A-Cyclopropyl esters

A successful trapping reaction of a cyclopropyl ester enolate with trimethylsilyl chloride (TMSC) was first performed by Ainsworth and coworkers . In the reaction of 232 with lithium diisopropyl amide at — 78°C, followed by addition of TMSC, the ketene acetal 233 was formed in 10% yield as well as the silylated cyclopropane 234 (40%). Ketene acetals other than 233 are formed in yields > 90 %. 

Olofson and co-workers have also prepared cyclopropanols by treatment of a chloromethyl ester (1) with this base to generate an intermediate acyloxycarbene (a). Reaction of the carbene with an alkene gives a cyclopropyl ester (2), which is converted into a cyclopropanol (3) by LiAlH or CHaLi. Both the cis- and... 

TT-Allyl palladium species normally only couple with soft nucleophiles (e.g. malonate enolates) it is thus of interest to note that, in the presence of EtaN-HMPA, the relatively hard enolate of methyl cyclohexanecarboxylate reacts with a rr-allyl palladium complex derived from allyl chloride to give the a-cyclopropyl ester (128) in 70% yield. Initial attack by the enolate appears to occur at the central carbon of the complex. The reaction may prove to be limited to enolates of esters with a-branching. The application of high pressures... 

Note that we predict ring opening of the cyclopropyl cation to require activation this at first sight seems to be at variance with evidence that rearrangement occurs as a concerted process in the solvolysis of cyclopropyl esters and indeed acts as a driving force 44). Moreover the evidence shows very clearly that this is so only for one of the possible disrotatory processes, i.e. that indicated in 25 ... 

A cyclopropanone thioacetal has also been observed to undergo Ci—C2 cleavage under the normal conditions for thioacetal solvolyses.110> Thus, the esters 135 a and 135 b are formed when the 1,3-dithiopropane ketal of 7,7-norcarane is reacted with mercuric chloride. In this case, HgCl+ acts as an electrophile and attacks the three-membered ring. However, under similar conditions, the cyclopropanone methyl thioketal 136 forms the mixed ketal 137. While the authors consider this result to represent an unusual example of a nucleophilic displacement at a cyclopropyl carbon atom 110), the reaction mechanism may involve the inter-... 

A methodology developed for the synthesis of cyclopropyl ketones from THFs (51) has been shown to suffer from stereochemical leakage resulting from the unexpected cleavage of a benzoate ester by potassium r-butoxide and the subsequent participation of the resulting hydroxyl group in the adjacent substitution reactions.90 This prob- lem has been solved, however, by the discovery of a simpler, more direct cascade reaction for the synthesis of single enantiomers of cyclopropanes with predictable stereochemistry.90 The mechanism of the reactions has been discussed. 

Pyrethroids are commercially important insecticides that usually contain a cyclopropyl unit that is m-substituted and a cyanohydrin derivative. They are usually sold as a mixture of isomers. However, asymmetric routes have been developed, especially because these compounds are related to chrysanthemic esters (Chapter 12).251 The pyrethroids can be resolved through salt formation or by enzymatic hydrolysis.252... 

Other investigators have used a new synthetic route103 in which the spiro[4,5]decane system is formed by condensation of a -dicarbonyl compound [e.g. (221)] with a cyclopropyl phosphonium salt (222).104 The bicyclic keto-ester (223) produced in this way was subsequently converted into ( )-anhydro-/3-rotunol (224), ( )-/3-vetivone (220), ( )-/3-vetispirene (225), ( )-linesol (226), and ( )-a-vetispirene (227) (Scheme 27). 03 An alternative approach to the vetispirane system involves Et[Pg.82]

Alumina-catalyzed conversion of either isomer of (193) to dihydrofuran (194) was reported as an alternative to acid-catalyzed conditions (equation 57). A methodology of a-methylene lactone synthesis relies on the solvolysis of cyclopropyl esters of type (195) to give u-methylote lactone (196) with Li2C03 in dioxane (equation 58). The formation of fte undesired diene (197) was diminished by the use OfAgC104.235... 

A variety of 1,2,3-triacyl- and 1,2,3-trisalkoxycarbonylcyclopropanes have been prepared from the corresponding acyl- or alkoxycarbonylmethylides, a-haloketones" " and a-halocarboxylic esters". The reactions of a-haloketones and a-halocarboxylic esters with three equivalents of sulfoxonium methylide afford cyclopropyl ketones and cyclopropa-necarboxylic esters, respectively (equation 99). The reagent prepared from CH2I2 and Zn/Cu reacts with a-hydroxyketones to give cyclopropylmethanols". ... 

The low tendency of cyclopropyl esters to form the ester enolate is also documented by the following examples Boche and Martens have reported that methyl cis-bicyclo[6.1.0]nona-2,4,6-triene-flnti-9-carboxylate (227) loses a proton at C(l) when treated with LDA to give, probably via the cyclopropyl anion 228", the allyl anion 229". Russell and coworkers have shown that ethyl 2-methyl-2-nitrocyclopropanecarboxylate (230) gives the 2-methylenecyclopropanecarboxylate (231) when treated with sodium hydride. 

Intermediate formation of a cyclopropyl ring has also been suggested in electrochemical reductions although to a lesser extent. 2-Alkyl-substituted acetoacetic esters undergo the Tafel rearrangement upon reduction at a lead cathode in an acidic medium with complete reduction of the functional groups Analysis of the reduction products... 

Most alkyl carbanions undergo facile pyramidal inversion. Cyclopropyl anions are an exception, presumably because the transition state, with a planar trigonal carbon, is more strained than the ground state. The configurational stability of cyclopropyl anions is of value in the synthesis of deuterated cyclopropanes by the Haller-Bauer reaction (see Section II.B). An interesting dilemma arises when a cyclopropyl anion is stabilized by a n-electron acceptor substituent such as a nitrile or an ester. Will the anion then retain its pyramidal equilibrium geometry for the strain reasons alluded to above, or will it become planar in order to maximize overlap of the filled orbital on carbon with the n orbital of the substituent Walborsky and coworkers addressed this question in a series of experiments in which rates of H/D exchange and racemization were compared for an optically active cyclopropane exposed to a base in a deuterated hydroxylic solvent. The outcome can be illustrated with the particular example of 1,1-diphenylcyclopropane-2-... 

Finally, there has also been research into the ozonolysis of allenes. Thus sterically hindered allenes react by transfer of one oxygen atom, forming a mixture of reaction products Recently, the ozonolysis of a cyclopropylallene has been shown to yield a diastereomeric mixture of cyclopropyl esters. ... 

So far, while there is a relative abundance of synthetically useful cyclopropana-tion catalysts, all of them provide a mixture of diastereomers with the anti product predominating. Thus, a catalyst able to provide optically active syn cyclopropyl esters would constitute a useful complement to existing methodology. Rhodium complexes of bulky porphyrins ( chiral fortress porphyrins) have been developed for this purpose [27]. The porphyrin ligands bear chiralbinaphthyl groups appended directly to the meso positions. Their rhodium(III) complexes provide predominantly the syn cyclopropane with diazoesters, with very good stereoselectivity in some cases. However, the enantioselectivities observed are modest. 

During the total synthesis of (+)-anthoplalone by K. Fukumoto et al. one of the intermediates was a cyclopropyl methyl ketone, and the synthetic sequence required the conversion of this functionality to the corresponding cyclopropane carboxylic acid methyl ester. This transformation was accomplished via the haloform reaction using bleach in methanol. The methyl ester and some carboxylic acid was obtained after this step, so the product mixture was treated with diazomethane to convert the acid side product to the methyl ester. 

A large number of cyclopropanes containing a bond from oxygen to a cyclopropyl carbon atom have been synthesized from other cyclopropanes by substitution of a variety of substituents. The reagents utilized and the reaction conditions employed to achieve the transformations depend on the type of compound being prepared. The compounds can be divided into four groups cyclopropanols, cyclopropyl ethers, cyclopropyl esters, and oxaspiropentanes. 

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