Diastereoselective Manipulations of Bicyclo[m.1.0]alkane Derivatives. 6. Stereocontrolled Synthesis of Tricyclo[m.n.0.0]alkenones

Abstract

Enolates derived from bicyclo[m.1.0]alkan-2-ones possessing 5-, 6-, and 7-membered rings were sequentially alkylated with iodomethane and with precursors to 2-oxopropyl or 3-oxobutyl substituents. High diastereoselectivities were observed. Product yields for more active electrophiles were generally good to very good and were fair for less active electrophiles. Following unmasking of the 2-oxopropyl or 3-oxobutyl substituents, ring closure and dehydration under basic conditions provided the corresponding tricyclic γ,δ-cyclopropyl-R, -enones. Reversal of the order of alkylation switched the configuration of the angular methyl substituent relative to the stereogenic cyclopropane in the tricyclo[m.n.0.0]alkenone product.

Total synthesis of taxane terpenes: cyclase phase

“…As for a three-carbon appendage onto ketone 57 , it was hoped that the increased s -character of the C–H bond in a cyclopropane would aid in deprotonation and functionalization. 22 However, treatment with an unhindered strong base only led to C5 deprotonation and functionalization, resulting in 73 and 74 upon allylation and 75 upon acrolein addition (Figure 12C). …”