Visible Light‐Mediated Synthesis of Enantiopure γ‐Cyclobutane Amino and 3‐(Aminomethyl)‐5‐phenylpentanoic Acids

Abstract

AbstractA visible light‐mediated [2+2] photocycloaddition of amide‐linked dienes using [Ir(dtb‐bpy)(dF(CF3)ppy)2]PF6 as triplet sensitizer was applied to generate a variety of N‐tert‐butyl, N‐benzyl‐ and N‐tert‐butoxycarbonyl‐protected 3‐azabicyclo[3.2.0]heptan‐2‐ones in good yields and with good diastereoselectivity. Density functional theory calculations shed light on the conformational prerequisites for the [2+2] photocycloaddition. The bicyclic key structures could be readily transformed into γ‐cyclobutane amino acids.For the obtained racemic 3‐phenyl‐2‐aminocyclobutane‐1‐carboxylic acid the resolution with chiral oxazolidin‐2‐one is demonstrated to allow access to both enantiomers. Alternatively, a chiral auxiliary approach led as well to the enantiomerically pure target compound. Finally, the synthesis of either enantiomer of 3‐(aminomethyl)‐5‐phenylpentanoic acid, the racemate being described as an anticonvulsant, is described.magnified image