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Wang et al. Chem Synth 2023;3:12 https://dx.doi.org/10.20517/cs.2023.01 Page 11 of 20

Figure 13. Chiral thiourea catalyzed enantioselective S-H insertion reactions of α-carbonyl sulfoxonium ylides to aryl thiols. This figure is
[69]
used with permission from the Wiley-VCH Verlag .

enantioselectivities ranging between 40%-84% ee [Figure 14] . A mechanism proposal was also proposed.
[72]
At first, the nucleophilic attack of sulfoxonium ylide 50 to copper complex generates copper carbene
intermediate 55, which could transform into ammonium ylide intermediate 56 by the attack of aniline 2.
And then, the intermediate 56 tautomerizes to the enol intermediate 57, which readily interacts with
copper-chiral squaramide complex through hydrogen bond to form transition state 58. Finally, under
asymmetric induction, protonation of the enol intermediate 57 leads to the formation of enantioenriched
N-H insertion products α-aryl glycine esters 5.

Almost at the same time, Guo et al. also reported a chiral phosphoric acid-catalyzed asymmetric N-H
[73]
insertion reaction of aryl amines 2 with α-carbonyl sulfoxonium ylides 50 [Figure 15] . With bulky chiral
phosphoric acid C2 as the catalyst, a wide range of α-aryl glycines were obtained in generally excellent yields
and enantiomeric excesses (34%-99% yield and 57%-97% ee). In the proposed mechanism, the weak basicity
of sulfoxonium ylides could cause the interaction with chiral phosphoric acid C2 to form the ion pair
intermediates 59 and 59', which undergo nucleophilic attack by the aryl amines 2, thus leading to the
formation of α-aryl glycine esters 5. After detailed mechanistic studies, the authors think that the
protonation of 50 favors the formation of intermediates 59 and 59'. Due to reversiblity of this step, the chiral
phosphate anion can control the stereochemistry in the C-N bond formation via dynamic kinetic
resolution. The C-N bond formation is also rate-determining step.

Although that catalytic asymmetric insertion reaction of metal carbenes into N-H bond with the
enantioselective control via metal-chiral metal interaction has been well-established [74,75] , the asymmetric
insertion reaction of free carbenes into N-H bond faces a challenge due to strong background reactions and
lack of any anchor for a catalyst interaction. Recently, Guo et al. made progress in the catalytic
enantioselective insertion reaction of free carbenes into N-H bond using an indirect approach . In their
[76]
developed protocol [Figure 16], with visible light as a promoter, the -diazoesters 60 could be converted to
free carbene intermediate 61, which was captured rapidly by DMSO to in situ form sulfoxonium ylide 50.
And then, chiral phosphoric acid catalyst C2 protonated ylide 50 to generate diastereomeric intermediates
62 and 62'. Ultimately, under the control of a chiral catalyst, the amine reactants 2 reacted preferentially
with one of the intermediates 62 and 62' to deliver a range of optically pure α-aminoesters with high
efficiency (45%-97% yield) and good enantioselectivity (67%-85% ee) through a dynamic kinetic resolution