Cyclopropanes procedure

Although many recent improvements in the preparation of the Simmons Smith reagent might be helpful23 24, the authors of this chapter would recommend one to consider an alternative two-step cyclopropanation procedure, which includes cycloaddition of dichloro- or dibromocarbene to methylenecycloalkane25 followed by reductive dehalo-genation (equation l)26. The first reaction is usually carried under phase transfer conditions and presents a very simple and efficient procedure. Reduction of gem-dihalocyclopropanes with lithium in tert-butanol or with sodium in liquid ammonia usually proceeds without complications and with high yield. 

Finally, aldehydes have also been reported to serve as alkylidene transfer reagents.93 Examples of these further cyclopropanation procedures are summarized in Table 6. 

Table 6 Further Cyclopropanation Procedures Related to the Simmons-Smith Reaction... 

The cyclopropanation procedure shown in Section 5.6 has been studied with many other metals (Rh, Ru, Co, Fe, Os, Pd, Pt, Cr) and with a variety of new asymmetric ligands such as the bis-oxazolines. 

Similar cyclopropanation procedures involving copper catalysis are encountered in the reaction of olefins with dibromomalonic esters (217) and Cu in dimethyl sulphoxide and the reaction of olefins with monobromomalonic esters in the presence of DBU and catalytic amounts of copper(II) halide (equation 62) The reaction of ethyl dibromo-acetoacetate (219) with styrene and copper produces the corresponding electrophilic... 

A number of modifications of the original Simmons-Smith cyclopropanation procedure have been reported. Furukawa s reagent, (iodomethyl)zinc derived from diethylzinc and diiodomethane, ° or its modification using chloroiodomethane instead of diiodomethane, ° allows more flexibility in the choice of solvent. The reagent is homogeneous and the cyclopropanation of olefins can be carried out in non-complexing solvents, such as dichloromethane or 1,2-dichloroethane, which greatly increase the reactivity of the zinc carbenoids. 

Another cyclopropanation procedure that is quite general involves the use of Rh-carbene complexes, which can act catalytically to effect ring formation. Scheme 10.7 shows some of the details of this method. Ccaibene is derived from corresponding diazo compounds, which were traditionally used directly as sources of free carbenes. The scheme includes a catalytic cycle for conversion of the diazo compound to the Rh-carbene complex, which then delivers Ccarbene to the alkene. Transfer of Ccaibene regenerates an active catalyst that can react with another mole of diazo compound. The detailed mechanism of step c in the cycle resembles path b from Scheme 10.6. 

General Cyclopropanation Procedure 0.2 g chlorobenzene, 3 ml dichloromethane and 4 (0.490 g, 4.70 mmol) were added to the catalyst (1 mol% maximum Rh-loading) and the mbcture was stirred. Over a period of 3-5 hours a solution of 5a (0.0517 g, 0.453 mmol) or 5b (0.0599 g, 0.461 mmol) in 3 ml dichloromethane was added. After stirring overnight at room temperature (5a) or under reflux (5b), the solvent was evaporated in vacuo and the residue was chromatographed (silicagel, hexane/ethyl acetate 9/1). Before chiral GC analysis. 

The Anal task was to carry out an enantioselective synthesis of the natural pheromone (2Z,6R,l S,5 S)-75. Figure 4.13 summarizes our synthesis of the pheromone.28 Hodgson s intramolecular cyclopropanation procedure (D->-E) could be employed successfully.29 The synthetic pheromone amounted to about 400 mg, which was enough to carry out further biological studies. The acetate of (2Z,6R,l,.S ,5,.S )-75 was shown to be identical with the acetate isolated in 1982 from an African plant Haplocarpha scaposa by Bohlmann and... 

Organometallic, Thermal, and Photochemical Methods. The Simmons-Smith cyclopropanation procedure has now been successfully applied to silyl vinyl ethers and... 

When trans-cyclododecen-3-ol is subjected to CH2l2-Cu/Zn treatment the trans,anti-bicyclotridecane (66) is produced in a highly stereoselective manner. The Simmons-Smith cyclopropanation procedure has also been employed in a new synthesis of (+ )-caryophyllene and in the preparation of the parent cyclohepta[a]acenaphthyl-enyl cation. ... 

Paxton, R. J. Taylor, R. J. K. Improved Dimethylsulfoxonium Methylide Cyclopropanation Procedures, including a Tandem Oxidation Variant. Synlett 2007,633-637. 

The procedure (with ethylene dibromide replacing trimethyleiie dibromide) described for cycZobutanecarboxylic acid (previous Section) does not give satisfactory results when applied to the cyclopropane analogue the yield of the cyclopropane-1 1 dicarboxylic acid is considerably lower and, furthermore, the decarboxylation of the latter gives a considerable proportion (about 30 per cent.) of butyrolactone ... 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

The above procedure was used for the preparation of all compounds except 104p, which was obtained from 104r by palladium-catalyzed coupling with tributylvinyl-stannane followed by palladium-catalyzed cyclopropanation of the resulting vinyl intermediate with diazomethane (Scheme 32) (99BMC3187). 

The possibility of a radical mechanism is supported by the observation of the accelerating effect of molecular oxygen on the cyclopropanation. Miyano et al. discovered that the addition of dioxygen accelerated the formation of the zinc carbenoid in the Furukawa procedure [24a, b]. The rate of this process was monitored by changes in the concentration of ethyl iodide, the by-product of reagent formation. Comparison of the reaction rate in the presence of oxygen with that in the... 

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. 

The procedure used in the preceding sections for cyclopropane serves equally well in the analytic determination of the numbers of structure and stereoisomeric compounds which obtain when essentially different radicals of valence one or alkyl radicals are substituted in the basic compound. We have to assume, however, that there is enough information on the basic compound to determine the three groups discussed in Sec. 56. This is certainly the case for the most important basic compounds, benzene and naphthalene. I omit the formulation of rules which are obvious in the preceding example. 

The present method gives better yields and is a simpler procedure than those described previously The ease of preparation of a-chloro ethers enables one to effectively remove a protecting methyl group from a phenol2 a-Chloroanisole is used to produce phenoxycarbene, a reactive intermediate in cyclopropane synthesis8... 

The Simmons-Smith reaction has been used as the basis of a method for the indirect a methylation of a ketone. The ketone (illustrated for cyclohexanone) is first converted to an enol ether, an enamine (16-12) or silyl enol ether (12-22) and cyclopropanation via the Simmons-Smith reaction is followed by hydrolysis to give a methylated ketone. A related procedure using diethylzinc and diiodomethane allows ketones to be chain extended by one carbon. In another variation, phenols can be ortho methylated in one laboratory step, by treatment with Et2Zn and... 

This procedure illustrates a new three-step reaction sequence for the one-carbon ring expansion of cyclic ketones to the homologous tt,/3-unsaturated ketones. The key step in the sequence is the iron(III) chloride-induced cleavage of the central bond of trimethyl-silyloxycyclopropanes which me obtained by cyclopropanation of trimethylsilyl enol ethers. The procedure for the preparation of 1-trimethylsilyloxycyclohexene from cyclohexanone described in Part A is that of House, Czuba, Gall, and Olmstead. ... 

The cyclopropanation of 1-trimethylsilyloxycyclohexene in the present procedure is accomplished by reaction with diiodomethane and diethylzinc in ethyl ether." This modification of the usual Simmons-Smith reaction in which diiodomethane and activated zinc are used has the advantage of being homogeneous and is often more effective for the cyclopropanation of olefins such as enol ethers which polymerize readily. However, in the case of trimethylsilyl enol ethers, the heterogeneous procedures with either zinc-copper couple or zinc-silver couple are also successful. Attempts by the checkers to carry out Part B in benzene or toluene at reflux instead of ethyl ether afforded the trimethylsilyl ether of 2-methylenecyclohexanol, evidently owing to zinc iodide-catalyzed isomerization of the initially formed cyclopropyl ether. The preparation of l-trimethylsilyloxybicyclo[4.1.0]heptane by cyclopropanation with diethylzinc and chloroiodomethane in the presence of oxygen has been reported. "... 

The present procedure for ring expansion has also been applied to l,2-bis(trimethylsilyloxy)bicyclo[n.l.0]alkanes, which are prepared by cyclopropanation of l,2-bis(silyloxy)cycloalkenes. The latter are readily available from acyloin condensations in the presence of chlorotrimethylsilane. " This reaction provides a new route to cyclic 1,3-diketones and macrocyclic compounds containing two 1,3-diketone units in the ring. 

Potential starting materials for the syntheses of exploded [n]rotanes via approaches B and C containing an even number of cyclopropane units may also be prepared by applying the Hay coupling procedure (Scheme 27) [48, 52]. 

Pagenkopf s group developed a novel domino process for the synthesis of pyrroles 4-183, which allows for the control over the installation of substituents at three positions and seems to be very suitable for combinatorial chemistry [62]. The process consists of a 1,3-dipolar cycloaddition of an intermediate 1,3-dipole formed from the cyclopropane derivative 4-181 with a nitrile to give 4-182 followed by dehydration and isomerization (Scheme 4.39). The yield ranges from 25 to 93 %, and the procedure also works well with condensed cyclopropanes. 

In the absence of ultrasonic waves, the reactions usually require two or three hours or heating to 80°. Using our procedure, the cyclopropane ring in cyclopropylbenzene was easily opened to give propylbenzene in >95% yield. 

With the rhodium and copper catalysts, even the combination of equimolar amounts of olefin and diazoester will allow high yields of cyclopropanes if the addition rate is controlled meticulously (see Table 6 for examples). This circumstance is particularly useful for cyclopropanation of olefins which are in short supply. In combination with Rhg(CO)16, the easy recovery of the unchanged catalyst (by diluting the mixture with hexane and separating the precipitated catalyst from the liquid65 may render such a procedure particularly attractive from an economical point of view. 

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