Cyclopropanation Of Alkenes Research Articles

Mutating a Highly Conserved Residue in Diverse Cytochrome P450s Facilitates Diastereoselective Olefin Cyclopropanation.

Cytochrome P450s and other heme-containing proteins have recently been shown to have promiscuous activity for the cyclopropanation of olefins using diazoacetate reagents. Despite the progress made thus far, engineering selective catalysts for all possible stereoisomers for the cyclopropanation reaction remains a considerable challenge. Previous investigations of a model P450 (P450BM3 ) revealed that mutation of a conserved active site threonine (Thr268) to alanine transformed the enzyme into a highly active and selective cyclopropanation catalyst. By incorporating this mutation into a diverse panel of P450 scaffolds, we were able to quickly identify enantioselective catalysts for all possible diastereomers in the model reaction of styrene with ethyl diazoacetate. Some alanine variants exhibited selectivities that were markedly different from the wild-type enzyme, with a few possessing moderate to high diastereoselectivity and enantioselectivities up to 97 % for synthetically challenging cis-cyclopropane diastereomers.

Reductive Cyclopropanations Catalyzed by Dinuclear Nickel Complexes

AbstractDinuclear Ni complexes supported by naphthyridine‐diimine (NDI) ligands catalyze the reductive cyclopropanation of alkenes with CH2Cl2 as the methylene source. The use of mild terminal reductants (Zn or Et2Zn) confers significant functional‐group tolerance, and the catalyst accommodates structurally and electronically diverse alkenes. Mononickel catalysts bearing related N chelates afford comparatively low cyclopropane yields (≤20 %). These results constitute an entry into catalytic carbene transformations from oxidized methylene precursors.

Reductive Cyclopropanations Catalyzed by Dinuclear Nickel Complexes.

Dinuclear Ni complexes supported by naphthyridine-diimine (NDI) ligands catalyze the reductive cyclopropanation of alkenes with CH2 Cl2 as the methylene source. The use of mild terminal reductants (Zn or Et2 Zn) confers significant functional-group tolerance, and the catalyst accommodates structurally and electronically diverse alkenes. Mononickel catalysts bearing related N chelates afford comparatively low cyclopropane yields (≤20 %). These results constitute an entry into catalytic carbene transformations from oxidized methylene precursors.

Nickel-catalysed cyclopropanation of electron-deficient alkenes with diiodomethane and diethylzinc.

In the presence of a nickel catalyst, the cyclopropanation of electron-deficient alkenes with diiodomethane and diethylzinc is drastically accelerated. A wide range of cyclopropyl ketones, esters and amides can be accessed under these conditions.

Cyclopropanation of Various Substrates via Simmons-Smith and Michael-Initiated Ring Closure (MIRC) Reactions

Cyclopropanation of various electron rich and electron deficient olefins via Simmons-Smith and Michael-initiated ring closure reactions was studied in our research. Cinnamyl alcohol 18 was succesfully cyclopropanated in a good to excellent yield using Simmons-Smith reactions. Methyl and benzyl crotonate 14 and 16 were labile in MIRC reaction condition indicated by the detection of starting material degradation in the NMR spectra of the crude reactions, and allowed a low to moderate product yield. The other starting materials, i.e., cinnamaldehyde 19 , methyl cinnamate 20 , mono- and di-protected cross-coupled product (4 R ,5 R , E )-methyl 5-( tert -butyldimethylsilyloxy)-4-hydroxyhepta-2,6-dienoate 25 and (4 R ,5 R , E )-methyl 5-( tert -butyldimethylsilyloxy)-4-(methoxymethoxy)hepta-2,6-dienoate 26 , were apparently incompatible to the reaction condition set in our study.

ChemInform Abstract: An Inexpensive and Recyclable Silver‐Foil Catalyst for the Cyclopropanation of Alkenes with Diazoacetates under Mechanochemical Conditions.

AbstractCyclopropanes are diastereoselectively prepared from diazoacetates and styrenes under solvent free conditions in a stainless‐steel ball mill.

Mutating a Highly Conserved Residue in Diverse Cytochrome P450s Facilitates Diastereoselective Olefin Cyclopropanation

Mutating a Highly Conserved Residue in Diverse Cytochrome P450s Facilitates Diastereoselective Olefin Cyclopropanation

Synthesis of cyclopropanated [2.2.1] heterobicycloalkenes: An improved procedure

ABSTRACTA safer and improved method to our previous report on palladium-catalyzed cyclopropanation of heterobicyclic alkenes has been developed. By using tetrahydrofuran as the solvent and a more dilute aqueous NaOH solution for the generation of diazomethane from Diazald, cyclopropanation could be achieved smoothly with minimal adjustment over the course of reaction. 7-Oxabicyclic substrates with bulky C1 or C2 groups, as well as 2,3-diazabicyclic substrates with various N-substituents, effectively underwent cyclopropanation. Using this methodology, yields to previously reported products were markedly increased, and 10 new cyclopropanated [2.2.1] heterobicyclic products were prepared. In addition, this work accounts for the first reported cyclopropanation of 2,3-diazabicyclic alkenes, which all gave excellent yields of >90%.

Intermolecular Cyclopropanation of Styrenes Using Iodine and Visible Light via Carbon-Iodine Bond Cleavage.

The intermolecular cyclopropanation of aromatic olefins with activated methylene compounds using iodine and visible light irradiation was described. This reaction proceeds under rare-metal-free conditions. Styrenes with various substituted groups (alkyl and electron-withdrawing groups) provided corresponding cyclopropanes in moderate to good yields.

Zinc-catalyzed alkene cyclopropanation through zinc vinyl carbenoids generated from cyclopropenes.

The zinc-catalyzed reaction of cyclopropenes with alkenes leading to vinylcyclopropane derivatives is reported. A broad range of alkenes (including highly substituted or functionalized alkenes) is compatible with this protocol. On the basis of trapping experiments and computational studies, this cyclopropanation reaction is proposed to proceed through initial formation of an electrophilic zinc vinyl carbenoid intermediate, which may be involved in a concerted cyclopropanation reaction. The reported protocol represents an unprecedented and simple strategy for the catalytic generation of zinc vinyl carbenoids, which are promising intermediates in organic synthesis.

Zinc‐Catalyzed Alkene Cyclopropanation through Zinc Vinyl Carbenoids Generated from Cyclopropenes

AbstractThe zinc‐catalyzed reaction of cyclopropenes with alkenes leading to vinylcyclopropane derivatives is reported. A broad range of alkenes (including highly substituted or functionalized alkenes) is compatible with this protocol. On the basis of trapping experiments and computational studies, this cyclopropanation reaction is proposed to proceed through initial formation of an electrophilic zinc vinyl carbenoid intermediate, which may be involved in a concerted cyclopropanation reaction. The reported protocol represents an unprecedented and simple strategy for the catalytic generation of zinc vinyl carbenoids, which are promising intermediates in organic synthesis.

An inexpensive and recyclable silver-foil catalyst for the cyclopropanation of alkenes with diazoacetates under mechanochemical conditions.

The diastereoselective cyclopropanation of various alkenes with diazoacetate derivatives can be achieved under mechanochemical conditions using metallic silver foil and a stainless-steel vial and ball system. This solvent-free method displays analogous reactivity and selectivity to solution-phase reactions without the need for slow diazoacetate addition or an inert atmosphere. The heterogeneous silver-foil catalyst system is easily recyclable without any appreciable loss of activity or selectivity being observed. The cyclopropanation products were obtained with excellent diastereoselectivities (up to 98:2 d.r.) and in high yields (up to 96 %).

An Inexpensive and Recyclable Silver‐Foil Catalyst for the Cyclopropanation of Alkenes with Diazoacetates under Mechanochemical Conditions

AbstractThe diastereoselective cyclopropanation of various alkenes with diazoacetate derivatives can be achieved under mechanochemical conditions using metallic silver foil and a stainless‐steel vial and ball system. This solvent‐free method displays analogous reactivity and selectivity to solution‐phase reactions without the need for slow diazoacetate addition or an inert atmosphere. The heterogeneous silver‐foil catalyst system is easily recyclable without any appreciable loss of activity or selectivity being observed. The cyclopropanation products were obtained with excellent diastereoselectivities (up to 98:2 d.r.) and in high yields (up to 96 %).

Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation.

Artificial metalloenzymes (ArMs) formed by incorporating synthetic metal catalysts into protein scaffolds have the potential to impart to chemical reactions selectivity that would be difficult to achieve using metal catalysts alone. In this work, we covalently link an alkyne-substituted dirhodium catalyst to a prolyl oligopeptidase containing a genetically encoded L-4-azidophenylalanine residue to create an ArM that catalyses olefin cyclopropanation. Scaffold mutagenesis is then used to improve the enantioselectivity of this reaction, and cyclopropanation of a range of styrenes and donor–acceptor carbene precursors were accepted. The ArM reduces the formation of byproducts, including those resulting from the reaction of dirhodium–carbene intermediates with water. This shows that an ArM can improve the substrate specificity of a catalyst and, for the first time, the water tolerance of a metal-catalysed reaction. Given the diversity of reactions catalysed by dirhodium complexes, we anticipate that dirhodium ArMs will provide many unique opportunities for selective catalysis.

Nickel-Catalyzed Cyclopropanation with NMe4OTf and nBuLi.

Nickel was identified as a catalyst for the cyclopropanation of unactivated olefins by using in situ generated lithiomethyl trimethylammonium triflate as a methylene donor. A mechanistic hypothesis is proposed in which the generation of a reactive nickel carbene explains several interesting observations. Additionally, our findings shed light on a report by Franzen and Wittig published in 1960 that had been retracted later owing to irreproducibility, and provide a rational basis for the systematic development of the reaction for preparative purposes as an alternative to diazomethane or Simmons-Smith conditions.

Dimeric TADDOL Phosphoramidites in Asymmetric Catalysis: Domino Deracemization and Cyclopropanation of Sulfonium Ylides.

A gold-catalyzed asymmetric cyclopropanation of unactivated olefins with sulfonium ylides in the presence of a bimetallic catalyst with a novel dimeric TADDOL-phosphoramidite ligand is reported. This transformation allows a rare gold-catalyzed dynamic deracemization of chiral racemic substrates, where the same catalyst is responsible for several synergistic tasks in solution. The products are useful building blocks in synthesis and enable expeditious access to natural products.

Copper-Catalyzed (2+1) Annulation of Acetophenones with Maleimides: Direct Synthesis of Cyclopropanes.

A practical copper-catalyzed direct oxidative cyclopropanation of electron-deficient alkenes with acetophenone derivatives is reported. The dehydrogenative annulation involves a double C-H bond functionalization at the α-position of the ketone using di-tert-butyl peroxide as oxidant. The broad scope of the reaction and excellent functional-group tolerance is demonstrated for the stereoselective synthesis of fused cyclopropanes. The developed transformation revealed an unprecedented reactivity for copper-catalyzed processes.

Enantioselective dirhodium(II)-catalyzed cyclopropanations with trimethylsilylethyl and trichloroethyl aryldiazoacetates

Highly functionalized cyclopropanecarboxylates were readily prepared by rhodium-catalyzed cyclopropanation of alkenes with aryldiazoacetates and styryldiazoaceates, in which the ester functionality is either trimethylsilylethyl (TMSE) or trichloroethyl (TCE). By having labile protecting groups on the ester, chiral triarylcyclopropane carboxylate ligands were conveniently prepared. The asymmetric induction during cyclopropanation is dependent on the nature of the ester group and the chiral dirhodium tetracarboxylate catalyst. The prolinate catalyst Rh2(S-DOSP)4 was the optimum catalyst for asymmetric intermolecular cyclopropanation of TMSE diazoesters with styrene, while Rh2(R-BPCP)4 was the optimum catalyst for TCE diazoesters.

Stereoselective gold(I) domino catalysis of allylic isomerization and olefin cyclopropanation: mechanistic studies.

Gold(I) catalysis of olefin activation is still a rare feature in the repertoire of that metal. Mechanistic studies on the gold(I)-catalyzed cyclopropanation of allyl-substituted sulfonium ylides, including kinetic analysis as well as detailed computational studies, reveal that the reaction proceeds through activation of the alkene moiety. Furthermore, a novel competitive allylic isomerization pathway that interconverts "linear" and "branched" allylic isomers is uncovered. The subtle interplay of cyclopropanation and olefin isomerization results in an intriguing domino process where two independent catalytic transformations combine with near-perfect regio- and stereoselectivities.

Ru(II)-Pheox-Catalyzed Asymmetric Intramolecular Cyclopropanation of Electron-Deficient Olefins.

The first highly enantioselective intramolecular cyclopropanation of electron-deficient olefins, in the presence of Ru(II)--Pheox catalyst, is reported. The corresponding cyclopropane-fused γ-lactones were obtained in high yields (up to 99%) with excellent enantioselectivities (ee up to 99%). Moreover, this method enables efficient access to enantioenriched dicarbonyl cyclopropane derivatives, which are important intermediates for the synthesis of various bioactive compounds.