[2+2] Cycloadditions to Access sp³-Rich Spirocycles

Key words

sp³-rich - spirocylces - [2+2] cycloaddition - photocatalysis - polycyclic alkaloids - energy transfer (EnT)

Significance

sp³-Rich chemotypes are becoming of greater importance in developing new molecular entities, improving structural novelty and physicochemical properties of the molecule. The Vassilikogiannakis group has developed a series of elegant photocatalyzed mediated cyclizations to obtain complex cyclobutane, spirocyclic lactams systems. These molecular frameworks are accessed through intramolecular [2+2] photocycloaddition to give compounds 1, or alternatively, intermolecular [2+2] delivers compound class 2. The latter series can be further elaborated, as showcased by a formic acid induced retro-Mannich reaction followed by intramolecular regiospecific Friedel–Crafts cyclization to form aromatic compounds such as 3b.

 

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Comment

Inspired by previous findings that γ-lactams could isomerize substantially when irritated with blue light in the presence of Ru(bpy₃]Cl, this energy transfer reaction (EnT) was harnessed to facilitate [2+2] cycloadditions. An optimal catalyst Ir(ppy)₃ was identified and used throughout. When R¹ = allyl, irradiation with blue light in MeCN (0.1 M) gave intermolecularly derived compounds 2a–e in high yields. Compounds 3 were obtained by first benzylating the lactam nitrogen, followed by intermolecular reaction with α,β-unsaturated esters, ketones, and aldehydes to give 3a–e in high yields. Although examples regarding the reaction scope are limited, this methodology is highly effective to deliver complex and unique sp³-rich molecules.

 

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Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2023