Cyclopropanation Of Alkenes Research Articles

Asymmetric Cyclopropanation with 4-Aryloxy-1-sulfonyl-1,2,3-triazoles: Expanding the Range of Rhodium-Stabilized Donor/Acceptor Carbenes to Systems with an Oxygen Donor Group.

Rhodium-catalyzed enantioselective synthesis of 1-phenoxycyclopropane-1-carbaldehydes by intermolecular cyclopropanation of terminal alkenes followed by imine hydrolysis is described. This methodology utilizes 4-aryloxy-1-sulfonyl-1,2,3-triazoles as the carbene precursors and the chiral dirhodium(II) tetracarboxylates Rh2(S-NTTL)4 or Rh2(S-DPCP)4 as the catalysts. These reactions are considered to proceed via rhodium-stabilized donor/acceptor carbene intermediates, and these studies demonstrate that a heteroatom donor group is compatible with an enantioselective transformation.

Intermolecular Metal‐Free Cyclopropanation and Aziridination of Alkenes with XH2(X=N, C) by Thianthrenation**

AbstractThree‐membered cyclic structures are widely existing in natural products and serve as enabling intermediates in organic synthesis. However, the efficient and straightforward access to such structures with diversity remains a formidable challenge. Herein, a general and practical protocol to aziridines and cyclopropanes synthesis using free XH2(X=C or N) with alkenes by thianthrenation is presented. This metal‐free protocol features the direct aziridination and cyclopropanation with unprotected XH2. Free sulfonamides, amides, carbamates, amines, and methylene with acidic protons, are good precursors, providing an attractive alternative for straightforward synthesis of aziridines and cyclopropanes from easily available starting materials.

Intermolecular Metal‐Free Cyclopropanation and Aziridination of Alkenes with XH2(X=N, C) by Thianthrenation**

Three-membered cyclic structures are widely existing in natural products and serve as enabling intermediates in organic synthesis. However, the efficient and straightforward access to such structures with diversity remains a formidable challenge. Herein, a general and practical protocol to aziridines and cyclopropanes synthesis using free XH2 (X=C or N) with alkenes by thianthrenation is presented. This metal-free protocol features the direct aziridination and cyclopropanation with unprotected XH2 . Free sulfonamides, amides, carbamates, amines, and methylene with acidic protons, are good precursors, providing an attractive alternative for straightforward synthesis of aziridines and cyclopropanes from easily available starting materials.

Mixed‐Ligand Mandelato‐Phosphine Copper(I) Complexes as Active Catalysts in Carbene Transfer Reactions

AbstractTwo mixed ligand copper(I) complexes, [Cu(PPh3)3(κ‐O‐mand)] (CuP3M) and [Cu(PPh3)2(κ2‐O,O’‐mand)] (CuP2M) (mand=dl‐mandelate) were synthesized and fully characterized. The different coordination modes of the α‐hydroxycarboxylate ligand in CuP2M and CuP3M are clearly demonstrated by infrared spectroscopy, with the asymmetric νC=O stretching being observed at 1626 (CuP3M) and 1593 (CuP2M) cm−1, respectively. Solution NMR studies (1H, 31P{1H}), elemental and X‐ray structure analyses confirmed the nature of the synthesized compounds. Complexes CuP2M and CuP3M were active in carbene transfer reactions towards unsaturated bonds, using ethyl diazoacetate (N2CHCOOEt, EDA) as carbene source. Indeed, they promoted the trans‐diastereoselective cyclopropanation of terminal and internal olefins under mild reaction conditions and low catalyst loading (1 % mol).

Asymmetric radical cyclopropanation of alkenes

Metalloradical catalysis (MRC), which utilizes metal-centered radicals to homolytically activate substrates for catalytic generation of metal-stabilized organic radicals as key intermediates, has emerged as a conceptually new approach for controlling both reactivity and stereoselectivity of radical reactions. As the first application of MRC, Co(II) complexes of chiral porphyrins, as stable 15e-metalloradicals, have been demonstrated as effective catalysts for asymmetric cyclopropanation of alkenes with diazo compounds via a stepwise radical mechanism.

Ruthenium-Catalyzed Geminal Hydroborative Cyclization of Enynes.

Disclosed here is the first geminal (gem-) hydroborative cyclization of enynes. Different from known hydroborative cyclizations, this process adds hydrogen and boron to the same position, leading to a new reaction mode. With [Cp*RuCl]4 as catalyst, a range of gem-hydroborated bicyclic products bearing a cyclopropane unit could be rapidly assembled from simple enyne substrates. Control experiments and density functional theory (DFT) calculations provided important insights into the reaction mechanism. Notably, two major competing pathways may operate with substrate-dependence. 1,6-Enynes favor initial oxidative cyclometalation to form a ruthenacyclopentene intermediate prior to engaging hydroborane, while other enynes (e.g., 1,7-enynes) that lack strong propensity toward cyclization prefer initial alkyne gem-(H,B)-addition to form an α-boryl ruthenium carbene followed by intramolecular olefin cyclopropanation. This process also represents the first ruthenium-catalyzed enyne hydroborative cyclization.

Ruthenium‐Catalyzed Geminal Hydroborative Cyclization of Enynes

AbstractDisclosed here is the first geminal (gem‐)hydroborative cyclization of enynes. Different from known hydroborative cyclizations, this process adds hydrogen and boron to the same position, leading to a new reaction mode. With [Cp*RuCl]4as catalyst, a range ofgem‐hydroborated bicyclic products bearing a cyclopropane unit could be rapidly assembled from simple enyne substrates. Control experiments and density functional theory (DFT) calculations provided important insights into the reaction mechanism. Notably, two major competing pathways may operate with substrate‐dependence. 1,6‐Enynes favor initial oxidative cyclometalation to form a ruthenacyclopentene intermediate prior to engaging hydroborane, while other enynes (e.g., 1,7‐enynes) that lack strong propensity toward cyclization prefer initial alkynegem‐(H,B)‐addition to form an α‐boryl ruthenium carbene followed by intramolecular olefin cyclopropanation. This process also represents the first ruthenium‐catalyzed enyne hydroborative cyclization.

Direct Photoexcitable Iodomethylborate Enabling Cyclopropanation of Reactive Alkenes

Abstract A radical-mediated cyclopropanation tool for reactive alkenes including dehydroamino acids (DHAAs) has been developed based on directly photoexcitable borate generating iodomethyl radical under visible light irradiation. The borate at the excited state serves as a strong single electron reductant. Therefore, this photoexcitable borate offers a simple protocol for cyclopropanation of DHAAs to forge medicinally-important cyclopropane amino acids.

Diastereoselective Transfer of Tri(di)fluoroacetylsilanes-Derived Carbenes to Alkenes.

Stereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet-metal-carbene intermediates. However, previous transition-metal-catalyzed cyclopropanation of alkenes with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible-light-induced transition-metal-free cyclopropanation reaction of terminal alkenes with trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic and aliphatic alkenes as well as electron-deficient alkenes are suitable substrates for the highly cis-selective [2+1] cyclization reaction. A combination of experimental and computational studies identified triplet carbenes as being key intermediates in this transformation. The gram scale reaction and late-stage functionalization demonstrated the synthetic potential of this strategy.

Diastereoselective Transfer of Tri(di)fluoroacetylsilanes‐Derived Carbenes to Alkenes

AbstractStereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet‐metal‐carbene intermediates. However, previous transition‐metal‐catalyzed cyclopropanation of alkenes with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible‐light‐induced transition‐metal‐free cyclopropanation reaction of terminal alkenes with trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic and aliphatic alkenes as well as electron‐deficient alkenes are suitable substrates for the highlycis‐selective [2+1] cyclization reaction. A combination of experimental and computational studies identified triplet carbenes as being key intermediates in this transformation. The gram scale reaction and late‐stage functionalization demonstrated the synthetic potential of this strategy.

Asymmetric Cyclopropanation and Epoxidation via a Catalytically Formed Chiral Auxiliary.

For the enantioselective diversification of a single starting material, a different chiral catalyst is usually required for each transformation. Herein, we extend the concept of catalytically formed chiral auxiliary from hydrogenation to the asymmetric cyclopropanation and epoxidation of tetra‐substituted olefins, alleviating the need for different chiral catalysts in the alkene functionalization step. The chiral auxiliary is catalytically constructed from propargylic amines in a Pd‐catalyzed enantioselective carboetherification step using a commercially available trifluoroacetaldehyde hemiacetal tether. The installed auxiliary is then controlling the stereochemistry of the cyclopropanation and the epoxidation using standard highly reactive reagents to give enantioenriched spirocyclic aminomethylcyclopropanols and α‐amino‐α‐hydroxy ketones.

Challenging asymmetric alkene cyclopropanation by unsymmetrical diazomalonates

In this issue of Chem Catalysis , Wang et al. report the synthesis of 1,1-cyclopropanediesters promoted by a D 2 -symmetric chiral amidoporphyrin catalyst. The carbene transfer from unsymmetrical diazomalonates to a large scope of challenging alkenes occurred with high stereocontrol thanks to the efficiency of Co(II)-based metalloradical catalytic system. In this issue of Chem Catalysis , Wang et al. report the synthesis of 1,1-cyclopropanediesters promoted by a D 2 -symmetric chiral amidoporphyrin catalyst. The carbene transfer from unsymmetrical diazomalonates to a large scope of challenging alkenes occurred with high stereocontrol thanks to the efficiency of Co(II)-based metalloradical catalytic system.

Organoelectrocatalysis Enables Direct Cyclopropanation of Methylene Compounds.

Cyclopropane is a prevalent structural unit in natural products and bioactive compounds. While the transition metal-catalyzed alkene cyclopropanation of functionalized compounds such as α-diazocarbonyl derivatives has been well established and provides straightforward access to cyclopropanes, cyclopropanation directly from the more stable and simpler methylene compounds has remained an unsolved challenge despite the highly desirable benefits of minimal prefunctionalization and increased operational safety. Herein we report an electrocatalytic strategy for the cyclopropanation of active methylene compounds, employing an organic catalyst. The method shows a broad substrate scope and excellent scalability, requires no metal catalyst or external chemical oxidant, and provides convenient access to several types of cyclopropane-fused heterocyclic and carbocyclic compounds. Mechanistic investigations suggest that the reactions proceed through a radical-polar crossover process to form the two new carbon-carbon bonds in the nascent cyclopropane ring.

Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes.

α-Alkynyldiazomethanes, generated in situ from the corresponding sulfonyl hydrazones in the presence of a base, can serve as effective metalloradicophiles in Co(II)-based metalloradical catalysis (MRC) for asymmetric cyclopropanation of alkenes. With D2-symmetric chiral amidoporphyrin 2,6-DiMeO-QingPhyrin as the optimal supporting ligand, the Co(II)-based metalloradical system can efficiently activate different α-alkynyldiazomethanes at room temperature for highly asymmetric cyclopropanation of a broad range of alkenes. This catalytic radical process provides a general synthetic tool for stereoselective construction of alkynyl cyclopropanes in high yields with high both diastereoselectivity and enantioselectivity. Combined computational and experimental studies offer several lines of evidence in support of the underlying stepwise radical mechanism for the Co(II)-catalyzed olefin cyclopropanation involving a unique α-metalloradical intermediate that is associated with two resonance forms of α-Co(III)-propargyl radical and γ-Co(III)-allenyl radical. The resulting enantioenriched alkynyl cyclopropanes, as showcased with several stereospecific transformations, may serve as valuable chiral building blocks for stereoselective organic synthesis.

Asymmetric cyclopropanation of electron-rich alkenes by the racemic diene rhodium catalyst: the chiral poisoning approach.

Asymmetric cyclopropanation of alkenes by aryldiazoacetates was achieved using the readily-available racemic (diene)rhodium complex in combination with the chiral oxazoline-phenol ligand, which acts as the chiral poison and selectively inhibits one of the enantiomers of the catalyst. This approach eliminates a common problematic step of the synthesis of chiral catalysts.

Silver-catalyzed cyclopropanation of alkenes with alkynyl N-nosylhydrazones leading to alkynyl cyclopropanes.

Here, a novel method for the stereoselective synthesis of alkynyl cyclopropanes, by the silver-catalyzed alkynylcyclopropanation of alkenes using alkynyl N-nosylhydrazones as alkynyl carbene precursors, is reported. This method provides a straightforward and powerful approach for preparing various alkynyl cyclopropanes in high yield with excellent stereoselectivities. In addition, the practicality of this method was demonstrated by gram-scale synthesis and late-stage modification of bioactive molecules.

BuLi—AlCl3—CH2I2 as a new reagent system for olefin cyclopropanation

BuLi—AlCl3—CH2I2 as a new reagent system for olefin cyclopropanation

Radical differentiation of two ester groups in unsymmetrical diazomalonates for highly asymmetric olefin cyclopropanation

Diazomalonates have been demonstrated as effective metalloradicophiles for asymmetric radical olefin cyclopropanation via Co(II)-metalloradical catalysis (MRC). Supported by D 2-symmetric chiral amidoporphyrin ligand, Co(II)-based metalloradical system can efficiently activate unsymmetrical methyl phenyl diazomalonate (MPDM) with effective differentiation of the two ester groups for asymmetric cyclopropanation, enabling stereoselective construction of 1,1-cyclopropanediesters bearing two contiguous chiral centers, including all-carbon quaternary stereogenic center. The Co(II)-catalyzed asymmetric cyclopropanation, which operates at room temperature without slow addition of the diazo compound, is generally applicable to broad-ranging olefins and tolerates various functionalities, providing a streamlined synthesis of chiral 1,1-cyclopropanediesters in high yields with both high diastereoselectivity and enantioselectivity. Combined computational and experimental studies support the underlying stepwise radical mechanism for Co(II)-catalyzed cyclopropanation. In addition to functioning as 1,3-dipoles for forming five-membered structures, enantioenriched (E)-1,1-cyclopropanediesters serve as useful building blocks for stereoselective synthesis of different cyclopropane derivatives. In addition, the enantioenriched (E)-1,1-cyclopropanediesters can be stereoselectively converted to (Z)-diastereomers.

Catalytic Deoxygenative Cyclopropanation of 1,2-Dicarbonyl or Monocarbonyl Compounds via Molybdenum Catalysis

AbstractThe cyclopropanation of alkenes through the transition-metal-catalyzed decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes. Nevertheless, the appeal of further application of this strategy is tempered by the potentially explosive nature of the diazo substrates. Therefore, it is highly desirable to develop sustainable and operationally safe surrogates for diazo compounds. In this Synpacts article, we discuss recent advances on the cyclopropane syntheses through the catalytic cyclopropanation of alkenes and metal carbenes generated in situ from nondiazo precursors as well as highlight our recent progress on the unprecedented molybdenum-catalyzed deoxygenative cyclopropanation reaction of 1,2-dicarbonyl or monocarbonyl compounds.

Mononuclear and Tetranuclear Copper(II) Complexes Bearing Amino Acid Schiff Base Ligands: Structural Characterization and Catalytic Applications.

Two new glycine-Schiff base copper(II) complexes were synthesized. Single crystal X-ray diffraction (SCXRD) allowed us to establish the structure of both complexes in the solid state. The glycine-Schiff base copper(II) complex derived from 2′-hydroxy-5′-nitroacetophenone showed a mononuclear hydrated structure, in which the Schiff base acted as a tridentate ligand, and the glycine-Schiff base copper(II) complex derived from 2′-hydroxy-5′-methylacetophenone showed a less common tetranuclear anhydrous metallocyclic structure, in which the Schiff base acted as a tetradentate ligand. In both compounds, copper(II) had a tetracoordinated square planar geometry. The results of vibrational, electronic, and paramagnetic spectroscopies, as well as thermal analysis, were consistent with the crystal structures. Both complexes were evaluated as catalysts in the olefin cyclopropanation by carbene transference, and both led to very high diastereoselectivity (greater than 98%).