A Facile Generation of a Cyclopropylzinc Compound from an Alkenylzinc Derivative and Its Reaction with Electrophiles

The one-pot synthesis of cyclopropyl compounds from 1-alkynes has been achieved by direct cyclopropanation of a 1-alkenylzinc species upon treatment with iodomethylzinc and trapping of the cyclopropylzinc intermediate with allyl bromide in the presence of CuCN⋅2 LiCl (see reaction scheme). This method proceeds under mild conditions and in good yield.     

Palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes initiated by C–H activation

A novel palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes has been developed. The reaction proceeded through palladium-catalyzed vinyl C–H bond activation of enamides followed by two migratory insertions, β-(N)H elimination and hydrolyzation cascade steps. The reaction tolerates a range of functional groups and provides an effective method for the synthesis of cyclopropane-fused norbornanes in good yields under mild conditions.     

Organocatalytic asymmetric cyclopropanation of α,β-unsaturated aldehydes with arsonium ylides

A novel organocatalytic asymmetric cyclopropanation of α,β-unsaturated aldehydes with arsonium ylides using diphenylprolinol silylether as a catalyst is described. A variety of chiral cyclopropyl aldehydes are obtained in moderate to good yields with up to 99:1 dr (diastereomeric ratio) and 99% ee under simple and mild reaction conditions.     

Asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters with stabilized sulfur ylides catalyzed by C2-symmetric ureas

A novel organocatalytic asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters with stabilized sulfur ylides using C(2)-symmetric urea as a hydrogen-bond catalyst has been described. This reaction allows an efficient access to 1,2,3-trisubstituted cyclopropane derivatives in moderate to good yields with up to 16:1 dr and 90:10 er under mild reaction conditions. The mechanism study proved that the high stereoinduction originated from the cooperative effect of the hydrogen-bond catalyst.     

Hypervalent iodine(III) reagents as safe alternatives to alpha-nitro-alpha-diazocarbonyls

A cyclopropanation reaction involving iodonium ylides generated in situ allows for efficient preparation of substituted 1-nitro-1-carbonyl cyclopropanes. This robust cyclopropanation reaction can be performed in organic solvents, biphasic aqueous media, or under solvent-free conditions with alkene substrates. The iodonium ylides generated in situ display some surprising differences in reactivity when compared to alpha-nitro-alpha-diazocarbonyl compounds. They do not undergo O-H insertion reactions and exhibit reduced reactivity with certain alkenes. [reaction: see text]     

Cobalt(II) Porphyrin‐Catalyzed Intramolecular Cyclopropanation of N‐Alkyl Indoles/Pyrroles with Alkylcarbene: Efficient Synthesis of Polycyclic N‐Heterocycles

A protocol on chemoselective cobalt(II) porphyrin‐catalyzed intramolecular cyclopropanation of N‐alkyl indoles/pyrroles with alkylcarbenes has been developed. The reaction enables the rapid construction of a range of nitrogen‐containing polycyclic compounds in moderate to high yields from readily accessible materials. These N‐containing polycyclic compounds can be converted into a variety of N‐heterocycles with potential synthetic and biological interest. Compared to their N‐tosylhydrazone counterparts, the use of bulky N‐2,4,6‐triisopropylbenzenesulfonyl hydrazones as carbene precursors allows cyclopropanation to occur under milder reaction conditions.     

Highly stereoselective cyclopropanation of glycals with cyclic diazoamides: a facile synthesis of spirooxindolyl sugar derivatives

Rhodium(II) acetate catalyzed intermolecular cyclopropanation of glycals with cyclic carbenoids generated from 3-diazo-2-oxindole has been achieved to produce a novel series of spirooxindolyl sugar derivatives in good yields under mild experimental conditions.     

Tandem gold(I)-catalyzed cyclization/electrophilic cyclopropanation of vinyl allenes

We have developed an expedient method for the synthesis of polycyclic compounds from propargyl acetates or vinyl allenes involving up to three Au(I)-catalyzed elemental steps: 3,3-rearrangement, metalla-Nazarov reaction, and electrophilic cyclopropanation. The reaction proceeds under very mild conditions and in short times. The mechanism has been studied by DFT computations.     

Asymmetric dearomative cyclopropanation of naphthalenes to construct polycyclic compounds

Catalytic asymmetric dearomatization (CADA) reactions is an important synthetic method for constructing enantioenriched complex cyclic systems from simple aromatic feedstocks. However, the CADA reactions of nonactivated arenes, such as naphthalenes and benzenes, have been far less explored than those of electronically activated arenes, such as phenols, naphthols and indoles. Herein, we disclose an asymmetric dearomative cyclopropanation of naphthalenes for the rapid construction of polycyclic compounds. With chiral dirhodium carboxylate as a catalyst, the dearomative cyclopropanation proceeded smoothly under mild conditions and afforded benzonorcaradiene-containing tetracycles in good yield and high enantioselectivity (up to 99% ee). Three stereogenic centers, including two all-carbon quaternary centers, were created in the dearomatization reaction. Moreover, a variety of functional groups are well-tolerated in the reaction. The products could be readily converted into other complex polycycles while maintaining the high ee value.

An enantioselective dearomative cyclopropanation of naphthalenes has been developed, which constructed a range of tetracyclic compounds bearing multichiral centers in high enantioselectivity.      

Diastereoselective synthesis of strained spiro-cyclopropanooxindoles from cyclic diazoamides

Reaction of cyclic diazoamides and cyclic olefins or heteroaromatic systems using copper(I) triflate as a catalyst furnished a variety of strained spiro-cyclopropanooxindoles in a diastereoselective manner under mild reaction conditions. The effect of copper(I) triflate and rhodium(II) acetate catalysts on the cyclopropanation was also studied.     

Divergent reactivity of allene-containing α-diazoesters using Cu and Rh catalysis

A versatile intramolecular reaction of allene-containing diazomalonates that exhibits excellent chemoselectivity for either allenic C–H insertion or cyclopropanation is demonstrated. The identity of the product depends on the transition metal catalyst that is employed for the reaction. Rh catalysts promote exclusive C–H insertion with good diastereoselectivity for the trans product, while Cu catalysis enables intramolecular cyclopropanation to yield methylenecyclopropanes with moderate to good E:Z ratios.     

Pybox monolithic miniflow reactors for continuous asymmetric cyclopropanation reaction under conventional and supercritical conditions

Supported catalysts having pybox chiral moieties were prepared as macroporous monolithic miniflow systems. These catalysts are based on styrene-divinylbenzene polymeric backbones having different compositions and pybox chiral moieties. Their corresponding ruthenium complexes were tested for the continuous flow cyclopropanation reaction between styrene and ethyldiazoacetate (EDA) under conventional conditions and in supercritical carbon dioxide (scCO2). Ru-Pybox monolithic miniflow reactors not only provided a highly efficient and robust heterogeneous chiral catalyst but also allowed us to develop more environmental reaction conditions without sacrificing the global efficiency of the process.     

Cyclopropanation of diazoesters with styrene derivatives catalyzed by magnetically recoverable copper-plated iron nanoparticles

Simple bare copper-plated iron nanoparticles catalyzed the cyclopropanation of diazoesters with styrene derivatives. The reaction proceeded smoothly and provided the desired products in moderate to good yields, with selectivity for the trans isomer in neat conditions. The reaction scope was explored and di or tri-substituted cyclopropanes were synthesized. The catalysts could be magnetically separated and reusable up to five times. It was also characterized by TEM, XPS, and ICP-MS. A gram-scale reaction was performed with a yield of 72%.     

Electrophilic cyclizations of vinylcyclopropanols to tethered aldehydes

[reaction: see text]. The intramolecular, stereoselective addition of 1-vinylcyclopropanols to tethered aldehydes has been achieved under mild conditions. Thus, sequential application of the titanium-mediated cyclopropanation of alpha,beta-unsaturated esters and the electrophilic cyclization of the aldehyde-tethered cyclopropanol products provides the facile formation of carbocyclic rings.     

A non-fluorous copper catalyst for the styrene cyclopropanation reaction in a fluorous medium

The complex Tp(Br3)Cu(NCMe) (1), containing no fluorine atoms, can be dissolved in the perfluoropolyether FOMBLIN and employed as a catalyst for the styrene cyclopropanation reaction with ethyl diazoacetate, with activities and diastereo-selectivities identical to those observed under homogeneous conditions with the advantage of being able to use a fluorous separation technique for catalyst recycling.     

Selective ortho methylation of nitroheteroaryls by vicarious nucleophilic substitution

An efficient and scalable three-step one-pot approach to 6-methyl-5-nitroisoquinoline (1) from inexpensive 5-nitroisoquinoline, utilizing the vicarious nucleophilic substitution (VNS) as a key step, is described. The optimized reaction conditions can be applied to a limited number of other aromatic and heteroaromatic nitro compounds. Attempts to understand the observed selectivity in the VNS step led to the discovery of two new reaction pathways under VNS conditions, one leading to an isoxazole and the other resulting in the formal cyclopropanation of an aromatic nitro compound.     

Stoichiometric Photochemical Carbene Transfer by Bamford–Stevens Reaction

The photolysis of diazoalkanes is a timely strategy to conduct carbene-transfer reactions under mild and metal-free reaction conditions, and has developed as an important alternative to conventional metal-catalyzed carbene-transfer reactions. One of the major limitations lies within the rapidly occurring side reaction of the carbene intermediate with remaining diazoalkane molecules that result in the use of an excess of the reaction partner and thus impacts on the reaction efficiency. Herein, we describe a protocol that takes advantage of the in situ generation of donor–acceptor diazoalkanes by Bamford–Stevens reaction. Following this strategy, the concentration of the diazoalkane reaction partner can be minimized to reduce unwanted side reactions and to now conduct photochemical carbene transfer reactions under stoichiometric reaction conditions. We have explored this approach in the C−H and N−H functionalization and cyclopropanation reaction of N-heterocycles and could demonstrate the applicability of this method in 51 examples.     

W(CO)5(L)-catalyzed tandem intramolecular cyclopropanation/cope rearrangement for the stereoselective construction of bicyclo[5.3.0]decane framework

Utilizing the biscarbene character of electrophilically activated alkynes, a novel tandem intramolecular cyclopropanation/Cope rearrangement of 3-siloxy-1,3,9-trien-7-ynes catalyzed by W(CO)5(L) for the stereoselective construction of bicyclo[5.3.0]decane framework is achieved. When 3-siloxy-1,3,9-trien-7-ynes were treated with a catalytic amount of W(CO)6 under photoirradiation, bicyclo[5.3.0]decanes were obtained in good yield stereoselectively. In this reaction, the Cope rearrangement of the divinylcyclopropane intermediates, generated by the intramolecular cyclopropanation of 3-siloxy-1,3,9-trien-7-ynes based on the W(CO)5(L)-catalyzed electrophilic activation of alkynes, occurs to give synthetically useful functionalized bicyclo[5.3.0]decane derivatives stereoselectively.     

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.     

Synthesis and ring opening reactions of a 2-silabicyclo[2.1.0]pentane

Methyl 2-silabicyclo[2.1.0]pentane-1-carboxylate, obtained by a photochemical intramolecular cyclopropanation reaction of an [small alpha]-allylsilyl-[small alpha]-diazoacetate, undergoes ring opening reactions under different conditions leading to methyl 2-[diisopropyl(methoxy)silylmethyl]cyclopropane-1-carboxylate, a 1-sila-4-cyclopentene-2-carboxylate or an allyl(methoxysilyl)ketene.