As mentioned earlier, this chapter had no intention to be comprehensive. Other
examples from the recent literature could have been chosen. It is aimed at illustrating
that theoretical treatments of experimental questions which could not be treated few
years ago can be done. As computational chemistry became more powerful, new
horizons opened and new difficulties appear but they can be overcome provided that
an appropriate protocol, which acts as quality control, is applied. We described in
detail the many facets of this protocol. They are associated with the chemical
complexity of the solute (what is in the flask and how to treat the vast number of
structural possibilities), the complexity created by the media (the numerous facets of
the effects of the solvent), and the diverse challenges associated with the calculations
of the electronic energies and the entropy. It is quite probable that this protocol needs
to be updated as new difficulties appear. However, in its present state it should help
the practitioner to navigate safely avoiding the many pitfalls that arise during the
study. The pleasure to reproduce in silico the experiment through a “good” computational study and thus to propose a mechanistic pathway based on a solid procedure
will be fulfilling.
Acknowledgments Financial support (GU and AL) was provided by the Spanish Ministerio de
Economía y Competitividad (MINECO) (Grant CTQ2017-87889-P). OE was in part supported by
Research Council of Norway (RCN) through the COE Hylleraas Center for Quantum Molecular
Sciences (Grant number 262695).
References
1. Cheng G-J, Zhang X, Chung LW, Xu L, Wu Y-D (2015) Computational organic chemistry:
bridging theory and experiment in establishing the mechanisms of chemical reactions. J Am
Chem Soc 137:1706–1725
2. Sperger T, Sanhueza IA, Kalvet I, Schoenebeck F (2015) Computational studies of synthetically relevant homogeneous organometallic catalysis involving Ni, Pd, Ir, and Rh: an overview of commonly employed DFT methods and mechanistic insights. Chem Rev
115:9532–9586
3. Salomó E, Gallen A, Sciortino G, Ujaque G, Grabulosa A, Lledós A, Riera A, Verdaguer X
(2018) Direct asymmetric hydrogenation of N-methyl and N-alkyl imines with an Ir(III)H
catalyst. J Am Chem Soc 140:16967–16970
4. Mai BK, Himo F (2020) Mechanisms of metal-catalyzed electrophilic F/CF 3 /SCF 3 transfer
reactions from quantum chemical calculations. Top Organomet Chem. https://doi.org/10.
1007/3418_2020_45
5. Sperger T, Sanhueza IA, Schoenebeck F (2016) Computation and experiment: a powerful
combination to understand and predict reactivities. Acc Chem Res 49:1311–1319
6. Eisenstein O (2019) Concluding remarks for “mechanistic processes in organometallic chemistry”: the importance of a multidisciplinary approach. Faraday Discuss 220:489–495
7. Noyori R, Richmond JP (2013) Ethical conduct in chemical research and publishing. Adv
Synth Catal 355:3–8
8. Plata RE, Singleton DA (2015) A case study of the mechanism of alcohol-mediated Morita
Baylis–Hillman reactions. The importance of experimental observations. J Am Chem Soc
137:3811–3826
9. Scott SL (2019) The burden of disproof. ACS Catal 9:4706–4708
32
O. Eisenstein et al.
examples from the recent literature could have been chosen. It is aimed at illustrating
that theoretical treatments of experimental questions which could not be treated few
years ago can be done. As computational chemistry became more powerful, new
horizons opened and new difficulties appear but they can be overcome provided that
an appropriate protocol, which acts as quality control, is applied. We described in
detail the many facets of this protocol. They are associated with the chemical
complexity of the solute (what is in the flask and how to treat the vast number of
structural possibilities), the complexity created by the media (the numerous facets of
the effects of the solvent), and the diverse challenges associated with the calculations
of the electronic energies and the entropy. It is quite probable that this protocol needs
to be updated as new difficulties appear. However, in its present state it should help
the practitioner to navigate safely avoiding the many pitfalls that arise during the
study. The pleasure to reproduce in silico the experiment through a “good” computational study and thus to propose a mechanistic pathway based on a solid procedure
will be fulfilling.
Acknowledgments Financial support (GU and AL) was provided by the Spanish Ministerio de
Economía y Competitividad (MINECO) (Grant CTQ2017-87889-P). OE was in part supported by
Research Council of Norway (RCN) through the COE Hylleraas Center for Quantum Molecular
Sciences (Grant number 262695).
References
1. Cheng G-J, Zhang X, Chung LW, Xu L, Wu Y-D (2015) Computational organic chemistry:
bridging theory and experiment in establishing the mechanisms of chemical reactions. J Am
Chem Soc 137:1706–1725
2. Sperger T, Sanhueza IA, Kalvet I, Schoenebeck F (2015) Computational studies of synthetically relevant homogeneous organometallic catalysis involving Ni, Pd, Ir, and Rh: an overview of commonly employed DFT methods and mechanistic insights. Chem Rev
115:9532–9586
3. Salomó E, Gallen A, Sciortino G, Ujaque G, Grabulosa A, Lledós A, Riera A, Verdaguer X
(2018) Direct asymmetric hydrogenation of N-methyl and N-alkyl imines with an Ir(III)H
catalyst. J Am Chem Soc 140:16967–16970
4. Mai BK, Himo F (2020) Mechanisms of metal-catalyzed electrophilic F/CF 3 /SCF 3 transfer
reactions from quantum chemical calculations. Top Organomet Chem. https://doi.org/10.
1007/3418_2020_45
5. Sperger T, Sanhueza IA, Schoenebeck F (2016) Computation and experiment: a powerful
combination to understand and predict reactivities. Acc Chem Res 49:1311–1319
6. Eisenstein O (2019) Concluding remarks for “mechanistic processes in organometallic chemistry”: the importance of a multidisciplinary approach. Faraday Discuss 220:489–495
7. Noyori R, Richmond JP (2013) Ethical conduct in chemical research and publishing. Adv
Synth Catal 355:3–8
8. Plata RE, Singleton DA (2015) A case study of the mechanism of alcohol-mediated Morita
Baylis–Hillman reactions. The importance of experimental observations. J Am Chem Soc
137:3811–3826
9. Scott SL (2019) The burden of disproof. ACS Catal 9:4706–4708
32
O. Eisenstein et al.