Trimethylsilyl deriv problems with enols

The rate of derivatization of different compounds varies when trimethylsilyl derivatives are prepared (Lundquist and Kirk 1971). Another complication arises from the fact that enolization and subsequent formation of enol derivatives occur during the derivatization treatment (Lundquist and Kirk 1971). Ketol la (Fig. 6.1.1), for example, has been shown to give rise to three different derivatives (Fig. 6.1.3) (Lapierre et al. 1983a). One approach for overcoming these difficulties consists of derivatization under mild conditions in combination with a gas chromatographic study of the rate of derivatization (Lundquist and Kirk 1971, Pometto and Crawford 1985). A second solution to this problem consists of performing the silylation under conditions that secure complete derivatization and analysis of all types of derivatives formed (Lapierre et al. 1983a). The latter principle has been adopted in the preferred acidolysis procedure. 

As mentioned earlier, the preparation of -enolates can present problems which render the anti aldols (74) inaccessible. Such products may be made efficiently with the trimethylsilyl derivative of R-triphenylethanediol as the chiral auxiliary.[26]... 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

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