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Graphical abstract Highlights • Direct access to diastereoselective spirooxindoles framework. • Control over [3 + 2] and [2 + 1] annulation by switching catalysts. • Construction of vicinal quaternary spiro centers with three contiguous stereocenters. • Broader substrate scope. • Total of 32 examples with very good yields and high diastereoselectivity. Abstract A highly diastereoselective organocatalytic synthesis of cyclopentenyl bis-spirooxindoles and cyclopropyl spirooxindoles has been achieved via [3 + 2] and [2 + 1] annulations. The tertiary amine catalysts have been effectively employed to tune the cycloaddition of isatin-derived MBH carbonates and 3-methyleneoxindoles for the outcome of two different spirooxindole frameworks with vicinal quaternary spiro centers and three contiguous stereocenters. The reactions worked under mild and practical conditions to afford the spirooxindoles in good to excellent yields with very high diastereoselectvity. [ABSTRACT FROM AUTHOR]

Abstract: Racemic cyclopropyl ketones undergo enantioselective rearrangement to deliver the corresponding dihydrofurans in the presence of a chiral phosphoric acid as the catalyst. The reaction involves activation of the donor‐acceptor cyclopropane substrate by the chiral Brønsted acid catalyst to promote the ring‐opening event, thus generating a carbocationic intermediate that subsequently undergoes cyclization. Computational studies and control experiments support this mechanistic pathway. [ABSTRACT FROM AUTHOR]

The reduction of 2-cyclopropylcarbonyl-, 2-(thiophen-2-yl)carbonyl-, and 2-arylcarbonylbenzonitriles with sodium tetrahydridoborate afforded 3-cyclopropyl-, 3-(2-thiophen-2-yl)-, and 3-arylphthalides, respectively, in high yields. Under analogous conditions, 3-cyanobenzophenones were converted to the corresponding 3-cyanobenzhydrols. [ABSTRACT FROM AUTHOR]

We report a stereoselective formal [3 + 2] cycloaddition of cyclopropyl ketones and radical-acceptor alkenes to form polysubstituted cyclopentane derivatives. Catalyzed by a chiral Ti(salen) complex, the cycloaddition occurs via a radical redox-relay mechanism and constructs two C-C bonds and two contiguous stereogenic centers with generally excellent diastereo- and enantioselectivity. [ABSTRACT FROM AUTHOR]

A method for intermolecular [3+2] cycloaddition between aryl cyclopropyl ketones and alkenes involving the combination of Lewis acid and photoredox catalysis is reported. In contrast to other more common methods for [3+2] cycloaddition, these conditions operate using a broad range of both electron-rich and electron-deficient reaction partners. The critical factors predicting the success of these reactions is the redox potential of the cyclopropyl ketone and the ability of the alkene to stabilize a key radical intermediate. [ABSTRACT FROM AUTHOR]

A Ni−Al bimetallic catalyzed enantioselective cycloaddition reaction of cyclopropyl carboxamides with alkynes has been developed. A series of cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient strategy for the C−C bond cleavage of unreactive cyclopropanes. [ABSTRACT FROM AUTHOR]

A mechanistic study using a cyclopropylmethyl radical clock as a probe to investigate the formation of a macrolactam ring via an SmI2-mediated intramolecular Reformatsky reaction is experimentally explored. The results of our study indicate that the key SmIII-enolate intermediate is formed by cleavage of a C−Br bond in an anion-mediated β-elimination, and then eventually undergoes an intramolecular aldol condensation to form the macrolactam ring. [ABSTRACT FROM AUTHOR]

A highly efficient asymmetric ring-opening/cyclization/retro-Mannich reaction of cyclopropyl ketones with aryl 1,2-diamines has been realized using a chiral N, N′-dioxide/ScIII catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole-substituted amide and cycloheptene derivatives. [ABSTRACT FROM AUTHOR]

A calcium-catalyzed, dehydrative, ring-opening cyclization of (hetero)aryl cyclopropyl carbinols is reported. The cyclopropyl carbinols are prepared directly from the corresponding donor-acceptor (D-A) cyclopropanes. The calcium catalyst catalyzes the formation of putative (hetero)aryl cyclopropyl carbinyl cations that undergo ring-opening to allylcarbinyl cations. Subsequent intramolecular Friedel-Crafts reaction affords (hetero)aryl-fused cyclohexa-1,3-dienes in up to 97% yield. This approach represents the first example of catalysis for this intramolecular, dehydrative ring-opening cyclization and outperforms the previous reports using stoichiometric Lewis acids. [ABSTRACT FROM AUTHOR]

A novel formal [3+2] cycloaddition of cyclopropylacetals and aldehydes was developed, and the resulting trisubstituted tetrahydrofurans display three new chiral centers formed with highly diastereoselectivity. This method is stereocomplementary to most previously reported cycloadditions of malonate diesters, relies on the transient generation of cyclopropyl oxocarbenium ions, proceeds under mild conditions, and is based on the concept of temporary activation of an otherwise inert protecting group. [ABSTRACT FROM AUTHOR]

The total synthesis of the resveratrol dimers (±)-ampelopsin B and (±)-ϵ-viniferin is reported. Highlights of the approach include the use of cyclopropylmethyl groups to protect aromatic alcohols. This group allows an acid promoted three-step, one-pot deprotection-epimerization-cyclization of an advanced intermediate to give (±)-ampelopsin B. An important advantage with our strategy is the possibility of synthesizing analogs to these natural products to further study the chemistry and biology of resveratrol oligomers. [ABSTRACT FROM AUTHOR]

A bioinspired synthesis of the sedaxane metabolite 2 from intermediate 3 using catalytic VO(acac)2 and O2 is described. Intermediate 3 was synthesized starting from 2-bromostyrene in four steps. The inner cyclopropyl ring of 3 was assembled with trans geometry using a highly diastereoselective Nishiyama cyclopropanation, and the outer hydroxycyclopropyl ring was installed using the Kulinkovich cyclopropanation. Additionally, conversion of 3 into 2 was demonstrated in in vitro microbial culture experiments consisting of bacteria and fungi. [ABSTRACT FROM AUTHOR]

A new cascade reaction provides a direct transformation of pyrazolin-5-ones and benzylidenemalononitriles by the action of bromine into substituted spirocyclopropylpyrazolones in 60-88% yields. This process can be realized in two variants, namely, (1) by treatment with bromine in the presence of base and (2) by treatment with bromine only with heating. These facile and efficient one-step cascade processes lead to the spirocyclopropylpyrazolone framework, which is present in a perspective class of compounds with prominent pharmacological and physiological activity. [ABSTRACT FROM AUTHOR]

The asymmetric ring-opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N, N′-dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3-dihydropyrroles as well as an effective procedure for the kinetic resolution of 2-substituted cyclopropyl ketones. [ABSTRACT FROM AUTHOR]

The mechanism of the [4+2] cycloaddition reaction of singlet oxygen (1O2) with simple acyclic dienes, i.e. (E)/(Z)-1 and (E,E)/(Z,E)-2, was investigated by employing the gem-diphenylcyclopropylcarbinyl radical clock as a hypersensitive mechanistic probe. In both cases, benzophenone, a decomposition product of the rearranged endoperoxide intermediates 11 and 12, was identified as the major product. The formation of this product is consistent with the intervention of an open biradical or dipolar intermediate having a lifetime greater than 2 psec. Our attempts to further trap any endoperoxide intermediate revealed a new mode of reactivity of these dienic systems with 3O2, that mainly affords the corresponding 1,2-dioxolane derivatives (E)-13 and (E,E)-14, respectively, through a photoinduced electron transfer mechanism, co-sensitized by methylene blue (MB) and thiourea. The structures of (E)-13 and (E,E)-14 were supported by experimental and theoretical NMR studies. [ABSTRACT FROM AUTHOR]

The first total synthesisof nardoaristolone B, a nor-sesquiterpenoidwith an unusual fused ring system and having protective effects onthe injury of neonatal rat cardiomyocytes, has been accomplished.Stereoselective synthesis of its novel analogues inlcuding exo-cyclopropyl ring fusion is also part of this disclosure.In addition, an alternate and more efficient one-step method to makea 3/5/6 tricyclic ring system using the Robinson annulation methodhas been developed toward the generation of a library of compoundsaround this skeleton. [ABSTRACT FROM AUTHOR]

The [PtCl2]- or [AuCl]-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols occurred smoothly at room temperature to afford a series of poly-substituted carbazoles efficiently. Compared with the [PtCl2]-catalyzed process, the [AuCl]-catalyzed reaction represents a significant advance in terms of the scope and the selectivity. Selective 1,2-alkyl or aryl migration of the gold carbene intermediate was observed: compared with the methyl group, the isopropyl, cyclopropyl, cyclobutyl, and cyclohexyl groups migrate exclusively; the cyclopropyl group shifts selectively over the ethyl group; the 1,2-migration of a non-methyl linear alkyl is faster than methyl group; the phenyl group migrates exclusively over methyl or ethyl group. DFT calculations show that water makes the elimination of H2O facile requiring a much lower energy and validates the migratory preferences of different alkyl or phenyl groups observed. [ABSTRACT FROM AUTHOR]

Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1-methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments. [ABSTRACT FROM AUTHOR]

Abstract: The consecutive treatment of 5-hydroxy-1-pentynyl 2,2-disubstituted-cyclopropyl ketones with Co2(CO)8 and BF3·OEt2 produced the corresponding Co2(CO)6-complexed dioxaspiro[4.6] derivatives. The one-carbon homologated substrates also afforded dioxaspiro[4.7]. It was found that this procedure can be applied to the substrates with gem-disubstituents as well as a mono-aryl substituent on the cyclopropane, but the mono-alkyl substituted cyclopropanes are insufficient. [Copyright &y& Elsevier]

Abstract: 1,3-Dipolar cycloadditions of dialkyl-substituted 2-benzylidenecyclopropane-1,1-dicarboxylates and a number of C-carbamoyl nitrones proceed with high efficiency and selectivity with the formation of single isomeric spiro[cyclopropane-1,4-isoxazolidine] cycloadduct. Obtained cycloadducts easily undergo cyclopropyl ring opening–cyclization to form new β-lactams fused with isoxazolidine ring in high yields. [Copyright &y& Elsevier]

We have developed two different types of tandem reactions for the synthesis of highly functionalized cyclohexenones from cyclopropyl substituted propargyl esters. Both reactions were initiated by rhodium-catalyzed Saucy--Marbet 1,3-acyloxy migration. The resulting cyclopropyl substituted allenes derived from acyloxy migration then underwent [5 + 1] cycloaddition with CO. The acyloxy group not only eased the access to allene intermediates but also provided a handle for further selective functionalizations. [ABSTRACT FROM AUTHOR]

Abstract: seco-Iso-cyclopropylfurano[e]indoline-trimethoxyindole 1 and seco-cyclopropylfurano[f]quinoline-trimethoxyindole 2 are potent cytotoxic agents. Previous synthesis of these compounds was inefficient and the approach required separation of a mixture containing the isomeric indoline and quinoline intermediates 11 and 12, formed from radical cyclization of allylic bromide 10. Reported herein is an efficient and selective synthesis of either intermediate 11 or 12, thus product 1 or 2, as needed. The conditions of the Stobbe condensation, bromination, 5-exo-trig radical cyclization, amine-carboxylic acid coupling, and debenzylation were optimized for multi gram scale. As a result, the reaction times were shortened, the products were readily isolated, and the yields and purity improved. [Copyright &y& Elsevier]

Allylsilanes add to oxyallyl cations, generated from homo-Nazarov cyclization of cyclopropyl vinyl ketones to give bicyclooctan-8-one derivatives in exo configuration. [ABSTRACT FROM AUTHOR]

A carefully designed process for the scalable synthesis of 1-methylcyclopropanol (III) is developed as well as the optimized conversion to the mixed carbonate (V). [ABSTRACT FROM AUTHOR]