Gold(I)-catalyzed intermolecular addition of carbon nucleophiles to 1,5- and 1,6-enynes

Gold(I)-catalyzed addition of carbon nucleophiles to 1,6-enynes gives two different type of products by reaction at the cyclopropane or at the carbene carbons of the intermediate cyclopropyl gold carbenes. The 5-exo-dig cyclization is followed by most 1,6-enynes, although those bearing internal alkynes and alkenes react by the 6-endo-dig pathway. The cyclopropane versus carbene site-selectivity can be controlled in some cases by the ligand on the gold catalyst. In addition to electron-rich arenes and heteroarenes, allylsilanes and 1,3-dicarbonyl compounds can be used as the nucleophiles. In the reaction of 1,5-enynes with carbon nucleophiles, the 5-endo-dig pathway is preferred.     

Electrosynthesis of cyclopropanes at the electrolysis of solutions of methyl esters of Di- and trichloroacetatic acids in aprotic media in the presence of acrylonitrile

The potentiostatic (galvanostatic) electrolysis of methyl esters of trichloroacetic acid on mercury (steel) cathodes in the cathodic compartment of a diaphragm cell in the presence of acrylonitrile affords a mixture of two stereoisomers of methyl ester of 1-chloro-2-cyanocyclopropanecarboxylic acid. The process involves a stage of dehalogenation of the original methyl ester followed by the reaction of the formed anion with acrylonitrile and proceeds more efficiently on a mercury cathode in the dimethylformamide medium with the current efficiency of 94% and the substance yield of 25%. In contrast to methyl trichloroacetate, the electrolysis of methyl dichloroacetate proceeds by an indirect mechanism involving its deprotonation on the steel cathode and by the cleavage of the C-Cl bond on the mercury cathode. In both cases, the acrylonitrile addition leads to formation of the corresponding cyclopropane structures. Moreover, the process is the most efficient on the steel cathode in the MeCN medium. In the latter case, the current efficiency of methyl ester of 1-chloro-2-cyanocyclopropanecarboxylic acid is 31% and substance yield is 41%. Peculiarities of these processes are discussed.     

Synthesis and cross-coupling reactions of 7-azaindoles via a new donor-acceptor cyclopropane

[reaction: see text] A new type of donor-acceptor cyclopropane has been prepared from commercially available cyclopropane-1,1-diesters. This cyclopropane reacts with triflic anhydride to produce an isolable tristrifloxy intermediate which when treated with primary amines gives 6-trifloxy-7-azaindolines which in turn can be dehydrogenated to the azaindoles. The 6-trifloxy substituent can be used to introduce diversity at this position via a variety of cross-coupling reactions thus preparing potentially interesting compounds based on the important 7-azaindole pharmacophore.     

Cyclopropane Adsorption on Zeolites Studied by IR Spectroscopy: II. Adsorption and Conversion of Cyclopropane on Na- and Ca-Exchanged Zeolite Y

The adsorption and isomerization of cyclopropane on the calcium- and sodium-exchanged zeolite Y are studied by IR spectroscopy. Cyclopropane is adsorbed on CaY in two different forms. Weaker adsorption is related to residual sodium ions, which were not completely removed from the zeolite by ion exchange. This form can be removed from the surface after evacuation of the samples at room temperature. Stronger adsorption is attributed to the Ca ions. It is stable up to 100°C. The corresponding diffuse-reflectance spectrum indicates the C _2v symmetry of the cyclopropane complex with Ca ions. At 200°C cyclopropane adsorbed on the calcium-exchanged zeolite converts to propylene. On the sodium-exchanged zeolite, this reaction only occurs at 400°C. The reaction coordinate of cyclopropane isomerization on CaY is related to the simultaneous cleavage of the C–C bond in the cyclopropane ring and hydrogen atom transfer from one of the CH₂ fragments to another. The reaction coordinate corresponds to a combination of the stretching vibration of the C–C bond with the fan vibration of the CH₂ group and the stretching vibration of the CH bond. These composite vibrations result in the strong polarization of the C–C and C–H bonds and, hence, exhibit anomalously high molar absorption coefficients in the IR spectrum.     

Zwitterion from a cyclopropane with geminal donor and acceptor groups

2,2-Dimethoxy-3,3-dicyanospiro[cyclopropane-1,9'-[9H]fluorene] reacted fast with methanol to afford 9-trimethoxymethyl-9-dicyanomethyl-9H-fluorene. Reaction with benzaldehydes also gave products of cyclopropane ring opening. Strong electron-donor p-substituents or a strong attractor enhanced the rate. Ring opening of the cyclopropane to a zwitterion that recloses or reacts with an aryl aldehyde, to form either a CO or a CC bond first, can explain the result. The former mode of closure is sensitive to p-substituents because they are directly conjugated to the positive charge at the benzylic carbon of the former aldehyde. The latter mode is sensitive to the ground-state electrophilicity of the carbonyl carbon of the former aldehyde. Thus, reaction of the cyclopropane with p-substituted aldehydes is accelerated by either electron-donor or -acceptor substituents. [reaction: see text].     

Bromination of exo-Tricyclo[3.2.2.0(2,4)]non-6-ene

In carbon tetrachloride reaction of 1 with bromine occurs at the double bond and is favored from the less hindered face, anti to the cyclopropane ring, to give 2 and 3 (2:1) over reaction from the syn face or at the corner of the cyclopropane to give 5. In the solvent methanol, corner attack of bromine at the cycloproane to give 30, 16, 17, and 37 competes with reaction at the double bond anti to the cyclopropane to give 18, 19, and 2.     

不对称环丙烷化反应

利用手性类卡宾分子对烯烃的加成,可合成非对称取代的环丙烷环。其不对称诱导一般受立体和电子因素控制。本文主要综述 Simmons-Smith 反应,重氮化合物,异丙叉三苯基膦,以及一些金属有机化合物的催化热解反应在不对称环丙烷环合成中的应用,并以潜在杀虫剂环丙烷甲酸化合物的合成为例进行了讨论。     

Silylium‐Ion‐Promoted (5+1) Cycloaddition of Aryl‐Substituted Vinylcyclopropanes and Hydrosilanes Involving Aryl Migration

A transition‐metal‐free (5+1) cycloaddition of aryl‐substituted vinylcyclopropanes (VCPs) and hydrosilanes to afford silacyclohexanes is reported. Catalytic amounts of the trityl cation initiate the reaction by hydride abstraction from the hydrosilane, and further progress of the reaction is maintained by self‐regeneration of the silylium ions. The new reaction involves a [1,2] migration of an aryl group, eventually furnishing 4‐ rather than 3‐aryl‐substituted silacyclohexane derivatives as major products. Various control experiments and quantum‐chemical calculations support a mechanistic picture where a silylium ion intramolecularly stabilized by a cyclopropane ring can either undergo a kinetically favored concerted [1,2] aryl migration/ring expansion or engage in a cyclopropane‐to‐cyclopropane rearrangement.     

Stereocontrolled synthesis of trisubstituted cyclopropanes: expedient, atom-economical, asymmetric syntheses of (+)-Bicifadine and DOV21947

[reaction: see text] An expedient, atom-economical, asymmetric synthesis of 1-aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.     

Diastereoselective intermolecular Pauson-Khand reactions of chiral cyclopropenes

In this Letter, it is demonstrated that the unusual reactivity of cyclopropenes can increase the scope and utility of intermolecular Pauson-Khand reactions. The well-defined chiral environment of cyclopropenes has a powerful influence on the diastereoselectivity of the reactions and leads to the production of a single cyclopentenone in each of the described cases. The cyclopropane ring strongly influences the stereochemistry of reactions at the enone, and the three-membered ring can subsequently be cleaved under mild conditions. [reaction: see text]     

Nucleophilic cleavage of spiroactivated cyclopropanes.1. Kinetic and thermodynamic parameters for reaction of 6,6-dimethyl-2-phenyl-5,7-dioxaspiro[2,5]octane-4,8-dione (2) with pyridine.

Reaction of the title spiroactivated cyclopropane(2) with pyridine in acetonitrite yields a zwitterionic addition product. The reaction is reversible which provides conditions under which rates and equilibria constants can be obtained along with the derived activation and thermodynamic parameters of reaction. An extended Bronsted treatment affords a β_nuc value for the reaction of 2 with substituted pyridines.     

Addition of hydrogen halides to alkylidenecyclopropanes: a highly efficient and stereoselective method for the preparation of homoallylic halides

The reaction of alkylidenecyclopropanes with HCl or with HBr proceeds very smoothly at 120°C to produce the corresponding homoallylic halides stereoselectively in good to excellent yields. For example, the reaction of (1-phenylbenzylidene)cyclopropane, (1-butylpentylidene)cyclopropane and octylidenecyclopropane with hydrochloric acid produced the corresponding homoallylic chlorides, 4-chloro-1,1-diphenyl-1-butene, 4-butyl-1-chloro-3-octene and (E)-1-chloro-3-undecene in 99, 96, and 87% yields, respectively. The reaction of (1-butylpentylidene)cyclopropane with hydrobromic acid yielded 1-bromo-4-butyl-3-octene in 95% yield.     

Aryl vinyl cyclopropane Cope rearrangements

While the divinyl cyclopropane Cope rearrangement is well-known, and has been broadly applied in synthesis, examples of the aryl vinyl cyclopropane Cope rearrangement are less common and generally limited in scope or reaction yield. The aryl vinyl cyclopropane Cope rearrangement gives access to the benzocycloheptene scaffold, which is present in a variety of naturally occurring and medicinally relevant products. Herein we report a method to obtain either of two regioisomeric benzocycloheptene products via an aryl vinyl cyclopropane Cope rearrangement, featuring additive-controlled regioselectivity. Mechanistic studies indicate a dynamic equilibration of cyclopropane stereoisomers, followed by rearrangement of the cis diastereomer.     

Electrophilic cleavage of cyclopropylmethystannanes: an experimental comparison of sigma-sigma and sigma-pi conjugation

[reaction: see text] Cyclopropylmethyltrimethylstannanes undergo electrophilic cyclopropane cleavage in chloroform with simple inorganic electrophiles (H(+), SO(2), I(2)) in a homologous reaction to the S(E)' cleavage of allylic stannanes. The sigma-sigma conjugation between the carbon-tin bond and cyclopropane orbitals observed spectroscopically in the parent cyclopropylmethyltrimethylstannane is responsible for a rate enhancement of ca. 10(2) toward iodinolysis, relative to comparable alkyl stannanes. This acceleration is considerably less, however, than the ca. 10(9)-fold rate enhancement provided by the corresponding sigma-pi conjugation in allylic stannanes. Methanol-tin coordination appears to reduce the activating influence of the metal, promoting methyl cleavage over cyclopropane fission with acid and iodine. Decreased sigma-sigma conjugation can also explain the decreased reactivity of cyclopropyltriphenylstannane compared with its trimethyltin counterpart. Cyclopropylmethylstannanes do not undergo the synthetically useful addition of aldehydes under conditions that facilitate the corresponding reaction of allylic stannanes.     

Reactions of carbenes in solidified organic molecules at low temperature

Studies on reactions of carbenes in reactive organic glasses at low temperatures clearly reveal that solution results and liquid phase mechanistic rules cannot be readily extrapolated to matrix conditions. Thus, the usual course of reaction of a carbene with an alkene in solution results in the formation of a cyclopropane for both the singlet and triplet states although a one-step addition possible for singlet carbene produces the cyclopropane stereospecifically and a stepwise pathway with the triplet state affords two possible stereoisomers of the cyclopropane. In a sharp contrast, the formal insertion products into the allylic C-H bonds of alkenes are produced at the expense of the cyclopropane when carbene is generated in alkene matrix at low temperature. Similar results are obtained in the reaction with alcohols, where the C-H insertion products are formed in low temperature alcoholic matrices at the expense of the O-H insertion products which are predominant products in the reaction with alcoholic solution at ambient temperature. The ¹³C labelling experiments as well as deuterium kinetic isotope effects suggest that these C-H insertion products are most probably produced from the triplet carbene, not from the singlet, by abstraction of H atom from the matrix followed by the recombination of the resulting radical pairs. Kinetic studies using ESR and laser flash photolysis techniques demonstrate that the mechanism of a H-atom transfer reaction changes from a completely classical process in a soft warm glass to a completely quantum mechanical tunneling process in a cold hard glass. Thus, as the reaction temperature is lowered, the classical reaction rate decreases, and eventually becomes much slower than decay by hydrogen atom tunneling. The members of the radical pairs which usually diffuse apart in a fluid solution are not able to diffuse apart owing to the limited diffusibility within a rigid matrix and therefore recombine with high efficiency to give the CH “insertion” products. A rather surprising and intriguing difference between the C-H insertion undergone by singlet carbenes in fluid solution at ambient temperatures and one by triplet carbenes in matrix at low temperature is noted. Thus, a marked increase in the primary and secondary C-H insertion over the tertiary is observed in the matrix reaction indicating that triplet carbenes tend to abstract H from less crowded C-H bonds. This is interpreted to indicate that the distance between carbenic center and tunneling H becomes important in H atom tunneling process. More surprisingly, the C-H insertion by triplet carbene by the abstraction-recombination mechanism in a rigid matrix proceeds with retention of the configuration, suggesting that the solid state prevents motion of the radicals to the extent that does not allow racemization to occur. Reactions with heteroatom substrates such as ethers, amines, alkyl halides and ketones are also subject to the matrix effects and the C-H insertion products increase at the expense of singlet carbene reaction products resulting from the interaction with the heteroatoms. Stereoselectivities of cyclopropanation to styrenes are also shown to be affected by the matrix effects. t-Butyl alcohol matrix is shown to be unreactive toward carbenes and thus can be used as a “solvent” in matrix carbene reactions presumably due to a large inert guest cavity provided by bulky tertiary alcohol which binds a molecular aggregate inside it. H atom tunneling in the matrix is also shown to compete with very efficient intramolecular migration of hydrogen to the carbenic center. Migration aptitude as well as stereochemistry are also found to be subject to the matrix effects.     

Diastereoselective zinco-cyclopropanation of chiral allylic alcohols with gem-dizinc carbenoids

The highly diastereoselective zinco-cyclopropanation of chiral allylic alcohols using gem-dizinc carbenoids is described. The reaction produces three contiguous stereogenic centers, and the resulting chiral cyclopropylzinc derivatives can be trapped with electrophiles with retention of configuration. Simple functional group manipulations lead to the efficient synthesis of orthogonally protected 1,2,3-substituted cyclopropane derivatives.     

New dimerization and cascade oligomerization reactions of dimethyl 2-phenylcyclopropan-1,1-dicarboxylate catalyzed by Lewis acids

New routes to transform donor-acceptor cyclopropanes in the presence of Lewis acids have been found. The reaction of dimethyl 2-phenylcyclopropan-1,1-dicarboxylate, a typical representative of this class of compounds, with an equimolar amount of anhydrous GaCl₃ gives, depending on the reaction time, (2-phenylethylidene)malonate or styrylmalonate after hydrolysis, whereas in the presence of 15-20 mol % GaCl₃ the starting cyclopropane undergoes dimerization to give the malonic derivative of 3,4-diphenylcyclopentane-1,1-dicarboxylate. In the presence of the GaCl₃·THF complex, the same cyclopropane gives a substituted 4-phenyltetraline-2,2-dicarboxylate in high yield, whereas in the presence of SnCl₄·THF it gives the dimer specified above along with products of chain oligomerization, the degree of which can be controlled by changing the concentration of the starting cyclopropane in solution.     

Control of regioselectivity in Pd(0)-catalyzed coupling-cyclization reaction of 2-(2',3'-allenyl)malonates with organic halides

The regioselectivity in the Pd(0)-catalyzed coupling-cyclization of 2-(2',3'-allenyl)malonates with organic halides is determined by the steric and electronic effects of both substrates. By deliberate control of the reaction conditions, the regioselectivity of this reaction can be tuned. With conditions A and B, the reaction afforded vinylic cyclopropane derivatives, while with conditions C and D, the reaction afforded cyclopentene derivatives in a highly selective manner. Under similar conditions, 1-alkenyl halides tend to form more three-membered cyclic products. The increased steric hindrance at the 2'-position of the allene moiety and aryl halides favors the formation of five-membered cyclic products. The regioselectivity of the reaction may be explained by the comparison of the relative stabilities of syn- and anti-type pi-allyl palladium intermediates.     

Highly Stereocontrolled Cyclopropanation by the 1,3-Elimination of a Bis(tributylstannyl)propanol Derivative

The highly stereoselective ring closure of gamma-hydroxystannyl derivative was realized. The aldol reaction of methyl bis(tributylstannyl)propionate (2) with aldehyde 5 proceeds stereoselectively to give (gamma-hydroxypropyl)stannane 6, and the cyclopropanation reaction of aldol product 6 proceeds smoothly in a highly stereoselective manner presumably via a W-shape transition state. The stannyl group on the cyclopropane ring can be converted into various electrophiles with a retention of configuration. As a result, various stereocontrolled 1,2,3-trisubstituted cyclopropanes can be obtained in high yields.     

Visible‐Light Photocatalytic Intramolecular Cyclopropane Ring Expansion

Described herein is a new visible‐light photocatalytic strategy for the synthesis of enantioenriched dihydrofurans and cyclopentenes by an intramolecular nitro cyclopropane ring expansion reaction. Mechanistic studies and DFT calculations are used to elucidate the key factors in this new ring expansion reaction, and the need for the nitro group on the cyclopropane.