Cyclopropane derivatives preparation

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

What alkenes would you choose as starting materials in order to prepare each of the following cyclopropane derivatives by reaction with lodomethylzmc iodide ... 

Cyclopropane Derivatives. 2,2-Dimethylcyclopropanenitrile [5722-11-2] (4) has been made by preparing the di-/)-toluenesulfonate of neopentyl glycol and treating the diester with potassium cyanide (35). 

While these rearrangements are used most often to prepare large rings, it should be noted that the expansion of cyclopropane derivatives to azetidines is also practical (Scheme 6 Section 5.09.3.3.3.a). 

Trifluoromethylzinc compounds can be prepared via the direct reaction of dihaloditluoromethane with zinc powder in DMF [J5] (equation 24) In this reaction, the DMF functions both as solvent and reactant Mechanistic experiments support a difluorocarbene reaction intermediate Indeed, a mixture of zinc and difluorodibromomethane in THF has been used for the synthesis of gewi-difluo-ro-cyclopropane derivatives [34 (equaUon 25)... 

The preparation of cyclopropane derivatives has been greatly facilitated by the development of carbene-type intermediates (see Chapter 13) and their ready reaction with olefins. The preparation of phenylcyclopropane from styrene and the methylene iodide-zinc reagent proceeds in only modest yield, however, and the classical preparation of cyclopropane derivatives by the decomposition of pyrazolines (first employed by Buchner in 1890) is therefore presented in the procedure as a convenient alternative. 

During preparation of cyclopropane derivatives, it is important to add the diiodomethane slowly to a solution of diethylzinc in the alkene. Addition of diethylzinc to an alkene-diiodomethane mixture may be explosively violent. 

A variety of cyclopropane derivatives has been prepared by generating dichlorocarbene in the presence of alknenes. 

In another study concerning the conformational requirements of I-cyclopropyl-quinolones and their relationship to DNA gyrase inhibition, the conformation-ally constrained cyclopropane derivative (62), related to ofloxacin was prepared and evaluated in whole cells and for inhibition of DNA gyrase [95] the gem-dimethyl analogue (35), discussed earlier in the context of QSAR studies... 

The electroreductive preparation of highly strained small-ring compounds is a useful general synthetic method [555-557]. The electroreduction of 1,3-dibromide (468), leading to the cyclopropane derivative (469) has been achieved via an organo Hg species, which involves sequential one-electron reductions with the intervention of organo Hg(I) radicals and dimeric Hg(I) species (Scheme 161) [558-560]. 

In another study involving C78, a pure sample of the C2v isomer was prepared using the cyclopropanation-retro-cyclopropanation reaction sequence [44, 64]. This reaction scheme consists of a controlled potential electrolytic (CPE) reduction of a previously synthesized cyclopropane derivative of the isomer, leading to removal of the cyclopropane moiety (s), (see Sect. 6.1.5). A pure sample of the D3 isomer was obtained by high performance Kquid chromatography (HPLC) as previously described [49, 65]. The redox behavior of both isomers, in DCM at room temperature, reveals that their cathodic electrochemistry is indeed very similar (although not identical) in this solvent [44]. The first two reductions are easier for the D3 isomer by 60 and 100 mV, respectively, while the third and fourth reductions are nearly identical for the two... 

The dianions of 1,2-dicarboxylates 13. prepared with LDA from the parent esters, react with dihalomethanes to form annulated cyclopropane derivatives 14101. 

Strained cyclotrisilane derivatives, which are silicon analogues of cyclopropane, are prepared by the reductive coupling of overcrowded dichlorodiarylsilanes using lithium naphthalenide (Scheme 14.9). 

Functionalized zinc carbenoids have been prepared from carbonyl compounds by an indirect strategy. The deoxygenation of a carbonyl compound to an organozinc carbenoid can be induced by a reaction with zinc and TMSCl. Therefore, the aldehyde or ketone, when treated with TMSCl or l,2-bis(chlorodimethylsilyl)ethane in the presence of an alkene, generates the cyclopropanation product. This method is quite effective for the production of alkoxy-substituted cyclopropane derivatives. A 55% yield of the... 

Moszner et al. (5) prepared low shrinkage dental compositions containing bicyclic cyclopropane derivatives, (V). 

Gem-Dihalocydopropanes belong to the most readily available cyclopropane derivatives known today. They have been shown to be extremely valuable starting materials for the preparation of cyclopropanes and cyclopropenes, they may be converted to bicyclobutane derivatives and spiropentanes, can lead to allenes and the higher cumulenes, cyclopentenes and cyclopentadienes, and many other classes of compounds, both hydrocarbon systems and derivatives with valuable functional groups. The article summarizes the preparative developments in the area of gem-dihalocyclopropane chemistry during the last decade. 

Bridged 1,5-benzodiazepines (204), prepared by condensation of o-phenyl-enediamine with 4,6-dimethylbicyclo[3.3.1]nona-3,6-diene-2,8-dione, give barbaralanes (205) on electrochemical reduction in acetonitrile in the presence of acetic anhydride338 [Eq. (119)]. The reaction is akin to the reduction of acetylacetone in which cyclopropane derivatives have been formed.339-340... 

Particularly interesting applications of isopropylidenediphenylsulfuran [459, 464] have been reported. Improvements in its preparation and use led [465] to a claimed industrially viable stereoselective synthesis of Deltamethrin, the most potent commercially available insecticide, as well as to other stereoselective syntheses of cyclopropane derivatives [466]. 

In tne preparation of trimethylene tnere can be obtained a number of metnyl aubatltution products of cyclopropane. Tnua by the action of zinc on the following bromides tne corresponding cyclopropane derivatives result. 

Very little is xnown ab.ut cyclopropane derivatives which contain a double bond in the cyclic system. Only two series of such su oet nces have been prepared and an exact proof of tr eir structure is lacking. 

Pyrazolines, in general, undergo a photochemically induced ring contraction in solution to form a cyclopropane derivative and nitrogen. This process, unlike some equivalent thermal decompositions, is stereospecific, and methyI-as-3,4-dimethyl-l-pyrazoline-3-carboxyl-ate (88) is converted in high yield into methyl-as-1,2-dimethylcyclo-propane carboxylate (89).69 This route is of considerable preparative... 

Another type of chiral Michael acceptor, the oxazepine derivatives (47), is prepared by condensation of the (-)-ephedrine-derived malonic acid derivative (46) with aldehydes (Scheme 18).51 52 Treatment of (47) with a variety of Grignard reagents in the presence of NiCh affords, after hydrolysis and decarboxylation, the 3-substituted carboxylic acids (48), in most cases with more than 90% ee. Diastereoselective Michael additions to (47) were also used for the preparation of optically active cyclopropane derivatives (49)53 and P-substituted-y-butyrolactones (50 Scheme 18).54 A total synthesis of indolmycin is based on this methodology.55... 

In the first attempts to use a chiral a-sulfinyi ester enolate as donor in Michael additions to a -un-saturated esters, only low selectivities were observed.185 186 Better results are obtained when the a-lithio sulfoxide (174), a chiral acyl anion equivalent, is employed. Conjugate addition of (174) to cyclopent-enone derivatives occurs with reasonably high degrees of asymmetric induction, as exemplified by the preparation of the 11-deoxy prostanoid (175 Scheme 63).187 188 Chiral oxosulfonium ylides and chiral li-thiosulfoximines can be used for the preparation of optically active cyclopropane derivatives (up to 49% ee) from a, -unsaturated carbonyl compounds.189... 

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