S. A. Shipilovskikh

Catalytic Asymmetric Crotylation of Aldehydes: Application in Total Synthesis of (−)‐Elisabethadione

A new, highly efficient Lewis base catalyst for a practical enantio- and diastereoselective crotylation of unsaturated aldehydes with E- and Z-crotyltrichlorosilanes has been developed. The method was employed as a key step in a novel asymmetric synthesis of bioactive serrulatane diterpene (-)-elisabethadione. Other strategic reactions for setting up the stereogenic centers included anionic oxy-Cope rearrangement and cationic cyclization. The synthetic route relies on simple, high yielding reactions and avoids use of protecting groups or chiral auxiliaries.

Iminofurans chemistry. Decyclization of ethyl 2-[2-oxo-5-phenylfuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate under the action of aliphatic amines

Publications on compounds containing in the structure 3-imino-3H-furan-2-one are scarce [1]. We formerly developed a simple preparation method for a series of ethyl 2-[5-aryl-2-oxofuran-3(2H)-ylideneamino]-4,5,6,7tetrahydrobenzo[b]thiophene-3-carboxylates through an intramolecular cyclization of (Z)-4-aryl-4-oxo-2-[3(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen2-ylamino]but-2-enoic acids under the action of acetic anhydride [2]. At the same time this rare type of furan-2one derivatives is promising in view of the high reactivity and possible biologic action. The introduction into the structure of a thiophene substituent [3–5] at the imine nitrogen atom even more increases the promising qualities of these compounds. Moreover, it has been shown that the proper (Z)-4-aryl-4-oxo-2-[3-(ethoxycarbonyl)4,5,6,7-tetrahydrobenzo[b]-thiophen-2-ylamino]but-2enoic acids exhibit the biological activity exceeding the activity of drugs used in medicine [6, 7]. It was shown by an example of 5-aryl-3-arylimino3H-furan-3-one that in reaction with anilines the furan ring suffered opening giving amides of 4-aryl-4-oxo-2arylaminobut-2-enoic acids [8]. In the molecule of ethyl 2-[2-oxo-5-phenylfuran-3(2H)-ylideneamino]-4,5,6,7tetrahydrobenzo[b]thiophene-3-carboxylate (I) at least two obvious sites are present for nucleophilic attack with aliphatic amines. The reaction of ethyl 2-[2-oxo-5-phenylfuran-3(2H)ylideneamino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxylate (I) with amines IIа–IIc in an inert aprotic solvent afforded the corresponding ethyl 2-[(Z)-3-oxo3-phenyl-1-(carbamoyl)-prop-1-enylamino]-4,5,6,7tetrahydrobenzo[b]thiophene-3-carboxylates IIIа–IIIc.

Chemistry of iminofurans. Recyclization of ethyl 2-[2-oxo-5-phenylfuran-3(2 H )-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate by the action of hydrazines

As we showed previously, 5-arylfuran-2,3-diones react with hydrazines to give 4-aryl-2,4-dioxobutanoic acid hydrazides [1–3]; however, introduction of a substituent into the 4-position of the furan ring changes the reaction direction toward formation of cyclic products, in particular pyridazin-3-ones [4–10] and pyrazolecarboxylic acid derivatives [4, 7–12]. On the other hand, replacement of the carbonyl oxygen atom in the 3-position by =CH2 group leads to the formation of both acyclic products, acrylic acid hydrazides [13–15], and pyridazin-3-one derivatives [13–16]. The goal of the present work was to study the reaction of hydrazines with 5-arylfuran-2,3-dione analogs in which the 3-oxo group is replaced by 3-ethoxycarbonylthiophen2-ylimino. We previously found that the reaction of hydrazines with 5-aryl-3-(1,5-dimethyl-3-oxo-2phenyl-1,2-dihydro-3H-pyrazol-4-ylimino)-3H-furan2-ones is governed by the substituent nature in the hydrazine and that the products are 3-iminopyrrol-2ones or pyridazin-3-ones [17–19]. Interest in this reaction is determined by the fact that some transformation products displayed various kinds of biological activity [2, 3, 10–13, 19]. Furthermore, introduction of a Gewald thiophene fragment [20–23] was expected to increase the probability of revealing biological activity of the products. The reactions of ethyl 2-[2-oxo-5-phenylfuran3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate (I) with hydrazines IIa–IId in an inert aprotic solvent resulted in the formation of the corresponding ethyl 2-(3-oxo-6-phenyl-2-R-2,3-dihydropyridazin-4-ylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates IIIa–IIId which were isolated as crystalline substances. Presumably, as in the reaction of compound I with amines, initial attack by the amino nitrogen atom of the hydrazine molecule on the carbonyl carbon atom in the dihydrofuran ring induces opening of the furan ring at the C–O bond [24]. The subsequent attack by the second nitrogen atom on the C=O carbonyl carbon atom of intermediate 4-oxo-4phenyl-2-[3-(ethoxycarbonyl)-4,5,6,7-tetrahydro-1benzothiophen-2-ylamino]but-2-enehydrazide leads to pyridazine ring closure with formation of 4-imino-6phenyl-1,2-dihydro-4H-pyridazin-3-one derivatives, and [1,5]-prototropic shift in the latter yields thermodynamically more stable isomer III. Ethyl 2-(3-oxo-6-phenyl-2,3-dihydropyridazin4-ylamino)-4,5,6,7-tetrahydro-1-benzothiophene3-carboxylate (IIIa). Hydrazine hydrate (IIa), 0.05 g (1 mmol), was added to a solution of 0.381 g (1 mmol) of compound I in 3 mL of anhydrous toluene, and the mixture was heated for 30 min to the boiling point.

Synthesis and Analgesic Activity of Substituted 4-(Het)aryl-4-oxo-2-thienylaminobut-2-enoic Acids

A series of 4-aryl-4-oxo-2-thienylaminobut-2-enoic acids was synthesized by interaction of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids with Gewald 2-aminothiophenes. All the compounds synthesized were found to have analgesic activity at or above the levels of the reference compounds.

Asymmetric Total Synthesis of (−)‐Erogorgiaene and Its C‐11 Epimer and Investigation of Their Antimycobacterial Activity

A short, nine-step, highly enantioselective synthesis of (-)-erogorgiaene and its C-11 epimer is reported. The key stereochemistry controlling steps involve catalytic asymmetric crotylation, anionic oxy-Cope rearrangement and cationic cyclisation. (-)-Erogorgiaene exhibited promising antitubercular activity against multidrug-resistant strains of Mycobacterium tuberculosis.

Dehydration of Amides to Nitriles under Conditions of a Catalytic Appel Reaction

A highly expedient protocol for a catalytic Appel-type dehydration of amides to nitriles has been developed that employs oxalyl chloride and triethylamine along with triphenylphosphine oxide as a catalyst. The reactions are usually complete in less than 10 min with only a 1 mol % catalyst loading. The reaction scope includes aromatic, heteroaromatic, and aliphatic amides, including derivatives of α-hydroxy and α-amino acids.

Chemistry of iminofurans: X. Synthesis and hydrolysis of 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2H)-ones

Abstract5-Aryl(hetaryl)furan-2,3-diones reacted with N-(triphenyl-λ5-phosphanylidene)-4,5,6,7-tetrahydro-1-benzothiophen-2-amines to give 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2H)-ones whose acid hydrolysis afforded 4-aryl(hetaryl)-2-hydroxy-4-oxo-N-(4,5,6,7-tetrahydro-1-benzothiophen- 2-yl)but-2-enamides.

Chemistry of iminofurans. Recyclization of ethyl 2-[2-oxo-5-phenylfuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate by the action of hydrazines

The reaction of ethyl 2-[2-oxo-5-phenylfuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene- 3-carboxylate with primary amines (RNH2) in toluene under reflux led to the formation of the corresponding ethyl 2-[(1-R-5-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrol-3-yl)amino]-4,5,6,7-tetrahydro- 1-benzothiophene-3-carboxylates. The product structure was determined by X-ray analysis.

Chemistry of Iminofurans: XV. Decyclization of Ethyl 2-[5-Aryl-2-oxofuran-3(2 H )-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates by the Action of Secondary Amines

Ethyl 2-[5-aryl-2-oxofuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates reacted with secondary amines to give 4-aryl-2-(thiophen-2-yl)-4-oxobutanamides, whereas their reaction with piperazine afforded N,N′-disubstituted piperazine derivatives regardless of the reactant ratio.

Oxidative Dehomologation of Aldehydes with Oxygen as a Terminal Oxidant

A mild, efficient protocol for oxidative cleavage of C-C bonds in aldehydes has been developed that employs alkali metal hydrides as reagents and oxygen from air as a terminal oxidant. The method is applicable to a broad substrate range.