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Page 38 of 54 Yang et al. Chem Synth 2023;3:7 https://dx.doi.org/10.20517/cs.2022.38

Scheme 50. Spirolactonization reaction of 3-hydroxyoxindoles 69 with 3-substituted saturated acid chlorides 104. This figure is used
with permission from the Royal Society of Chemistry [124] .

The spirocyclic oxindole-lactone 105 could be applied to the synthesis of the 3-hydroxy-indole natural
[125]
product maremycin B according to the literature methods [Scheme 51] .

Spirolactonization reaction of isatins
The development of efficient strategies for the stereoselective construction of highly modified heterocyclic
molecules is always a key goal in chemical synthesis. Isatins, also known as tribulin, are an important class
of heterocyclic compounds. The germinal carbonyls are as exceptional electrophiles in asymmetric catalysis.
Thus, reaction of isatins with electron-rich species via nucleophilic aldol addition followed by an
intramolecular lactonization could give the spirocyclics products [Scheme 52].

Recently, the 3-alkylidene oxindoles could act as vinylogous nucleophiles to functionalize at the γ-position
with electrophiles [126,127] . The research involving vinylogous reaction of enolates derived from 3-alkylidene
oxindole derivatives is one of the most efficient protocols in organic synthesis. Many efficient and elegant
methodologies have been created using 3-alkylidene oxindoles as nucleophiles for the direct formation of
allylic compounds, which is a key structural element in a number of natural products and synthetic
bioactive molecules.

Pentenelactone scaffolds are widely present in a number of natural and unnatural compounds which
possess potent biological activities. Oxindoles are also regarded as one of the privileged skeletons in
bioactive compounds; thus, there is an urgent need for the combination of an oxindole scaffold and a
pentenelactone motif in one molecule, which will be interesting not only to synthetic but also to medicinal
chemists.

In 2016, a direct enantioselective organocatalytic reaction of 3-alkylidene oxindoles 107 with isatins 106 in
the presence of C28 was developed by Han et al. for the synthesis of spirocyclic product 108 via vinylogous
[128]
aldol/ring opening and subsequent intramolecular lactonization [Scheme 53] .