Page 112 - Read Online

Wang et al. Chem Synth 2023;3:12 https://dx.doi.org/10.20517/cs.2023.01 Page 5 of 20

Figure 4. Proposed mechanism for chiral phosphoric acid catalyzed asymmetric N-H bond insertion reaction by α-carbonyl sulfonium
[43]
ylides. This figure is used with permission from the American Chemical Society .

Figure 5. Chiral 2-carboxylic acid dihydroindole catalyzed enantioselective cyclopropanations of α,β-unsaturated aldehydes. This figure
is used with permission from the American Chemical Society [44] .

this report, the authors proposed a directed electrostatic activation (DEA) mechanism, in which the
negative carboxylate group interacts with the positive thionium moiety, thus reducing the activation energy
and increasing the reaction rate. However, Mayr disapproved of some MacMillan’s conclusions, but
accepted the DEA mechanism as a justification for the experimental high reaction rates . On the base of
[45]
former research on this aspect, Santos and coworkers demonstrated that the cyclopropanation reaction
occurs through a two-step mechanism and that the overall enantioselectivity relies on the relative energies
of the two steps by taking advantage of computational study .
[46]

In 2007, Hartikka et al. also described the enantioselective cyclopropanation of α,β-unsaturated aldehydes
with sulfonium ylides by using newly developed chiral amine catalysts [Figure 6] [47,48] . With the tetrazolic
acid functionalized dihydroindol C6 as the catalyst, chiral cyclopropanes 10 could be obtained in 99% ee for
[29]
the seven examples . In the presence of C7 or C8, the reactions gave the products with moderate yields
[30]
with good to excellent diastereo- and enantioselectivities . In their work, it was demonstrated that the
larger steric bulk catalysts could increase enantioselective induction, thus leading to better
enantioselectivities compared with the results obtained in Kunz and MacMillan’s work .
[44]