Cyclopropanes, activated: ring opening synthesis

One of the most efficient procedures for the synthesis of cyclopropanes is the reaction of alkenes with electrophilic carbene complexes. In this process up to three stereogenic centers can be generated in one step. Cyclopropanes are a key structural element encountered in many natural products with interesting biological activity. Further, by virtue of the ability of cyclopropanes to undergo ring-opening reactions these compounds can be valuable synthetic intermediates. 

Activated cyclopropanes 33 react with nucleophilic selenium species to give the ring-opened products 34 in moderate to good yields (Scheme 33) [56]. This reaction has been used for natural product synthesis [57]. 

In the early seventies Stork and his students have shown that the intermediate enolate can be trapped by suitable electrophiles, e.g. alkyl halides, giving substituted ring-opened products. These modes of cyclopropane opening have been used for the synthesis of several natural compounds ". A tetra-activated cyclopropane is cleaved by sodium naphthalene in a preparation of a specifkally substituted semibullvalene (equation 36) . ... 

Ring-opening of functionalized oxiranes (439) has been used in the synthesis of pyrethroid derivatives (440), but does not find any application in the preparation of doubly activated cyclopropanes (equation 148). 

Ring-opening of electrophilic cyclopropanes by carbanions derived from active methylene functions has already been observed during the synthesis of diethyl... 

Semicorrin ligands have also been used in asymmetric cyclopropanation of silyl enol ethers to give optically active silyloxycyclopropanes which, after acid-catalyzed ring opening, serve as convenient precursors in the synthesis of chiral y-oxo carboxylic esters50. 

In fight of the successful methodology used by Young and Kerr in the ability of activated cyclopropanes to undergo nucleophilic ring-opening/cycloaddition reactions with indoles and nitrones [21], Johnson and coworkers reported the synthesis of tetrahydrofurans via an adaptation of this... 

In addition to epoxides, aziridinium ions and activated cyclopropane ring openings have been reported. In 2004, a large-scale synthesis of Schering-Plough s D1/D5 dopamine antagonist being developed for the treatment of addiction and obesity was disclosed. Cu(i) catalysis in the key multistep sequence (Scheme 11.66) was found to increase yields by 20-25% in comparison to the uncatalysed reaction. 

Scheme 11.67 Synthesis of a 5-substituted ketone via cuprate opening of an activated cyclopropane ring.

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