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Review
. 2020 Sep 9;11(46):12423-12427.
doi: 10.1039/d0sc03876h.

Synthetic half-reactions

Andrei K Yudin  1
Affiliations
Review

Synthetic half-reactions

Andrei K Yudin. Chem Sci. .

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.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
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
Fig. 2. Representative examples of commonly encountered uphill and downhill processes.
Fig. 3
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
Fig. 4. Allylic strain relief matched with an equatorial-to-axial transition in acylated piperidine.
Fig. 5
Fig. 5. Aromaticity-driven relief of allylic strain.
Fig. 6
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
Fig. 7. A retro-conjugate addition in the context of carbonyl-based driving forces.
Fig. 8
Fig. 8. The “cross-talk” between nucleophilic addition and electrocyclization.
Fig. 9
Fig. 9. Addressing the question of sequence in spatioenergetic matching.
Fig. 10
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.
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