Synthesis, equilibration, and coupling of 4-lithio-1,3-dioxanes: Synthons for syn- and anti-1,3-diols

Configurationally defined alpha-alkoxylithium reagents were prepared by red uctive lithiation of 4-(phenylthio)-1,3-dioxanes. A new and more general sy nthesis of 4-(phenylthio)-1,3-dioxanes has been developed on the basis of t he reduction and in situ acetylation of 1,3-dioxan-4-ones. For each of the substitution patterns examined (23a-d), reductive lithiation gave the axial alkyllithium (24a-d) with 99:1 stereoselectivity. Equilibrations of these alkyllithium reagents were possible with unhindered substrates to give the equatorial alkyllithiums 26a and 26b with excellent stereoselectivities. Th e more hindered axial alkyllithium reagents (24c, 24d) did not equilibrate efficiently. The equilibrium between alkyllithium reagents 24c and 26c stro ngly favors the equatorial isomer 26c. The inefficient equilibration with t his hindered substrate is attributed to a slow rate of equilibration rather than insufficient driving force. These alkyllithium reagents could be coup led with a variety of electrophiles with retention of configuration by dire ct addition, copper-mediated coupling, or transmetalation to the correspond ing alkylzinc reagent followed by copper-mediated coupling.