## 4 Discussion  
The mechanism arising from our density-functional studies (Figure 12) differs in important respects from the previously postulated reaction sequence. First, the transition state for the postulated carbocupration was shown to lie far above the energies compatible with measurable reaction rates, and the alkylation of the alkyne instead proceeds through direct alkylation of the Cu\({}^{+}\)-complexed alkyne by the Grignard reagent. Second, the removal of the MgBr\({}^{+}\) moiety left behind by the Grignard reagent requires the active involvement of the solvent, which entails that eventual modifications of this method must retain the use of a solvent with sufficient Mg\({}^{2+}\)-chelating ability. Third, the reaction with the zinc carbenoid is not independent of the Cu\({}^{+}\) catalyst but instead proceeds through methylene transfer to Cu\({}^{+}\). This reaction step may, against expectation, occur either with (leading to Int2\(\gamma\)/\(\delta\)) or without (leading to Int2\(\alpha\)) the assistance of a Zn\({}^{2+}\)-carbonyl stabilizing interaction. Finally, the stereoselectivity of the carbonyl insertion does not arise from interactions between the aldehyde sidechains and the bulky substituent on the oxazolidinone ring: inspection of the transition states of the most favorable reactions (Figure 11B,C, and Supplementary Materials) shows that the aldehyde actually lies quite far from the oxazolidinone ring. Instead, in both cases (Int2\(\alpha\) and Int2\(\gamma\)), the disfavored transition state is the one where the bulky substituent on the aldehyde lies immediately above both of the R\({}_{1}\) and R\({}_{2}\) substituents present on the other, newly formed, stereocenter. We expect these insights will prove useful for the continuing development of this important methodology and to further increase its scope and stereoselectivity.  
Figure 11: Transition states leading to products with two stereocenters. (**A**) From Int2\(\alpha\) to the (S)(S) product without Zn\({}^{2+}\) complexation by carbonyl; (**B**) from Int2\(\alpha\) to the (S)(R) product; (**C**) from Int2\(\gamma\) to the (S)(R) product; (**D**) from Int2\(\beta\) to the (R)(S) product; (**E**) from Int2\(\delta\) to the (R)(S) product.  
**Supplementary Materials:** Coordinates of all molecules described in the text, as well as individual energetic data, are available online at [[https://www.mdpi.com/article/10.3390/app11115002/s1](https://www.mdpi.com/article/10.3390/app11115002/s1)]([https://www.mdpi.com/article/10.3390/app11115002/s1](https://www.mdpi.com/article/10.3390/app11115002/s1)).  
**Author Contributions:** [PERSON] and [PERSON] jointly performed the computations. [PERSON] further analyzed the results, conceived and designed the study, and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This work has been financed by FEDER through Programa Operacional Factores de Competitividade-COMPETE and by Portuguese Funds through FCT-Fundacao para a Ciencia e a Tecnologia under project PTDC/QUI-QUI/111288/2009. This work was also supported by the Applied Molecular Biosciences Unit-UCIBO, which is financed by national funds from FCT (UIDB/04378/2020).  
**Data Availability Statement:** Full inputs and output files may be downloaded from figshare (DOI: 10.6084/m9.figshare.5481541, accessed date on 27 May 2021).  
**Conflicts of Interest:** The authors declare no conflict of interest.