A future history of selectivity in organic chemistry: Whence, where, and whither?

A series of historical snippets of milestones in the development of selectivity in organic synthesis is presented, followed by a few prognostications about future directions in selectivity in organic synthesis—contingent on the cautionary observation that major advances are not always recognized as such at the time. The historical snippets include the foundational landmarks: the unambiguous synthesis of acetic acid from only inorganic substances by Kolbe, the Structural Theory by Couper and Kekulé and its modification by Butlerov in 1861, and the tetrahedral carbon of van’t Hoff and Le Bel. Physical chemists and physical organic chemists provided insights into rates and mechanisms of reaction. In the space of a century and a half, organic synthesis had passed through eras of chemoselectivity, regioselectivity, and diastereoselectivity, to enantioselectivity. Along with advances in spectroscopy and separations techniques, the rise of computational chemistry has added yet another tool to the arsenal of organic chemists.