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Page 10 of 54 Yang et al. Chem Synth 2023;3:7 https://dx.doi.org/10.20517/cs.2022.38

Scheme 9. Organocascade double Michael addition of benzolactone-derived olefins 1 and α, β-unsaturated ketones19. This figure is
used with permission from the Royal Society of Chemistry [50] .

[52]
By combining cycloisomerization with trienamine catalysis, in 2016, Chintalapudi et al. reported the
enantioselective trienamine-organocatalyzed cycloadditions of pyrrolidinyl dienals, prepared by palladium-
catalyzed cycloisomerization, successfully delivered two spiro[benzolactone-hexahydroindole] cycloadducts
in high enantioselectivity with no preference of endo/exo selectivity.

The development of an efficient and straightforward methodology and enhancement of the structural
diversity of these sulfur-containing 3,3’-pyrrolidonyl spirobenzolactones may have a promising impact on
the physicochemical and biological characteristics of target molecules.

In this context, an efficient organocatalyzed asymmetric sequential Michael/cyclization of α-isothiocyanato
[53]
imide 24 with benzothiolactone 1 under mild conditions was reported by Cao et al. . However, only two
sulfur-containing 3,3’-pyrrolidonyl spirobenzolactones 25 and 26 were reported . Notably, when the
[53]
oxygen atom of benzolactone-derived olefin 1 was replaced by sulfur, the enantioselective
Michael/Cyclization reaction of thiobenzolactone-derived olefin 1 with α-isothiocyanato imide 24 also
proceeded smoothly, which provided the spirothiobenzolactone skeleton 26 with greater than 99% ee and
moderate distereoselectivity [Scheme 11].

α, β-Unsaturated butyrolactones/valerolactones as 2C synthons
The scaffold-inspired compounds encouraged us further to build a library of molecular complexity around
the biologically relevant framework for further biological evaluation. The prevalent spiro