Thioamides as useful synthons in the synthesis of heterocycles.

The hetero Diels-Alder reaction is one of the most important methods for the synthesis of heterocycles. In this article an overview is given for the period since 1989 describing the reaction of heterobutadienes such as oxabutadienes, thiabutadienes, azabutadienes, diaazabutadienes, nitroso-alkenes and nitroalkenes as well as of heterodienophiles such as carbonyls, thiocarbonyls, imines, iminium salts, azo- and nitroso compounds. In addition, several other less common hetero Diels-Alder reactions such as cycloadditions of thiaazabutadienes, oxaazabutadienes, dioxabutadienes, dithiabutadienes, oxathiabutadienes, diazaoxabutadienes as well as the use of N-sulfinyl-phosphaalkynes and other dienophiles are mentioned. A main point of discussion is the stereoselectivity of the reactions and the preparation of enantiopure compounds either using dienes and dienophiles carrying a chiral auxiliary or employing chiral Lewis acids. A point stressed is the synthesis of natural products using hetero Diels-Alder reactions leading to carbohydrates, alkaloids, terpenes, antibiotics, mycotoxins, cytochalasans, antitumor agents and several other classes of natural products.

Hetero diels-alder reactions in organic chemistry

In 1894 Knoevenagel published a paper in the journal Chemisehe Berichte on the reaction of formaldehyde and diethyl malonate in the presence of diethylamine as catalyst.1 He obtained the bis adduct (1). Two years later he was able to show that the reaction of benzaldehyde and ethyl acetoacetate in the presence of piperidine gives the bis adduct (2) at room temperature and at 0 °C the benzylidene-1,3-di- carbonyl (3; Scheme 1).2

1.11 – The Knoevenagel Reaction

The review surveys the state-of-the-art in the methodology of multicomponent cascade heterocyclisation and its prospects as applied to the targeted synthesis of polyfunctional pyridines and their hydrogenated and fused analogues. The bibliography includes 405 references.

Multicomponent cascade heterocyclisation as a promising route to targeted synthesis of polyfunctional pyridines

This review is concerned with the synthesis, structure, physico-chemical properties and reactivity of 3-cyanopyridin-2(1H)-ones, -thiones, and -selenones and their derivatives. The 3-cyanopyridin-2(1H)-ones, -thiones, and -selenones being bifunctional compounds containing nitrile and amide, thioamide, or selenoamide groups with an endocyclic nitrogen atom are widely used in the synthesis of different classes of annelated heterocycles possessing practically important properties.

Advances in the chemistry of 3-cyanopyridin-2(1h)-ones, -thiones, and -selenones

A new route to the cycloalkeno-pyridines2 and cycloalkeno-thiopyrans5 by the reaction of malononitrile with enamines of cyclic β-ketocarbothionic acid anilides is presented. The elucidation of the structure of compounds obtained is based on MS spectral data. The reaction is proposed to be a sequence of addition, elimination and cyclization.

TheKnoevenagel reaction of malononitrile with some cyclic β-ketocarbothionic acid anilides synthesis of cycloalkeno-pyridines and cycloalkeno-thiopyrans

Stereoselective synthesis of bridged azepine derivatives via polyfunctionalized spiroannulated thiophene. Novel rearrangement of oxime esters.

The hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propenenitriles1a–d with enol ethers2a–c yieldscis/trans diastereoisomers of 2-alkoxy-4,6-diaryl-3,4-dihydro-2H-pyran-5-carbonitriles3 and4 in 79–98% yield. The similar reaction of1a–c with cyclic enol ether5 affords diastereoisomeric cycloadducts6 and7 withcis annulated pyran rings. Reaction of3 with sulfuric acid leads to 2-hydroxy-3,4-dihydro-2H-pyran-5-carbonitriles8 and9.

Hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propenenitriles with enol ethers. Synthesis of 2-alkoxy-3,4-dihydro-2H-pyran-5-carbonitriles

The reaction of benzoylacetonitrile, methyl cyanoacetate, and ethyl benzoylacetate with 2-allyloxy- and 2-(3-methyl-2-butenyloxy)-benzaldehyde as well as 2-(3-methyl-2-butenyloxy)-1-naphthaldehyde afforded the corresponding Knoevenagel condensation products. Some of those underwent spontaneous intramolecular cycloaddition to give cis-fused 2H-pyran derivatives as major products. One-pot reactions of 1,3-cyclohexanedione and 5,5-dimethyl-1,3-cyclohexanedione with 2-(3-methyl-2-butenyloxy)-benzaldehyde and 2-(3-methyl-2-butenyloxy)-1-naphthaldehyde resulted in Diels-Alder cycloadducts.

Intramolecular Hetero-Diels-Alder Reactions of Functionalized α, β-Unsaturated Carbonyl Compounds: Polycyclic 2H-Pyran Derivatives

Reaction of 1-(phenylsulfenyl)-, 1-(phenylsulfinyl)-, and 1-(phenylsulfonyl)-2- propanones as well as 2-(phenylsulfonyl)-acetophenone with 2-(3-methyl-2-butenyloxy)- and 2-((E)-3-phenyl-2-propenyloxy)-benzaldehydes yielded the corresponding Knoevenagel condensation products. The latter compounds underwent intramolecular cycloadditions affording cis-fused 2H-pyran derivatives as the major products.

Krystyna Bogdanowicz-Szwed

Papers

TheKnoevenagel reaction of malononitrile with some cyclic β-ketocarbothionic acid anilides synthesis of cycloalkeno-pyridines and cycloalkeno-thiopyrans

Stereoselective synthesis of bridged azepine derivatives via polyfunctionalized spiroannulated thiophene. Novel rearrangement of oxime esters.

Hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propenenitriles with enol ethers. Synthesis of 2-alkoxy-3,4-dihydro-2H-pyran-5-carbonitriles

Intramolecular Hetero-Diels-Alder Reactions of Functionalized α, β-Unsaturated Carbonyl Compounds: Polycyclic 2H-Pyran Derivatives

Polycyclic 2H-Pyran Derivatives by Intramolecular Hetero-Diels-Alder Reactionsof a-Sulfur-Substituted a,b-UnsaturatedCarbonyl Compounds