Unusually Chemoselective Photocyclization of 2-(Hydroxyimino)aldehydes to Cyclobutanol Oximes: Synthetic, Stereochemical, and Mechanistic Aspects

Abstract

Photocyclization of carbonyl compounds (known as the Norrish−Yang reaction) to yield cyclobutanols is, in general, accompanied by fragmentation reactions. The latter are predominant in the case of aldehydes so that secondary cyclobutanols are not considered accessible via the straightforward Norrish−Yang reaction. A noteworthy exception has been reported in our laboratory, where cyclobutanols bearing a secondary alcohol function were observed upon UV light irradiation of 2-(hydroxyimino)aldehydes (HIAs). This reaction is here investigated in detail by combining synthesis, spectroscopic data, molecular dynamics, and DFT calculations. The synthetic methodology is generally applicable to a series of HIAs, affording the corresponding cyclobutanol oximes (CBOs) chemoselectively (i.e., without sizable fragmentation side-reactions), diastereoselectively (up to >99:1), and in good to excellent yields (up to 95%). CBO oxime ether derivatives can be purified and diastereomers isolated by standard column chromatography. The mechanistic and stereochemical picture of this photocyclization reaction, as well as of the postcyclization E/Z isomerization of the oxime double bond is completed.

Catalyst-Free Photoinduced C–C Bond Formations

“…81 Gentili and co-workers demonstrated a diastereoselective Norrish-Yang cyclization of 2-(hydroxyimino)aldehydes 32a to afford cyclobutanol oximes 32b without giving any traditional fragmentation product upon irradiation of 365 nm UV-LED (Scheme 32). 82 This efficient stratigy offered a libray of cyclobutanol oximes without the use of any photosensitizer in short reaction time. Broad class of functional group tolerance including both aliphatic and aromatic was observed with excellent chemoselectivity and diastereoselectivity.…”