Novel unsymmetrical leuco-TAM, (2E, 2′E)-2,2′-{(E)-4-phenylpent-2-ene-1,5-diylidene}bis(1,3,3-trimethylindoline) derivatives: Synthesis and structure elucidation

Novel unsymmetrical leuco-TAM, (2E, 2′E)-2,2′-{(E)-4-phenylpent-2-ene-1,5-diylidene}bis(1,3,3-trimethylindoline) derivatives were synthesized from a reaction of commercially available 2-methylene-1,3,3-trimethylindoline (FB) and substituted cinnamaldehyde derivatives. The chemical structures of the resulting molecules were determined using 1D and 2D NMR spectroscopy experiments, including COSY, HMBC and NOESY. The compounds had the EEE configuration and were potent precursors for Cy5 TAM+ dyes. This is different from the Malachite green FB-analogs, which generally have a ZE configuration and are precursors to Cy3 TAM+ dyes. The formation of unsymmetrical LTAM molecules as the sole product suggests that the Michael-type addition of a FB molecule occurs on the δ-carbon of the α, β, γ, δ-unsaturated imminium salts, which were formed as an intermediate at the first step.

Research highlights
► Unsymmetrical leuco-TAM, (2E, 2′E)-2,2′-{(E)-4-phenylpent-2-ene-1,5-diylidene}bis(1,3,3-trimethylindoline) derivatives were obtained from a reaction of FB with cinnamaldehyde derivatives.
► The unsymmetrical LTAM compounds, which were potent precursors for Cy5 TAM+ dyes, had the EEE configuration unlikely to the Malachite green FB-analogs.
► Formation of the unsymmetrical LTAM molecules suggests that the Michael-type addition of a FB molecule occurs on the δ-carbon of the α, β, γ, δ-unsaturated imminium salts.