Oxygen acidity of ring methoxylated 1,1-diarylalkanol radical cations bearing alpha-cyclopropyl groups. The competition between O-neophyl shift and C-cyclopropyl beta-scission in the intermediate 1,1-diarylalkoxyl radicals

A product and time-resolved kinetic study on the reactivity of the radical cations generated from cyclopropyl(4-methoxyphenyl)phenylmethanol (1) and cyclopropyl[bis(4-methoxyphenyl)]methanol (2) has been carried out in aqueous solution. In acidic solution, 1*+ and 2*+ display very low reactivities toward fragmentation, consistent with the presence of groups at Calpha (aryl and cyclopropyl) that after Calpha-Cbeta bond cleavage would produce relatively unstable carbon-centered radicals. In basic solution, 1*+ and 2*+ display oxygen acidity, undergoing -OH-induced deprotonation from the alpha-OH group, leading to the corresponding 1,1-diarylalkoxyl radicals 1r* and 2r*, respectively, as directly observed by time-resolved spectroscopy. The product distributions observed in the reactions of 1*+ and 2*+ under these conditions (cyclopropyl phenyl ketone, cyclopropyl(4-methoxyphenyl) ketone, and 4-methoxybenzophenone from 1*+; cyclopropyl(4-methoxyphenyl) ketone and 4,4'-dimethoxybenzophenone from 2*+) have been rationalized in terms of a water-induced competition between O-neophyl shift and C-cyclopropyl beta-scission in the intermediate 1,1-diarylalkoxyl radicals 1r* and 2r*.     

Cyclopropyl-substituted pyrylium salts

The previously unknown 2,4,6-trisubstituted pyrylium salts 1-4 , carrying cyclopropyl and methyl or phenyl substituents in the same molecule, and 5-8 , substituted with isopropyl groups instead of cyclopropyl, were synthesized as perchlorates. The electronic spectra and the C-13 nmr spectra of the two groups of compounds were compared. A cyclopropyl group has a batochromic effect on the electronic spectrum roughly half that exerted by a phenyl; replacement of an alkyl by a cyclopropyl shifts the highest wavelength absorption band by about 20 nm. Presence of phenyl substituents reduces the batochromic effects of cyclopropyl substituents. The effects of both cyclopropyl and phenyl substituents on the electronic spectra are smaller for pyrylium than for tropylium. The nmr signals for all the ring carbons are shifted upfield upon replacement of isopropyl by cyclopropyl; in particular, the effect of substituents in position 2 upon the chemical shift of C(4) indicates that the electron-releasing effect varies in the series alkyl < phenyl < cyclopropyl, in agreement with the findings for 2,6-disubstituted pyrylium salts. The difference between the chemical shifts for the methine and methylene carbons of the three-membered ring is a function of the electron demand of the cationic heterocycle.     

Density function studies on the PtCl2‐catalyzed asymmetric cycloisomerization reaction of hydroxylated enynes

The PtCl₂‐catalyzed asymmetric cycloisomerization reaction of hydroxylated enynes was studied using density functional theory (DFT). All structures have been optimized completely at the B3LYP/6‐311G(d,p) level. As shown, the cycloisomerization reaction is exothermic. The cycloisomerization reaction mainly undergoes the formation of catalyst‐hydroxylated enzyme coordination, the asymmetric cyclopropyl platinum carbene, catalyst–cyclopropyl enol coordination, and catalyst–cyclopropyl ketone coordination. The chirality‐limiting step for the asymmetric cycloisomerization reaction is the formation of the asymmetric cyclopropyl platinum carbene, and the rate‐determining step for this reaction is the formation of the catalyst–cyclopropyl ketone coordination. The dominant products predicted theoretically are (R,S) ‐syn_5a, in agreement with the experiment. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Acid- and Pd(0)-catalyzed ring opening of 1-(1-cycloalkenyl)cyclopropyl sulfonates

We report herein facile acid-catalyzed isomerization of 1-(1'-cycloalkenyl)cyclopropyl sulfonates under mild conditions. The remarkable ease of ring opening is attributed to the presence of a 1'-alkyl substituent. Also included is a palladium-catalyzed ring opening reaction of 1-(1'-cycloalkenyl)cyclopropyl tosylates for convenient preparation of substituted 1,3-dienylamines, which complements previously reported nucleophilic substitution reactions of (1-vinyl)cyclopropyl tosylates.     

On the regioselectivity of the Ru-catalyzed intramolecular [5 + 2] cycloaddition

The influence of substituents on which cyclopropyl bond cleaves in the cycloisomerization of cyclopropylenynes catalyzed by CpRu(N&tbd1;CCH(3))(3)(+)PF(6)(-) is compared to the corresponding Rh-catalyzed reaction. With the trans cyclopropyl substrates, the bond energy of the cleaving bond appears to be an important factor. With cis cyclopropyl substrates, steric effects appear to dominate.     

Syntheses of Some Oyclopopxl Conjugated 1, 2-Diketojjes

A very recent publication by Guillaud, Pierre and Arnaud ¹ on the preparation and reactivity in basic media of some cyclopropyl conjugated 1,2-diketones prompted us to report our synthetic results in the same field. In connection with our interest in cyclopropyl conjugated carbonyl systeams way of preparing cyclopropyl conjugated 1,2-diketones is by oxidation of aither compound (I)or (II) with selenium dioxide.     

Domino carbocationic rearrangements of α-[bis(methylthio)methylene]alkyl-2-(heteroaryl)cyclopropyl ketones

Domino carbocationic rearrangements of α-[bis(methylthio)methylene]alkyl-2-(heteroaryl)cyclopropyl ketones (X=O, S, NMe) bearing five-membered heteroaryl group have been investigated. Although the cyclopropyl ketones (R¹=H) gave similar products like their aryl counterparts under these conditions, the corresponding α-methylcyclopropyl ketones (R¹=Me) yielded a variety of unexpected products depending on the nature of heteroaryl group in the substrate cyclopropyl ketones and the type of acid catalyst used. A probable mechanism for the formation of various products in these transformations has been proposed.     

Asymmetric Synthesis of 2,3‐Dihydropyrroles by Ring‐Opening/Cyclization of Cyclopropyl Ketones Using Primary Amines

The asymmetric ring‐opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′‐dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3‐dihydropyrroles as well as an effective procedure for the kinetic resolution of 2‐substituted cyclopropyl ketones.     

单分子断键反应的理论研究

利用微扰理论和对称性规则,得到了单分子断键反应中反应物结构、过渡态和所断键之间的关系．据此,对环丙基自由基及其正负离子的热开环反应和过氧化氢基态均裂反应作出预言,其中对环丙基自由基及其正负离子的热开环反应作出以下三方面的预言：是否存在过渡态;产物的立体选择;反应的相对难易程度．并分别使用UHF方法和CASSCF方法做势能面计算,结果和理论预言相符．     

Palladium‐Catalyzed Direct Cyclopropylation of Heterocycles

Many 1,3‐azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three‐membered rings is retained in the products. Thus, the cyclopropyl–halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway.     

The rates of deprotonation of some p-cyclopropyltoluene derivatives in search for the effect of the conformation of cyclopropyl groups on the stabi

p-Cyclopropyltoluene and 2-cyclopropylmesitylene have been prepared and the rates of base-catalyzed H-D exchange of the benzylic hydrogen atoms, para positioned with respect to the cyclopropyl group, have been compared with those of suitable model compounds. The results are in accord with earlier findings, where a cyclopropyl group exerts more stabilization to the carbanionic centres than do other alkyl groups. The present results suggest that this stabilization is independent of the conformation of the cyclopropyl group (perpendicular or bisected) with respect to the carbanionic centre.     

Small ring compounds—XXX : Homolytical aromatic substitution and hydrogen abstraction reaction with cyclopropyl radical

Homolytic aromatic substitution and hydrogen abstraction reactions with cyclopropyl radical were carried out to determine the reactivity and ionic character of cyclopropyl radical by examination of the orientation effect, partial rate factor and influence of substituents. By thermal decomposition of biscyclopropaneformyl peroxide in a series of substituted benzenes, the corresponding cyclopropylated benzene derivatives (the mixture of ortho, meta and para isomers) were obtained in moderate yield. In view of the orientation effect and the partial rate factor, the cyclopropyl radical seems to be fairly free from polar effect, and to resemble the phenyl radical more than the common alkyl radical although the cyclopropyl radical has a slightly higher reactivity than the phenyl radical. The relative reactivity of the 2-phenylcyclopropyl radical in the hydrogen abstraction reaction toward the benzylic position of ring-substituted toluenes gave good Hammett's correlation with the slope of + 0·20 suggesting little ionic character in the transition state. This result was in good agreement with the conclusion obtained from homolytic aromatic substitution reaction and with the chemical reactivity to be expected from the non-planar nearly sp²-hybridized conformation of the cyclopropyl radical.     

A systematic study of the hydride reduction of cyclopropyl ketones with structurally simplified substrates. highly stereoselective reductions of trans-substituted cyclopropyl ketones via the bisected s-cis conformation

The stereoselective hydride reduction of the cis- and trans-substituted cyclopropyl ketones was systematically investigated using a series of structurally simplified substrates, trans-[tert-butyldiphenylsilyloxymethyl]cyclopropyl ketones 1a-e and trans-(benzyloxymethyl)cyclopropyl methyl ketone (2), and the corresponding cis congeners 3a,b,e and 4. The results showed that, not only in the reduction of the cis-substituted cyclopropyl ketones but also in that of the trans-substituted ketones, high stereoselectivity can be realized when the substrate has a bulky substituent on the cyclopropane ring, even though it is attached to the position trans to the acyl moiety. Ab initio calculations based on the density functional theory (DFT) of cyclopropyl ketones showed that (1) the bisected s-cis and s-trans conformers were the only two minimum energy conformers, while the s-cis conformer was more stable than the s-trans and (2) a bulky alkyl group in the acyl moiety and a cis substituent on the cyclopropane ring made the bisected s-cis conformer much more stable. On the basis of these calculations and experimental results, it is likely that the more stable the bisected s-cis conformer of the substrate, the more stereoselective the hydride reduction. Thus, the stereochemistry can be explained by hydride attack on the bisected s-cis conformation of the substrate from the less-hindered face. The predictability of the stereochemical results is predicated on the bisected s-cis transition-state model, which is very important from the viewpoint of synthetic organic chemistry.     

A novel synthesis of functionalized allylsilanes

A novel facile synthesis of substituted and functionalized allylsilane has been developed. This essentially one-pot procedure involves (1) (dimethylphenylsilyl)methyl cerium chloride addition to cyclopropyl ketone and (2) MgI(2) etherate-mediated Julia homoallylic transposition of the corresponding cyclopropyl carbinol. The bifunctional homoiodo allylsilanes, readily accessible by this method, would be useful and versatile synthons in organic synthesis. [reaction: see text]     

Some new information on the formation of substituted 4‐amino‐1‐substituted phenyl‐1H‐pyrazoles from β‐enaminones and diazonium tetrafluoroborates

Upon reaction of 2‐methyl‐, 3‐ethoxycarbonyl, and 4‐ethoxycarbonylbenzenediazonium tetrafluoroborate with 1‐cyclopropyl‐3‐phenylaminohex‐2‐en‐1‐one 3‐cyclopropylcarbonyl‐1‐(substituted phenyl)‐5‐ethyl‐4‐phenylamino‐1H‐pyrazoles are formed. On the other hand, the reaction of 1‐cyclopropyl‐3‐phenylaminohex‐2‐en‐1‐one and 5‐methylaminohept‐4‐en‐3‐one with sterically more demanding 2‐ethoxycarbonylbenzenediazonium tetrafluoroborate does not give the corresponding pyrazoles but the probable intermediates on the route to the pyrazoles: 1‐cyclopropyl‐3‐phenyliminohexane‐1,2,4‐trione 2,4‐bis(2‐ethoxycarbonylphenylhydrazone) and 3‐methyliminoheptane‐2,4,5‐trione 2,4‐bis(2‐ethoxycarbonylphenylhydrazone), respectively. All the compounds were identified on the basis of ¹H‐ and ¹³C‐NMR spectra. The structure of 1‐cyclopropyl‐3‐phenyliminohexane‐1,2,4‐trione 2,4‐bis(2‐ethoxycarbonylphenylhydrazone) was confirmed by means of ¹⁵N‐NMR spectra and X‐ray. The bis(2‐ethoxycarbonylphenylhydrazones) were found to show atropoisomerism due to a hindered rotation around the bond between the carbons of imino group and the hydrazono group next to carbonyl. In the case of the crystalline cyclopropyl derivative, the unit cell was found out to contain two molecules of opposite chirality. J. Heterocyclic Chem., (2011).     

3+2] cycloaddition reactions of cyclopropyl imines with enones

A nickel-catalyzed [3+2] cycloaddition of cyclopropyl aldimines and enones has been developed. The process provides direct access to trisubstituted cyclopentanes, and the scope exceeds that of the corresponding reactions involving cyclopropyl ketones. A basis for the improved performance of cyclopropyl aldimines compared with cyclopropyl ketones is provided.     

Diastereo‐ and Enantioselective Iridium Catalyzed Carbonyl (α‐Cyclopropyl)allylation via Transfer Hydrogenation

The first examples of diastereo‐ and enantioselective carbonyl α‐(cyclopropyl)allylation are reported. Under the conditions of iridium catalyzed transfer hydrogenation using the chiral precatalyst (R)‐Ir‐ I modified by SEGPHOS, carbonyl α‐(cyclopropyl)allylation may be achieved with equal facility from alcohol or aldehyde oxidation levels. This methodology provides a conduit to hitherto inaccessible inaccessible enantiomerically enriched cyclopropane‐containing architectures.     

Cyclopropyl iminium activation: reactivity umpolung in enantioselective organocatalytic reaction design

Trick the iminium! The concept of cyclopropyl iminium activation for the organocatalytic desymmetrization of meso-cyclopropylcarbaldehydes is presented. A combination of nucleophilic and electrophilic chlorinating reagents leads to a formal addition of Cl(2) across one of the cyclopropyl bonds giving access to 1,3-dichlorides in an enantioselective, catalytic fashion.     

Structural and coordination properties of 1,2-bis(cyclopropyl)-3,4-bis(2,4,6-tri-tert-butylphenyl)-3,4-diphosphinidenecyclobutene prepared by dehydrogenative homocoupling of 3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphaallene

According to a protocol for the synthesis of phosphaallenes we recently established, 3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphallene was obtained from (Z)-2-bromo-3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphapropene. A novel bidentate ligand, 1,2-bis(cyclopropyl)-3,4-bis(2,4,6-tri-tert-butylphenyl)-3,4-diphosphinidenecyclobutene, was prepared by oxidative homocoupling of 3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphaallene in the presence of butyllithium, together with the generation of hydrogen gas. The 1,2-bis(cyclopropyl)-3,4-diphosphinidenecyclobutene was allowed to react with (tht)AuCl (tht = tetrahydrothiophene) to afford the corresponding digold(I) complex of a six-membered metallacycle containing the P=C-C=P skeleton. The molecular structures of the 2-bromo-3-cyclopropyl-1-phosphapropene, 1,2-bis(cyclopropyl)-3,4-diphosphinidenecyclobutene and the digold complex were unambiguously determined by X-ray crystallography and are discussed from the point of view of the cyclopropyl conjugation.     

环丙基甲基酮的合成研究进展

环丙基甲基酮是合成环丙氟哌酸类广谱抗菌药物和抗艾滋特效药依法韦仑的重要中间体,在医药、化工及农林等领域均有广泛应用。环丙基甲基酮的合成方法大致分为4类,分别以酮类、酯类、醇类及呋喃有机物为原料,在一定条件下生成环丙基甲基酮粗品,经萃取及精馏得到环丙基甲基酮纯品。本文综述了环丙基甲基酮的合成研究进展。