Description:
<jats:title>Abstract</jats:title><jats:p>The synthesis of diester <jats:bold>3</jats:bold>, a synthon for the C(19)‐to‐C(27) segment of rifamycin S (<jats:bold>1</jats:bold>), is described, starting from the <jats:italic>meso</jats:italic>‐diester <jats:bold>4</jats:bold> (<jats:italic>Schemes 2</jats:italic> and <jats:italic>3</jats:italic>). Inversion of the configuration at the later C(23) and two aldol condensations with the lithium enolate <jats:bold>18</jats:bold> of 2,6‐dimethylphenyl propionate each producing two new chiral centres of <jats:italic>threo</jats:italic>‐configuration, led to the desired diester <jats:bold>3</jats:bold>. The absolute configuration of the new chiral centres was proven by a single X‐ray analysis of intermediate <jats:bold>19</jats:bold> (<jats:italic>Fig.</jats:italic>) and by converting diester <jats:bold>3</jats:bold> into meso‐diester <jats:bold>25</jats:bold>.</jats:p>