Substitution halo-substituted cyclopropanes

The synthesis of halo-substituted cyclopropanes using zinc carbenoids can be accomplished using three different approaches by the cyclopropanation of a halo-substituted alkene, by the cyclopropanation using a halo-substituted zinc carbenoid, or by the cyclopropanation using, gem-dizinc carbenoids followed by trapping the cyclopropylzinc with an electrophilic halide source. 

Similarly, 4-halobutanoate (see Table 2) and 5-halo-l-(trimethylsilyl)alkynyl derivatives (Scheme 2) can undergo the base-catalyzed cyclopropane ring-forming reaction. With alkoxy substituents in the starting materials, synthetically versatile donor-acceptor substituted cyclopropanes (see Section l.B.2.1.4.) are thus formed. 

The issue of 1,2- versus 1,4-addition, as shown in Scheme 22, in the phase transfer catalyzed (benzyl-triethylammonium chloride TEBA) version of this cyclopropanation reaction, was addressed in a more recent publication. Simple a-halo esters do not react with acrolein, methyl vinyl ketone or 2-chloroac-rylonitrile under the conditions examined. However several electrophilic alkenes do react with diethyl bromomalonate to give good yields of substituted cyclopropanes (equation 38 Table 13). The only side... 

In terms of the synthesis of substituted cyclopropane derivatives using either halo- or alkyl-substituted reagents, endo exo selectivity of the product is often poor. For example, cyclohexene (39) was converted into an approximately 2 1 ratio of 40 and 41 on exposure to bromoform and diethylzinc. ... 

Carbenes and substituted carbenes add to double bonds to give cyclopropane derivatives ([1 -f 2]-cycloaddition). Many derivatives of carbene (e.g., PhCH, ROCH) ° and Me2C=C, and C(CN)2, have been added to double bonds, but the reaction is most often performed with CH2 itself, with halo and dihalocarbenes, " and with carbalkoxycarbenes (generated from diazoacetic esters). Alkylcarbenes (HCR) have been added to alkenes, but more often these rearrange to give alkenes (p. 252). The carbene can be generated in any of the ways normally used (p. 249). However, most reactions in which a cyclopropane is formed by treatment of an alkene with a carbene precursor do not actually involve free carbene... 

The stabilization of reaction intermediates RCjq and RC q to form dihydrofullerene derivatives can also be achieved by intramolecular nucleophilic substitutions (SjJ), if R contains a leaving group. As shown by Bingel [31], the generation of a carbon nucleophile by deprotonation of a-halo esters or a-halo ketones leads to a clean cyclopropanation of Cjq. 

Support-bound alkylating agents have been used to N-alkylate pyridines and dihydropyridines (Entries 7 and 8, Table 15.21). Similarly, resin-bound pyridines can be N-alkylated by treatment with a-halo ketones (DMF, 45 °C, 1 h [267]) or other alkylating agents [246]. Polystyrene-bound l-[(alkoxycarbonyl)methyl]pyridinium salts can be prepared by N-alkylating pyridine with immobilized haloacetates (Entry 8, Table 15.21). These pyridinium salts react with acceptor-substituted alkenes to yield cyclopropanes (Section 5.1.3.6). Pyridinium salts have also been prepared by reaction of resin-bound primary amines with /V-(2,4-dinitrophenyl)pyridinium salts [268,269]. 

However, a respectable alternative to the direct [2 + l]-routes (a)-(c) is the variant using halo- or dihalocyclopropanes as precursors for the desired target molecules (path d). The cyclopropane ring is formed by addition of halocarbenes to the olefin and subsequent change of functionalities is achieved by treatment with nucleophiles. It is very unlikely that a direct substitution incorporates the donor-substituent. Instead an elimination/addition sequence with the intermediacy of a cyclopropene has to be assumed. 

The reduction of chiral 1-substituted l-halo-2,2-diphenylcyclopropanes at a mercury cathode to the chiral cyclopropanes has been reported by some workers [387-389]. 

The earlier reported palladium-catalyzed, regioselective nucleophilic substitution reaction of 1-halo-l-vinylcyclopropanes 10 to give alkylidenecyclopropanes can also be extended to stabilized carbanion nucleophiles. Use of a BINAP-modified catalyst leads to asymmetric induction with up to 47% ee. Again no ring opening of cyclopropanes was observed. 

Cyclopropanes without electron-withdrawing substituents usually resist the attack of nucleophiles. Exceptions are strained systems and a-halo-substituted derivatives which undergo homoallylic substitution reactions.[l.l.l]Propellane structures, though usually formed only as intermediates, underwent addition of benzenethiol with cleavage of the central cyclopropyl bond. This addition possibly follows a radical chain mechanism. 

This method can be extended to applications with halo-substituted allyl dichlorides. Chloro(2,2-dichlorovinyl)carbenes 6 have been formed by deprotonation with lithium tetramethylpiperid-ide, but yields were improved when sodium hexamethyldisilazanide was used (see Houben-Weyl, Vol. E19b, Table 97). 1,2,3,3-Tetrachloroprop-l-ene can also easily be deprotonated, but in this case subsequent decomposition formed two isomeric carbenes, as observed in the product ratio after cyclopropanation.2 However, treatment of 1,1,2,3,3-pentachloropropene (11) with a base gave only the [2 + 2] dimer 14 of tetrachloroallene 13, generated by jS-elimination of lithium chloride.2 Other pentahalopropenes with a fluorine in the 3-position (e.g. 15) reacted with x-elimination, forming the corresponding cyclopropanes 17 in the presence of alkenes (see Houben-Weyl, Vol. E 19b, Table 97). 

The most used nucleophilic synthesis reaction to form fuUerenes is cyclopropanation. The original method was developed by Bingel, and it employs the generation of a carbon nucleophile starting from a-halo esters in the presence of a base (such as NaH), and the subsequent addition to After the addition of the anions of a-halo ester, an intramolecular substitution of the halide takes place with the intermediate fullerene anion, giving the corresponding methanofullerene derivative (Scheme 2.1e). Further modification of this method consist of preparing the a-halomalonate in situ. 

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