Local desymmetrization as an engine of stereochemical elaboration in total synthesis

Desymmetrization strategies have unlocked numerous possibilities in complex target-driven synthesis by enabling the construction of diverse three-dimensional molecular architectures. While methods of achieving enantiotopic group discrimination have found a central role in asymmetric synthesis by providing access to enantiopure intermediates, diastereotopic group discrimination (or “local desymmetrization”) has evolved in parallel as a means of elaborating upon existing stereochemical features through substrate control. In this Digest, selected synthetic efforts from the last five years are examined through the lens of local desymmetrization, framing each advance on the basis of stereochemical generalities.