Enantioselective Synthesis of cis-Decalin Derivatives by the Inverse-Electron-Demand Diels–Alder Reaction of 2-Pyrones

A novel strategy for the synthesis of cis-decalins by an ytterbium-catalyzed asymmetric inverse-electron-demand Diels–Alder reaction of 2-pyrones and silyl cyclohexadienol ethers is reported here. A broad range of synthetically important cis-decalin derivatives with multiple contiguous stereogenic centers and functionalities are obtained in good yields and stereoselectivities. A full set of diastereomeric substituted cis-decalin motifs are readily accessible by tuning the absolute configurations of substituted silyl cyclohexadienol ethers (R or S) as well as the ligands (R or S). The synthetic potential is showcased by the enantioselective total synthesis of 4-amorphen-11-ol, and further demonstrated by the first total synthesis of cis-crotonin.     

Highly Enantioselective Diels–Alder Reaction Catalyzed by Chiral Imidazolidinone

New chiral imidazolidinone with an indole group was synthesized and used to catalyze the Diels–Alder reaction of α,β-unsaturated aldehyde with diene. High enantiomeric excesses and good yields were obtained. The reaction media were also surveyed. The best result in terms of enantioselectivity was achieved using acrolein and 2,3-dimethylbutdiene (up to 95% ee) in CH₃OH/H₂O.     

Inverse-Electron-Demand Diels–Alder Reactions of 2-Pyrones: Bridged Lactones and Beyond

Inverse-electron-demand Diels–Alder (IEDDA) reactions of electron-poor 2-pyrones as electrophilic dienes have been extensively studied in the past fifty years. These reactions provide an efficient access to bridged bicyclic lactones and their derivatives, such as densely functionalized 1,3-cyclohexadienes after CO₂ extrusion and polysubstituted aromatic compounds through elimination. This reaction has been used for the synthesis of many biologically active natural products and drug candidates. In this review, the developments of these IEDDA reactions including non-catalytic, Lewis acid-catalyzed and organocatalytic IEDDA reactions, and their applications in total synthesis are discussed in detail.     

Synthesis of Chiral Bis-Thiazolines and Asymmetric Diels–Alder Reactions

Abstract

New chiral ligands, bis-thiazoline derivatives (sulfur analogues of known oxazolines) were prepared from chiral bis-(N-acylamino alcohols) with Lawesson's reagent. Bis-thiazolines thus obtained proved to be useful chiral ligands for metal in asymmetric Diels–Alder reaction.     

Synthesis of Functionalized Δ3 Phosphabenzenes by Means of Diels Alder Reaction with Phosphaalkenes

Abstract

Diels Alder reaction provides an easy and general access to functionalized Δ³ phosphabenzenes after aromatization with the possibilities of introducing the functional group either with the diene or the phosphaalkene.     

Enantioselective Synthesis of Complex Fused Heterocycles through Chiral Phosphoric Acid Catalyzed Intramolecular Inverse-Electron-Demand Aza-Diels–Alder Reactions

A stable asymmetric intramolecular Povarov reaction has been established to provide an efficient method to access structurally diverse trans,trans-trisubstituted tetrahydrochromeno[4,3-b]quinolines in high stereoselectivities of up to >99:1 diastereomeric ratio and 99 % enantiomeric excess, without any purification step. Additionally, to facilitate large-scale application of this method, a low catalyst loading protocol was employed, 0.2 mol % chiral phosphoric acid, which provided the cycloadducts without any loss in yield and enantioselectivity. Theoretical studies revealed that the reaction occurred through a sequential Mannich reaction and an intramolecular Friedel–Crafts reaction, wherein the phosphoric acid acted as a bifunctional catalyst to activate the para-phenolic dienophile and N-2-hydroxy-2-azadiene simultaneously.     

Synthesis of tetrahydroanthracen-9-ones by the domino aldol condensation/Diels–Alder cycloaddition

A facile protocol toward several substituted 3-aryl-3,4,4a,10-tetrahydro-2H-anthracen-9-ones 1 starting with substituted 2-allylbenzaldehydes 2 was described. The overall synthetic process was carried out by the domino aldol condensation/Diels–Alder cycloaddition of skeleton 2 with substituted cinnamaldehydes 3 in an alkalic aqueous-methanolic solution followed by base-induced double migration of the resulting cycloadducts. Skeleton 2 was prepared from isovanillin (4) in moderate yield in five-steps via the known procedures with the synthetic sequence of O-allylation, Claisen rearrangement, O-methylation, Grignard methylation, and PCC-mediated oxidation.     

Anomalies in the Change of Volumetric Parameters of the Diels–Alder Reaction in Solution

In this article negative values of the activation volume in retro-Diels–Alder reactions are interpreted in terms of the different possibilities of penetration of the solvent molecules into the sterically branched structures of the adduct and activated complex. Empty spaces, inaccessible to penetration of solvent molecules, lead to increases of the molar volume of the screened adducts in solution and, consequently, to a less negative value of the Diels–Alder reaction volume. The values of partial molar volumes of anthracene, maleic anhydride and the adducts cyclopentadiene–maleic anhydride, anthracene–maleic anhydride and anthracene–tetracyanoethylene, in several solvents, were calculated from the solution density data.     

Re-Evaluation of a Fulvene-Based Self-Replicating Diels–Alder Reaction System

We re-evaluate our claim of a high diastereoselectivity in the self-relicating Diels–Alder reaction between maleimide 1 and fulvene 3 . It was shown that the system has a diastereoselectivity of 1.8:1 for NN-4 : NX-4 , which is contrary to the 16:1 ratio claimed by Dieckmann et al. The analysis of ¹H NMR monitoring of the reaction revealed that both replicators show sigmoidal growth which is typical for auto-catalytic systems.     

Reaction of the levoglucosenone Diels–Alder adducts with acetaldehyde under the McMurry conditions

Reactions of acetaldehyde with Diels–Alder adducts of levoglucosenone with butadiene, isoprene, and cyclohexa-diene assisted by low-valence titanium afford products of acetaldehyde addition to the acetal center with opening of the 1,6-anhydro bridge. In the case of the cyclopentadiene adduct, the reaction gives the product of addition of the ethyl substituent to the acetal center while the 1,6-anhydro bridge remains unchanged.     

Generation of Selenoaldehydes via Retro Diels–Alder Reaction and Their Behavior in the Reaction with Some Enophiles

Abstract

The [4, 2] cycloadducts of selenoaldehydes and anthracene regenerate selenoaldehydes in situ quantitatively under neutral conditions via thermal retro Diels–Alder reaction. The reactions of selenoaldehydes generated by this method with 2-silyloxy-1,3-butadiene, 2-methoxyfuran, and 5-ethoxyoxazoles are described.     

Hetero Diels–Alder Cycloaddition of Indene for the Formal Synthesis of Onychnine

A highly regio‐ and stereoselective hetero Diels–Alder cycloaddition of indene with N‐sulfonyl‐1‐aza‐1,3‐butadiene was achieved. Subsequent transformation of the 5H‐indeno [l,2‐b]pyridine via elimination and reduction provides a new route to azafluorenone (e.g., 1‐methyl‐4‐azafluorene) for the synthesis of onychnine.     

Organocatalytic Enantioselective Diels–Alder Reaction of 2-Trifluoroacetamido-1,3-dienes with α,β-Unsaturated Ketones

We report herein the first examples of chiral phosphoric acid-catalyzed enantioselective Diels–Alder reactions between 2-trifluoroacetamido-1,3-dienes 1 and α,β-unsaturated carbonyl compounds 2 . Polysubstituted 1-acetamido cyclohexenes 3 were formed in high yields with excellent diastereo- and enantioselectivities. The reaction proceeds through a stepwise process as shown by deuterium labelling experiments. A catalytic enantioselective three-component reaction of 1 , 2 and ortho-hydroxybenzhydryl alcohols 4 was subsequently developed furnishing the densely functionalized hexahydroxanthenes 5 in a highly stereoselective manner. This multicomponent reaction generates four chemical bonds with concurrent creation of five contiguous stereocenters.     

Imino Diels–Alder Reactions: Efficient Synthesis of Pyrano and Furoquinolines Catalyzed by ZrCl4

Abstract

Anhydrous zirconium tetrachloride is found to be an efficient catalyst for the Imino Diels–Alder reactions of N‐benzylideneanilines with 3,4‐dihydro‐2H‐pyran and 2,3‐dihydrofuran to afford pyrano and furo [3,2‐c] quinolines in good yields.     

Practical One‐Pot Procedure for the Synthesis of 1,2,3,4‐Tetrahydroquinolines by the Imino‐Diels‐Alder Reaction

A novel‐one‐pot procedure for the synthesis of tetrahydroquinolines via the imino‐Diels‐Alder reaction is described. This procedure gives better yields and exhibits better versatility for alkene substrates than the existing hemi‐aminal based methodologies.     

Mono-Gold(I)-Catalyzed Enantioselective Intermolecular Reaction of Ynones with Styrenes: Tandem Diels–Alder and Ene Sequence

Gold-catalyzed intermolecular reaction leading to dihydronaphthalene derivatives in one pot from two equivalents of ynones with respect to styrene is uncovered. The [4+2] Diels–Alder cycloaddition of ynones and styrenes is catalyzed by a mono-gold(I) complex and the conjugated acid to provide an unstable 3,8a-dihydronaphthalene to subsequently undergo an intermolecular ene-type reaction with the π-activated ynone to afford multi-component coupling dihydronaphthalene products. Linear relationships between chiral ligand-gold complexes and chiral dihydronaphthalene products proves mono-gold catalysis that triggers an asymmetric tandem Diels–Alder and ene reaction sequence.     

Total Synthesis of (−)-Lepadin F based on a Stereoselective Diels–Alder Reaction Controlled by a Ketolactone-type Dienophile

An efficient approach to the type III lepadin alkaloids (lepadins F and G) has been developed through a key Diels–Alder reaction, in which a novel ketolactone-type dienophile with chiral diol unit is employed to generate the desirable all-cis-trisubstituted cyclohexene with excellent regio- and stereoselectivity control. The subsequent selective sulfonylation of the diol unit followed by S_N2 cyclization under hydrogenation conditions could construct the substituted piperidine ring. By using this approach, (−)-lepadin F is synthesized from ethyl l -lactate for the first time.     

Synthesis of isoindolinones via inverse-electron demand Diels–Alder cycloadditions

A new synthetic method has been developed for the synthesis of 2,4,5-substituted isoindolinones by means of intramolecular inverse-electron demand Diels–Alder cycloaddition reactions of substituted pyridazines. By taking advantage of the inherent reactivity of an intermediate chloropyridazine, a diverse set of analogues were prepared from common reagents and intermediates.     

Self-Accelerating Diels–Alder Reaction for Preparing Polymers of Intrinsic Microporosity

It is a formidable challenge in polycondensation to simultaneously construct multiple covalent bonds to prepare double-stranded polymers of intrinsic microporosity (PIMs) with fused multicyclic linkages. To the best of our knowledge, this is the first study to develop a self-accelerating Diels–Alder reaction for successfully preparing double-stranded PIMs with fused multicyclic backbone structures. A self-accelerating Diels–Alder reaction was developed based on the [4+2] cycloaddition of sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DIBOD) and ortho-quinone compounds. In this reaction, the cycloaddition of ortho-quinone with the first alkyne of DIBOD activates the second alkyne, which reacts with ortho-quinone at a rate constant 192 times larger than that of the original alkyne. Using this self-accelerating reaction to polymerize DIBOD and spirocyclic/cyclic difunctional ortho-quinone monomers, a novel stoichiometric imbalance-promoted step-growth polymerization method was developed to prepare PIMs. The resultant PIMs possess intrinsic ultramicropores with pore sizes between 0.45 to 0.7 nm, high specific surface areas above 646 m² g⁻¹, and good H₂ separation performance.     

Stereoselective Synthesis of Novel Diels–Alder Adducts of p-Substituted Methyl Thiocinnamates and Cyclopentadiene

This article describes the Diels–Alder reaction between methyl thiocinnamates, substituted at the para position by electron-donating and electron-withdrawing groups, with cyclopentadiene in the presence of catechol boron bromide (CBB) as a Lewis acid catalyst. The adduct configuration was confirmed by ¹H NMR coupling constants and single-crystal x-ray diffraction. Total endo stereoselectivity was observed in all reactions and was attributed to the effective secondary interaction between the boron atom and the incipient double bond in the norbonene resulting from the planar geometry of the catalyst. ¹³C NMR chemical shifts of the coordinated dienophile carbonyl carbons with CBB compared to those of the non coordinated thiocinammates suggest a strong complexation with the catalyst.