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

A 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 gamma-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.