Halocyclopropane opening

The formation of allyl cations from halocyclopropanes via ring opening of the unstable cyclopropyl cations also has been investigated159,161,162 [Eq. (3.35)]. 

This chapter focuses on the use of silver(I) salts as Lewis acids in the ring-opening reactions of halocyclopropanes. Both the classical and most recent examples of this type of chemistry are examined with emphasis on the use of this simple transformation to build up complex intermediates that are potentially useful in the construction of natural products. 

While cationic ring opening of halocyclopropanes can be induced under strictly thermal conditions, it is most often performed in the presence of a Lewis acid.8 The Lewis acids commonly used in these reactions are silver(I) salts due the inherent halophilicity of the silver cation. The silver(I)-mediated reactions can be carried out at lower temperatures due to activation of the departing halide by coordination to silver in what has been described as a highly concerted push-pull mechanism.13 Under these conditions the halide-substituted carbon atom bears slightly increased positive character, which enables the cationic ring opening to proceed under mild conditions (Fig. 4.4). 

Figure 4.4. Silver assistance in the ring opening of halocyclopropanes.

The construction of complex intermediates from simple and readily available starting materials has been accomplished using the electrocyclic ring-opening reaction of halocyclopropanes. This is typically achieved through interception of the cationic haloallyl intermediate by solvent, the silver(I) counteranion, or some alternate tethered heteroatom or carbon-based nucleophile. Examples of these processes are described below. 

Scheme 4.9. Intramolecular ketal formation from ring opening of a halocyclopropane.

The silver(I)-mediated ring opening of halocyclopropanes has been used to construct complex frameworks through the inter- and intramolecular trapping of cationic intermediates with heteronucleophiles. An obvious extension of this work is the involvement of carbon-based nucleophiles to form new carbon-carbon bonds. In 1996, Kostikov and coworkers reported the participation of aromatic solvents in the capture of halocyclopropane-derived allyl cations even in the absence of silver(I).30 However, this early example of intermolecular attack by a carbon nucleophile is one of very few such reports. In the same year, Gassman et al. reported cationic cyclizations of gem-dibromocyclopropanes tethered to remote diene moieties (Scheme 4.16).31... 

The silver(I)-mediated electrocyclic ring opening of halocyclopropanes has been used to induce extensive skeletal rearrangements in gcm-dibromospiropentanes, providing rapid construction of naphthalenes and/or indenes (Scheme4.21 ).34 A variety of Lewis acids, Brpnsted acids, and solvent effects were carefully examined before optimal conditions were identified. It was found that subjection of spirocycle 60 to silver acetate in trifluoroacetic acid afforded rearrangement products 61 and 62 in moderate to good yields. The proposed mechanism of the reaction is illustrated in Scheme 4.21. 

The majority of yc/n-dichIorocycIopropane substrates examined in this study provided the desired a-chlorocyclopentenones as a result of sequential electrocyclic ring opening and Nazarov cyclization. In general, those substrates lacking additional substitution on the cyclopropane moiety provided products 75 selectively as a result of regioselective elimination to deliver the more electron-rich olefin. The mechanism for this transformation is believed to involve disrotatory halocyclopropane ring opening... 

The cascade sequences presented herein demonstrate unprecedented modes of reactivity in Nazarov chemistry that are initiated by the silver(I)-promoted ring opening of halocyclopropanes. The ease with which the gem-dichlorocyclopropanes can be prepared, the relatively mild reaction conditions, and the efficiency of these processes make these substrates attractive intermediates for an application in natural product synthesis. 

The pericyclic ring opening of halocyclopropanes that occurs on solvolysis was directly paralleled by the gas phase ionic reactivity of the same compounds. ) The ring opening of 42 was the most facile in a series (Eq. (28)). The same compound eliminated bromide from the molecule ion much more readily than related isomers. Evidently it makes little difference to the reactivity if the leaving group is Br— or Br . 

The opening of halocyclopropanes to allyl systems according to equation 124 can happen thermally or with the assistance of electrophiles and nucleophiles . Some recent examples include an efficient cyclopentenone synthesis (equation 125) ", an electrocyclic opening/cyclization sequence giving functionalized furan and pyran derivatives (equation 126), an elegant total synthesis of the very fast death factor alkaloid ( ) anatoxin and a nice application of the well known nucleophilic opening to the preparation of crystalline methylene aziridines (equation 127) . 

This rearrangement is also a remakable illustration of the Woodward-Hoffmann-DePuy rules concerning the disrotatory ring-opening of halocyclopropanes. ... 

Halocyclopropanes undergo electrocyclic ring openings. Consider the two diastereomers of l-bromo-c/s-2,3-dimethylcyclopropane. If the Br- left first... 

Whereas thermolysis of halocyclopropanes in inert solvents occurs via cationic rearrangement, gas-phase pyrolyses of halocyclopropanes, e.g. 1, are believed to proceed by a concerted unimolecular chlorine atom migration and ring opening. From the preparative viewpoint this difference is not significant. 

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