Intramolecular Diels-Alder Cyclization Research Articles

Silacycle-Templated Intramolecular Diels-Alder Cyclizations for the Diastereoselective Construction of Complex Carbon Skeletons.

The utility of the dioxasiline ring as a π-facial directing group in the intramolecular Diels-Alder cyclization is explored. An initial investigation of substrate scope demonstrates that the rigidity of this directing group delivers robust stereocontrol across a number of substrates, affording single diastereomers in moderate to good yields. A mechanistic investigation reveals that the reactive diene is formed through γ deprotonation followed by [1,5] hydride shifts.

The electronic effect of N-protecting groups on Diels–Alder cycloaddition reaction of furan-cored compounds

Furan-derived nitrogen side-chain molecules were used to investigate the effect of nitrogen-protecting groups on intramolecular Diels–Alder cyclization reaction yields. The protection reactions were carried out in both dichloromethane and water. The protected molecules were synthesized in dichloromethane and then cycled in toluene. On the other hand, in water as a reaction media both protection and cyclization were carried out in the same environment which provides advantages in saving time and chemicals. To study the electronic effects of protecting groups, various electron-withdrawing and electron-donating protective groups were used and their effects on cyclization were evaluated. As a result, the mesomeric electron-withdrawing and sterically large protecting groups increased the yield of Diels–Alder cycling reactions effectively. In addition, the iminium ion formed between some protecting groups and the molecule caused the formation of E/Z isomers and this was demonstrated by dynamic NMR experiments.

Synthesis of an Isomer of the Decalinoyltetramic Acid Methiosetin by a Stereocontrolled IMDA Reaction of a Metal-Chelated 3-Trienoyltetramate.

An isomer of the 3-decalinoyltetramic acid methiosetin was synthesized for the first time. The decalin moiety was established by a late-stage intramolecular Diels-Alder cyclization catalyzed by Me2AlCl or La(OTf)3. Its high diastereoselectivity arose from stereoinduction by a well-defined metal O,O-chelate complex of the 3-acyltetramic acid moiety. The nature of the metal and the bulkiness of the residues at the tetramic acid chelator are decisive for the stereochemical outcome.

Quantification of Nonstatistical Dynamics in an Intramolecular Diels–Alder Cyclization without Trajectory Computation

Experimental and computational (DFT) investigations reveal that enyne-allenes with an aryl group as probe at the allene terminus follow a dynamic non-IRC Diels-Alder cyclization pathway. Starting from two separate C(2)-C(6) (Schmittel) transition states (TS), two distinct reaction paths originate that share a common diradical intermediate, however, without mixing! Because the momentum of the initial TS is transmitted into product formation, we suggest a simple protocol without trajectory computations to estimate the fraction of molecules that follow nonstatistical dynamics: It was calculated from the partitioning at the TSs, as derived from DFT computations, and the experimental ratio. The thus-determined percentage of dynamically reacting molecules only slightly depends on the depth of the intermediate well but rather on ΔΔG(‡) of the initial and the follow-up transition states.

The First Stereoselective Total Synthesis of the Immunosuppressive Decalin Derivative Monascusic Acid B

The first stereoselective total synthesis of the immunosuppressive decalin derivative monascusic acid B has been accomplished from ( R )-(+)-pulegone involving Horner–Wadsworth–Emmons and Julia–Kocienski olefination reactions and Lewis acid catalyzed intramolecular Diels–Alder cyclization.

Synthetic studies directed toward the AB decalin common to HMP-Y1 and hibarimicinone

Efforts toward the synthesis of the decalin ring system common to the hibarimicin shunt metabolite HMP-Y1 and parent aglycone hibarimicinone are reported herein. An intramolecular Diels–Alder cyclization rapidly generated the decalin framework. Two approaches toward completion of the AB decalin were vetted. Incorporation of a phenylsulfonyl leaving group β- to both a ketone and a γ-lactone followed by base-induced elimination of sulfinate led to the undesired α,β-unsaturated lactone. Methanolysis of the γ-lactone followed by elimination produced the unexpected bridged cyclic ether by way of an intramolecular oxy-Michael addition of the endo oriented C13 alcohol.

Diastereoselective Synthesis of Bridged Polycyclic Alkaloids via Tandem Acylation/Intramolecular Diels–Alder Reaction

A mild and efficient stereoselective synthesis of hexacyclic indole alkaloids with a tetrahydro-β-carboline motif has been developed by utilizing the Pictet-Spengler reaction and tandem N-acylation followed by intramolecular Diels-Alder cyclization. Initially, a diene unit was installed in the tetrahedron β-carboline skeleton through Pictet-Spengler cyclization of the corresponding aldehyde with tryptophan ester. The dienophile moiety was introduced by N-acylation of tetrahydro-β-carboline. Successive, in situ, [4 + 2] intramolecular Diels-Alder cycloaddition of the activated dienophile and conjugated diene containing intermediate furnished bridged polycyclic heterocycles with high diastereoselectivity. Formation of four new rings, five new covalent bonds, and five new chiral centers with excellent stereoselectivity is the key feature of this strategy. The diastereoselective formation of product was attributed to intramolecular chirality transfer through a chiral amino acid. The stereoselective outcome of this tandem reaction was confirmed by X-ray crystallographic studies. The developed synthetic strategy was also explored on a soluble polymer support to incorporate the advantage of rapid synthesis and a high-throughput workup process toward the development of a green synthetic protocol for polycyclic alkaloids.

ChemInform Abstract: Synthesis of Phenanthridine Derivatives by Microwave‐Mediated Cyclization of o‐Furyl(allylamino)arenes.

A novel and efficient synthesis of phenanthridines and aza analogues is reported. The key step is a microwave-mediated intramolecular Diels–Alder cyclization of o-furyl(allylamino)arenes. In the pr...

Synthesis of Phenanthridine Derivatives by Microwave-Mediated Cyclization of o-Furyl(allylamino)arenes

A novel and efficient synthesis of phenanthridines and aza analogues is reported. The key step is a microwave-mediated intramolecular Diels-Alder cyclization of o-furyl(allylamino)arenes. In the presence of a catalytic amount of acid, the DA-adduct reacts further to give the dihydrophenanthridines, which easily can be oxidized to fully aromatic compounds by air in the presence of UV light or by DDQ.

Total Synthesis of (±)-Maoecrystal V

The total synthesis of racemic maoecrystal V has been accomplished. Key steps include an intramolecular Diels-Alder cyclization to rapidly construct the core system from simple starting materials and the creation of the A-C ring trans-fusion through intramolecular delivery of a hydrogen to the hindered β-face of the ring system.

Intramolecular Nitroalkene Diels-Alder Reaction Catalyzed by Brønsted Acids

Bronsted acid catalysis of intramolecular Diels―Alder cyclizations of (E)-1-nitro-1,6,8-nonatrienes and (E)-1-nitro-1,7,9-decatrienes was investigated. Catalyzed reactions showed significantly higher endo selectivities than the corresponding thermal reactions. To our knowledge, this is the first example of catalysis (substoichiometric amount of catalysts) of the intramolecular nitroalkene Diels―Alder reaction.

Unexpected exo selectivity for an intramolecular Diels–Alder reaction involving a doubly-activated δ-pentenolide dienophile

The intramolecular Diels–Alder cyclization of a homochiral doubly-activated δ-pentenolide system is described, proceeding predominantly via an exo transition state to provide an advanced precursor toward unique stereochemical analogs of (+)-symbioimine.

Toward the total synthesis of maoecrystal V: an intramolecular Diels–Alder route to the maoecrystal V pentacyclic core with the appropriate relative stereochemistry

A diastereoselective route to the maoecrystal V core compound ( 6) has been achieved. Key transformations include an intramolecular Diels–Alder cyclization and an exo-glycal epoxide rearrangement sequence.

Stereoselective synthesis of the decahydrofluorene core of the hirsutellones

A stereoselective synthesis of the decahydrofluorene core of the hirsutellones was accomplished in eight steps and in 43% overall yield. The key step of the synthesis is the highly stereoselective intramolecular Diels–Alder cyclization of the siloxacyclopentene-constrained tetraene 1.

ChemInform Abstract: Intramolecular Diels—Alder Cyclization of Biodihydroxylated Benzoic Acid Derivatives Towards Novel Heterocyclic Scaffolds.

AbstractThe potential of bio‐dihydroxylated benzoic acid (II) as a versatile precursor for the construction of novel polycyclic scaffolds utilizing intramolecular Diels—Alder cyclization reaction is demonstrated.

ChemInform Abstract: Synthesis of Octahydro 1H-Pyrrolo[1,2-a]indol-3-ones via Intramolecular Diels-Alder Reaction of 5-Substituted N-Dienyl Lactams.

Abstract N-dienyl-5-alkenyl-lactams can be prepared from succinimide. Heating leads to an intramolecular Diels-Alder cyclization that produces tricyclic products useful for the preparation of related alkaloids.

Exploring the Original Proposed Biosynthesis of (+)-Symbioimine: Remote Exocyclic Stereocontrol in a Type I IMDA Reaction

The originally proposed biosynthesis of (+)-symbioimine was explored, resulting in the successful intramolecular Diels-Alder (IMDA) cyclization of an appropriate (E,E,E)-1,7,9-decatrien-3-one. In contrast to the originally proposed biosynthesis, the IMDA reaction appears to proceed via an endo transition state. Remarkably, a single exocyclic stereogenic center effectively controls the pi-facial selectivity affording a highly diastereoselective cycloaddition.

Intramolecular Diels–Alder cyclization of biodihydroxylated benzoic acid derivatives towards novel heterocyclic scaffolds

The potential of biodihydroxylated benzoic acid derivatives as versatile precursors for the construction of polycyclic scaffolds was investigated. Ralstonia eutropha B9 was used to biodihydroxylate sodium benzoate to sodium (1S,2R)-1,2-dihydroxycyclohexa-3,5-diene-1-carboxylate in high optical purity (>95% ee). The required cyclization precursors could be obtained in moderate to excellent yields after protection of the intermediate and subsequent functional group transformation. Intramolecular Diels–Alder cylizations were carried out under thermal or microwave conditions leading to enantiomerically pure products with five chiral centers.

Synthesis of a key intermediate for the total synthesis of pseudopteroxazole

A facile synthesis of a key intermediate for the total synthesis of anti-mycobacterial compound pseudopteroxazole is described employing an intramolecular Diels–Alder cyclization and an iodine-mediated oxidative aromatization step.

Expedient Stereoselective Synthesis of Coronafacic Acid Through Intramolecular Diels—Alder Cyclization.

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