Mikhail Ya. Melnikov

Ring Opening of Donor–Acceptor Cyclopropanes with the Azide Ion: A Tool for Construction of N-Heterocycles

A general method for ring opening of various donor-acceptor cyclopropanes with the azide ion through an SN 2-like reaction has been developed. This highly regioselective and stereospecific process proceeds through nucleophilic attack on the more-substituted C2 atom of a cyclopropane with complete inversion of configuration at this center. Results of DFT calculations support the SN 2 mechanism and demonstrate good qualitative correlation between the relative experimental reactivity of cyclopropanes and the calculated energy barriers. The reaction provides a straightforward approach to a variety of polyfunctional azides in up to 91 % yield. The high synthetic utility of these azides and the possibilities of their involvement in diversity-oriented synthesis were demonstrated by the developed multipath strategy of their transformations into five-, six-, and seven-membered N-heterocycles, as well as complex annulated compounds, including natural products and medicines such as (-)-nicotine and atorvastatin.

(3 + 3)-Cyclodimerization of donor-acceptor cyclopropanes. Three routes to six-membered rings.

The ability of donor-acceptor cyclopropanes to (3 + 3)-cyclodimerize is disclosed. It has been found that Lewis acid-induced transformations of 2-(hetero)arylcyclopropane-1,1-dicarboxylates containing electron-abundant aromatic substituents led to the construction of six-membered cyclic systems. Depending on the substrate properties and the Lewis acid applied, three types of products can be obtained: (1) 1,4-diarylcyclohexanes, (2) 1-aryl-1,2,3,4-tetrahydronaphthalenes, and (3) 9,10-dihydroanthracenes.

Duality of Donor–Acceptor Cyclopropane Reactivity as a Three‐Carbon Component in Five‐Membered Ring Construction: [3+2] Annulation Versus [3+2] Cycloaddition

Quo vadis? The Lewis acid catalyzed reaction of (hetero)aryl-derived donor-acceptor cyclopropanes with alkenes can be selectively directed along a [3+2] annulation pathway (see scheme). This new process provides convenient and efficient access to indanes and other cyclopentannulated (hetero)arenes, among which polyoxygenated 1-arylindanes exhibit significant cytotoxicity against several cancer cell lines with an IC50 of 10(-6)-10(-5)  M.

Domino Cyclodimerization of Indole-Derived Donor–Acceptor Cyclopropanes: One-Step Construction of the Pentaleno[1,6-a,b]indole Skeleton

Bisindoles represent an extensive group of both naturally occurring and synthetically available compounds with a broad range of biological activities, such as antitumor, antiviral, and antibacterial activities. To date, over 200 bisACHTUNGTRENNUNGindole alkaloids have been isolated from various natural sources (Figure 1). Furthermore, considerable attention is currently being paid to the development of synthetic routes to bisindoles. Structurally, bisindoles vary significantly, resulting in a lack of general methods for the synthesis of these compounds, although, most synthetic approaches are based on the coupling of two indole-containing molecules. Herein, we report a new synthetic strategy towards bisACHTUNGTRENNUNGindoles through an interaction of two indole-derived donor– acceptor (DA) cyclopropane molecules. DA cyclopropanes are of particular interest because they are promising synthetic reagents with versatile reactivity. In particular, DA cyclopropanes with aryl and heteroaryl substituents are widely used for the synthesis and modification of various indole-containing molecules. In this study, we investigate in detail the dimerization of indole-containing DA cyclopropanes and present evidence for a new type of reactivity of DA cyclopropanes, which opens up routes to a novel bisindole scaffold. Coupling of DA cyclopropanes has received very little attention in the literature, with only one report thus far, which deals with the transformation of aryl 2-(3-indolyl)cyclopropyl ketones into cyclopentacarbazoles. As part of our investigation into DA cyclopropane dimerization, we studied the Lewis acid induced transformation of 2-(3-indolyl)cyclopropane-1,1-dicarboxylates (1). We found that this reaction yields angularly fused tetracyclic compounds 2, containing the previously unknown pentalenoACHTUNGTRENNUNG[1,6a–b]indole scaffold. Reagent cyclopropanes 1 are readily available from the corresponding indole-3-carbaldehydes through a standard synthetic sequence of Knoevenagel/Corey–Chaykovsky reactions. These cyclopropanes have low stability at elevated temperatures and on silica gel, but can be isolated as pure materials by chromatography on neutral alumina. N-BenACHTUNGTRENNUNGzylindoles 1 were found to be more stable during storage than their N-methyl analogues. To find the optimal conditions for the Lewis acid induced DA cyclopropane dimerization, we selected cyclopropane 1 a as a model substrate. Building on a previous study of the related indole-substituted DA cyclopropanes, we started by using the SnCl4/CH3NO2 system as the reaction initiator (Table 1). It is noteworthy that the reaction without Lewis acid leads to complete destruction of 1 a into a mixture of polymeric and ring-opened byproducts (Table 1, entry 1). If [a] Dr. O. A. Ivanova, Dr. E. M. Budynina, Dr. A. O. Chagarovskiy, E. R. Rakhmankulov, Dr. I. V. Trushkov, Prof. M. Y. Melnikov Department of Chemistry M. V. Lomonosov Moscow State University Leninskie Gory 1–3, Moscow 119991 (Russia) Fax: (+7) 495-9391814 E-mail : melnikov@excite.chem.msu.ru [b] Dr. E. M. Budynina, Dr. A. O. Chagarovskiy, Dr. I. V. Trushkov Laboratory of Chemical Synthesis, Federal Research Center of Pediatric Hematology, Oncology, and Immunology Leninskii av. 117/2, Moscow 117997 (Russia) [c] Dr. A. V. Semeykin, Prof. N. L. Shimanovskii Medico-Biological Faculty, The Russian State Medical University Bolshaya Pirogovskaya st. 9A, Moscow 119435 (Russia) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201101687. Figure 1. Examples of biologically active bisindole alkaloids.

From Umpolung to Alternation: Modified Reactivity of Donor–Acceptor Cyclopropanes Towards Nucleophiles in Reaction with Nitroalkanes

A conceptually new type of donor-acceptor cyclopropane reactivity towards nucleophiles has been disclosed. An essential characteristic of the process is an unusual nucleophilic attack on the C(3)-position of a cyclopropane, combined with typical small ring-opening by cleavage of the C(1)-C(2) bond between the acceptor and the donor. Based on this new reaction between cyclopropane-1,1-diesters and nitroalkanes, we developed a convenient approach to γ-nitroesters that can be efficiently transformed to the substituted pyrrolidones, structural analogues of racetame family drugs (rolipram, phenylpiracetam, etc.).

Lewis and Brønsted acid induced (3 + 2)-annulation of donor-acceptor cyclopropanes to alkynes: indene assembly.

(3 + 2)-Annulation of donor-acceptor cyclopropanes to alkynes induced by both Lewis and Brønsted acids has been developed. The reaction provides a rapid approach to functionalized indenes displaying intense visible emission (λmax = 430 nm, Φ = 0.28-0.34).

Reaction of Corey ylide with α,β-unsaturated ketones: tuning of chemoselectivity toward dihydrofuran synthesis.

A straightforward, efficient, and reliable approach to synthetically valuable 2,3-dihydrofurans via a reaction between Corey ylide and α,β-unsaturated ketones has been developed. The use of simple and widely spread starting materials as well as mild reaction conditions and scalability provide a broad scope of 2,3-dihydrofurans.

Formal [3 + 2]-Cycloaddition of Donor–Acceptor Cyclopropanes to 1,3-Dienes: Cyclopentane Assembly

We report a new simple method to access highly substituted cyclopentanes via Lewis acid-initiated formal [3 + 2]-cycloaddition of donor-acceptor cyclopropanes to 1,3-dienes. This process displays exceptional chemo- and regioselectivity as well as high diastereoselectivity, allowing for the synthesis of functionalized cyclopentanes and bicyclic cyclopentane-based structures in moderate to high yields. Moreover, one-pot synthesis of biologically relevant cyclopentafuranones, based on reaction of donor-acceptor cyclopropanes with dienes, has been developed.

A Straightforward Approach to Tetrahydroindolo[3,2-b]carbazoles and 1-Indolyltetrahydrocarbazoles through [3+3] Cyclodimerization of Indole-Derived Cyclopropanes.

A rapid new approach to produce biologically relevant bisindoles, namely indolyltetrahydrocarbazoles and indolo[3,2-b]carbazoles, has been developed, based on the Ga(OTf)3 -catalyzed [3+3] cyclodimerization of indole-derived donor-acceptor cyclopropanes. Chemoselectivity of the process depends on the location of the three-membered ring at the indole core.

Complexation of Donor-Acceptor Substituted Aza-Crowns with Alkali and Alkaline Earth Metal Cations. Charge Transfer and Recoordination in Excited State

Complexation between two aza-15-crown-5 ethers bearing electron donor and acceptor fragments and alkali and alkaline earth perchlorates has been studied using absorption, steady-state fluorescence and femtosecond transient absorption spectroscopy. The spectral-luminescent parameters, the stability and dissociation constants of the complexes were calculated. The intramolecular charge transfer reaction takes place both in the excited state of the crowns and their complexes 1:1; the latter is subjected to photorecoordination resulting in a weakening or a complete disruption of coordination bond between nitrogen atom and metal cation, disposed within a cavity of the crown. The compounds investigated can be viewed as novel optical molecular sensors for alkali and alkaline-earth metal cations. The photoejection of a metal cation into the bulk was not observed.