Cyclopropanation Of Alkenes Research Articles

Ruthenium–arene catalysts bearing N-heterocyclic carbene ligands for olefin cyclopropanation and metathesis

Ruthenium–arene complexes bearing N-heterocyclic carbene (NHC) ligands with the generic formula [RuCl2(p-cymene)(NHC)] are efficient catalyst precursors for the cyclopropanation of activated olefins with ethyl diazoacetate, and the cis/trans diastereoselectivity of the reaction markedly depends on the steric bulk of the NHC. The procedure was successfully applied to styrene, α-methylstyrene, and various other styrenic derivatives bearing electron-withdrawing or donating substituents on their aromatic rings. The reaction of unactivated internal or terminal alkenes was more sluggish, and the use of norbornene as a substrate afforded only olefin metathesis. Further investigation of the ring-opening metathesis polymerization of this strained cycloolefin in the presence of trimethylsilyldiazomethane led to high molecular weight polynorbornene whose microstructure was not significantly affected by the choice of the NHC ancillary ligand.

Assessment of Catalysis by Arene‐Ruthenium Complexes Containing Phosphane or NHC Groups bearing Pendant Conjugated Diene Systems

AbstractTwo p‐cymene‐ruthenium complexes 1 and 2 were isolated in high yields by treating the [RuCl2(p‐cymene)]2 dimer with new hybrid phosphane‐ or NHC‐linked diene ligands. Both complexes were fully characterized by NMR spectroscopy, and the molecular structure of the ruthenium–p‐cymene complex 1, containing the phosphane–diene ligand system, was determined by X‐ray diffraction analysis. The catalytic activities of both compounds were probed in atom‐transfer radical addition (ATRA) and polymerization (ATRP), in the cyclopropanation of olefins, in the ring‐opening metathesis polymerization (ROMP) of norbornene, and in the synthesis of enol esters from hex‐1‐yne and 4‐acetoxybenzoic acid.

Structures and Reactivity of Group 9 Metalloporphyrin Complexes

The importance of metalloporphyrins is highlighted by their wide occurrence and use in nature. Essential biological roles of metalloporphyrins include electron-, energy-, and oxygen-transfer, oxygen activation, and diverse functions in enzyme active sites. Due to a broad range of physical and chemical properties, metalloporphyrins have been modified for a variety of applications such as novel components in advanced materials, sensors, medical research, and synthetic chemistry. Metalloporphyrins are also of great utility for non-biological chemical catalysis, spanning reactions such as aziridination,1 C-H activation,1 and olefination.2 Moreover, metalloporphyrins are useful, atom-efficient catalysts for the generation of new carbon-carbon and heteroatom bonds using diazo carbonyl compounds.1 Thus, understanding the structures and reactivities of metalloporphyins is vital for developing and optimizing new uses. Our current work focuses on group 9 (Rh, Ir) metalloporphyrins. This includes probing the reactivity of coordination complexes and determining the structures of the subsequent products.3 Recently, tetratolylporphyrinato (TTP) methyliridium, Ir(TTP)CH3, was shown to be an active and robust catalyst for the cyclopropanation of olefins using diazo reagents as carbene sources.4 Ir(TTP)CH3 also catalyzes N–H insertion reactions between ethyl diazoacetate (EDA) or methyl phenyldiazoacetate (MPDA) and a variety of aryl, aliphatic, primary, and secondary amines.5 Reactions with aryl amines produce the highest yields with up to 105 catalyst turnovers and without the need for slow addition of the diazo reagent. Mechanistic aspects of diazo insertion reactions are examined. In addition, a comparison of the molecular structures of RhIII(TTP) and IrIII(TTP) carbene complexes provides insights for understanding reactivity differences for the two metals complexes.6

Interfacing Microbial Styrene Production with a Biocompatible Cyclopropanation Reaction

AbstractThe introduction of new reactivity into living organisms is a major challenge in synthetic biology. Despite an increasing interest in both the development of small‐molecule catalysts that are compatible with aqueous media and the engineering of enzymes to perform new chemistry in vitro, the integration of non‐native reactivity into metabolic pathways for small‐molecule production has been underexplored. Herein we report a biocompatible iron(III) phthalocyanine catalyst capable of efficient olefin cyclopropanation in the presence of a living microorganism. By interfacing this catalyst with E. coli engineered to produce styrene, we synthesized non‐natural phenyl cyclopropanes directly from D‐glucose in single‐vessel fermentations. This process is the first example of the combination of nonbiological carbene‐transfer reactivity with cellular metabolism for small‐molecule production.

Interfacing microbial styrene production with a biocompatible cyclopropanation reaction.

The introduction of new reactivity into living organisms is a major challenge in synthetic biology. Despite an increasing interest in both the development of small-molecule catalysts that are compatible with aqueous media and the engineering of enzymes to perform new chemistry in vitro, the integration of non-native reactivity into metabolic pathways for small-molecule production has been underexplored. Herein we report a biocompatible iron(III) phthalocyanine catalyst capable of efficient olefin cyclopropanation in the presence of a living microorganism. By interfacing this catalyst with E. coli engineered to produce styrene, we synthesized non-natural phenyl cyclopropanes directly from D-glucose in single-vessel fermentations. This process is the first example of the combination of nonbiological carbene-transfer reactivity with cellular metabolism for small-molecule production.

ChemInform Abstract: Diastereoselective Synthesis of Functionalized Spirocyclopropyl Oxindoles via P(NMe2)3‐Mediated Reductive Cyclopropanation.

A P(NMe2)3-mediated reductive cyclopropanation reaction of α-keto esters or amides with isatin-derived alkenes has been developed, providing efficient and diastereoselective synthesis of highly functionalized spirocyclopropyl oxindoles bearing two all-carbon quaternary centers. This reaction also represents a complementary and nonmetal-involving protocol for the challenging cyclopropanation of electron-deficient alkenes.

ChemInform Abstract: Hypoiodite‐Mediated Catalytic Cyclopropanation of Alkenes with Malononitrile.

AbstractHypoiodite species are generated from catalytic amounts of iodine and the terminal oxidant tBuOOH.

Inside Back Cover: Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin-Based Catalysts (Angew. Chem. Int. Ed. 6/2015)

Inside Back Cover: Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin-Based Catalysts (Angew. Chem. Int. Ed. 6/2015)

Visible light induced cyclopropanation of dibromomalonates with alkenes via double-SET by photoredox catalysis.

We report herein a visible light induced generation of a carbanion via double-SET and its application in cyclopropanation of alkenes. This new synthetic approach to form cyclopropane derivatives was conducted under mild conditions, using sunlight in open air, showing the features such as environmental benignness and an easy to handle procedure.

An entry to vinylcyclopropane through palladium-catalyzed intramolecular cyclopropanation of alkenes with unstabilized allylic tosylhydrazones.

A diastereoselective Pd-catalyzed intramolecular cyclopropanation of alkenes with unstabilized allylic tosylhydrazones was developed. This methodology provides an efficient entry toward synthesis of the bicyclo[3.1.0] hexane system with an exo-double bond, and sets the basis for future elaboration of more complex polycyclic motifs.

Highly diastereoselective and enantioselective olefin cyclopropanation using engineered myoglobin-based catalysts.

Using rational design, an engineered myoglobin-based catalyst capable of catalyzing the cyclopropanation of aryl-substituted olefins with catalytic proficiency (up to 46,800 turnovers) and excellent diastereo- and enantioselectivity (98-99.9%) was developed. This transformation could be carried out in the presence of up to 20 g L(-1) olefin substrate with no loss in diastereo- and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme-bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene-transfer reactivity.

Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin‐Based Catalysts

AbstractUsing rational design, an engineered myoglobin‐based catalyst capable of catalyzing the cyclopropanation of aryl‐substituted olefins with catalytic proficiency (up to 46 800 turnovers) and excellent diastereo‐ and enantioselectivity (98–99.9 %) was developed. This transformation could be carried out in the presence of up to 20 g L−1 olefin substrate with no loss in diastereo‐ and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme‐bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene‐transfer reactivity.

Cyclopropanation of Alkenes with Diazoesters Using Cu@FeNPs

Cyclopropanation of Alkenes with Diazoesters Using Cu@FeNPs

ChemInform Abstract: Highly Stereoselective Synthesis of Cyclopropylphosphonates Catalyzed by Chiral Ru(II)‐Pheox Complex.

AbstractA highly stereoselective cyclopropanation of alkenes with diethyl diazomethylphosphonate is achieved in the presence of the Ru(II)‐Pheox complex (RPH) as catalyst.

Quinone Diazides for Olefin Functionalization

AbstractThe utility of quinone diazides in materials science is vast and well‐documented, yet this potentially useful motif has languished in the annals of organic synthesis. Herein we show that modern tools of catalysis can be employed with free or suitably masked quinone diazides to unleash the power of these classic diazo compounds in the context of both inter‐ and intramolecular olefin cyclopropanation.

Quinone diazides for olefin functionalization.

The utility of quinone diazides in materials science is vast and well-documented, yet this potentially useful motif has languished in the annals of organic synthesis. Herein we show that modern tools of catalysis can be employed with free or suitably masked quinone diazides to unleash the power of these classic diazo compounds in the context of both inter- and intramolecular olefin cyclopropanation.

Catalyst and solvent-free cyclopropanation of electron-deficient olefins with cyclic diazoamides for the synthesis of spiro[cyclopropane-1,3′-indolin]-2′-one derivatives

A novel series of spirooxindolylcyclopropane derivatives have been synthesized in high yields from 3-diazooxindole and electron deficient olefins under catalyst/solvent-free conditions.

Diastereoselective synthesis of functionalized spirocyclopropyl oxindoles via P(NMe2)3-mediated reductive cyclopropanation.

A P(NMe2)3-mediated reductive cyclopropanation reaction of α-keto esters or amides with isatin-derived alkenes has been developed, providing efficient and diastereoselective synthesis of highly functionalized spirocyclopropyl oxindoles bearing two all-carbon quaternary centers. This reaction also represents a complementary and nonmetal-involving protocol for the challenging cyclopropanation of electron-deficient alkenes.

Non-natural olefin cyclopropanation catalyzed by diverse cytochrome P450s and other hemoproteins.

Recent work has shown that engineered variants of cytochrome P450BM3 (CYP102A1) efficiently catalyze non-natural reactions, including carbene and nitrene transfer reactions. Given the broad substrate range of natural P450 enzymes, we set out to explore if this diversity could be leveraged to generate a broad panel of new catalysts for olefin cyclopropanation (i.e., carbene transfer). Here, we took a step towards this goal by characterizing the carbene transfer activities of four new wild-type P450s that have different native substrates. All four were active and exhibited a range of product selectivities in the model reaction: cyclopropanation of styrene by using ethyl diazoacetate (EDA). Previous work on P450BM3 demonstrated that mutation of the axial coordinating cysteine, universally conserved among P450 enzymes, to a serine residue, increased activity for this non-natural reaction. The equivalent mutation in the selected P450s was found to activate carbene transfer chemistry both in vitro and in vivo. Furthermore, serum albumins complexed with hemin were also found to be efficient in vitro cyclopropanation catalysts.

ChemInform Abstract: 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.