Cyclobutanes, spiro-fused

Marine natural products Spiro-fused cyclobutanes... 

Welwitindolinone A isonitrile also has a number of structural features that make it a very challenging target, most notably the sterically crowded spiro-fused cyclobutane ring, which at first sight might seem thermodynamically unstable (Fig. 3). 

Scheme 7.18 Stereoselective Michael/Michael cascade reaction to 3 -spiro-oxindoles fused with cyclobutane catalysed by prolinol lb.

In a novel approach, Trost and Keeley (102) used the annelation reagent lithiocyclopropylphenyl sulfide (85) to prepare first cyclobutanone (88) and then the fused biscyclobutane spiro system (89) as a mixture of diastereomers with the desired conformer in fom fold excess (Scheme 16). Haloform-type cleavage afforded cyclobutane derivative (90), which upon transformation of the various functionalities yielded grandisol. 

Cydopentenone 64 bearing a carbonyl group in the substitutent R may serve for the synthesis of the angularly fused triquinane skeleton 66 based on a double Michael addition to the cyclopentadienone generated via base-promoted elimination of the dialkylamine [45]. Spiro[4.4]nonenone 65 appears as the relevant intermediate from the first Michael addition. Biscyclopentannulated cyclobutane 67... 

---