Introduction

There are many resources or outlets that review new literature in chemistry, but few highlight classics. The exception to this is of course the “Classics in Total Synthesis” series of books. Here I will showcase some of my favourites from the literature, with a focus on mechanism, along with a brief explanation of my assessment of the importance of the work. If I can find the time, this will become a running series, until the relevant Zotero folder has been exhausted.

Papers 1 & 2

Citations:

Seyferth, Dietmar. “The Grignard Reagents.” Organometallics 28, no. 6 (March 23, 2009): 1598–1605. https://doi.org/10.1021/om900088z.

and

Peltzer, Raphael Mathias, Jürgen Gauss, Odile Eisenstein, and Michele Cascella. “The Grignard Reaction – Unraveling a Chemical Puzzle.” Journal of the American Chemical Society 142, no. 6 (February 12, 2020): 2984–94. https://doi.org/10.1021/jacs.9b11829.

The first essay provides a much deeper look into the long history of organomagnesium halides and many of the overlooked mechanistic intricacies. The organic chemistry textbook view of these reactions misses many important points, which are partially rectified by examining speciation, as done in main group organometallic chemistry. However, that picture is still incomplete, as illustrated in the essay, as there is no consideration of alternative reactivity such as radical reactivity which has been shown to be present with certain substrates.

The second paper is a modern thorough computational investigation of this polar/radical competition and the substrate dependence is explained through reduction potential. It really is worth reading, in full, it is of exceptional quality.

Taken together, these papers illustrate how an electron tranfer pathway is always an alternative to be considered when a carbon-metal bond is present. This applies to alkyl organomagnesiums as illustrated, not only to complexes bearing frontier electron density on the metal or ligand (typically pi - thinking of noninnocent ligands here) orbitals.

Paper 3

Citation:

Kozuch, Sebastian, and Jan M. L. Martin. “The Rate-Determining Step Is Dead. Long Live the Rate-Determining State!” ChemPhysChem 12, no. 8 (2011): 1413–18. https://doi.org/10.1002/cphc.201100137.

This is simply required reading in order to correctly understand the relationship between elementary steps, barriers and rates. A surprising deficit in far too many introductory classes on kinetics.

Paper 4 & 5

Citations:

Mayr, Herbert, and Armin R. Ofial. “Philicities, Fugalities, and Equilibrium Constants.” Accounts of Chemical Research 49, no. 5 (May 17, 2016): 952–65. https://doi.org/10.1021/acs.accounts.6b00071.

Mayr, Herbert, Martin Breugst, and Armin R. Ofial. “Farewell to the HSAB Treatment of Ambident Reactivity.” Angewandte Chemie International Edition 50, no. 29 (2011): 6470–6505. https://doi.org/10.1002/anie.201007100.

These two absolute takedowns of commonly-taught rules-of-thumb in organic chemistry are also required reading in my opinion. Hard-soft acid-base theory for explaining ambident reactivity (hard/soft nucleophiles/electrophiles) is simply not an adequate framework. HOWEVER, this does not apply to bonding interactions (hard/soft metals/ligands), which have a much more sound basis for the rationale. The philicities review reveals important nuances in the understanding of what is commonly treated as “driving force” in organic chemistry and also regarding the pKa/leaving group ability correlation and its limits.