One-Pot Synthesis of Four Chlorin Derivatives by a Divergent Ylide. Academic Article uri icon

abstract

  • Chlorins have unique photophysical properties that are exploited in diverse biological and materials applications. De novo chlorin synthesis with specific exocyclic motifs can be challenging and many are not stable to photobleaching and/or oxidation. A facile approach to a stable synthetic chlorin with a fused N-methyl pyrrolidine uses cyclo addition of a sarcosine-based azomethine ylide on 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)-porphyrin (TPPF20) is reported, but this approach has limitations. We report the synthesis of stable chlorin scaffolds starting with TPPF20 using a new glycine-based N-(hydroxymethyl)- N-methelenemethanideaminium ylide. Careful control of the 1,3-dipolar cycloaddition reaction allows a divergent use of the glycine derived ylide to yield four new chlorins, including the fused NH-pyrrolidine, two dimers, and the same N-methyl chlorin product from the sarcosine ylide reaction. The mechanism begins with the formation of a bis(hydroxymethyl)glycine, which then dehydrates and decarboxylates to form the active N-(hydroxymethyl)- N-methelenemethanideaminium ylide, which then reacts with TPPF20 to form a key N-(hydroxymethyl)-17,18-pyrrolidinyl-chlorin intermediate. Deformylation of this intermediate affords the (17,18-pyrrolidinyl)-chlorin, whereas a Cannizzaro-type reaction promotes a hydride attack to an imine chlorin cation to yield the N-methyl chlorin. The exocyclic NH-pyrrolidine provides a unique mode of attaching chiral moieties that avoids formation of diasteromers at the bridgehead carbons.

published proceedings

  • J Org Chem

altmetric score

  • 1

author list (cited authors)

  • Gonzales, J., Bhupathiraju, N., Hart, D., Yuen, M., Sifuentes, M. P., Samarxhiu, B., ... Drain, C. M.

citation count

  • 6

complete list of authors

  • Gonzales, Junior||Bhupathiraju, NVS Dinesh K||Hart, Daniel||Yuen, Man||Sifuentes, Maria Pia||Samarxhiu, Bleron||Maranan, Mark||Berisha, Naxhije||Batteas, James||Drain, Charles Michael

publication date

  • June 2018