Cyclopropanation Of Alkenes Research Articles

Efficient, scalable and economical preparation of tris(deuterium)- and 13C-labelled N-methyl-N-nitroso-p-toluenesulfonamide (Diazald®) and their conversion to labelled diazomethane.

A method for the preparation of multi-gramme quantities of N-methyl-d3-N-nitroso-p-toluenesulfonamide (Diazald-d3) and N-methyl-(13)C-N-nitroso-p-toluenesulfonamide (Diazald-(13)C) and their conversion to diazomethane-d2 and diazomethane-(13) C, respectively, is presented. This approach uses robust and reliable chemistry, and critically, employs readily commercially available and inexpensive methanol as the label source. Several reactions of labelled diazomethane are also reported, including alkene cyclopropanation, phenol methylation and α-diazoketone formation, as well as deuterium scrambling in the preparation of diazomethane-d2 and subsequent methyl esterification of benzoic acid.

Hypoiodite‐Mediated Catalytic Cyclopropanation of Alkenes with Malononitrile

AbstractAn efficient synthetic procedure for dicyano‐cyclopropanation of alkenes using catalytic amounts of molecular iodine as a precatalyst and tert‐butyl hydroperoxide (TBHP) as a terminal oxidant under mild conditions has been developed. This catalytic reaction works especially well for the aryl‐substituted double bond affording products of cyclopropanation in high yields. A catalytic cycle based on the generated in situ hypoiodite species has been proposed.magnified image

Quantitative description of structural effects on the stability of gold(I) carbenes.

The gas-phase bond-dissociation energies of a SO2 -imidazolylidene leaving group of three gold(I) benzyl imidazolium sulfone complexes are reported (E0 =46.6±1.7, 49.6±1.7, and 48.9±2.1 kcal mol(-1) ). Although these energies are similar to each other, they are reproducibly distinguishable. The energy-resolved collision-induced dissociation experiments of the three [L]-gold(I) (L=ligand) carbene precursor complexes were performed by using a modified tandem mass spectrometer. The measurements quantitatively describe the structural and electronic effects a p-methoxy substituent on the benzyl fragment, and trans [NHC] and [P] gold ligands, have towards gold carbene formation. Evidence for the formation of the electrophilic gold carbene in solution was obtained through the stoichiometric and catalytic cyclopropanation of olefins under thermal conditions. The observed cyclopropane yields are dependent on the rate of gold carbene formation, which in turn is influenced by the ligand and substituent. The donation of electron density to the carbene carbon by the p-methoxy benzyl substituent and [NHC] ligand stabilizes the gold carbene intermediate and lowers the dissociation barrier. Through the careful comparison of gas-phase and solution chemistry, the results suggest that even gas-phase leaving-group bond-dissociation energy differences of 2-3 kcal mol(-1) enormously affect the rate of gold carbene formation in solution, especially when there are competing reactions. The thermal decay of the gold carbene precursor complex was observed to follow first-order kinetics, whereas cyclopropanation was found to follow pseudo-first-order kinetics. Density-functional-theory calculations at the M06-L and BP86-D3 levels of theory were used to confirm the observed gas-phase reactivity and model the measured bond-dissociation energies.

P450BM3‐Axial Mutations: A Gateway to Non‐Natural Reactivity

AbstractEnzymes capable of catalyzing non‐natural reactions have the potential to alter the way relevant molecules are prepared on‐scale. Efforts to this end have largely focused on combining non‐natural cofactors with proteins lacking catalytic function to obtain non‐natural reactivity. An alternative approach is to utilize a native cofactor to catalyze non‐natural reactions. Recently, our group demonstrated that heme‐containing cytochrome P450s are able to catalyze the highly selective cyclopropanation of alkenes. Superior activity was observed upon changing the axial cysteine to serine (“P411”). Mutation at the conserved axial ligand has enabled P450s to catalyze other non‐natural reactions such as NH insertion and CH amination.

ChemInform Abstract: Elevated Catalytic Activity of Ruthenium(II)—Porphyrin‐Catalyzed Carbene/Nitrene Transfer and Insertion Reactions with N‐Heterocyclic Carbene Ligands.

Bis(NHC)ruthenium(II)–porphyrin complexes were designed, synthesized, and characterized. Owing to the strong donor strength of axial NHC ligands in stabilizing the trans MCRR′/MNR moiety, these complexes showed unprecedently high catalytic activity towards alkene cyclopropanation, carbene CH, NH, SH, and OH insertion, alkene aziridination, and nitrene CH insertion with turnover frequencies up to 1950 min−1. The use of chiral [Ru(D4-Por)(BIMe)2] (1 g) as a catalyst led to highly enantioselective carbene/nitrene transfer and insertion reactions with up to 98 % ee. Carbene modification of the N terminus of peptides at 37 °C was possible. DFT calculations revealed that the trans axial NHC ligand facilitates the decomposition of diazo compounds by stabilizing the metal–carbene reaction intermediate.

Stereoselective synthesis of cis-2-fluorocyclopropanecarboxylic acid.

A rhodium-catalyzed cyclopropanation of 1-fluoro-1-(phenylsulfonyl)ethylene and diazo esters is described as an effective method for the stereoselective synthesis of cis-2-fluorocyclopropanecarboxylic acid. This process provides an example of the cyclopropanation of electron-deficient olefin and diazoacetates.

Theoretical Mechanistic Studies on Methyltrioxorhenium-Catalyzed Olefin Cyclopropanation: Stepwise Transfer of a Terminal Methylene Group

Methyltrioxorhenium (MTO)-catalyzed transfer of a methylene group to styrene has been computationally found to preferably follow a stepwise mechanism to give phenylcyclopropane via formation of a pseudo-metallacyclic intermediate and subsequent alkylative cyclization. The present result serves as the first theoretical evidence for d0 transition metal mediated transfer of methylene as a terminal form rather than a metal carbene or carbenoid fashion, accompanied by the cleavage of a H2C═O double bond. The mechanism presented here is in contrast to the carbenoid or metal carbene promoted methylene transfer and to the MTO-catalyzed isoelectronic atom (group) transfer in MeRe(O)2(η2-O–NH) or MeRe(O)2(η2-O–O). This study not only enriches the chemistry of olefin cyclopropanation and the MTO-catalyzed group (atom) transfer event but also sheds new light on the reaction chemistry of formaldehyde.

ChemInform Abstract: Highly Stereoselective Cyclopropanation of Olefins Catalyzed by a Novel C3‐Symmetric Arsine.

ChemInform Abstract: Highly Stereoselective Cyclopropanation of Olefins Catalyzed by a Novel C₃‐Symmetric Arsine.

Copper(II)–acid catalyzed cyclopropanation of 1,3-dienamides by electrophilic activation of α-aryl diazoesters

Copper(II)–acid catalyzed cyclopropanation of electron-rich alkenes, such as 1,3-dienamides, with α-aryl diazoesters are described. The reaction could be performed without rare metal catalysts, excess substrate, or the need for the slow addition of the diazoesters.

Highly Diastereoselective Cyclopropanation of Olefins Catalysed By a C2-Symmetrical Chiral Iron Porphyrin Complex

Compounds containing cyclopropane units play a crucial role in both synthetic and pharmaceutical chemistry due to high reactivity and biological properties of the three-membered ring.[1] Consequently, the interest of the research community in developing new methodologies to synthesise cyclopropanes is strongly increasing. Amongst the synthetic procedures available, the one-pot reaction of diazo compounds with olefins is a sustainable and atom-efficient strategy due to the formation of N2as the only stoichiometric by product.Catalytic enantio- and diasteroselective olefin cyclopropanations [2] have been extensively explored and metal porphyrin complexes represent a very active and stereoselective class of catalysts. Some years ago we reported on the catalytic efficiency of chiral cobalt(II)-binaphthyl porphyrins in asymmetric cyclopropanations, [3] and recorded positive data encouraging us to synthesise the structurally related chiral porphyrin 1 and its iron(III) complex 2 (see figure). The catalytic activity of 2 in the asymmetric cyclopropanation of olefins by diazo compounds was investigated. Cyclopropanes were obtained with excellent yields (up to 99%), enantio- and diasteroselectivities (eetrans up to 80%, cis/trans ratios up to 99%). In addition to that, outstanding values of TON and TOF (20,000 and 120,000/h respectively) were achieved. [4] References [1] A. K. Kumar, Intern. J. Pharm. and Pharm. Sci. 2013, 5, 467-472.[2] D. Intrieri, A. Caselli and E. Gallo, Eur. J. Inorg. Chem. 2011, 5071-5081.[3] (a) S. Fantauzzi, E. Gallo, E. Rose, N. Raoul, A. Caselli, S. Issa, F. Ragaini and S. Cenini, Organometallics, 2008, 27, 6143-6151. (b) A. Penoni, R. Wanke, S. Tollari, E. Gallo, D. Musella, F. Ragaini, F. Demartin and S. Cenini, Eur. J. Inorg. Chem. 2003, 1452-1460.[4] D. Intrieri, S. Le Gac, A. Caselli, E. Rose, B. Boitrel and E. Gallo submitted

Hypoiodite‐Mediated Cyclopropanation of Alkenes

An efficient, transition metal-free procedure for the cyclopropanation of alkenes using malononitrile and the LiI-tBuOCl combination under mild reaction conditions is described. The reaction mechanism most likely involves tBuOI generated in situ from LiI and tBuOCl. The utility of this new methodology has been demonstrated by the synthesis of a potential HIV-1 RT inhibitor.

ChemInform Abstract: Cobalt(II)‐Catalyzed Asymmetric Olefin Cyclopropanation with α‐Ketodiazoacetates.

AbstractIt is demonstrated that a metalloradical Co‐porphyrin catalyst is highly effective for the asymmetric cyclopropanation of olefins with α‐ketodiazoacetates.

Elevated Catalytic Activity of Ruthenium(II)–Porphyrin‐Catalyzed Carbene/Nitrene Transfer and Insertion Reactions with N‐Heterocyclic Carbene Ligands

Bis(NHC)ruthenium(II)-porphyrin complexes were designed, synthesized, and characterized. Owing to the strong donor strength of axial NHC ligands in stabilizing the trans M=CRR'/M=NR moiety, these complexes showed unprecedently high catalytic activity towards alkene cyclopropanation, carbene C-H, N-H, S-H, and O-H insertion, alkene aziridination, and nitrene C-H insertion with turnover frequencies up to 1950 min(-1). The use of chiral [Ru(D4-Por)(BIMe)2] (1 g) as a catalyst led to highly enantioselective carbene/nitrene transfer and insertion reactions with up to 98% ee. Carbene modification of the N terminus of peptides at 37 °C was possible. DFT calculations revealed that the trans axial NHC ligand facilitates the decomposition of diazo compounds by stabilizing the metal-carbene reaction intermediate.

Elevated Catalytic Activity of Ruthenium(II)–Porphyrin‐Catalyzed Carbene/Nitrene Transfer and Insertion Reactions with N‐Heterocyclic Carbene Ligands

AbstractBis(NHC)ruthenium(II)–porphyrin complexes were designed, synthesized, and characterized. Owing to the strong donor strength of axial NHC ligands in stabilizing the trans MCRR′/MNR moiety, these complexes showed unprecedently high catalytic activity towards alkene cyclopropanation, carbene CH, NH, SH, and OH insertion, alkene aziridination, and nitrene CH insertion with turnover frequencies up to 1950 min−1. The use of chiral [Ru(D4‐Por)(BIMe)2] (1 g) as a catalyst led to highly enantioselective carbene/nitrene transfer and insertion reactions with up to 98 % ee. Carbene modification of the N terminus of peptides at 37 °C was possible. DFT calculations revealed that the trans axial NHC ligand facilitates the decomposition of diazo compounds by stabilizing the metal–carbene reaction intermediate.

Advance of Glucosamine and Their Derivatives as Chiral Ligands in Asymmetric Syntheses

Glucosamine is a chiral compound degraded from widely existed natural product chitosan. It is becoming an ideal raw material for preparation chiral amine, amine/phosphine ligands due to its more chiral centers and strong coordination ability. The application of glucosamine derivatives as chiral ligands in asymmetric organic reactions has become a very active research area. In this paper, the application of glucosamine derivatives in asymmetric allylic alkylation, Heck reaction, 1,4conjugate addition reaction, epoxidation reaction of olefins and cyclopropanation of olefin has been reviewed.

Highly Stereoselective Cyclopropanation of Olefins Catalyzed by a Novel C 3-Symmetric Arsine

A novel C 3-symmetric arsine was employed in the one-pot cyclopropanation of olefins with carbonyl-stabilized arsonium ylides formed in situ from phenacyl bromide in the presence of NaHCO3. This new arsine demonstrates good stereoselectivity and activity in the one-pot cyclopropanation of arylidenemalononitrile. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

ChemInform Abstract: Synergistic Effect of Additives on Cyclopropanation of Olefins.

AbstractThe Simmons—Smith type cyclopropanation of a variety of olefins in the presence of trichloroacetic acid as the catalyst is efficiently promoted by 1,2‐dimethoxyethane as an additive.

ChemInform Abstract: Highly Stereoselective Olefin Cyclopropanation of Diazooxindoles Catalyzed by a C2‐Symmetric Spiroketal Bisphosphine/Au(I) Complex.

AbstractThe reaction applies a wide range of alkenes, including cyclic, cis‐ and trans‐1,2‐disubstituted as well as 1,1‐disubstituted ones.

Palladacycle-Catalyzed Methylenecyclopropanation of Bicyclic Alkenes with Propiolates

An efficient way to access functionalized methylenecyclopropanes has been developed by palladacycle-catalyzed cyclopropanation of bicyclic alkenes with propiolates in high yields. The structure of the palladacycle was kept intact in the reaction, shown by (31)P NMR spectrum studies. A rational mechanism has been proposed with a deuterium-labeled experiment. The usefulness of the functionalized methylenecyclopropanes has also been demonstrated.

Cobalt(II)‐Catalyzed Asymmetric Olefin Cyclopropanation with α‐Ketodiazoacetates

Cobalt(II)‐Catalyzed Asymmetric Olefin Cyclopropanation with α‐Ketodiazoacetates