Theoretical investigations toward the tandem reactions of N-aziridinyl imine compounds forming triquinanes via trimethylenemethane diyls: mechanisms and stereoselectivity

Abstract

In this paper, we have investigated the tandem reaction mechanism for the N-aziridinyl imine compounds forming triquinanes via trimethylenemethane (TMM) diyls in detail. Based on the calculated results, the reaction is initiated by the cleavage of the N-aziridinyl in the substrate, followed by an intramolecular 1,3-dipolar (3 + 2) cycloaddition preferentially leading to a linearly-fused tetrahydrocyclopentapyrazole intermediate. Next, the intermediate loses N2 to form the singlet TMM diyl M3S, which can then undergo another concerted (3 + 2) cycloaddition to generate the linearly-fused cis–trans or cis–syn triquinane products. In addition, M3S can also undergo intersystem crossing to the triplet TMM diyl M3T, and the six possible reaction pathways associated with M3T have also been identified. The calculated results reveal that the cis–trans fused pathway associated with M3S is energetically preferred with the highest free energy barrier of 25.0 kcal mol(−1). In comparison, the cyclization of M3T requires much higher activation free energies (ΔG(≠) = 34.4–57.8 kcal mol(−1)). At the experimental temperature 110 °C, only the linearly-fused cis–trans and cis–syn pathways associated with M3T (ΔG(≠) = 34.4 and 35.5 kcal mol(−1) respectively) are possible. The calculated results also indicate that for both M3S and M3T, the linearly-fused cis–trans triquinane should be the main product, which is consistent with the experimental observation. At last, conformational and NBO analyses on key transition states identified the cis–trans stereocontrol factors. Further calculations indicate that the methyl substituent on the allene group of the reactant substrate improves the stereoselectivity of the reaction but does not affect the rate-determining step.

Thiolation of symmetrical and unsymmetrical diketopiperazines

“…DKP 23 was obtained through dimerization of amino acid 22, which was prepared in 4 steps according to the literature. 20 Its thiolation result proves the compatibility of the presented method with pyrroloindole units which can be found in many natural products. 21 It can furthermore be seen as another example for the selective preparation of monomethylthio-DKPs.…”

Unexpected Selectivity of Intramolecular [3+2] Cycloaddition of Trimethylenemethane (TMM) Diyl toward Total Synthesis of Conidiogenone B

“…At this point, as we verified that the frontier molecular orbital (FMO) consideration cannot account for other factors than electronic factors on olefins and TMM diyls, it would be valuable to have more elaborate means that could explain the outcome of the cycloaddition reaction and could be capable of predicting selectivity of the reaction. Therefore, we calculated the actual cycloaddition barriers of singlet TMM diyls, and compare the barriers with the corresponding regioselectivity outcomes. Gibbs‐free energy barriers (Δ G sol ‡ ) of singlet cycloadditions are calculated to include entropy, zero‐point energy, and solvation corrections as well as the steric influence (Table ).…”

Organocatalysts Derived from Unnatural α‐Amino Acids: Scope and Applications

“…Bicyclic organocatalyst 206 did not prove to be efficient in Michael reactions. However, its tricyclic analogue, 210 , gave excellent results in the conjugate addition of aldehydes 211 to nitroalkenes 25 , both in terms of chemical yield and stereocontrol (Scheme ) …”