Appendage disconnection

Disconnections which leave stereocenters on newly created appendages are not strategic unless the stereocenters can be removed with stereocontrol prior to the disconnection (see section 4.3). 

If the disconnection of a bond found to be strategic by criteria 1-3 produces a new ring appendage bearing stereocenters, those centers should be removed if possible (by stereocontrolled transforms) before the disconnection is made. 

The Y appendage of 2-cyclohexenone 191 cannot be directly disconnected by an alkylation transform. (y-Extended enolates derived from 2-cyclohexenones undergo alkylation a- rather than y- to the carbonyl group). However, 191 can be converted to 192 by application of the retro-Michael transform. The synthesis of 192 from methoxybenzene by way of the Birch reduction product 193 is straightforward. Another synthesis of 191 (free acid) is outlined in... 

Disconnection of that appendage-ring bond was a key step in the synthesis of ovalicin, a close structural relative to fumagillol.16... 

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