1 3
Topics in Current Chemistry (2020) 378:1
From a precise mechanistic analysis of a precedent report [133], MacMillan was
able to demonstrate that the oxyamination reaction occurred via addition of the transient enamine to an electrophilic metal-TEMPO complex. Therefore, the interaction
of specific Lewis acids with TEMPO was examined, and copper(II) was found to be
a suitable Lewis acid able to coordinate TEMPO. In other words, the metal is not
participating as an oxidant but the coordination of copper to the nitroxyl radical of
TEMPO is pivotal, generating an η
2
-type of complex with an electrophilic oxygen.
The reaction showed a wide applicability and highly enantioselectivity, with newly
designed imidazolidinones.
11 Conclusions
The compatibility of Lewis acids with the various activation modes of organocatalysis have considerably enhanced the arsenal of the possible chemical reactions in the
context of organocatalysis. Although the Lewis acids compatible with organocatalytic conditions seem quite limited, many dual processes have been realized. Related
to these synergistic or cooperative catalytic processes, many other possibilities can
be explored, such as embedding Lewis acids in MOFs, or attaching Lewis acids onto
solid supports, thus modifying stability or inactivation pathways. In addition, flow
chemistry and other advanced technological methodologies should be taken into
account for further insights on these reactions, allowing for incompatible combinations between organocatalysts and Lewis acids. Not only the activation of carbonyls
and imines by chiral Lewis acids can enhance the reactivity of such systems, but all
stereoisomers can be accessible now though matching/mismatching protocols. For
sure, the combination between organocatalysts and chiral Lewis acids can be used
to address stereochemical problems. The activity of Lewis acids can be finely tuned
combining them with the proper ligands. Such tunability can enhance the compatibility and new interesting combinations could be possible. Organocatalysis will be
combined with Lewis acids more and more in the future, in order to address challenging problems and to find new reactivities. The future of these combinations is
limited only by the creativity of researchers.
Acknowledgements The authors kindly thank Letizia Vanni d’Archirafi and Benedetta Gaggio for their
suggestions to improve the readability of this review. The authors also want to thank the reviewers for
their valuable advices to improve the scientific quality of this review.
References
1. Dalko P (2013) Comprehensive enantioselective organocatalysis: catalysts, reactions, and applications. Wiley, New York
2. Ahrendt KA, Borths CJ, MacMillan DWC (2000) New strategies for organic catalysis: the first
highly enantioselective organocatalytic Diels–Alder reaction. J Am Chem Soc 122(17):4243–4244
3. List B, Lerner R, Barbas CF (2000) Proline-catalyzed direct asymmetric aldol reactions. J Am
Chem Soc 122(10):2395–2396
Reprinted from the journal
59
Topics in Current Chemistry (2020) 378:1
From a precise mechanistic analysis of a precedent report [133], MacMillan was
able to demonstrate that the oxyamination reaction occurred via addition of the transient enamine to an electrophilic metal-TEMPO complex. Therefore, the interaction
of specific Lewis acids with TEMPO was examined, and copper(II) was found to be
a suitable Lewis acid able to coordinate TEMPO. In other words, the metal is not
participating as an oxidant but the coordination of copper to the nitroxyl radical of
TEMPO is pivotal, generating an η
2
-type of complex with an electrophilic oxygen.
The reaction showed a wide applicability and highly enantioselectivity, with newly
designed imidazolidinones.
11 Conclusions
The compatibility of Lewis acids with the various activation modes of organocatalysis have considerably enhanced the arsenal of the possible chemical reactions in the
context of organocatalysis. Although the Lewis acids compatible with organocatalytic conditions seem quite limited, many dual processes have been realized. Related
to these synergistic or cooperative catalytic processes, many other possibilities can
be explored, such as embedding Lewis acids in MOFs, or attaching Lewis acids onto
solid supports, thus modifying stability or inactivation pathways. In addition, flow
chemistry and other advanced technological methodologies should be taken into
account for further insights on these reactions, allowing for incompatible combinations between organocatalysts and Lewis acids. Not only the activation of carbonyls
and imines by chiral Lewis acids can enhance the reactivity of such systems, but all
stereoisomers can be accessible now though matching/mismatching protocols. For
sure, the combination between organocatalysts and chiral Lewis acids can be used
to address stereochemical problems. The activity of Lewis acids can be finely tuned
combining them with the proper ligands. Such tunability can enhance the compatibility and new interesting combinations could be possible. Organocatalysis will be
combined with Lewis acids more and more in the future, in order to address challenging problems and to find new reactivities. The future of these combinations is
limited only by the creativity of researchers.
Acknowledgements The authors kindly thank Letizia Vanni d’Archirafi and Benedetta Gaggio for their
suggestions to improve the readability of this review. The authors also want to thank the reviewers for
their valuable advices to improve the scientific quality of this review.
References
1. Dalko P (2013) Comprehensive enantioselective organocatalysis: catalysts, reactions, and applications. Wiley, New York
2. Ahrendt KA, Borths CJ, MacMillan DWC (2000) New strategies for organic catalysis: the first
highly enantioselective organocatalytic Diels–Alder reaction. J Am Chem Soc 122(17):4243–4244
3. List B, Lerner R, Barbas CF (2000) Proline-catalyzed direct asymmetric aldol reactions. J Am
Chem Soc 122(10):2395–2396
Reprinted from the journal
59