The data on the reactions of various classes of functionalized alkynyl cyclopropanes that proceed with simultaneous participation of triple bond, three-membered ring, and functional group at a cyclopropane ring are systematized. The syntheses of polysubstituted and fused furans and indoles based on electrophile-induced and catalytic transformations of alkynyl cyclopropyl carbonyl compounds and their derivatives are considered separately. The methods for isomerization of 1-alkynyl cyclopropanols and their ethers to 3-methylenecyclobutanones are described. Information on the reactions of other types of alkynyl cyclopropanes containing one or more functional groups at three-membered ring leading to different acyclic, carbo-, and heterocyclic compounds is given. Transformations of alkynyl cyclopropanes lacking the functional groups, which simultaneously involved the cyclopropane ring and the alkynyl fragment, are also discussed.

N-Alkyl-N-Boc-substituted 1-amino-2-alkynylcyclopropanes undergo selective lithiation at the carbon atom in α-position relative to the triple bond under the action of BunLi in THF at −65 °C. Lithiation of the starting compounds representing mixtures of cis- and trans-isomers affords the trans-isomers of organolithium derivatives which react with electrophiles (acetaldehyde, acetone, dimethyl disulfide, CO2, methyl chloroformate, and iodomethane) to give the corresponding 2-substituted 1-amino-2-alkynylcyclopropanes in up to 93

Data on methods for the synthesis of various classes of functionalized alkynylcyclopropanes (FACPs) reported in the last two decades are systematized. Synthetic routes to FACPs based on cyclopropanation of unsaturated compounds with various carbenes, carbenoids, and ylides are considered separately. Methods for introducing functional groups into the three-membered ring of alkynylcyclopropanes via metalation and elimination—addition processes as well as other synthetic routes to functionalized cyclopropanes are discussed.

The review summarizes some of the most prominent results obtained in the laboratory headed by Academician Oleg M. Nefedov at the N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences in the field of chemistry of carbenes, their heavy analogs, and related intermediates, as well as small-sized cycles. Those include elaboration of safe methodology of cyclopropanation using diazomethane, development and extension of synthetic applications of diazoesters and other diazo compounds in the preparation of valuable chemical products, design of functionalized alkynylcyclopropanes on the basis of alkynylcarbene reactions, creation of versatile synthetic approaches to preparation of various practically useful fluoroorganic compounds on the basis of reactions of fluorocarbenes, development of synthetic applications of heavy carbene analogs and synthesis of small-sized heterocycles containing silicon and germanium atoms, analysis of mechanisms of some important reactions of carbenes, their analogs and related intermediates on the basis of physicochemical studies, direct spectroscopic studies of various labile intermediates of chemical reactions.

A comprehensive study of previously unknown chloro(4-methylpent-3-en-1-ynyl)carbene generated by photolysis of newly synthesized 5-chloroethynyl-3,3-dimethyl-3H-pyrazole was carried out both in low-temperature argon matrix and in solution at room temperature. Irradiation at 330 nm < λ < 380 nm causes the pyrazole to undergo a selective transformation to 1-chloro-3-diazo-5-methylhexa-4-en-1-yne. Photolysis of the latter at λ >520 nm leads to elimination of dinitrogen, thus producing the title carbene. Key structural parameters of this species were determined using matrix IR spectroscopy and quantum chemical calculations. It was established that the more stable state of the carbene is a singlet one. Further phototransformations of chloro(4-methylpent-3-en-1-ynyl)carbene lead to formation of isomeric 6-chloro-2-methylhexa-1,3-diene-5-yne. A preparative method for the synthesis of alkynylchlorocyclopropanes with yields up to 76% was proposed. It is based on photolysis of 5-chloroethynyl-3,3-dimethyl-3H-pyrazole in benzene in the presence of excess amounts of various alkenes. The possibility of using this approach for selective cyclopropanation of double bonds in the presence of hydroxyl groups in the substrate molecule was demonstrated taking 3-methylbut-2-enol as an example.

New N-Boc-alkyl(2-alkynylcyclopropyl)amines were synthesized from 1-alkynyl-1-chlorocyclopropanes and N-Boc- alkylamines under the action of ButOK in DMSO, the intermediates having been the corresponding conjugated alkynylcyclopropenes. The Boc-derivatives can be converted into free secondary 2-alkynylcyclopropylamines, as well as β-lithiated with subsequent alkylation.

The first representative of singlet carbenes bearing both ethynyl and methylthio groups at the carbene center, (4-methylpent-3-en-1-ynyl)methylthiocarbene, has been generated in a low-temperature Ar matrix upon UV photolysis of 3,3-dimethyl-5-methylthioethynyl-3H-pyrazole and detected by FTIR spectroscopy. The generation of the carbene proceeds via intermediate (3-diazo-5-methylhex-4-en-1-ynyl)methylsulfane. The comparison of FTIR spectroscopy data with the results of quantum chemical calculations (B3LYP/aug-cc-pVTZ) and NRT analysis shows that (4-methylpent-3-en-1-ynyl)methylthiocarbene has a singlet ground state with the localization of the unpaired spins on the carbon atom in the α-position to methylthio moiety. Two major pathways of further phototransformation of the studied carbene have been found. One of them produces photochemically stable thioketone (S═CMe-C≡C-CH═CMe2) as a result of methyl group migration from sulfur to the neighboring carbon atom, and the other one leads to the formation of labile thioketene (S═C═C(Me)-CH═CH-CMe═CH2). Ability of (4-methylpent-3-en-1-ynyl)methylthiocarbene to insert into the H-Cl bond was established, which additionally confirms the singlet nature of this intermediate.

1-Alkynyl-1-chlorocyclopropanes undergo chlorine-lithium exchange on treatment with Bu n Li in THF at -40—0 °C. Thus generated organolithium species react with carbon dioxide (dry ice) and acetone to give selectively hitherto unknown 1-alkynylcyclopropanecarboxylic acids and the corresponding alcohols in up to 74% yields. Similar reactions involving methyl chloroformate result in the mixtures of cyclopropylacetylenic and vinylidenecyclopropanic esters, while the use of aliphatic aldehydes as electrophiles provides secondary allenic alcohols in up to 64% yields.

3,3-Disubstituted piperidin-2-ones were obtained by alkylation of carboxylic acid esters with 1-(3-halopropyl)-2,5-dimethylpyrroles using lithium diisopropylamide as a base followed by the removal of 2,5-dimethylpyrrole protection and intramolecular cyclization. The overall yields of the target products amounted to 78% in two synthetic steps.

New singlet alkylthio(4-methylpent-3-en-1-ynyl)carbenes were generated by photolysis of corresponding 5-alkylthioethynyl-3,3-dimethyl-3H-pyrazoles and subsequently trapped by alkenes giving rise to 1-alkynyl-1-(alkylthio)cyclopropanes in yields up to 60%.

One-pot cyclization of alk-4-ynals with primary aliphatic amines and azoles in DMSO under the action of KOH affords 1-alkyl-2-azolyl-5-arylmethylidenepyrrolidines. Similar processes with lithium monoalkylamides in THF give rise to 3-iminocyclopentenes.

trans-1-Alkoxy-2-(phenylethynyl)cyclopropanes undergo lithiation at the hydrogen atom in the α-position to the triple bond on treatment with BuLi in THF at–(65—70) °C. The resulting organolithium derivatives react with acetaldehyde, acetone, dimethyl disulfide, and methyl chloroformate giving the corresponding alcohols, sulfides, and esters with the yields up to 69% with complete retention of cyclopropane ring stereoconfiguration. The obtained methyl 3-alkoxy-2,2-dimethyl-1-(phenylethynyl)cyclopropanecarboxylates and the corre-sponding acid readily undergo ring opening with addition of water molecule or HCl.

Cyclization of o-alkynylbenzaldehydes with o-diaminobenzenes in DMSO under the sequential action of NH4Br and K2CO3 affords 11-arylmethylidene-11H-isoindolo[2,1-a]-benzimidazoles as a result of 5-exo-dig ring closure; whereas replacement of treating with K2CO3 by heating at 110–115°C results in 6-endo-dig cyclization with formation of 6-arylbenzimidazo[2,1-a]isoquinolines.

Cyclization of alk-4-ynals with o-diaminobenzene in DMSO under the sequential action of NH4Br and base (KOH or K2CO3) affords 1-arylmethylidene-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazoles, which are formed selectively as E- or Z-isomers depending on the base used.

A one-pot synthesis of arylmethylidene-substituted 2,3-dihydro-1 H -pyrrolo[1,2- a ]benzimidazoles based on the reaction of alk-4-ynals with 1,2-diaminobenzenes in DMSO at sequential catalysis with NH 4 Br and bases was suggested. The use in these processes of KOH as a base led to the selective formation of E -isomers of the final products in 48–66% yields, whereas less basic K 2 CO 3 gave the corresponding Z -isomers in 32–82% yields. Similar cyclization reactions involving 2,3-diaminopyridine gave 7,8-dihydro-6 H -pyrrolo[1’,2’:1,2]imidazo[4,5- b ]pyridines in up to 56% yields. The distinguishing feature of the processes under study is proceeding of their key step that is intramolecular hydroamination of the triple bond, as a 5- exo-dig -cyclization. The necessity for the application of drastic conditions required for these processes is in agreement with the results of quantum chemical calculations of PES of their most probable rate-determining step, namely, the cyclization of the corresponding benzimidazolide anions to cyclic vinyl anions.

ChemInformVolume 47, Issue 7 Preparative Organic Chemistry ChemInform Abstract: One-Pot Synthesis of 1-Arylmethylidene-1,2,3,3a-tetrahydro-5H-pyrrolo[1,2-a] [3,1]benzoxazines and 1-Arylmethylidene-1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinazolines from 5-Arylalk-4-ynals and o-Aminobenzylic Alcohol/Amine. Valentin D. Gvozdev, Valentin D. Gvozdev Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this authorKonstantin N. Shavrin, Konstantin N. Shavrin Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this authorMikhail P. Egorov, Mikhail P. Egorov Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this authorOleg M. Nefedov, Oleg M. Nefedov Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this author Valentin D. Gvozdev, Valentin D. Gvozdev Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this authorKonstantin N. Shavrin, Konstantin N. Shavrin Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this authorMikhail P. Egorov, Mikhail P. Egorov Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this authorOleg M. Nefedov, Oleg M. Nefedov Zelinsky Inst. Org. Chem., Russ. Acad. Sci., Moscow 119991, RussiaSearch for more papers by this author First published: 28 January 2016 https://doi.org/10.1002/chin.201607036Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume47, Issue7January, 2016 RelatedInformation

Cyclization of 5-arylalk-4-ynals with o-aminobenzylamine or o-aminobenzyl alcohol in DMSO under the sequential action of NH4Br and KOH affords (E)-1-arylmethylidene-1,2,3,3 a,4,5-hexahydropyrrolo[1,2-a]quinazolines or (E)-1-arylmethylidene-1,2,3,3a-tetrahydro-5H-pyrrolo-[1,2-a][3,1]benzoxazines;the latter without substituents in the 3-position easily isomerize into the corresponding 2-arylmethyl-1-(2-hydroxymethylphenyl)pyrroles.

A reaction of alk-4-ynals with aliphatic amino alcohols or 2-aminoethanethiol in the system DMSO—KOH gives bicyclic N,O- and N,S-enaminals: 6-methylidenehexahydro-2H-pyrrolo[2,1-b][1,3]oxazines, 5-methylidenehexahydropyrrolo[2,1-b]oxazoles, or 5-methyl-idenehexahydropyrrolo[2,1-b]thiazoles. The reaction proceeds through the formation of equilibrium mixtures of the corresponding imines and monocyclic aminals with subsequent 5-exodig-cyclization catalyzed by the superbasic system DMSO-KOH.

Cyclization of alk-4-ynals with alpha,omega-diaminoalkanes in DMSO under the action of KOH affords bicyclic N,N-enaminals - 6-(arylmethylidene)octahydro[1,2-a]pyrimidines and 5-(arylmethylidene)hexahydro[1,2-a]imidazoles.