Cyclopropanes preparation from

It is possible that a dialkylzinc-methylene iodide reagent may further improve the yield as in the case with cyclopropanes prepared from vinyl ethers (Fura-kawa, J., Kawabata, N., Nishimura, J. Tetrahedron 24, 53 (1968)). 

In 1958 Simmons and Smith described a new and general synthesis of cyclopropanes by treatment of olefins with a reagent prepared from methylene iodide and a zinc-copper couple in ether solution. 

TABLE 9. Preparation of cyclopropanes 111 from a,/ -unsaturated sulfones 109 and a-metallated nitriles 11071... 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

Cyclopropanes 13 have been prepared from a NHC-rhodium catalysed decarbonylation of cyclobutanones 11 (Scheme 5.4) [6]. The isolated complex 12... 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

A quarter of a century later complex (97), structurally related to CoII(salen), was prepared from camphor and used as the catalyst for cyclopropanation. Although diastereselectivity was modest, good enantioselectivity was achieved in the reaction of 1-octene (Scheme 70).266... 

Various alkyl- and aryl-substituted [3]radialenes could be prepared from 1,1-dihaloal-kenes using organometallic pathways. Hexamethyl-[3]radialene (25), the first [3]radialene to be synthesized, was obtained in a very low yield by treatment of l,l-dibromo-2-methyl-1-propene (22) with butyllithium8,9. The lithium carbenoid 23 and the butatriene 24 are likely intermediates of this transformation (Scheme 2), the former being the source of an unsaturated carbene moiety which is transferred onto the latter. However, the outer double bonds of 24 are more readily cyclopropanated than the central one. 

Functionalised cyclopropanes can be prepared from 1,2-dioxines by reaction with stabilised phosphorus ylides . 

The reductive cyclopropanation with in situ generated titanacyclopropanes can also be applied to alkyldiformylamines 58, which are easily prepared from inexpensive formamide (57). Both formyl groups are converted to cyclopropyl groups, and the alkyldicyclopropyl-... 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

Pillai and Pines (84) found that neopentyl alcohol, mixed with 10% by weight of piperidine and passed over alumina prepared from aluminum isopropoxide, yielded 2-methyl-l-butene and 2-methyl-2-butene, in a maximum ratio of 3, and small amounts of 1,1-dimethylcyclo-propane. However, lert-pentyl alcohol yielded these two olefins in a maximum ratio of only 1.4, and none of the cyclopropane was produced (Table VI). Because of these facts a carbonium ion mechanism which is applicable to ferf-pentyl alcohol is not adequate to explain the rearrangement taking place during the dehydration of neopentyl alcohol,... 

Hall et al. (63) found that the active species in the hydrogenolysis of cyclopropane are Mo(IV) in reduced M0O3-AI2O3 catalysts. Also, Burwell and Bowman found that the hydrogenolysis of cyclopropane at 100 C (64) and also propane at 300°C (65) occurs over Mo(IV), Mo(II), and Mo(0) catalysts, which were prepared from Mo(CO)g on AI2O3. The average valence state... 

Bromo- and iodocyclopropanes cannot be prepared by the direct halogenation of cyclopropanes. Substituted chloro- and bromocyclopropanes have been synthesized by the photochemical decomposition of a-halodiazomethanes in the presence of olefins iodocyclopropanes have been prepared from the reaction of an olefin, iodoform and potassium f-butoxide followed by the reduction of diiodocyclopropane formed with tri-w-butyl tin hydride. The method described employs a readily available light source and common laboratory equipment, and is relatively safe to carry out. The method is adaptable for the preparation of bromo- and chlorocyclopropanes as well by using bromodiiodomethane or chlorodiiodomethane instead of iodoform. If the olefin used will give two isomeric halocyclopropanes, the isomers are usually separable by chromatography. ... 

The vinylcyclopropane 10 is a useful chiral building block for organic synthesis, as the vinyl group can be oxidatively cleaved if desired and further functionahzed (Scheme 14.1). Either diastereomer 20 or 21 of the cyclopropane analog of phenylalanine can be readily prepared from 10 [40]. Corey has reported another elegant appHcation of the vinylcyclopropane 10 in the asymmetric synthesis of the antidepressant (-i-)-sertraline 22 [52]. 

Finally, an entirely different approach to milnacipran (2) was recently reported in the literature (Scheme 14.6). In this case, the general strategy is based on position-selective deprotonation of cyclopropane carboxamides. Thus, cyclopropane amide 27, which was easily prepared from commercially available cyclopropane carboxylic acid, underwent... 

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... 

Trimethylsilyloxy-substituted alkenes are by far the most widely used enol ethers because of their straightforward preparation from the corresponding ketones (equation 20)78-82 -pjjg electron-rich character of silyl enol ethers allows for highly chemoselective cyclopropanations in the presence of additional double bonds (eqnation 21). ... 

There are numerous examples of highly syn diastereoselective cyclopropanation of allylic ethers in the literature, and most of them are alkenes prepared from protected glyc-eraldehyde. Some examples are illustrated in Figure 596.140-143 jjj cases, the... 

The tartaric acid scaffold also led to the design of one of the most effective and general methods to generate enantiomerically enriched substituted cyclopropyhnethanol derivatives. Indeed, the chiral dioxaborolane ligand 19, prepared from tetramethyltartramide and butylboronic acid, is a superb chiral additive in allylic alcohol-directed cyclopropanation reactions (equation 83) . The best procedure requires the use of the soluble bis(iodomethyl)zinc DME complex . The reaction affords high yields and enantiomeric... 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

Phase transfer-catalyzed reactions have recently been employed to dehydro-halogenate gem-dihalocyclopropanes [156, 157]. Thus, 1-methylene-2-vinylcyclo-propane has been prepared from l,l-dichloro-2-ethyl-3-methylcyclopropane in 60 % yield. Under the reactipn conditions (solid KOH, DMSO in the presence of dibenzo-18-crown-6, 100-130 °C) further transformations may take place, however. For example, monoalkylated cyclopropanes have been converted to mixtures of acyclic enynes and conjugated trienes. And 7,7-dichloronorcarane is converted to toluene under these conditions. 

Trifluoromethylzinc reagent can be prepared from the direct reaction of dihalodifluoromethane and zinc in DMF [42] (Scheme 13). In this remarkable reaction, DMF functions both as a solvent and reactant, and difluorocarbene is the reactive intermediate, based on mechanistic experiments. Dolbier et al. have utilized this reaction as a difluoromethylene cyclopropanation reaction [43] (Scheme 14). 

Methylene difluorocyclopropanes are relatively rare and their rearrangement chemistry has been reviewed recently [14]. In addition, electron deficient alkenes such as sesquiterpenoid methylene lactones may be competent substrates. Two crystal structures of compounds prepared in this way were reported recently [15,16]. Other relatively recent methods use dibromodifluoromethane, a relatively inexpensive and liquid precursor. Dolbier and co-workers described a simple zinc-mediated protocol [17], while Balcerzak and Jonczyk described a useful reproducible phase transfer catalysed procedure (Eq. 6) using bromo-form and dibromodifluoromethane [18]. The only problem here appears to be in separating cyclopropane products from alkene starting material (the authors recommend titration with bromine which is not particularly amenable for small scale use). Schlosser and co-workers have also described a mild ylide-based approach using dibromodifluoromethane [19] which reacts particularly well with highly nucleophilic alkenes such as enol ethers [20], and remarkably, with alkynes [21] to afford labile difluorocyclopropenes (Eq. 7). 

Cyclopropanation reagent. A similar reagent, prepared from EtZnI + CH2I2, [I-CH2-Zn-Et] [33598-72-0] is known as the Sawada Reagent. [P. Knochel, Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons, Inc., L. A. Paquette, Ed., New York, 1995,4 2473]... 

The dihydropyridazine (764) is unstable and loses nitrogen rapidly to yield a 1,3-diene (765) (69JA777, 72CC1260). Since (764) is generated by hydrolysis and oxidation of the cycloadduct (763) prepared from azodicarboxylate and2,4-hexadiene, it has proven possible to functionalize the double bond of (763) prior to nitrogen extrusion. Cyclopropanation, hydrolysis, decarboxylation and oxidation of (763) produce the 2,4-heptadiene (767) in a stereospecific manner via a concerted, orbital symmetry allowed retro-Diels-Alder process (Scheme 177). 

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