Studies on Mercury(II)-Mediated Opening of Bi- and Tercyclopropane Arrays

Abstract

The first examples of the mercury(II)-mediated ring opening of bicyclopropane and tercyclopropane arrays have been investigated. The presence of an adjacent cyclopropyl group dramatically increased the rate of the mercury-mediated opening of the first cyclopropane in a cyclopropane array. In contrast to the mercury-mediated ring opening of monocyclopropanes which usually undergo a concerted ring-opening mechanism, electrophilic openings of cyclopropane arrays occurred through a stabilized, free carbocation. Excellent regio-and stereoselectivities were observed in the mercurymediated intramolecular openings of the second cyclopropanes in the cyclopropane arrays, giving rise to the formation of enantiomerically pure, highly substituted tetrahydrofurans. Scheme 2. Mercury-Mediated Opening of Bicyclopropanedimethanol 3 Scheme 3. Formation of Acetonides 26 and 28 Scheme 4. Mercury-Mediated Intramolecular Openings of 23 and 24 Hg(II)-Mediated Opening of Bi-and Tercyclopropane Arrays

Stereoselective Synthesis of Polypropionate Units and Heterocyclic Compounds by Cyclopropylcarbinol Ring-Opening with Mercury(II) Salts

“…An interesting extension of the oxymercuration to bicyclopropane arrays was reported by Barrett . Although the bicyclopropanedimethanol 3 reacted rapidly with mercuric trifluoroacetate in the presence of methanol, a mono ring-opening reaction leading to 4 occurred with essentially no diastereoselectivity.…”

“…Although the nucleophilicity of the carbon−carbon bond of cyclopropanes has been well described theoretically and experimentally for more than 100 years, the most synthetically useful three-membered ring scissions promoted by electrophilic species have usually involved cyclopropylcarbinyl cations or related species, cyclopropanes activated by electron-donating groups, , and electrocyclic cleavage of dihalocyclopropanes . Even if cyclopropanes are much less nucleophilic than alkenes, they can react with electrophiles such as a proton, , halogens, and transition 2c,2e,8 or nontransition metal salts such as lead(IV), thallium(III), 9c, and mercury(II). 2b,3f,10c,− The mechanism of the electrophilic ring-opening has been investigated and was demonstrated to involve a stereospecific “edge attack” for reagents capable of back-donation [halogens, Pd(II), Pt(II), ...], whereas the alternative “corner opening” mechanism was observed for poor back-donors [H + , Hg(II) and Tl(III) salts]. In both cases, the observed stereo- and regioselectivities are consistent with a scenario involving backside attack of the nucleophile at the carbon best able to stabilize a positive charge (Scheme ). −

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“…Even if cyclopropanes are much less nucleophilic than alkenes, they can react with electrophiles such as a proton, , halogens, and transition 2c,2e,8 or nontransition metal salts such as lead(IV), thallium(III), 9c, and mercury(II). 2b,3f,10c,− The mechanism of the electrophilic ring-opening has been investigated and was demonstrated to involve a stereospecific “edge attack” for reagents capable of back-donation [halogens, Pd(II), Pt(II), ...], whereas the alternative “corner opening” mechanism was observed for poor back-donors [H + , Hg(II) and Tl(III) salts]. In both cases, the observed stereo- and regioselectivities are consistent with a scenario involving backside attack of the nucleophile at the carbon best able to stabilize a positive charge (Scheme ). −

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“…Indeed, polar solvents which may compete with the substrate in ligating the mercury cation resulted in longer reaction times . Nevertheless, oxymercuration of cyclopropane derivatives can also be carried out in protic solvents (MeOH, BnOH, AcOH, ...) which directly act as nucleophiles and are therefore incorporated in the final product. −

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Creating Stereocenters within Acyclic Systems by C–C Bond Cleavage of Cyclopropanes

“…A final approach for the electrophilic ring-opening reaction of cyclopropanes is the oxymercuration reaction. From the pioneering acetoxymercuration of cyclopropanols, the regioselective acetoxymercuration of stereodefined substituted cyclopropyl carbinol 120 was reported. − When a Hg­(II) salt was added to 120 , polarization of one of the cyclopropyl σ bonds is induced and promotes a subsequent addition of an oxygen nucleophile. The combination of this transformation with the enantioselective Simmons–Smith cyclopropanation reaction of allylic alcohols and diastereoselective hydroboration/oxidation allowed access to various polypropionate derivatives 121 (Scheme ).…”