Diels Alder Approach Research Articles

Enantioselective Diels–Alder Approach to Cannabinoids

Enantioselective Diels–Alder Approach to Cannabinoids

A Convenient Diels-Alder Approach toward Potential Polyketide-like Antibiotics Using α-Activated α,β-Unsaturated 4,4-Dimethyl-1-tetralones as Dienophiles.

Making use of a Diels-Alder approach based on various α,β-unsaturated 2-carbomethoxy-4,4-dimethyl-1-tetralones as novel dienophiles, the corresponding polycyclic adducts could be efficiently synthesized in good to high yields (74~99%) in the presence of Lewis acid (e.g., SnCl4). Accordingly, a synthetically useful platform is established to provide a focused aromatic polyketide-like library for screening of potential natural and non-natural antimicrobial agents.

Studies towards the Synthesis of (+)-Dictyoxetane.

The dolabellane-type diterpene dictyoxetane represents a significant challenge to synthetic organic chemistry. Methodology directed towards the total synthesis of naturally occurring (+)-dictyoxetane is reported. Catalytic asymmetric synthesis of the trans-hydrindane ring system is achieved through chemoselective deoxygenation of the Hajos-Parrish ketone. An alternative to the Garst-Spencer furan annulation is developed for the synthesis of a 2,5-dimethyl, tetrasubstituted furan, employing a tandem 5-exo-dig alcohol to alkyne cyclisation/aromatisation reaction as a key step. The (4+3) cycloaddition reaction of an oxyallyl cation with a tetrasubstituted furan is established on a cyclohexanone-derived model system, and a range of related (4+3) cycloadditions investigated on a homochiral, trans-hydrindane-fused furan, where regio- and diastereoselectivity is required for the natural product synthesis. In an alternative (4+2) Diels-Alder approach, a C2 -symmetric vinyl sulfoxide-based chiral ketene equivalent is used to prepare oxanorbornenes with the same oxygen bridge stereochemistry found in the 2,7-dioxatricyclo[4.2.1.03,8 ]nonane ring system of the natural product.

Sustainable Solvent-Free Diels–Alder Approaches in the Development of Constructive Heterocycles and Functionalized Materials: A Review

The Diels-Alder reaction (DAR) is found in myriad applications in organic synthesis and medicinal chemistry for drug development, as it is the method of choice for the expedient synthesis of complex natural compounds and innovative materials including nanomaterials, graphene expanses, and polymeric nanofibers. Furthermore, the greatest focus of attention of DARs is on the consistent reaction procedure with stimulus yields by highly stereo- and regioselective mechanistic pathways. Therefore, the present review is intended to summarize conventional solvent-free (SF) DARs for the expedient synthesis of heterocyclic compounds and materials. In particular, this review deals with the DARs of mechanochemical grinding, catalysis (including stereoselective catalysts), thermal, and electromagnetic radiation (such as microwave [MW], infrared [IR], and ultraviolet [UV] irradiation) in SF procedures. Therefore, this comprehensive review validates the application of DARs to pharmaceutical innovations and biorenewable materials through consistent synthetic approaches.

Functionalization of Meldrum’s Acid by Diels‒Alder Approach

Functionalization of Meldrum’s Acid by Diels‒Alder Approach

The Diels-Alder Approach towards Cannabinoid Derivatives and Formal Synthesis of Tetrahydrocannabinol (THC).

Based on the Diels‐Alder reaction of vinylchromenes with electron‐poor dienophiles, we developed a strategy for the synthesis of tetrahydrocannabinol derivatives. Substituted vinyl chromenes could be converted with several dienophiles to successfully isolate several complex molecules. These molecules already contain the cannabinoid‐like base structure and further processing of one such derivative led to a precursor of Δ9‐tetrahydrocannabinol. The most challenging step towards this precursor was an epoxidation step that was ultimately achieved via dimethyl dioxirane.

Stereoselective Diels-Alder Reactions of gem-Diborylalkenes: Toward the Synthesis of gem-Diboron-Based Polymers.

Although gem-diborylalkenes are known to be among the most valuable reagents in modern organic synthesis, providing a rapid access to a wide array of transformations, including the construction of C–C and C-heteroatom bonds, their use as dienophile-reactive groups has been rare. Herein we report the Diels–Alder (DA) reaction of (unsymmetrical) gem-diborylalkenes. These reactions provide a general and efficient method for the stereoselective conversion of gem-diborylalkenes to rapidly access 1,1-bisborylcyclohexenes. Using the same DA reaction manifold with borylated-dienes and gem-diborylalkenes, we also developed a concise, highly regioselective synthesis of 1,1,2-tris- and 1,1,3,4-tetrakis(boronates)cyclohexenes, a family of compounds that currently lack efficient synthetic access. Furthermore, DFT calculations provided insight into the underlying factors that control the chemo-, regio-, and stereoselectivity of these DA reactions. This method also provides stereodivergent syntheses of gem-diborylnorbornenes. The utility of the gem-diborylnorbornene building blocks was demonstrated by ring-opening metathesis polymerization (ROMP), providing a highly modular approach to the first synthesis of the gem-diboron-based polymers. Additionally, these polymers have been successfully submitted to postpolymerization modification reactions. Given its simplicity and versatility, we believe that this novel DA and ROMP approach holds great promise for organoboron synthesis as well as organoboron-based polymers and that it will result in more novel transformations in both academic and industrial research.

A Diels-Alder Approach to Cannabinoid Derivatives

A Diels-Alder Approach to Cannabinoid Derivatives

A versatile Diels-Alder approach to functionalized hydroanthraquinones.

The synthesis of highly substituted hydroanthraquinone derivatives with up to three stereogenic centres via a Diels–Alder reaction, starting from easily accessible 2-substituted naphthoquinones, is described. The [4+2]-cycloaddition is applicable for a broad range of substrates, runs under mild conditions and results in high yields. The highly regioselective outcome of the reactions is enabled by a benzoyl substituent at C2 of the dienophiles. The obtained hydroanthraquinones can be further modified and represent ideal substrates for follow-up intramolecular coupling reactions to create unique bicyclo[3.3.1] or -[3.2.2]nonane ring systems which are important natural product skeletons.

New pyridylphenylene cyclopentadienon as a building block for dendrimer synthesis

The synthesis of new tetrasubstituted pyridyl-containing cyclopentadienone, namely, 3,4-bis(4-(phenylethynyl)phenyl)-2,5-di(pyridin-2-yl)cyclopenta-2,4-dien-1-one is reported for the first time as a monomer for dendrimer synthesis. The synthesis by Diels—Alder approach allowed to prepare 2nd generation dendrimer with phenylethynyl peripherial fragments. A presence of triple bonds in the structure of dendrimers determines the possibility of their subsequent modification, in particular, by coordinating with metal compounds to obtain catalytically active nanocomposites.

Synthesis and Optoelectronic Properties of Iptycene–Naphthazarin Dyes

We report the synthesis and characterization of iptycene–naphthazarin dyes by using a sequential Diels–Alder approach. The tautomerization of naphthazarin was used as the key step in the synthesis, with structures confirmed by single-crystal X-ray and NMR analysis. The systematic trends in electronic properties were investigated by UV/Vis spectroscopy. BF2 complexes of the dyes were prepared by reaction with BF3·OEt2 in CH2Cl2.

Total Synthesis of (±)-Prostratin

Summary Prostratin, a highly complex diterpene natural product, is a pre-clinical candidate in developing a cure for HIV-1 infection and also a potent and selective inhibitor of several tumors. Despite nearly 40 years of progress, prostratin and related natural products still present formidable challenges for synthetic chemists. Here, we report a total synthesis of (±)-prostratin that proceeds in 23 steps from cyclopentadiene. The synthetic strategy includes rapid assembly of the tricyclic core and highly controlled establishment of the densely functionalized C ring, featuring an array of stereoselective transformations including alkoxide-guided 1,4-additions and cyclopropane formation. This work should enable further explorations of chemical and biological spaces based on prostratin and related natural products.

Exploration of synthetic strategies for the stereoselective preparation of novel tetrahydrofuran-containing biaryls: A high-pressure promoted Diels-Alder approach

Three stereoselective synthetic approaches to tetrahydrofuran-containing biaryl scaffolds are described. All approaches involve a high-pressure promoted Diels-Alder reaction of substituted diene with methyl propiolate to give, after aromatization, the corresponding biaryl. The tetrahydrofuran moiety can be created starting from aryl-Br or aryl-CO2Me functional groups through a γ-phenylseleno ketone intermediate.

ChemInform Abstract: Diels—Alder Approaches for the Synthesis of Bridged Bicyclic Systems: Synthetic Applications of (7‐Hetero)norbornadienes

AbstractReview: approaches used in the last ten years for the synthesis of (7‐hetero)norbornadenes and their synthetic applications

Diels-Alder Approaches for the Synthesis of Bridged Bicyclic Systems: Synthetic Applications of (7-hetero)norbornadienes

Diels-Alder Approaches for the Synthesis of Bridged Bicyclic Systems: Synthetic Applications of (7-hetero)norbornadienes

Synthetic Approaches to Coronafacic Acid, Coronamic Acid, and Coronatine

The phytotoxin coronatine (COR) is a functional mimic of the active plant hormone (+)-7-iso-jasmonoyl- l -isoleucine (JA-IIe), which regulates stress responses. Structurally, COR is composed of a core unit, coronafacic acid (CFA), which is connected to coronamic acid (CMA), via an amide linkage. COR has been found to induce a range of biological activity in plants and based on its biological profile, COR, as well as CFA, and CMA are attractive starting points for agrochemical discovery, resulting in numerous total synthesis efforts. This review will discuss the synthetic approaches towards CFA, CMA and, ultimately COR, to date. 1 Introduction 2 Total Synthesis of Coronafacic Acid (CFA, 4) 2.1 Mapping Synthetic Strategies 2.2 Intermolecular Diels–Alder Approaches 2.3 Intramolecular Diels–Alder Approaches 2.4 Conjugate Addition Approaches 2.5 Haller–Bauer Approaches 2.6 Intramolecular Cyclisation Approaches 2.7 Oxy-Cope Approaches 3 Total Synthesis of Coronamic Acid (CMA, 5) 3.1 Mapping Synthetic Strategies 3.2 Final Installation of C1 3.3 Final Installation of C2 3.4 Final Installation of C3 4 Total Synthesis of Coronatine (COR, 1) 5 Conclusions

A Sustainable Route to a Terephthalic Acid Precursor.

A new synthetic pathway for the production of p-toluic acid has been developed starting from reagents derived from renewable resources. A Diels-Alder reaction between sorbic and acrylic acids is followed by a combined dehydrogenation/ decarboxylation process, providing p-toluic acid in high yields. This route permits to use milder conditions compared to other Diels-Alder approaches reported in the literature, and therefore can contribute to a more sustainable terephthalic acid production.

A Domino Diels–Alder Approach toward the Tetracyclic Nicandrenone Framework

The tetracarbocyclic framework of the nicandrenone natural products is formed in one step from a linear precursor via a domino intramolecular Diels-Alder/intramolecular furan Diels-Alder/aromatization sequence. The approach represents a new 0 → ABCD strategy for the preparation of aromatic steroids.

Total synthesis of (+)-gelsemine via an organocatalytic Diels-Alder approach.

The structurally complex alkaloid gelsemine was previously thought to have no significant biological activities, but a recent study has shown that it has potent and specific antinociception in chronic pain. While this molecule has attracted significant interests from the synthetic community, an efficient synthetic strategy is still the goal of many synthetic chemists. Here we report the asymmetric total synthesis of (+)-gelsemine, including a highly diastereoselective and enantioselective organocatalytic Diels–Alder reaction, an efficient intramolecular trans-annular aldol condensation furnishing the prolidine ring and establishing the configuration of the C20 quaternary carbon stereochemical centre. The entire gelsemine skeleton was constructed through a late-stage intramolecular SN2 substitution. The enantiomeric excess of this total synthesis is over 99%, and the overall yield is around 5%.

A Diels–Alder Approach to a Communesin Model: A/B‐Cyclization Route

AbstractCompound 3, a model system for communesin F, was approached by using a Diels–Alder reaction for the introduction of the vicinal quaternary stereocentres. Subsequent introduction of A/B‐ring system followed by D/E‐ring closure gave hexacyclic system 22. All attempts to reduce this material to give compound 3 were, however, unproductive.