From the previous eight initial structures, we can get eight corresponding intermediate structures of the [3+2] cycloaddition that combine the final CF3­substituted pyrazolidine and the Cu(OTf)2 molecule as shown in Figure 4.
Figure 4. The UB3LYP+D3 optimized eight intermediate structures of [3+2] cycloaddition which include both the final product structures and the Cu(OTf)2 molecule. Also shown are relevant bond lengths (in angstrom).
As expected, the C1­C3/C1­C2 bond is shortened from ≤ 3.00 Å to ca. 1.55 Å, which is the typical bond length of C­C single bond. At the same time, the C2­N4/C3­N4 bond is shortened to ca. 1.50 Å and the C2­C3 bond is elongated to 1.55 Å. All these parameter changes indicate the formation of the [3+2] cycloaddition products. Similarly, the enantiomers of CR1­CR8 will result eight mirror structures of M1 to M8 with exactly the same energies.
With the departure of Cu(OTf)2, we can finally obtain the eight final products as depicted in Figure 5. The bond length parameters are similar to above intermediate structures with the C­C bond is ca. 1.55 Å and the C­N bond is 1.50 Å. A carefully analysis of these structures indicate that P1 and P5, P2 and P6, P3 and P7, P4 and P8 are actually four pairs of enantiomers, which have nearly the same energy and structural parameters (see Table S2). For example, all C1­C3/C1­C2, C2­C3, C2­N4/C3­C4 bond lengths for each pair of enantiomers are exactly the same. Apart from this, all other pairs of products are diastereoisomers. In addition, the P1, P3, P5, P7 can be classified into the syn structures mentioned in previous experimental study while the remaining P2, P4, P6 and P8 can be regarded as the anti structures. 33 However, the experimental study reveals that the syn product is the major products when using the Cu(OTf)2 as a catalyst under room temperature with a ratio of 72:28. To clarify such diastereoselectivity, we need to further investigate the detail of the reaction processes.
Figure 5. The UB3LYP+D3 optimized eight final products structures of [3+2] cycloaddition. Also shown are the relevant bond lengths (in angstrom).
Potential Energy Surfaces of Cu(OTf)2 Catalyzed Reactions
Basically, there are two possible mechanisms for the cycloaddition reactions: the concerted mechanism and the stepwise mechanism. In the present case, the concerted mechanism means the C­C and C­N bond form at nearly the same time while the stepwise mechanism means the C­C or C­N bond forms first while another bond forms from the resulted intermediate. To elucidate the exact mechanism of the cycloaddition, we have tried to locate all possible transition states and intermediates. However, all our attempts that try to locate the intermediates in the stepwise mechanism failed and only one transition state structure is located for each initial structure. These results indicate that the [3+2] reactions follow a concerted mechanism. All possible reaction paths and relevant transition state structures are summarized in Figure 6.