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Page 42 of 54 Yang et al. Chem Synth 2023;3:7 https://dx.doi.org/10.20517/cs.2022.38

Scheme 56. Spirolactonization reaction of isatins 106 with olefinic azlactones 113. This figure is used with permission from the Royal
[132]
Society of Chemistry .
In the proposed reaction mechanism, the C25-catalyzed 96-oxidized activation of the Csp of α-
3
methylindole-3-carboxaldehydes 117 to give ortho-quinodimethane intermediates, which undergoes formal
[4 + 2] cycloaddition with an isatin 106 to give a spirocyclic oxindole-pentenelactone 118 [Scheme 58]. Both
the pre-catalyst C25 and oxidizer 96 play a critical role in the activation of the 117.

Recently, pyrazoleamides have been used as special donors in enantioselective Mannich and Michael
reactions. In these reactions, the versatile pyrazoleamide functions as an activating group, a directing group
for enhancing stereocontrol, as well as a good leaving group for subsequent transformations.

In 2014, the synthesis of optically active spirocyclic oxindole-pentenelactones 120 was reported by Li
[135]
et al. via the enantioselective vinylogous aldol-cyclization cascade reaction of allyl pyrazoleamides 119
with isatins 106 in the presence of Takemoto catalyst C29 in acetonitrile at ambient temperature. Various
spirocyclic products 120 were obtained in excellent yields (93%-99%) and enantioselectivities (82%-97% ee).
It is worth mentioning that the protection of the nitrogen atom in the indole ring is not necessary, although
the yield and enantioselectivity of the product 120d are relatively lower. Thus, the reported method
establishes a new protocol for the asymmetric construction of structurally novel spirocyclic oxindole-
pentenelactones 120 employing β, γ-unsaturated aldehyde derivatives [Scheme 59].

Recently, Zhang et al. reported a series of NHCs derived from L-pyroglutamic acid. Due to the high
[136]
enantioselectivity of L-pyroglutamic acid NHCs, in 2011, further exploration of the chiral NHCs catalyzed
enantioselective umpolung reactions of enals 121 was performed.

It was found that the proximal hydroxyl group of L-pyroglutamic acid C31 was an efficient catalyst for the
activation of isatins 106 by the formation of intermolecular hydrogen bonds between the two geminal
carbonyl groups. It also plays a role in directing the addition of the homoenolate to the carbonyl group of
isatin 106. Thus, followed by the [3 + 2] annulation of enals 121 and activated isatins 106, the corresponding