Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll a

Bacteriochlorophylls contain a bacteriochlorin macrocycle bearing an annulated fifth ring. The fifth ring, termed the isocyclic ring or ring E, is equipped with 13(1)-oxo and 13(2)-carbomethoxy substituents. Herein, a general route to stable, synthetic bacteriochlorophyll analogues is described. Knoevenagel condensation (similar to 40 mM, rt, CH2Cl2, piperidine/AcOH/molecular sieves) of a dihydrodipyrrin- carboxaldehyde (AD half) and a dihydrodipyrrin substituted with a,ss-ketoester (BC half) forms a propenone bearing the two halves (a hydrobilin analogue). Subsequent treatment (0.2 mM) with acid (Yb(OTf)(3), CH3CN, 80 degrees C) promotes a double ring-closure process: (0 condensation between the alpha-position of pyrrole ring A and the a-acetal unit attached to pyrroline ring B forms the bacteriochlorin macrocycle, and (ii) Nazarov cyclization of the,ss-(propenoy1)-substituted ring C forms the isocyclic ring (E). Five new bacteriochlorins bearing various substituents (alkyl/alkyl, aryl, and alkyl/ester) at positions 2 and 3 (ss-pyrrole sites, ring A) and 132 carboalkoxy groups (R = Me or Et) were constructed in 37-61% yield from the hydrobilin analogues. The BC half and AD half are available in five and eight steps, respectively, from the corresponding pyrrole-2-carboxaldehyde and unsaturated ketone. The bacteriochlorins exhibit absorption spectra typical of bacteriopheophytins (free base bacteriochlorophylls), with a strong near-infrared absorption band (707-751 nm).