One-Pot Synthesis of Four Chlorin Derivatives by a Divergent Ylide

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 (TPPF) is reported, but this approach has limitations. We report the synthesis of stable chlorin scaffolds starting with TPPF 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 TPPF 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.

Synthesis of chlorins and bacteriochlorins from cycloaddition reactions with porphyrins

“…Later, the authors revisited the synthetic approach previously reported by Cavaleiro and co-workers 32 to obtain the NH-chlorin 35 from paraformaldehyde and glycine (AZ3), and an improvement of its formation by using microwave heating was reported. 57 During this endeavor, besides the expected NH-pyrrolidine, two dimers, and the same N-methyl chlorin obtained from the sarcosine ylide reaction were isolated. A mechanism based on the formation of the divergent N-(hydroxymethyl)-N-methylenemethanideaminium ylide was considered.…”

“…Structures of the cationic meso-tetrakis(pentafluorophenyl)chlorin (56) and isobacteriochlorin (57).…”

Applications of Fluorous Porphyrinoids: An Update†

“…Among these fluorous porphyrinoids, perfluorophenylporphyrin (TPPF 20 ), perfluorophthalocyanine (PcF 16 ) and perfluorophenylcorrole (CorF 15 ) are all commercially available in metallated and in their free-base forms. However, Diels-Alder and 1,3-dipolar cycloaddition reactions can be used to reduce TPPF 20 to the corresponding ChlF 20 , IbacF 20 and BacF 20 derivatives in high yields (15)(16)(17)(18). Because of their commercial availability and stability, the fluorinated porphyrinoids have become the center of attention of researchers developing advanced functional materials for applications such as sensors, photonic devices, solar cells, biomedical imaging, theranostics, catalysts, etc (10)(11)(12)(13).…”

1,3‐Dipolar Cycloadditions of Stabilized Azomethine Ylides and Electrophilic Alkenes Mediated by a Recyclable TSIL·AgOAc Catalyst

“…These features convert this cycloaddition in a very attractive subject for implementing the green chemistry concepts. The ability to run these reactions using multicomponent versions [8] and the employment of more efficient microwave-assisted heating, [9,10] were also adapted. For example, heterogeneous graphene oxide, [4] zinc oxide nanoparticles, [5] heterogeneous silver nanoparticle, [6] bentonite, [7] were used as a recyclable catalyst.…”