A plausible route for the spontaneous synthesis of an activated ribonucleotide that is poised for polymerization has been put forth (Powner et al. (2009) Nature, 459, 239-242). A key step in this route necessitates the regioselective phosphorylation of the secondary alcohol on C(3') of an anhydroarabinonucleoside in the presence of the primary alcohol on C(5'). Here, we propose that this regioselectivity relies on electron delocalization between a lone pair (n) of O(5') and an antibonding orbital (pi*) of C(2) horizontal lineN(3). This n-->pi* interaction modulates reactivity without the use of a protecting group. Thus, a stereoelectronic effect could have opened a gateway to the "RNA world", the chemical milieu from which the first forms of life are thought to have emerged on Earth some 4 billion years ago.