scholarly journals A Novel Dual Organocatalyst for the Asymmetric Pinder Reaction and a Mechanistic Proposal Consistent with the Isoinversion Effect Thereof

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6398
Author(s):  
Fotini Moschona ◽  
Athena Vagena ◽  
Veroniki P. Vidali ◽  
Gerasimos Rassias
Keyword(s):  
Natural Products ◽  
Transition State ◽  
Organic Synthesis ◽  
Lewis Acid ◽  
Medicinal Chemistry ◽  
Aromatic Aldehydes ◽  
Bioactive Molecules ◽  
Knoevenagel Reaction ◽  
Chiral Centers

In general, the Pinder reaction concerns the reaction between an enolisable anhydride and an aldehyde proceeding initially through a Knoevenagel reaction followed by the ring closing process generating lactones with at least two chiral centers. These scaffolds are frequently present in natural products and synthetic bioactive molecules, hence it has attracted intense interest in organic synthesis and medicinal chemistry, particularly with respect to controlling the diastereo- and enantioselectivity. To the best of our knowledge, there has been only one attempt prior to this work towards the development of a catalytic enantioselective Pinder reaction. In our approach, we designed, synthesized, and tested dual chiral organocatalysts by combining BIMAH amines, (2-(α-(alkyl)methanamine)-1H-benzimidazoles, and a Lewis acid motif, such as squaramides, ureas and thioureas. The optimum catalyst was the derivative of isopropyl BIMAH bearing a bis(3,5-trifluoromethyl) thiourea, which afforded the Pinder products from various aromatic aldehydes with diastereomeric ratio >98:2 and enatioselectivity up to 92 ee%. Interestingly, the enantioselectivity of this catalyzed process is increased at higher concentrations and exhibits an isoinversion effect, namely an inverted "U" shaped dependency with respect to the temperature. Mechanistically, these features, point to a transition state involving an entropy-favored heterodimer interaction between a catalyst/anhydride and a catalyst/aldehyde complex when all other processes leading to this are much faster in comparison above the isoinversion temperature.

Enantioselective Syntheses of Flavonoid Diels-Alder Natural Products: A Review

2018 ◽  
Vol 15 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Shah Bakhtiar Nasir ◽  
Noorsaadah Abd Rahman ◽  
Chin Fei Chee
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Lewis Acid ◽  
Alder Reaction ◽  
Diels Alder ◽  
Enantioselective Synthesis ◽  
Chiral Ligand ◽  
Asymmetric Syntheses ◽  
Diels Alder Reaction ◽  
Enantioselective Syntheses

Background: The Diels-Alder reaction has been widely utilised in the syntheses of biologically important natural products over the years and continues to greatly impact modern synthetic methodology. Recent discovery of chiral organocatalysts, auxiliaries and ligands in organic synthesis has paved the way for their application in Diels-Alder chemistry with the goal to improve efficiency as well as stereochemistry. Objective: The review focuses on asymmetric syntheses of flavonoid Diels-Alder natural products that utilize chiral ligand-Lewis acid complexes through various illustrative examples. Conclusion: It is clear from the review that a significant amount of research has been done investigating various types of catalysts and chiral ligand-Lewis acid complexes for the enantioselective synthesis of flavonoid Diels-Alder natural products. The results have demonstrated improved yield and enantioselectivity. Much emphasis has been placed on the synthesis but important mechanistic work aimed at understanding the enantioselectivity has also been discussed.

Construction of N-heterocycles via Pd-mediated C–H activation/annulation strategies

2022 ◽  
Author(s):  
Mengyu Qiu ◽  
Xuegang Fu ◽  
Peng Fu ◽  
Jianhui Huang
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Material Science ◽  
Medicinal Chemistry ◽  
Drug Molecules

N-heterocycles can be found in natural products and drug molecules, which are indispensable components in the area of organic synthesis, medicinal chemistry and material science. The construction of these N-containing...

scholarly journals Synthetic Strategies in the Preparation of Phenanthridinones

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5560
Author(s):  
Rajeshwar Reddy Aleti ◽  
Alexey A. Festa ◽  
Leonid G. Voskressensky ◽  
Erik V. Van der Eycken
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Medicinal Chemistry ◽  
Coupling Reactions ◽  
Structural Importance ◽  
Wide Range ◽  
Biaryl Coupling ◽  
Synthetic Methodologies

Phenanthridinones are important heterocyclic frameworks present in a variety of complex natural products, pharmaceuticals and displaying wide range of pharmacological actions. Its structural importance has evoked a great deal of interest in the domains of organic synthesis and medicinal chemistry to develop new synthetic methodologies, as well as novel compounds of pharmaceutical interest. This review focuses on the synthesis of phenanthridinone scaffolds by employing aryl-aryl, N-aryl, and biaryl coupling reactions, decarboxylative amidations, and photocatalyzed reactions.

6.1 Thiol–Ene/Yne Click Reactions: A Powerful Tool Toward Diversity-Oriented Synthesis

2022 ◽  
Author(s):  
A. K. Sinha ◽  
R. Singh
Keyword(s):  
Natural Products ◽  
Double Bond ◽  
Triple Bond ◽  
Medicinal Chemistry ◽  
Bioactive Molecules ◽  
Polymer Chemistry ◽  
Atom Economy ◽  
Diversity Oriented Synthesis ◽  
Click Reactions ◽  
Vinyl Sulfides

AbstractThe clickable addition reaction between thiols and unsaturated compounds leading to the generation of (branched/linear) thioethers or (branched/linear) vinyl sulfides is known as the hydrothiolation reaction. Based upon the nature of unsaturation, i.e. double bond or triple bond, hydrothiolation reactions are classified as thiol–ene and thiol–yne click reactions, respectively. These reactions have emerged as a powerful and widely used strategy for the generation of carbon–sulfur bonds due to several associated benefits including versatile synthetic procedures, wide functional-group tolerance, high atom economy with few to no byproducts, and simple purification. The hydrothiolation reactions have numerous trapping applications in the fields of polymer chemistry, nanoengineering, pharmaceuticals, natural products, and perhaps most importantly in medicinal chemistry for the synthesis of many drugs and bioactive molecules.

scholarly journals Lewis Acid Mediated Cyclizations: Diastereoselective Synthesis of Six- to Eight-Membered Substituted Cyclic Ethers

Synthesis ◽  
2017 ◽  
Vol 49 (18) ◽  
pp. 4229-4246 ◽  
Author(s):  
Arun Ghosh ◽  
Anthony Tomaine ◽  
Kelsey Cantwell
Keyword(s):  
Natural Products ◽  
Drug Design ◽  
Lewis Acid ◽  
Medicinal Chemistry ◽  
Cyclic Ether ◽  
Cyclic Ethers ◽  
Diastereoselective Synthesis ◽  
Acid Catalyzed

Cyclic ethers are widely abundant in natural products. Cyclic ether templates are also utilized in drug design and medicinal chemistry. Although the synthetic processes for this class of compounds have been studied extensively with respect to five- and six-membered rings, medium-sized cyclic ethers are synthetically more challenging due to a variety of factors. Herein, we report our results on the Lewis acid catalyzed synthesis of medium-sized cyclic ethers in a diastereoselective manner.

scholarly journals Dialkylation of Indoles with Trichloroacetimidates to Access 3,3-Disubstituted Indolenines

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4143
Author(s):  
Tamie Suzuki ◽  
Nilamber A. Mate ◽  
Arijit A. Adhikari ◽  
John D. Chisholm
Keyword(s):  
Natural Products ◽  
Transition Metal ◽  
Small Molecule ◽  
Lewis Acid ◽  
Medicinal Chemistry ◽  
Transition Metal Catalysis ◽  
Metal Catalysis ◽  
Rapid Access ◽  
Privileged Scaffolds

2-Substituted indoles may be directly transformed to 3,3-dialkyl indolenines with trichloroacetimidate electrophiles and the Lewis acid TMSOTf. These reactions provide rapid access to complex indolenines which are present in a variety of complex natural products and medicinally relevant small molecule structures. This method provides an alternative to the use of transition metal catalysis. The indolenines are readily transformed into spiroindoline systems which are privileged scaffolds in medicinal chemistry.

scholarly journals Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

2020 ◽  
Author(s):  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Bioactive Molecules ◽  
Reaction Conditions ◽  
Common Procedure ◽  
Broad Scope ◽  
Palladium Catalyzed

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

scholarly journals Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

2020 ◽  
Author(s):  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Bioactive Molecules ◽  
Reaction Conditions ◽  
Common Procedure ◽  
Broad Scope ◽  
Palladium Catalyzed

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

Indolylvinyl Ketones: Building Blocks for the Synthesis of Natural Products and Bioactive Compounds

Synthesis ◽  
2019 ◽  
Vol 51 (04) ◽  
pp. 787-815 ◽  
Author(s):  
Olga Serdyuk ◽  
Igor Trushkov ◽  
Maxim Uchuskin ◽  
Vladimir Abaev
Keyword(s):  
Natural Products ◽  
Organometallic Compounds ◽  
Building Blocks ◽  
Biologically Active ◽  
Bioactive Molecules ◽  
Knoevenagel Reaction ◽  
Core Motif ◽  
Conjugate System ◽  
Electrocyclic Reactions ◽  
Methylene Group

Indolylvinyl ketones are valuable building blocks that can be utilized for the synthesis of numerous natural products and bioactive molecules containing an indole core motif. Herein, we describe their application for the total synthesis of some alkaloids, their analogues, and a variety of other important compounds, with an emphasis on biologically active examples.1 Introduction2 Functionalization of the Enone C=C Bond2.1 Reduction2.2 Michael Addition2.3 Cycloaddition3 Transformation of the Carbonyl Group3.1 Reduction3.2 Knoevenagel Reaction3.3 Addition of Organometallic Compounds3.4 Olefination4 Reactions Involving the Enone Conjugate System С=С–С=О4.1 Reactions with 1,2-Dinucleophiles4.2 Reactions with Compounds Bearing an Active Methylene Group4.3 Reactions with 1,3-Dinucleophiles4.4 Reactions with 1,4-Dinucleophiles5 Functionalization of the Enone Methylene Group C(O)–CH2R5.1 Acylation/Crotonic Condensation and Related Transformations5.2 Enolization6 Functionalization of the Indole Core6.1 [4+2] Cycloaddition6.2 [3+3] Annulation6.3 Electrocyclic Reactions7 Miscellaneous8 Conclusions

Self-Assembly of a Chiral Cubic Three-Connected Net from the High Symmetry Molecules C60 and SnI4

2020 ◽  
Author(s):  
Daniel B. Straus ◽  
Robert J. Cava
Keyword(s):  
Organic Synthesis ◽  
Self Assembly ◽  
Van Der Waals ◽  
Van Der Waals Forces ◽  
High Symmetry ◽  
Molecular Chirality ◽  
Chiral Materials ◽  
Self Assembled ◽  
Chiral Centers

The design of new chiral materials usually requires stereoselective organic synthesis to create molecules with chiral centers. Less commonly, achiral molecules can self-assemble into chiral materials, despite the absence of intrinsic molecular chirality. Here, we demonstrate the assembly of high-symmetry molecules into a chiral van der Waals structure by synthesizing crystals of C<sub>60</sub>(SnI<sub>4</sub>)<sub>2</sub> from icosahedral buckminsterfullerene (C<sub>60</sub>) and tetrahedral SnI4 molecules through spontaneous self-assembly. The SnI<sub>4</sub> tetrahedra template the Sn atoms into a chiral cubic three-connected net of the SrSi<sub>2</sub> type that is held together by van der Waals forces. Our results represent the remarkable emergence of a self-assembled chiral material from two of the most highly symmetric molecules, demonstrating that almost any molecular, nanocrystalline, or engineered precursor can be considered when designing chiral assemblies.

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