Microwave-induced domino-Knoevenagel-hetero Diels–Alder reaction—an easy route to di[1]benzopyrano[2,3-b:4′,3′-d]pyridine

MW-irradiation of a well-ground equimolar mixture of 2-(N-alkynyl-N-aryl)aminochromone-3-carbaldehyde and dimedone underwent domino-Knoevenagel-hetero Diels–Alder (DKHDA) reaction for nonterminal alkynes, whereas conventional heating of the above reaction mixture in ethanol in the presence of pyridine accomplished alkyne-carbonyl metathesis (ACM) reaction or both ACM and DKHDA reaction. Here is the first example of an organo-catalyzed ACM reaction.     

An organocatalytic rearrangement of 2-(N-alkyl-/aryl-)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde

2-(Arylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 4-oxo-4H-1-benzopyran-3-carbanilide when treated with glycine in the presence of formalin, but under similar conditions 2-(alkylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 3-alkylaminomethylenechroman-2,4-dione.     

Angular hydroxymethyl directed intramolecular Diels-Alder approach for the stereo- and regioselective synthesis of pimaraditerpenes

The stereo- and regioselective synthetic route to pimaraditerpenes, employing an angular hydroxymethyl directed intramolecular Diels-Alder reaction of the decaline intermediate, has been developed. This synthetic approach allows prompt access to both natural pimaraditerpenes and the unnatural regioisomers, which would be potentially new anti-inflammatory pimaraditerpenes.     

Strategic innovations for the synthesis of vinigrol

Since the isolation of unique tricyclic diterpenoid vinigrol, its promising biological activities and complex framework have resulted in numerous synthetic efforts to the total synthesis of this venerable molecule for the past two and half decades. This mini review highlights the significance of various synthetic strategies towards this structurally unique and challenging natural product.     

A one-pot three-component reaction in aqueous micellar medium: an easy route to chromeno[2,3-b]quinolinedione

An efficient and green synthesis of hitherto unreported 5-aryl-3,3-dimethyl-2,3-dihydro-5aH-chromeno[2,3-b]quinoline-1,11(4H,5H)dione has been accomplished by a three-component reaction involving chromone-3-carbaldehyde, an aromatic amine, and 5,5-dimethyl-1,3-cyclohexanedione (dimedone) in 1.8 M aqueous TBAB solution. It is noteworthy that the TBAB/H₂O system can be recovered and reused for seven cycles directly.     

Synthetic studies of GKK1032s: the asymmetric synthesis of the decahydrofluorene skeleton via a novel cyclization of silyl enol ether and sequential retro Diels-Alder and intramolecular Diels-Alder reactions

GKK1032s, which were isolated from the culture broth of Penicillium sp. GKK1032, exhibit antitumor activity. We constructed the fully elaborated decahydrofluorene skeleton of GKK1032s. The C-ring was constructed by intramolecular cyclization reaction between a chiral epoxide and silyl enol ether, and the dienophile moiety was introduced concurrently. In addition, the AB-rings were stereoselectively constructed using novel sequential retro Diels-Alder (DA) and intramolecular Diels-Alder (IMDA) reactions. Several further modifications of the IMDA adduct were carried out, leading to the asymmetric synthesis of the desired hydroxyester including nine stereo centers.     

Stereoselective intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes: a novel approach for the synthesis of complex annulated uracils

The intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes 4, obtained from salicylaldehyde 1 via O-allylation followed by Knoevenagel condensation with barbituric acids 3 in the presence of hydrochloric acid as catalyst, affords the tetracyclic uracil derivatives 5 and 6 in a stereoselective manner and high overall yields.     

Intramolecular Diels-Alder Reactions of Thio-Substituted Dienes with Enones

Thio-substituted dienes bearing an enone moiety were readily prepared from 3-sulfolenes, and their intramolecular Diels-Alder (IMDA) reactions were studied. Octahydronaphthalenones were produced in good yield with high stereoselectivity. Hexahydroindenones were also obtained, but the stereoselectivity was lower.     

Investigations of the stereoselectivity of the intramolecular Diels-Alder reaction of a spiculoic acid model system

Model linear precursors to the spiculoic acids were prepared and underwent thermally induced IMDA reactions. The configuration of C5 in the stereotriad was found to dominate any inherent endo/exo selectivity of the IMDA reaction. The isomer (2E,5S)-20 underwent the IMDA to give the spiculoic acid stereochemistry in 84% yield and 94% ds. The required stereotriads were synthesised using stereoselective substrate-controlled aldol reactions; an anti-boron aldol reaction, controlled by the π-facial preference of (S)-2-benzoyloxypentan-3-one ((S)-27) led to (5R)-(22) and a syn-titanium aldol reaction, under the stereocontrol of a chiral N-acylthiazolidinethione (42) led to (5S)-(22). Chain extension using standard Wittig, HWE and ‘modified’ Julia olefinations installed the diene and dienophile components giving the linear precursors to the IMDA reactions.     

Synthesis and domino metathesis of functionalized 7-oxanorbornene analogs toward cis-fused heterocycles

Here, we report our strategy to synthesize structurally diverse cis-fused heterocycles via 7-oxanorbornene analogs. By the intramolecular Diels-Alder reaction of 3-iodoacrylamide, followed by the domino metathesis reaction, the cis-fused heterobicyclic skeleton was efficiently constructed in 5-8 steps.     

Microwave-assisted organocatalytic multicomponent Knoevenagel/hetero Diels-Alder reaction for the synthesis of 2,3-dihydropyran[2,3-c]pyrazoles

A rapid protocol for the multicomponent microwave-assisted organocatalytic domino Knoevenagel/hetero Diels-Alder reaction (DKHDA) has been developed for the synthesis of 2,3-dihydropyran[2,3-c]pyrazoles. The reported procedure could be used for the fast generation of novel substituted 2,3-dihydropyran[2,3-c]pyrazoles with potential anti-tuberculosis activity.     

Intramolecular Diels-Alder Reactions of Furans with Allenyl Ethers. Formation of Indanone and Tetralone

The intramolecular Diels-Alder reactions of the furans 3 , 11a and 11b produced indanone 6 and tetralones 14a and 14b respectively, presumably via the corresponding allenyl ethers 4 , 12a and 12b and the intramolecular cycloadducts 5 , 13a and 13b .     

Catalytic imino Diels-Alder reaction by triflic imide and its application to one-pot synthesis from three components

An imino Diels-Alder reaction of 2-siloxydienes with aldimines catalyzed by triflic imide (Tf₂NH; 0.1∼10 mol % amount) has been developed leading to substituted piperidin-4-ones. Tf₂NH catalyst is compatible with basic functions, such as pyridine and indole rings in the imino Diels-Alder reaction. Furthermore, X-ray crystallographic analysis indicates that trans-2,6-diphenyl-4-piperidinone 4a obtained by this reaction has a unique conformation in the solid state.     

Propylphosphonic anhydride(T3P~) catalyzed one-pot synthesis of α-aminonitriles

The Strecker reaction was performed via a one-pot three component condensation of hetero aromatic/aromatic aldehydes, secondary amines and trimetylsilyl cyanide in the presence of propylphosphonic anhydride(T3P~) to accomplish the corresponding a-aminonitriles. The main advantages of this method are very short reaction time and excellent yields.     

Intramolecular Diels-Alder Reactions via 3-(Phenylthio)-4-(Trimethylsilyl)-3-Sulfolene

Deprotonation of the title compound 2 followed by treatment with 5-iodo-1-pentene or 6-iodo-l-hexene gave the alkylated products 3 and 4 which upon refluxing in toluene yielded the dienes 8a and 8b. Intramolecular Diels-Alder reactions were achieved by heating the dienes 8a and 8b in toluene in a sealed tube at 160–180°C to give bicyclo[4.3.0]nonene 9 and bicyclo[4.4.0]decene 10, respectively, in good yield. The stereochemistry of the cyclization products was determined, and was rationalized by comparison of the possible transition states involved.     

Synthesis of 2-Acyl-2H-1,2,3-diazaphospholes and Their Diels-Alder Reaction with Cyclopentadiene

2H-1,2,3-Diazaphospholes 3a-3h were prepared from various ketone acylhydrazones and phosphorus trichloride in the presence of triethylamine. Compounds 3 underwent feasible hetero-Diels-Alder reactions with cyclopentadiene to afford the respective anellated [1,2,3]diazaphospholes 4a--4d as well as 4a‘--4d‘ in moderate yields. The endo rule in the reaction was observed under kinetic control conditions.     

Efficient one-pot synthesis of benzopyranobenzopyrans and naphthopyranobenzopyrans by domino aldol-type reaction/hetero Diels-Alder reaction of resorcinols and naphthols

The efficient one-pot synthetic approaches for benzopyranobenzopyrans and naphthopyranobenzopyrans are described. The key strategies involve ethylenediamine diacetate-catalyzed cyclization by domino aldol-type reaction/hetero Diels-Alder reaction of resorcinols and naphthols to benzaldehydes with O-allyl ether groups. These reactions provide a rapid route for the synthesis of novel types of polyheterocycles with stereochemically defined quaternary carbon centers.     

Towards the total synthesis of tangutorine by intramolecular Diels-Alder reaction

The syntheses of 3,5-disubstituted-2-sulfolenes, and their participation in Pictet-Spengler reactions to give precursors of tangutorine, are described.     

Diels-Alder modification of monoterpenes and Alder-ene synthesis involving 3-methyl-3-cyanocyclopropene

Monoterpene derivatives with a cyclopropane moiety in the molecule were prepared by reactions of 3-methyl-3-cyanocyclopropene with several monoterpenes and terpenoids (β-myrcene, neoalloocimene, alloocimene, β-pinene, carvone). They were formed using the Diels-Alder reaction, Alder-ene synthesis, conjugated Alder-ene addition, and Diels-Alder cyclization. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 350–353, July–August, 2006.     

A one-pot synthesis of 3,3′-methylenebis(2-arylamino-4H-chromen-4-one) from C-(4-oxo-4H-1-benzopyran-3-yl)-N-arylnitrone

2-(Arylamino)-4-oxo-4H-chromene-3-carbaldehyde 3 (R² = aryl) produces 12H-chromeno[2,3-b]quinolin-12-one 4 when treated with sarcosine, piperidine or diethylamine, but produces 3,3′-methylenebis(2-arylamino-4H-chromen-4-one) 8 when treated with the same amine in the presence of an excess of formaldehyde. Compound 3 (R² = alkyl) was found to be less reactive than the N-aryl analogues towards the deformylative Mannich-type reaction.