E. Yu. Schmidt

Pyrroles and N-Vinylpyrroles from Ketones and Acetylenes: Recent Strides

Publisher Summary This chapter describes the methods of synthesis of pyrroles and n-vinylpyrroles, their reactions, and their physicochemical and quantum chemical studies. The significant attention given to pyrroles is, mainly, due to the fact that the pyrrole nucleus is the structural unit of many fundamental compounds, important from the biological point of view, and which take part in the accumulation of solar energy, oxygen transfer processes, and other life-supporting reactions. The synthesis of pyrroles from ketones and acetylenes are considerably gaining strength as a powerful tool of pyrrole chemistry. The success of this synthesis approach, for the construction of the pyrrole nucleus, comes by complementing existing methods, for the synthesis of pyrroles, that enables easy synthesis of pyrroles, with alkyl, aryl, and hetaryl substituents, as well as various annulated pyrroles. This reaction makes available, practically, an unlimited series of N-vinylpyrroles that are readily protected NH-pyrroles, pyrrole ring-carriers, and monomers, having a wide synthetic potential.Publisher Summary This chapter describes the methods of synthesis of pyrroles and n-vinylpyrroles, their reactions, and their physicochemical and quantum chemical studies. The significant attention given to pyrroles is, mainly, due to the fact that the pyrrole nucleus is the structural unit of many fundamental compounds, important from the biological point of view, and which take part in the accumulation of solar energy, oxygen transfer processes, and other life-supporting reactions. The synthesis of pyrroles from ketones and acetylenes are considerably gaining strength as a powerful tool of pyrrole chemistry. The success of this synthesis approach, for the construction of the pyrrole nucleus, comes by complementing existing methods, for the synthesis of pyrroles, that enables easy synthesis of pyrroles, with alkyl, aryl, and hetaryl substituents, as well as various annulated pyrroles. This reaction makes available, practically, an unlimited series of N -vinylpyrroles that are readily protected NH -pyrroles, pyrrole ring-carriers, and monomers, having a wide synthetic potential.

CHAPTER 7 - Pyrroles and N-Vinylpyrroles from Ketones and Acetylenes: Recent Strides

Publisher Summary This chapter describes the methods of synthesis of pyrroles and n-vinylpyrroles, their reactions, and their physicochemical and quantum chemical studies. The significant attention given to pyrroles is, mainly, due to the fact that the pyrrole nucleus is the structural unit of many fundamental compounds, important from the biological point of view, and which take part in the accumulation of solar energy, oxygen transfer processes, and other life-supporting reactions. The synthesis of pyrroles from ketones and acetylenes are considerably gaining strength as a powerful tool of pyrrole chemistry. The success of this synthesis approach, for the construction of the pyrrole nucleus, comes by complementing existing methods, for the synthesis of pyrroles, that enables easy synthesis of pyrroles, with alkyl, aryl, and hetaryl substituents, as well as various annulated pyrroles. This reaction makes available, practically, an unlimited series of N-vinylpyrroles that are readily protected NH-pyrroles, pyrrole ring-carriers, and monomers, having a wide synthetic potential.Publisher Summary This chapter describes the methods of synthesis of pyrroles and n-vinylpyrroles, their reactions, and their physicochemical and quantum chemical studies. The significant attention given to pyrroles is, mainly, due to the fact that the pyrrole nucleus is the structural unit of many fundamental compounds, important from the biological point of view, and which take part in the accumulation of solar energy, oxygen transfer processes, and other life-supporting reactions. The synthesis of pyrroles from ketones and acetylenes are considerably gaining strength as a powerful tool of pyrrole chemistry. The success of this synthesis approach, for the construction of the pyrrole nucleus, comes by complementing existing methods, for the synthesis of pyrroles, that enables easy synthesis of pyrroles, with alkyl, aryl, and hetaryl substituents, as well as various annulated pyrroles. This reaction makes available, practically, an unlimited series of N -vinylpyrroles that are readily protected NH -pyrroles, pyrrole ring-carriers, and monomers, having a wide synthetic potential.

1,2-Dioximes in the trofimov reaction

Abstract3,3′-Dimethyl-1,1′-divinyl-2,2′-dipyrrole was obtained during the reaction of 3,4-hexanedione dioximes with acetylene under pressure in the potassium hydroxide-DMSO system. In the case of 1,2-cyclohexanedione dioxime 2,2′-dipyrrole and 2-pyridyl-and 2-acylpyrroles were isolated. α-Benzil and α-furil dioximes give 3,4-diphenyl-and 3,4-di(2-furyl)-1,2,5-oxadiazoles respectively in addition to their mono-and divinyl derivatives.

Dioximes of 1,3-diketones in the trofimov reaction : New 3-substituted pyrroles

Dioximes of 1,3-diketones enter into the Trofimov reaction forming pyrroles containing an acyl or an O-vinyloxime substituent in position 3 of the pyrrole. In the case of sterically hindered dioximes the main reaction products are isoxazoles.

Alkyland arylketone reactions with phenylacetylene promoted by KOH—DMSO superbase: a quantum chemical study

Mechanisms of ethynylation and vinylation of ketones with phenylacetylene in the presence of KOH•5DMSO superbase were studied using the MP2/6-311++G**//B3LYP/6-31+G* approach. The thermal effects and activation barriers to individual reaction stages were evaluated. It was shown that stereoscpecificity of ketone vinylation with PhC≡CH is due to the possibility of isomerization of both carbanion intermediates and enolate anions originating from the final β,γ-unsaturated ketones. The calculated activation energies of the vinylation of substituted ketones are in good agreement with the experimentally observed differences in their reactivity with respect to the addition of phenylacetylene.

Formation of 2-ethynyl-3,4-dihydro-2H-pyrroles in the synthesis of 3H-pyrroles from ketoximes and acetylene in the system KOH—DMSO—hexane

3H-Pyrroles constitute a difficultly accessible and therefore poorly studied group of nonaromatic pyrroles. On the other hand, they exhibit potentially rich chemistry due to intrinsic tendency to undergo various rearrangements and addition and cycloaddition reactions [1]. Despite obvious interest attracted by 3H-pyrroles and their undoubted promises for organic synthesis as reactive intermediates with unique reactivity, no somewhat general method for their synthesis has been developed so far.

New reactions of alkynes with ketones in superbasic media

The present work reviews new reactions of alkynes with ketones in the superbasic media MOH—DMSO (M = Na, K, Cs) and KOBut—DMSO: the stereoselective nucleophilic addition of deprotonated ketones to the triple bond to form the E-isomers of β,γ-enones; vinylation of tertiary acetylenic alcohols that formed in situ from acetylene and ketones; the direct synthesis of vinyl ethers of tertiary acetylenic alcohols from acetylene and ketones; the stereoselective synthesis of dispirocyclic ketals containing the Z-ethylene fragment from arylalkynes and two molecules of a cyclic ketone; the stereoselective cascade synthesis of hexahydroazulenones from two arylalkyne molecules and 2-alkylcyclohexanones; the stereoselective cascade assembly of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from two acetylene molecules and two ketone molecules; the stereoselective cascade synthesis of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from acetylenes and 1,5-diketones; and the three-component cascade reaction of acetylene, ketones, and oximes to afford 4-methylidene-3-oxa-1-azabicyclo-[3.1.0]hexanes.

Formation of 2-methyl-3,5-diphenylfuran from chalcone and acetylene in the system KOH–DMSO

Chalcone reacted with acetylene in a suspension of KOH in DMSO at 90°C (30 min) to give 36% of 2-methyl-3,5-diphenylfuran.

Alkanethiol-promoted stereoselective radical rearrangement of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes to 2-acetyl-3,4-dihydropyrans

We have recently discovered diastereoselective self-assembly of ketones with acetylene in superbasic systems MOH‒DMSO (M = K, Cs; 80°C, 1 h,) to produce 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes 1 [1] (Scheme 1) that are close structural analogs of insect pheromones [2, 3] and mammalian hormones [4, 5]. This one-pot transformation of simple and readily accessible reagents to complex functionalized heterocyclic systems combining bicyclic acetal and vinyl ether moieties in a single molecule opens unexpected prospects for the development of organic synthesis where the synthon (building block) approach is now increasingly used for the design of molecular systems with a desired structure. While performing a systematic study of the synthetic potential of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes 1 that have become readily accessible we revealed their unusual reaction with alkanethiols under radical initiation conditions. It is known that radical addition of thiols to vinyl ethers leads to the formation of the corresponding anti-Markovnikov adducts [6, 7]. However, contrary to expectations, 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes 1a–1d in the reaction with propane-1-thiol in the presence of azobis(isobutyronitrile) (AIBN; 60–65°C, 4 h) were stereoselectively and almost quantitatively converted into 2-acetyl-3,4-dihydropyrans 2a–2d without addition of the thiol (Scheme 2).

C-vinylation of enolates with acetylenes in a one-pot synthesis of 4,5-dihydro-1 H -pyrazole-1-carbothioamides

β,γ-Unsaturated ketones are important building blocks in target-oriented syntheses of complex structures [2–4] and key intermediates in drug design [5–8]; therefore, addition of ketones to acetylenes opens new prospects in organic synthesis. Dienes A formed as intermediates in this reaction are equally or even more promising synthons. These intermediates can be subjected in situ to Oand C-alkylation and Diels– Alder reactions and converted into various heterocyclic compounds via addition of binucleophiles. In fact, we have recently synthesized 4,5-dihydroisoxazole derivatives by one-pot reaction from ketones, acetylenes, and hydroxylamine [9]. In order to extend the scope of the above synthetic approach, we have synthesized 4,5-dihydropyrazole1-carbothioamides 4a and 4b by one-pot three-component condensation of acetophenones 1a and 1b with phenylacetylene (2), and thiosemicarbazide (5) (Scheme 2). Presumably, the pyrazole ring is formed via addition of the NH2 group of thiosemicarbazide (5) to the carbonyl group of β,γ-unsaturated ketone 3 produced by hydrolysis of potassium enolate A (Scheme 3). The second reaction step is likely to be prototropic migration of the double bond to the α,β-position with respect to the hydrazone moiety. As a result, the nucleophilicity of the latter sharply increases, which facilitates pyrazole ring closure. Prototropic rearrangement should be favored by the presence of an equimolar ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 136–138.