Diastereoselective Synthesis of Axially Chiral Xylose-Derived 1,3-Disubstituted Alkoxyallenes: Scope, Structure, and Mechanism

The
deprotonation of differently substituted propargyl xylosides
with s-BuLi/TMEDA followed by protonation with t-butanol at −115 °C provided a range of new
axially chiral 1,3-disubstituted alkoxyallenes in a diastereoselective
way. Numerous reaction parameters such as solvent, temperature, or
protonating agent were examined as well as protecting groups on the
xyloside moiety and the influence of the substituents on the alkyne
part. The configuration of the main diastereoisomer of 3-methyl-1-xyloside-allene
was determined for the first time by single-crystal X-ray diffraction
analysis and nOe NMR experiments. Furthermore, DFT calculations on
the propargyl/allenyl lithium intermediates formed in the course of
the deprotonation reaction provided new structural insights of these
complexes. The subsequent protonation process with alcohols was investigated
by theoretical surface exploration, revealing the importance of the
approach of the alcohol toward the lithium compounds on the reaction
outcome.