Supporting Information s7

S2

Supporting Information

Electrophilic activation of CO2 in cycloaddition reactions towards a nucleophilic carbenoid intermediate: new defying insights from the Molecular Electron Density Theory

Luis R. Domingo,1* Mar Ríos-Gutierrez,1 Eduardo Chamorro2 and Patricia Pérez2*

1 Department of Organic Chemistry, University of Valencia, Dr. Moliner 50, E-46100 Burjassot, Valencia, Spain.

2 Universidad Andres Bello, Facultad de Ciencias Exactas, Departamento de Ciencias Químicas, Millennium Nucleus Chemical Processes and Catalysis,

Av. República 498, 8370146 Santiago, Chile.

e.mail: ;

Index

S2 ELF topological analysis of the reactions of the carbenoid intermediate IN with CO2 3, and with lactone 4.

S9 Table S2. MPWB1K/6-311G(d,p) gas phase and in toluene electronic energies, enthalpies, entropies, and Gibbs free energies of the stationary points involved in the domino reaction between 1, 2 and 3.

S10 Cartesian coordinates in gas phase at the MPWB1K/6-311G(d,p) level for all species of Scheme 5 are included.

ELF topological analysis of the cycloaddition reactions of carbenoid intermediate IN with CO2 3 and with lactone 4.

Recent theoretical works have emphasised that the ELF topological analysis of the bonding changes along the IRC curve of a reaction path is a valuable tool to characterise the molecular mechanism of the reaction.1 Accordingly, an ELF topological analysis of the MPWB1K/6-311G(d,p) wavefunctions of the stationary points involved in the reactions of the carbenoid intermediate IN with the CO2 3, and with lactone 4, was performed in order to characterise the molecular mechanisms of these reactions. The N populations of the most significant ELF valence basins in specific points along the two reactions paths are displayed in Table S1. The attractor positions and atom numbering for the most relevant points are shown in Figure S1.

First, the ELF features of the reagents involved in the first reaction between IN and CO2 3, will be commented on. At the carbenoid intermediate IN, the more relevant ELF features are the presence of one V(C1,C3) disynaptic basin, integrating 2.65e, one V(C3,C4) disynaptic basin, integrating 3.14e, and the presence of one V(C4) monosynaptic basin with an electron population of 2.06e (Figure S1a). Interestingly, the V(C4) monosynaptic basin is associated with the lone pair present in C4, which is responsible for the high nucleophilic character on IN. On the other hand, the ELF topology of CO2 molecule 3, shows the presence of two disynaptic basins, i.e. V(C5,O6) and V(C5,O7), integrating 3.19e each one, associated with the C5-O6 and C5-O7 double bond, and the presence of two monosynaptic basins, i.e. V(O6) and V(O7), integrating 4.62e each one, associated with the O6 and O7 lone pairs.

The first reaction takes place between the carbenoid intermediate IN and the CO2 molecule 3 yielding the lactone 4. The most relevant ELF topological features of TS2 is the presence of two monosynaptic basins, i.e. V(C4) and V(C5), with an electronic population of 1.90e and 0.06e, respectively (Figure S1b). Besides, the population of the V(C3,C4) disynaptic basin has slightly increased to 3.20e. Note that the V(C4) monosynaptic basin was already present in IN. Analysis of the atomic movements along the IRC on going to TS2 shows that the CO2 molecule 3 approaches to IN with a symmetric angular movement of the two oxygen atoms of CO2, in the direction of the sp2 C4 lone pair. Interestingly, the formation of the new C4-C5 single bond takes place after to pass the TS2 through the nucleophilic attacks of the sp2 C4 lone pair on the sp hybridised C5 carbon of CO2 3. After passing the TS2, formation of the new C4-C5 is achieved mainly by the electron density provided by V(C4) monosynaptic basin belonging to the IN fragment. This behaviour is similar to that recently found in the formation of the C-N single bond in the first step of the Staudinger reaction between imines and ketenes, in which the imine nitrogen lone pair nucleophilically attacks on the central carbon atom of the ketene.2

After passing the TS2, the O-C-O fragment twits in order to approach the carbonyl O6 oxygen to the C1 carbon, allowing the subsequent formation of the second C1-O6 single bond. The ELF topology of the IRC point P1, d(C4-C5) = 1.929 Å and d(C1-O6) = 2.667 Å, the two V(C4) and V(C5) monosynaptic basins present in TS2 have merged into a new V(C4,C5) disynaptic basin integrating 2.13e (Figure S1c). The formation of this new disynaptic basin indicates that the formation of the first C4-C5 single bond have started at 1.929 Å. Note that the electron density of the new disynaptic basin comes from the V(C4) monosynaptic basin present in the IN. Together with the formation of the new C4-C5 single bond, the population of the V(C5,O7) disynaptic basing has been depopulated by 0.45e.

The ELF topology of the IRC point P2, d(C4-C5) = 1.514 Å and d(C1-O6) = 1.934 Å, shows the presence of two new monosynaptic basins, V(C1) and V(O6), integrating 0.12e and 0.80e, respectively (Figure S1d). Note that the V(O6) monosynaptic basin of the O6 oxygen atom is also located in sp2 hybridised orbitals. In addition, a new V(N2) monosynaptic basin at the N2 nitrogen, integrating 2.17e, appears, whereas C1-N2 bonding region has been depopulated by 1.63e. At P2, the population of the V(C4,C5) disynaptic basin is increased to 2.21e, indicating the first C4-C5 single is practically formed, while the formation of the second C1-O6 single bond has not yet started. At this point, the V(C3,C4) disynaptic basin present in IN splits newly into two disynaptic basins, V(C3,C4) and V’(C3,C4), integrating to 1.70 and 1.68e, respectively. These disynaptic basins are associated with the C3-C4 double bond present in lactone 4.

At point P3, d(C4-C5) = 1.483 Å and d(C1-O6) = 1.662 Å, the two V(C1) and V(O6) monosynaptic basins present in P2 have merged into a new V(C1,O6) disynaptic basin integrating 1.13e. The formation of this new disynaptic basin indicates that the formation of the second C1-O6 single bond has started at 1.662 Å (Figure S1e).

At lactone 4, the two V(C4,C5) and V(C1,O6) disynaptic basins created along the reaction have reached a population of 2.34e and 1.62e, respectively (see Figure S1f). The low population of the V(C1,O6) disynaptic basin indicates that the C1-O6 single bond is very polarised. Finally, the V(N2) monosynaptic basin created at P2 has increased the population to 2.65e. The ELF electronic structure of lactone 4 agrees well with the Lewis structure shown in Scheme 3.

The second reaction is associated with the capture of lactone 4 by a second molecule of the carbenoid intermediate IN, yielding spiro-compound 5. At TS3, the most remarkable feature of the ELF is the presence of a V(C9) monosynaptic basin, integrating to 1.89e (Figure S1g). Note that this monosynaptic basin was already contained in IN. On the other hand, the V(O6) monosynaptic basin present in 4 has been split in two V(O6) and V’(O6) monosynaptic basins integrating 2.74e and 2.65e.

At point P4, d(C5-C9) = 1.901 Å and d(O7-C8) = 2.659 Å, while the V(C9) monosynaptic basin present in TS3 has disappeared, a new V(C5,C9) disynaptic basin is created integrating 2.02e (Figure S1h). This disynaptic basin indicates that the first C5-C9 single bond has been practically created at a C5-C9 distance of 1.901 Å. Similar to that found at P1, the electron density of the new disynaptic basin comes from the V(C4) monosynaptic basin present in IN.

At point P5, d(C5-C9) = 1.579 Å and d(O7-C8) = 1.954 Å, a new V(C8) monosynaptic basin, integrating to 0.17e, is found. This monosynaptic basin will participate in the formation of the O7-C8 single bond in a following stage of the reaction (see Figure S1i). At this stage of the reaction, the population of the V(O7) and V’(O7) monosynaptic basins associated with the two lone pairs of the O7 oxygen atom have reached an electron density of 2.96 and 2.91e.

At point P6, d(C5-C9) = 1.520 Å and d(O7-C8) = 1.682 Å, while the V(C8) monosynaptic basin present at P5 has disappeared, a new V(O7,C8) disynaptic basin is created integrating 0.92e (see Figure S1j). At this stage of the reaction, the population of the V(O7) and V’(O7) monosynaptic basins associated with the two lone pairs of the O7 oxygen atom have been decreased by ca 0.60e. Consequently, similar to the C1-O6 single bond formation along the first reaction, the electron-density of the new O7-C8 single bond provides mainly from the O7 lone pairs.

Finally, ELF topological analysis of spiro-compound 5 shows a similar bonding pattern that lactone 4 (Figure S1k). The main differences is the absence of the V(C5,O7) disynaptic basin associated with the carbonyl C5-O7 double bond present in lactone 4, the slight increase in the electronic population of the V(C5,C9) disynaptic basin, 2.18e, and the creation of the V(C7,O8) disynaptic basin, which integrates to 1.53e, associated with the new C7-O8 single bond formed along the second reaction. Such as lactone 4, the C3-C4 and C3'-C4' bonding regions are topologically characterised by the presence of two pairs of dysinaptic basins, i.e. V(C3,C4) and V’(C3,C4), and V(C3',C4') and V’(C3',C4'), integrating ca 1.70e each one. The ELF electronic structure of spiro-compound 5 agrees well with the Lewis structure shown in Scheme 3.

References

1 (a) V. Polo, J. Andres, S. Berski, L. R. Domingo and B. Silvi, J. Phys. Chem. A 2008, 112, 7128; (b) J. Andres, S. Berski, L. R. Domingo, V. Polo and B. Silvi, Curr. Org. Chem. 2011, 15, 3566; (c) J. Andrés, P. González-Navarrete and V. S. Safont, Int. J. Quant. Chem. 2014, 114, 1239. (d) J. Andrés, L. Gracia, P. González-Navarrete and V. S. Safont, Theoretical and Computational Chemistry, 2015, 1053, 17.

2 (a) L. R. Domingo and J. A. Sáez, RSC Adv. 2014, 4, 58559; (b) L. R. Domingo, M. Ríos-Gutiérez and J. A. Sáez, RSC Adv. 2015, 5, 37119.

S2

Table S1. Valence basin populations N (in e units) calculated from the ELF of some selected points associated with the IRCs of the two consecutive reactions of IN with CO2 3 and with lactone 4. Distances are given in Å.

a Numerical integration of the electronic population of two equivalent disynaptic basins.

S7

Figure S1. Attractor positions of the ELF for some relevant points along the IRC for the reaction between MeCN 1 , DMAD 2 and CO2 3.

S7

Table S2. MPWB1K/6-311G(d,p) gas phase and in toluene electronic energies (a.u.), enthalpies (a.u.), entropies (cal/molK), and Gibbs free energies (a.u.), at 80 ºC, 1 atm in toluene, of the stationary points involved in the MC reaction between 1, 2 and 3.

Cartesian Coordinates in gas phase at MPWB1K/6-311G(d,p) level of theory

1, E = -132.674951 a.u.

N 0.00000000 0.00000000 0.30958700

C 0.00000000 0.00000000 1.46896800

C 0.00000000 0.00000000 -1.09793100

H 0.00000000 1.02010100 -1.46444100