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Page 40 of 54 Yang et al. Chem Synth 2023;3:7 https://dx.doi.org/10.20517/cs.2022.38

In recent years, due to the presence of multiple functional groups, the α, β-unsaturated butenolides have
been known as versatile candidates for the synthesis of various oxygen-containing heterocyclic
analogues [129,130] . The privileged moiety has been found in several bioactive compounds as well.

[128]
Similar to the work of Han et al. , another synthetic route toward the enantioenriched functionalized
spirocyclic oxindole-pentenelactone scaffolds 110 was reported by Wang et al. [Scheme 54] . Treatment of
[131]
α, β-unsaturated butenolides 109 with isatins 106 in the presence of Takemoto’s amine-thiourea catalyst C29
in toluene at 0 °C gave the desired spirocyclic product 110 in good to excellent yields (73%-99%) and
enantioselectivities (71%-97% ee).

A similar mechanism of the sequential vinylogous aldol reaction/ring opening and subsequent
intramolecular lactonization was proposed. It is important to mention that the intermolecular hydrogen
bonding between the C29 and two substates plays a critical role in the control of the stereoselectivity
[Scheme 54].

Moreover, in order to further expand the application of α, β-unsaturated butenolides 109 in the construction
of chiral spirocyclic pentenelactone scaffolds, the spirolactonization of α, β-unsaturated butenolides 109
with other electrophiles were also attempted. Upon using phenanthrenequinone 111 instead of isatin 106 as
an electrophile, desired products 112 and 113 were obtained in excellent yields and good selectivities. So it is
an attractive combination of pharmacologically significant phenanthrenequinone and pentenelactone units
[Scheme 55].

The hetero-Diels-Alder (HDA) reactions of the carbonyl group with α, β-unsaturated carbonyl has been
developed for the rapid generation of six-membered oxygen-containing heterocycles. Azlactones, as
versatile reactants, are great candidates for the synthesis of potentially bioactive α,α-disubstituted α-amino
acids.

In 2017, Gao et al. reported a catalytic asymmetric hetero-Diels-Alder (HDA) reaction olefinic azlactones
[132]
113 with isatins 106 in the presence of C30 in DCE at 30 °C for 48 h for the synthesis of spirocyclic product
114 [Scheme 56].

It was found that the vinylogous reactivity of azlactones 113 was realized hydrogen-bond directed activation
of both of the reaction partners via γ-addition of 113 to 106, and the desired medicinally important
spirocyclic oxindole-pentenelactone scaffolds 114 were obtained in good yields and enantioselectivity
[Scheme 56].

In recent years, the NHC-bonded intermediates’ generation and their corresponding reaction with polar
double bonds moiety of the substrates have drawn a lot of attention since a variety of highly functionalized
molecules could be easily obtained in such a simple reaction.

In 2015, using the HOBt esters of carboxylic acids and isatins as substrates, an attractive alternative NHC-
catalyzed cascade synthetic route toward the potential biological enantioenriched spirocyclic oxindole-
[133]
pentenelactone scaffolds was reported by Que et al. [Scheme 57, top] . The spirocyclic oxindole-
pentenelactones 116 were obtained in good yields with high enantioselectivity.