The Outer-Sphere Mechanism of Nitrene Transfer onto Gold(I) Alkyne Complexes Ismael Costa, Marta Marín-Luna, Marta Gonzµlez ComesaÇa, Olalla Nieto Faza, and Carlos Silva López* [a] Introduction Gold metal is a soft Lewis acid that presents potent reactivity and a unique ability to coordinate to unsaturated bonds. For the last two decades, the chemistry of homogeneous gold cat- alysis has experienced a significant increase in attention and has become the subject of a great number of experimental [1–8] and theoretical [9–12] studies. In addition, gold-catalyzed reac- tions of alkynes with nucleophiles are recognized as one of the most powerful and useful tools in organic synthesis. [13–17] It is well known that a-oxo metal carbene/carbenoids are powerful intermediates in organic transformations such as C H activa- tion, ylide formation, and cyclopropanation reactions. [18, 19] However, a classic approach to these compounds involves diazo carbonyl compounds, which require complicated manip- ulation. Significant effort has therefore been directed toward the development of novel and safer synthetic methods to gen- erate, for instance, a-oxo gold carbenes by using oxidant re- agents that promote intra- [20–23] or intermolecular [24, 25] oxygen transfer to alkynes, which thus avoids the undesired diazo compounds. [26–28] Access to difficult-to-obtain and synthetically versatile a- imino carbenes was recently realized by using an approach that mimics that of oxo derivatives. Nitrogenation is achieved via a nitrene or nitrenoid reagent that promotes a nitrene- transfer reaction. This process is suggested to occur through outer-sphere transfer, for which the gold center is essentially a spectator, and is still far from being fully explored. Most early studies report intramolecular nitrene transfer from an azide group to a gold-activated alkyne as the key step of the reac- tion in the formation of azacycles [29–32] (see Figure 1 a), whereas only a few studies consider an external compound as the ni- trene- or nitrenoid-transfer reagent. [33–35] This trend, however, has reversed in the latest contributions to this chemistry owing to the higher potential of the intermolecular version, particularly in the field of complex heterocyclic alkaloids [36–40] (Figure 1 b). In this work, we focused our attention on this second mode of transferring nitrene. In this arena, of relevance is the work published by Zhang, who developed the first example of this type of reaction. [34] Zhang et al. revealed a new mode of ni- trene transfer not involving a gold nitrene complex but occur- ring through outer-sphere attack. They also emphasized that “this new mode of nitrene transfer makes alkynes equivalent to a-diazo imines, which are difficult to access”. The synthetic approach followed by Zhang led to the formation of a,b-unsa- The recently developed nitrene transfer reaction onto gold-ac- tivated alkynes provides a route to safe and accessible syn- thons of a-diazo imides. This reaction is rather unique in that it requires Au I in catalytic amounts; however, this promiscuous metal is only used to activate the alkyne moiety. After such ac- tivation is obtained, the nitrene-transfer process occurs through an outer-sphere mechanism, in which the metal acts only as a spectator. Density functional theory was applied to elucidate this peculiar reaction and to provide a mechanistic explanation for the experimentally observed isomers at the double bond and imine sites. Figure 1. a) Intramolecular and b) intermolecular mode of nitrene transfer to activated alkynes by gold. [a] I. Costa, Dr. M. Marín-Luna, M. G. ComesaÇa, Prof.Dr. O. N. Faza, Prof.Dr. C. Silva López Departamento de Química Orgµnica Universidad de Vigo Lagoas-Marcosende, 36310, Vigo (Spain) E-mail : carlos.silva@uvigo.es Supporting Information (Cartesian coordinates, electronic energies, and the number of imaginary frequencies for all the structures) and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.doi.org/10.1002/cctc.201600354. ChemCatChem 2016, 8, 2387 – 2392 # 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2387 Full Papers DOI: 10.1002/cctc.201600354