Three Complementary One-Pot Four-Component Reaction Sequences for Rapid, General and Direct Spiropyran Synthesis

Three one-pot three-step four-component reaction sequences for spiropyran synthesis have been developed, based around three different methods for in situ generation of 1,2,3-trisubstituted indoles (indole N-alkylation, Fischer indolisation and indole C-alkylation). The reaction sequences give access to a broad swathe of spiropyran structures. Each sequence is operationally straightforward, rapid and high yielding. We have synthesized 58 structurally diverse spiropyrans bearing a wide range of useful functional groups, and their utility were demonstrated in the targeted synthesis of potential ratiometric fluorescence probes for metal ions and spiropyran-cholesterol conjugates. Finally, we showed that our one-pot N-alkylation-C-alkylation-condensation sequence can underpin combinatorial spiropyran synthesis through generation of a 16-member spiropyran library.