Goldilocks Effect of Base Strength on Site Selectivity in Acylation of Amphiphilic Diols

Synlett ◽  
2021 ◽  
Author(s):  
Reut Fallek ◽  
Natali Ashush ◽  
Amit Fallek ◽  
Moshe Portnoy
Keyword(s):  
Tertiary Amine ◽  
Substrate Selectivity ◽  
Strong Change ◽  
Site Selectivity ◽  
Base Strength

Two series of competitive acylation experiments with a polar and an apolar alcohol substrates, imitating two parts of amphiphilic diols, examined the influence of bases of varying strength on the substrate selectivity. While weakly basic 2,4,6-collidine only mildly accelerates the acylation of the polar substrate without affecting that of the apolar one, the acylation of both substrates is drastically hastened by strongly basic DBU. In both cases there is a notable, though not overwhelming, shift of the substrate selectivity towards the polar substrate, compared to the base-free acylation, which strongly favors that of the apolar one. The extraordinarily strong change in the substrate selectivity in favor of the polar substrate was induced, however, by aliphatic tertiary amine bases, DIPEA and TEA, of “Goldilocks” moderate base strength, which strongly accelerate the acylation of the polar substrate, while almost not affecting that of the apolar one. These effects of the bases on the substrate selectivity are reflected in the site selectivity trends observed in the acylation of a model diol amphiphile.

Chelation-assisted transition metal-catalysed C–H chalcogenylations

2020 ◽  
Vol 7 (8) ◽  
pp. 1022-1060 ◽  
Author(s):  
Wenbo Ma ◽  
Nikolaos Kaplaneris ◽  
Xinyue Fang ◽  
Linghui Gu ◽  
Ruhuai Mei ◽  
...  
Keyword(s):  
Transition Metal ◽  
Recent Advances ◽  
Site Selectivity ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed

This review summarizes recent advances in C–S and C–Se formations via transition metal-catalyzed C–H functionalization utilizing directing groups to control the site-selectivity.

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C–H Activation

2020 ◽  
Author(s):  
Chang-Sheng Wang ◽  
Sabrina Monaco ◽  
Anh Ngoc Thai ◽  
Md. Shafiqur Rahman ◽  
Chen Wang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Lewis Acid ◽  
Hydrogen Transfer ◽  
Acid Catalysis ◽  
Rate Limiting Step ◽  
Site Selectivity ◽  
Set Up ◽  
Site Selective ◽  
First Time ◽  
Rate Limiting

A catalytic system comprised of a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic system for analogous transformations, the present catalytic system not only feature convenient set up using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp), but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Mechanistic stidies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkyl(carbamoyl)cobalt intermediate.

Imine as a Linchpin Approach for Distal C(sp2)–H Functionalization

2020 ◽  
Author(s):  
Sukdev Bag ◽  
Sadhan Jana ◽  
Sukumar Pradhan ◽  
Suman Bhowmick ◽  
Nupur Goswami ◽  
...  
Keyword(s):  
Organic Molecules ◽  
Bond Activation ◽  
Bond Formation ◽  
Ancillary Ligand ◽  
Significant Challenge ◽  
Site Selectivity ◽  
Directing Group ◽  
Covalently Linked ◽  
Complex Organic ◽  
Post Functionalization

<p>Despite the widespread applications of C–H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing group (DG) served as an ancillary ligand to ensure proximal <i>ortho</i>-, distal <i>meta</i>- and <i>para</i>-C-H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C–H functionalization: introduction of DG prior to C–H activation and removal of DG post-functionalization. We introduce here a transient directing group for distal C(<i>sp<sup>2</sup></i>)-H functionalization <i>via</i> reversible imine formation. By overruling facile proximal C-H bond activation by imine-<i>N</i> atom, a suitably designed pyrimidine-based transient directing group (TDG) successfully delivered selective distal C-C bond formation. Application of this transient directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the distal position has been explored.</p>

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

2017 ◽  
Author(s):  
Haibo Ge ◽  
Lei Pan ◽  
Piaoping Tang ◽  
Ke Yang ◽  
Mian Wang ◽  
...  
Keyword(s):  
Bond Activation ◽  
Theoretical Calculations ◽  
Experimental Studies ◽  
Bond Functionalization ◽  
Aliphatic Ketones ◽  
Site Selectivity ◽  
Mechanistic Investigation ◽  
Palladium Catalyzed ◽  
Metal Catalyzed ◽  
Site Selective

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp<sup>3</sup> carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>

scholarly journals Orpiment under compression: metavalent bonding at high pressure

2020 ◽  
Vol 22 (6) ◽  
pp. 3352-3369 ◽  
Author(s):  
Vanesa Paula Cuenca-Gotor ◽  
Juan Ángel Sans ◽  
Oscar Gomis ◽  
Andres Mujica ◽  
Silvana Radescu ◽  
...  
Keyword(s):  
Phase Transition ◽  
High Pressure ◽  
Strong Change ◽  
Isostructural Phase Transition

Orpiment (α-As2S3) under compression reports a strong change in the coordination of As atoms at 25 GPa, which can be ascribed to an isostructural phase transition. These changes are consistent with the formation of metavalent bonds in orpiment.

scholarly journals Design of ferrocenylseleno-dopamine derivatives to optimize the Fenton-like reaction efficiency and antitumor efficacy

RSC Advances ◽  
2021 ◽  
Vol 11 (41) ◽  
pp. 25477-25483
Author(s):  
Qianya Cheng ◽  
Tong Zhou ◽  
Qing Xia ◽  
Xiulian Lu ◽  
Heng Xu ◽  
...  
Keyword(s):  
Tertiary Amine ◽  
Antitumor Efficacy ◽  
Reaction Efficiency

The tertiary amine in F4b facilitates the Fenton-like reaction to generate toxic ˙OH which induces apoptosis through CDK-2 inactivation.

scholarly journals Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence

2021 ◽  
Vol 22 (6) ◽  
pp. 3012
Author(s):  
James I. Mitchell-White ◽  
Thomas Stockner ◽  
Nicholas Holliday ◽  
Stephen J. Briddon ◽  
Ian D. Kerr
Keyword(s):  
Substrate Specificity ◽  
Functional Divergence ◽  
3D Structure ◽  
Sequence Divergence ◽  
Conformational Flexibility ◽  
Substrate Selectivity ◽  
Multiple Sequence ◽  
Atp Binding Cassette Transporters ◽  
Structural Network ◽  
Wide Substrate Specificity

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.

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