Page 113 - Read Online

Page 6 of 20 Wang et al. Chem Synth 2023;3:12 https://dx.doi.org/10.20517/cs.2023.01

Figure 6. Chiral dihydroindole derived amines catalyzed enantioselective cyclopropanation of α,β-unsaturated aldehydes. This figure is
used with permission from the American Chemical Society [47] and Elsevier Ltd [48] .

In the area of asymmetric organocatalysis, asymmetric hydrogen-bonding catalysis, which takes advantage
of the hydrogen bonding interactions between the chiral catalysts and reactants to promote organic
transformation and concurrently induce the stereoselectivity through lowering the LUMO of electrophiles,
occupies a very important position [49-51] . In 2011, Cheng et al. employed C -symmetric urea as a hydrogen-
2
bond catalyst for the asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters 15 with stabilized
sulfonium ylides 1, providing a series of optically pure 1,2,3-trisubstituted cyclopropane derivatives 16 in
[52] 1
moderate to good yields, diastereoselectivities, and enantioselectivities [Figure 7] . H NMR spectroscopic
studies were conducted to demonstrate that the existence of H-bond interaction between C -symmetric urea
2
C9 and sulfonium ylide 1 could form complex 17. In the proposed pathway, complex 17 incorporates with β,
γ-unsaturated α-ketoester 15 to form transition state 18. Then sulfonium ylide attacks the γ-position of
ketoester to generate intermediate 19. Finally, intermediate 19 undergoes an intramolecular nucleophilic
substitution reaction to give intermediate 20 that delivers corresponding chiral cyclopropane derivatives 16
and releases the hydrogen-bond urea catalyst for the next catalytic cycle.

Until 2013, organocatalyzed asymmetric cyclopropanation of α,β-unsaturated ketone substrates with
stabilized sulfonium ylides was reported by Wang et al.[Figure 8] . In the developed method, the primary
[53]
amine part of chiral diamine catalyst C10 combines with α,β-unsaturated ketones 21 to form the iminium
ion intermediates 23. Simultaneously, the secondary amine moiety of C10 incorporates with sulfonium
ylides 1 through H-bond interaction. Then a Michael addition reaction is then performed from sulfonium
ylides 1 to the Si face of iminium ion moiety, leading to the formation of intermediates 25. Subsequently, an
intramolecular cyclization generates the desired cyclopropanation adducts 22 and releases the catalyst into
the nest cycle.

Organocatalyzed asymmetric [4 + 1] cyclization reactions
There have been many reports on catalytic asymmetric [4 + 1] cyclization of sulfonium ylides for the
construction of diverse five-membered cycles by using sulfide-centric catalysis, transition-metal catalysis,
and organocatalysis. In particular, the organocatalysis strategy in this research area has gained increasing
interest from the synthetic community due to its sustainable and green features.