the two β+ − α– anesthetic binding sites on the GABAA receptor’s open state, suggesting that the binding pocket where etomidate’s phenyl ring lies becomes smaller as the receptor isomerizes from closed to open.

scholarly journals The role of steric hindrance in the intramolecular oxidative aromatic coupling of pyrrolo[3,2-b]pyrroles

2016 ◽  
Vol 52 (77) ◽  
pp. 11539-11542 ◽  
Author(s):  
Maciej Krzeszewski ◽  
Paweł Świder ◽  
Łukasz Dobrzycki ◽  
Michał K. Cyrański ◽  
Witold Danikiewicz ◽  
...  
Keyword(s):  
Carbon Atom ◽  
Steric Hindrance ◽  
Sterically Hindered

Sterically hindered tetraaryl-pyrrolo[3,2-b]pyrroles undergo oxidative aromatic coupling, forming a fluorene scaffold linked via a spiro carbon atom with a novel π-conjugated scaffold.

High- and low-spin complexes with similar, ligands. II. Iron(II) complexes with sterically hindered analogues of 2,2'-bipyridyl

1972 ◽  
Vol 25 (8) ◽  
pp. 1631 ◽  
Author(s):  
CM Harris ◽  
S Kokot ◽  
HRH Patil ◽  
E Sinn ◽  
H Wong
Keyword(s):  
Spectral Data ◽  
High Spin ◽  
Steric Hindrance ◽  
Field Potential ◽  
Ligand Field ◽  
Apparent Difference ◽  
Field Splitting ◽  
Analogous Complex ◽  
Sterically Hindered ◽  
Direct Change

Benzo substitution cis to the nitrogen of 2,2'-bipyridyl (bipy), to form 2-(2'-pyridyl)quinoline (pq), transforms the tris-complex with iron(11) from low spin in Fe(bipy)32+ to essentially high spin but near the crossover in Fe(pq)32+. For this complex, the ligand field splitting near the crossover, Δc is estimated from magnetic and spectral data as c. 12000 cm-l. A similar value but 150 cm-l lower is estimated for the analogous complex with the sterically related ligand 2-methyl-1,10-phenanthroline. This apparent difference in Δ values could arise from a direct change in ligand field potential, or from other factors, such as a change in distortion effects. Due to steric hindrance, pq prefers to form bis-complexes Fe(pq)2X2, pseudooctahedral and high spin, with suitable monodentates, X = Cl2 Br, NCS, ClO4. Double benzo substitution of bipy to form 2,2'-biquinolyl (biq) so increases steric hindrance that the tris-complex could not be formed. Instead biq forms pseudotetrahedral complexes Fe(biq)22+ and Fe(biq)X2 (X = Cl, Br).

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