Synthetic half-reactions

Abstract

This perspective on reactivity introduces Synthetic Half-Reactions (SHRs) as a way to analyze chemical transformations. SHRs denote either an uphill transformation leading to a higher energy state or a downhill transformation leading to a lower energy state. Using well-established processes, I show how the matching of different classes of SHRs offers a tool to classify chemical transformations. This raises the possibility to discover new processes by finding underappreciated combinations of endergonic and exergonic steps.

Fig. 1. A schematic representation of the two conceptual domains of organic chemistry: the ground state space (blue rectangle) and the higher energy space (yellow rectangle).

Fig. 2. Representative examples of commonly encountered uphill and downhill processes.

Fig. 3. (a) The use of electrochemical half-reactions to evaluate the feasibility of metal ion reduction; (b) electrophilic aromatic substitution as an example of spatioenergetic matching between endergonic (N-type) and exergonic (X-type) processes.

Fig. 4. Allylic strain relief matched with an equatorial-to-axial transition in acylated piperidine.

Fig. 5. Aromaticity-driven relief of allylic strain.

Fig. 6. The use of carbonyl group-based driving forces to disrupt aromaticity: (a) pyridine/pyridone system; (b) the use of Claisen rearrangement to disrupt aromaticity.

Fig. 7. A retro-conjugate addition in the context of carbonyl-based driving forces.

Fig. 8. The “cross-talk” between nucleophilic addition and electrocyclization.

Fig. 9. Addressing the question of sequence in spatioenergetic matching.

Fig. 10. Core motif analysis as a means to illustrate the divergence of pathways: (a) collapse of the tetrahedral intermediate during ester hydrolysis; (b) the Baeyer–Villiger pathway; (c) nucleophilic attack with concomitant O–O bond scission; (c) oxygen atom transfer; (d) Favorskii rearrangement; (e) semipinacol pathway.