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Wang et al. Chem Synth 2023;3:12 https://dx.doi.org/10.20517/cs.2023.01 Page 9 of 20

Figure 11. Formal [4 + 1]/[3 + 2] cycloaddition cascade of sulfonium ylides and alkene-tethered nitroolefins. This figure is used with
permission from the Wiley-VCH Verlag [58] .

diastereocontrol, but also smoothly delivers a range of important N-containing polycyclic compounds (±)-
43 bearing five consecutive stereogenic centers in good to high yields (75%-99%) with excellent
diastereoselectivities (all cases > 95:5 dr). In the cascade process, sulfonium ylides 1 and alkene-tethered
nitroolefins 42 firstly undergo a Michael addition and cyclization to form an important intermediate 44,
which quickly converts to products 43 through an intramolecular [3 + 2] cycloaddition. In addition,
asymmetric synthesis of the polycyclic product was also investigated. Selecting chiral C -symmetric urea C9
2
as multiple hydrogen bond catalyst, the reaction proceeded smoothly and afforded chiral product 43a in
80% yield with > 95:5 dr and 80% ee.

Chiral 2,3-dihydrobenzofurans are ubiquitous and important ring structures embedded in some natural
products and synthetic drugs with diverse bioactivities. Consequently, the synthesis of structurally diverse
2,3-dihydrobenzofuran compounds via a catalytic asymmetric manner has attracted tremendous attention
from synthetic chemists [59,60] . In 2015, Lei et al. reported a facile synthesis of racemic 2,3-dihydrobenzofurans
via formal [4 + 1] cyclization of sulfonium ylides and in situ generated ortho-quinone methides (o-QMs)
from O-silylated phenols . Two years later, Yang and Xiao developed a catalytic asymmetric version of the
[61]
same reaction as reported by Sun and Xu, using the chiral C -symmetric multiple hydrogen-bonding urea
2
catalyst C9 [Figure 12] . The developed asymmetric catalytic protocol exhibits a broad substrate scope and
[62]
high functional group tolerance. A wide range of chiral 2,3-dihydrobenzofurans could be obtained in good
to excellent yields with moderate stereoselectivities. In the proposed reaction mechanism, the organocatalyst
C9 simultaneously interacts with sulfonium ylide 1 and the in situ generated ortho-quinone methide 47 by
H-bonding interactions to form complex 48. Subsequently, asymmetric Michael addition leads to the
formation of complex 49, which then undergoes an intramolecular S 2 displacement to deliver chiral 2,3-
N
dihydrobenzofuran products 46.

ORGANOCATALYTIC ASYMMETRIC REACTION OF SULFOXONIUM YLIDES
Compared to sulfonium ylides, sulfoxonium ylides contain a positively charged sulfur(VI) atom in the ylide
form or a C = S(VI) double bond in the ylene form due to the binding of one oxygen atom to the sulfur
atom. Therefore, the sulfur oxidation state would result in some differences in the property and the
reactivity for the ylides. The sulfoxonium ylides are relatively more stable and have lower nucleophilicity. In
addition, the electronegative oxygen atom readily coordinates with a chiral Lewis acid catalyst or combines
with the hydrogen bond of organocatalysts, thereby enhancing the stereoselectivity control in asymmetric
catalysis. Consequently, in the past three decades, many elegant implementations of sulfoxonium ylides in
organic synthesis have been reported by many research communities and those in the industry [17,23,24] .