Programmed Synthesis of a Contiguous Stereotriad Motif by Triple Stereospecific Reagent-Controlled Homologation

All distinct diastereoisomers of a contiguous stereotriad motif were separately targeted by a triple chain extension of B-phenethyl boronic esters using four unique presentation sequences of enantiomorphs of 1-[H-2]-1-chloro-2-(1,3-dioxolan-2-yl)ethyllithium. The (R)- or (S)-configured chloroalkyllithium reagents were generated by sulfoxide lithium exchange from the appropriate scalemic p-tolyl chloroalkyl sulfoxides using phenyllithium (THF, -78 degrees C). Stereotriad synthesis was accomplished in a single reaction vessel [7-19% yield, typical dr >= 74 (target):26 (Sigma all other isomers)] and implemented by a simple algorithm consisting of reagent charging and temperature cycling events.