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

2017-02-22T14:05:12Z (GMT) by Shaofei Zhang Jonathan S. Lindsey
Bacteriochlorophylls contain a bacteriochlorin macrocycle bearing an annulated fifth ring. The fifth ring, termed the isocyclic ring or ring E, is equipped with 13<sup>1</sup>-oxo and 13<sup>2</sup>-carbomethoxy substituents. Herein, a general route to stable, synthetic bacteriochlorophyll analogues is described. Knoevenagel condensation (∼40 mM, rt, CH<sub>2</sub>Cl<sub>2</sub>, piperidine/AcOH/molecular sieves) of a dihydrodipyrrin–carboxaldehyde (AD half) and a dihydrodipyrrin substituted with a β-ketoester (BC half) forms a propenone bearing the two halves (a hydrobilin analogue). Subsequent treatment (0.2 mM) with acid (Yb­(OTf)<sub>3</sub>, CH<sub>3</sub>CN, 80 °C) promotes a double ring-closure process: (i) condensation between the α-position of pyrrole ring A and the α-acetal unit attached to pyrroline ring B forms the bacteriochlorin macrocycle, and (ii) Nazarov cyclization of the β-(propenoyl)-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 (β-pyrrole sites, ring A) and 13<sup>2</sup> 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).