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Wang et al. Chem Synth 2023;3:12 https://dx.doi.org/10.20517/cs.2023.01 Page 13 of 20

process. Moreover, the authors declared that the key to the success of the method lay in the formation of
sulfoxonium ylide by the additive DMSO capturing the free carbene intermediate.

Almost immediately, the same group also discovered an efficient organocatalytic formal N-H insertion
reaction of α-keto sulfoxonium ylides 50 bearing two aryl groups and arylamines 2 using chiral phosphoric
acid C14 as catalyst [Figure 17] . With the developed protocol, a broad range of α-tertiary aminoketones 5
[77]
could be smoothly obtained in good to excellent yields (up to 90%) and ee values (up to 94%). Their
mechanistic study supported that the C-N bond formation via dynamic kinetic resolution is not only the
rate-determining step but also the enantio-determining step. In addition, the synthetic utility of the method
was also demonstrated by the preparation of 2-amino-1,2-diphenylethanol 63 in 65% yield with 81% ee
through a two-step transformation from 5a. More delightfully, enantiopure 63 could be readily obtained by
single recrystallization in 60% yield.

Very recently, Guo et al. discovered an organocatalytic asymmetric azidation of α-carbonyl sulfoxonium
[78]
ylides through a H-N insertion process [Figure 18] . In the developed method, with the in situ formed H
3
N as nitrogen source and a superb chiral squaramide C15 as the catalyst, a series of α-carbonyl sulfoxonium
3
ylides 50 could be smoothly converted into optically active α-azido ketones 65 in 46%-96% yield with 67%-
96% ee. In the proposed mechanism, the catalyst C15 with the double N-H motifs activates sulfoxonium
ylides 50, giving intermediate 66. And then, the in situ generated HN promotes the protonation of
3
intermediate 66 to form ion pair intermediate 67 as diastereomeric mixture, in which the azide anion also
interacts with the squaramide catalyst through hydrogen bond. Notably, the reversible protonation process
in the 66 to 67 step allows (R)-67 and (S)-67 to rapidly equilibrate with each other, resulting in the
epimerization of the stereogenic center. Finally, the enantioenriched (S)-65 could be preferentially generated
by the azide substitution via dynamic kinetic resolution process under the stereoselective control of chiral
squaramide catalyst C15.

After the catalytic asymmetric S-H, N-H insertion reaction of sulfoxonium ylides, Leveille et al. recently
reported the first organocatalytic enantioselective C-H insertion reaction of sulfoxonium ylides to indoles
[79]
with chiral phosphoric acid as the catalyst 2021 [Figure 19] . The authors investigated 29 examples using α-
carbonyl sulfoxonium ylides insertion into C-H bond of free indoles, obtaining moderate yields (ranging
from 12% to 50%) with 20%-93% ee values. A proposed pathway for the C-H insertion reaction was also
introduced. Initially, chiral phosphoric acid C16 protonates the α-carbonyl sulfoxonium ylides 50 to form
an ion pair intermediate 70. And then, the indole partners attack the intermediate 70 via a substitution
reaction under the enantioselective induction of chiral phosphoric acid catalyst to give rise to the chiral
product 69, simultaneously reprotonation of catalyst ion to release C15 into the next cycle. Notably, the N-
H moiety of indole 68 is crucial to enantioselectivity in this transformation. The reaction involving N-Me
indole proceeded smoothly to furnish product 69d in 35% yield, but essentially no enantiomeric excess was
observed.

Asymmetric cyclization reaction of sulfoxonium ylides
Similarly to sulfonium ylides, in addition to the participation in the above-mentioned catalytic asymmetric
X-H (X = S, N, C) bond insertion reactions, sulfoxonium ylides can also be employed as nucleophilic 1C
synthons for the cyclization reaction to access cyclic compounds. However, the asymmetric cyclization
reaction involving sulfoxonium ylides by means of an organocatalysis tactic is rarely studied. Until recently,
Bernardi, Fochi, and coworkers reported the first organocatalytic tandem cyclopropanation/
hemiaminalization reaction between 2’-hydroxycinnamaldehydes 72 and stabilized α-carbonyl sulfoxonium
ylides 50 by using Jørgensen-Hayashi catalyst C17, providing cyclopropane-fused chromane derivatives 74