Visible-Light-Driven Synthesis of Bicyclo[2.1.1]hexanes

Visible-Light-Driven Synthesis of Bicyclo[2.1.1]hexanes

Author: ChemistryViews

In pharmaceutical chemistry, bicyclo[2.2.1]hexanes can serve as useful building blocks and, e.g., serve as replacements for disubstituted benzene rings in drug candidates. 1,4-Disubstituted bicyclo[2.2.1]hexanes provide similar structural properties to meta-disubstituted benzenes in this context, but with a slightly different angle between the two substituents. This can be useful to tune the properties of a candidate compound in medicinal chemistry. This type of disubstituted bicyclo[2.2.1]hexane can be synthesized, e.g., by an intramolecular photocycloaddition (example pictured), and a general strategy for this type of reaction would be useful.

Thomas Rigotti and Thorsten Bach, Technical University of Munich, Garching, Germany, have developed a visible-light-driven, intramolecular crossed [2 + 2] photocycloaddition of 2,5-disubstituted hexa-1,5-dienes to give the desired 1,4-disubstituted bicyclo[2.1.1]hexanes. The team used a variety of 2,5-disubstituted hexa-1,5-dienes in which one substituent is an aryl group as substrates, Ir(dFCF3ppy)2(dtbbpy)PF6 (dtbbpy = 2,2′-bis(4-tert-butylpyridine), dFCF3ppy = 2-(2′,4′-difluorophenyl)-5-trifluoromethylpyridine) as a photocatalyst, and acetone as the solvent.

The reactions were performed under irradiation with 414 nm light from a high-power LED. The desired 1,4-disubstituted bicyclo[2.2.1]hexanes were obtained in good to excellent yields (up to quantitative yield). The protocol tolerates a wide range of substituents, e.g., different primary and secondary alkyl groups, aromatic units with both electron-poor and electron-donating substituents, or heteroaromatic units. The products can be further transformed, leading to a broad variety of useful building blocks for organic synthesis.


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