| Abstract
| - Chlorin building blocks incorporating a geminal dimethyl group in the reduced ring and synthetichandles in specific patterns at the perimeter of the macrocycle are expected to have utility inbiomimetic and materials chemistry. A prior route employed condensation of a dihydrodipyrrin(Western half) and a bromodipyrromethane-monocarbinol (Eastern half), followed by oxidativecyclization of the putative dihydrobilene-a to form the meso-substituted zinc chlorin in yields of∼10%. The limited stability of the dihydrodipyrrin precluded study of the chlorin-forming process.We now have refined this methodology. A tetrahydrodipyrrin Western half (2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin) has been synthesized and found to be quite stable. The condensation ofthe Western half and an Eastern half (100 mM each) proceeded smoothly in CH3CN containing100 mM TFA at room temperature for 30 min. The resulting linear tetrapyrrole, a 2,3,4,5-tetrahydrobilene-a, also is quite stable, enabling study of the conversion to chlorin. Refinedconditions for the oxidative cyclization were found to include the following: the tetrahydrobilene-a(10 mM), AgTf (3−5 molar equiv), Zn(OAc)2 (15 molar equiv), and 2,2,6,6-tetramethylpiperidine(15 molar equiv) in CH3CN at reflux exposed to air for 4−6 h, affording the zinc chlorin. The chlorin-forming process could be implemented in either a two-flask process or a one-flask process. Thetwo-flask process was applied to form six zinc chlorins bearing substituents such as pentafluorophenyl, 3,5-di-tert-butylphenyl, TMS-ethyl benzoate, iodophenyl, or ethynylphenyl (deprotectionof the TMS-ethynyl group occurred during the oxidative cyclization process). The stepwise yields(isolated) for the condensation and oxidative cyclization processes forming the tetrahydrobileneand zinc chlorin were 32−72% and 27−62%, respectively, giving overall yields of zinc chlorin fromthe Eastern and Western halves of 12−45%. Taken together, the refinements introduced enable100-mg quantities of chlorin building blocks to be prepared in a facile and rational manner.
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