Substitutive Spiroannulation

Indeed, exposure of the vinylcyclobutanone 67 to acid produces the perhydro-azulene skeleton 68 as summarized in Eq. 78 112). With more ready access to the types of substituted cyclobutanones required for this lateral cyclopentannulation (see substitutive spiroannulation), milder conditions and thus better processes will probably ultimately be developed. 

Substitutive spiroannulation of 1-donor-substituted vinylcyclopropanes initiated by electrophiles gives access to a wide range of spirobicyclic and spirotricyclic systems. Generally, the electrophile undergoes addition from the sterically less demanding face and the rearrangement proceeds through back-side attack. The net result is a turns addition. 

In a projected synthesis of verrucarol in which the tetrahydropyranone 175 is envisioned to play a role, the lactone 176 can serve as a viable intermediate (Scheme 6)7S>. Using cyclobutanone annulation methodology, 177 becomes the required intermediate. The geminal substitution of 177 can also be recognized to derive from a spiroannulation approach as previously analyzed. 

It was demonstrated in Section 3 that spiroannulation of cyclopropane to four- and higher-membered rings does not cause an increase in the strain energy of the molecule. It is not surprising, then, that the chemistry of these compounds does not differ from that of simple alkyl substituted cyclopropanes. Since exciting reviews on the chemistry of cyclopropanes are available42, the authors of this chapter will limit the description of properties of SPC of these types to some of their interesting applications. 

When 2-methyleneindolines (Fischer s bases) are used as the nucleophilic species, 2-spiroannulated indolines result with high diastereomeric purity (95JPR368). When R1 = Ph, an acid catalysed isomerisation leads to a highly substituted benzophenone (23). 

Allylic alcohols can serve as 7t-allyl cation precursors to act as electrophiles in Sn reactions with a tethered O-nucleophile giving rise to the formation of spiroannulated tetrahydrofurans <2000TL3411>. Michael acceptors are also suitable electrophiles for the cyclization to tetrahydrofuran rings <2003T1613>. The Tsuji-Trost allylation has found widespread application in the synthesis of carbo- and heterocyclic compounds. Allylic substitution has been employed in the stereoselective synthesis of 2-vinyl-5-substituted tetrahydrofurans <2001H(54)419>. A formal total synthesis of uvaricin makes twofold use of the Tsuji-Trost reaction in a double cyclization to bis-tetrahydrofurans (Equation 73) <20010L1953>. 

Spiroannulations Using Substituted (2-Butene< 1,4-diyi)magnesium Complexes... 

Spiroannulation The overall conversion of a ketone, RCOR, to a di-a-substituted cyclobutanone. The reaction may be performed by the addition of diphenylsulphoniumcyclopropylide with the ketone RCOR to give the oxaspiropentane that, on treatment with a proton or a Lewis acid, rearranges to give the cyclobutanone. 

Cyclopropanation. Sodium enolates of /3-ketophosphonate esters react with ethylene oxide in a sealed tube to form spiroannulated cyclopropyl ketones in moderate yields. Other epoxides give substituted cyclopropane derivatives. 

Knolker et al. have developed a one-pot diastereoselective spiroannela-tion by electrophilic substitution of an aromatic system with an iron-complexed cation, which led to the construction of the A, B, C, and D rings of the prianosins and discorhabdins. This novel diastereoselective spiroannulation involved the reaction between the tricarbonyliron-complexed cation 520, which was prepared in six steps (2/9), and an arylam-ine, the 6-aminoindoline (521), to construct A, B, C, and D rings (512) (Scheme 61) (220). The stereochemistry of the product was determined by X-ray crystallographic analysis the stereodirecting effect of Fe(CO)3 was indicated to be anti to the aryl ring (2/9). 

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