An Approach toward the Triquinane-Type Skeleton via Reagent-Controlled Skeletal Rearrangements. A Facile Method for Protection−Deprotection of Organomercurials, Tuning the Selectivity of Wagner−Meerwein Migrations, and a New Route to Annulated Lactones

Abstract

Nonlinear triquinane-type building blocks have been synthesized using three strategic steps, namely, (1) Hg(2+)-mediated opening of a cyclopropane ring involving a skeletal rearrangement (3 --> 8), (2) an intramolecular organometallic addition across a C=O bond triggered by activation of the C-HgX group by means of Me(3)CuLi(2) (14 --> 26), and (3) selective, reagent-controlled skeletal rearrangements (43 --> 47 with Tl(3+) or Hg(2+); 43 --> 51 + 52 with Pd(2+); 44 --> 47 with Pd(2+)). A new method for protection/deprotection of organomercurials has been developed, which allows selective reduction of a carbonyl group with NaBH(4) and other hydrides (8 --> 14 --> 16 --> 20) and Tebbe methylenation (14 --> 31 --> 32). Oxidative demercuration (8 --> 11 + 28) and Pd(2+)-catalyzed carbonylation of organomercurials (20 --> 53) allowed syntheses of gamma- and delta-lactones.

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

“…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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“…Other related processes involve oxidation with molecular oxygen and radical-chain alkylations . Organomercuric compounds can be transmetalated to organocopper reagents and Kocovsky demonstrated the synthetic utility of several organomercurial cuprations coupled with subsequent intramolecular 1,2-additions to carbonyl compounds and 1,4-additions to Michael acceptors. 10c, Organomercuric halides can be transmetalated to organopalladium 14 or organorhodium intermediates, and these transformations are of great synthetic value when used in conjunction with carbonylations. Therefore, the oxymercuration of cyclopropanes coupled with subsequent transformations of the intermediate organomercuric compounds nicely complement epoxide ring-opening with carbon nucleophiles, as both effect the addition of oxygen and carbon containing units across a carbon−carbon double bond …”

Electrophilic Cyclizations of Vinylcyclopropanols to Tethered Aldehydes

“…Sequential treatment of 14 with triisopropylsilyl triflate and 1 N HCl gave 23 in 93% yield. Trimethylaluminum-mediated one-carbon ring enlargement of 23 by TMSCHN 2 took place smoothly according to the method of Yamamoto to afford a triquinane 24 in 65% yield. ,

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