Cyclic compounds cyclopropanes, synthesis

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-/ r/-butyl malonate, their preparations in satisfactory yields are realized (equation 134). The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135) Asynunetric synthesis... 

The formation of cyclic compounds by intramolecular alkylations of stabilized enolates has been widely used in organic synthesis. A recent study of the kinetics of the reaction of diethyl (a)-bromoalkyl)ma-lonates in DMSO using tetramethylammonium hydroxide as the base has shown that relative rates of closure of rings of varying size follow the order 3>5>6>4>7> 12-21 > 8 > 9 > 11 > 10. These results are consistent with earlier studies in which other base-solvent combinations were employed. The high rates of closure of three-membered rings allow the formation of a variety of cyclopropane deriva-... 

Synthesis of cyclic compounds. Review. Metallic copper also forms complexes with isonitriles, which have been used for the synthesis of cyclopropanes, as formulated in equations I and II. The reaction has been extended to a syn-... 

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

Three-membered cyclic ethers are important as reactive intermediates in organic synthesis. Like the cyclopropanes, the vicinal2 disubstituted compounds have cis and trans isomers ... 

Cyclopropanes occur among several classes of natural products, they have a number of commercial applications, and they serve as useful synthetic intermediates leading to other classes of cyclic and acyclic compounds. Methods for the synthesis of cyclopiopanes have been the subject of several earlier reviews.1 The principal methods may be divided into two broad categories (i) addition of a one-carbon... 

Examples of the preparation of cyclopropanes by intramolecular nucleophilic substitution are illustrated in Scheme9.17. The first example is a synthesis of [l.l.ljpro-pellane, which yields the product in acceptable yields, despite the high strain and poor stability of this compound [66]. The second and third examples illustrate the remarkable ease with which 3-halopropyl ketones cyclize to yield cyclopropanes instead of cyclic, five-membered enol ethers or ketones. Similarly, carbamates of 2-haloethylglycine esters do not undergo intramolecular N- or O-alkylation on treatment with bases, but yield cyclopropanes instead [67, 68]. Some nucleophiles can undergo Michael addition to 3-halomethyl acrylates faster than direct Sn2 reaction, to yield cyclopropanes by cyclization of the intermediate enolates (fourth example, Scheme9.17) [69]. 

The formation of cyclopropanes by the addition of carbenes to alkenes was first reported by Doering and Hoffmann in 1954/ Since then, this most characteristic reaction of carbenes has been successfully exploited for the synthesis of cyclopropanes. The cyclopropane ring system is not only found as a structural element in a wide range of natural products, but is also a very useful synthetic intermediate leading to a variety of cyclic and acyclic compounds. ... 

Sharpless and Kim reported a one-pot synthesis of cyclic sulfates 96 from 1,2-diols via catalytic oxidation with ruthenium chloride51. The cyclic sulfates 96 thus formed on treatment with nucleophiles give /2-sulfates 97, which in turn are hydrolyzed to the / -hydroxy compounds 98 (equation 54). Hence the cyclic sulfates 96 are synthetically equivalent to epoxides. The results of ring opening of cyclic sulfates 96 are shown in Table 4. When the reaction of 99 with malonate anion is carried out in DME, the /2-sulfate moiety serves as a leaving group to give cyclopropane 100 (equation 55)51. 

All these studies set up the basis to apply this class of organocatalysts in MIRC-type processes for the synthesis of cyclopropane-containing molecules. Indeed, these compounds are, together with epoxides and aziridines, among the most useful cyclic scaffolds, present in several biological relevant products and pharmaceuticals. 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

Dipolar cycloadditions are important as a means of synthesis of heterocyclic molecules. The cycloaddition of diazo compounds has also been used in the synthesis of cyclopropanes and other strained molecules. The cyclic adducts (pyrazolines) contain the azo linkage, and molecular nitrogen is lost on thermal or photolytic decomposition. Usually, the two carbon centers resulting from elimination of... 

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