Synthesis of a BC-Dihydrodipyrrin Building Block of Bacteriochlorophyll a

A strategy for the synthesis of bacteriochlorophyll a relies on joining AD and BC halves that contain the requisitestereochemicalconfigurations of the target macrocycle. The BC half (1) is a dihydrodipyrrin bearing a dimethoxymethyl group at the 1-position,a & beta;-ketoester at the 8-position, and (R)-2-methyland (R)-3-ethyl substituents in the pyrroline ring.An established route to AD-dihydrodipyrrins (Pd-mediated couplingof a 2-halopyrrole with a chiral 4-pentynoic acid followed by Petasismethenylation, acidic hydrolysis, Paal-Knorr ring closure,and Riley oxidation) proved to be unviable for BC-dihydrodipyrrinsgiven the presence of the & beta;-ketoester unit. A route presentedhere entails Pd-mediated coupling of a 2-halopyrrole (2) with (3R,4R)-4-ethyl-1,1-dimethoxy-3-methylhex-5-yn-2-one(3), anti-Markovnikov hydration of the alkyne to givethe 1,4-diketone, and Paal-Knorr ring closure. Compound 3 was prepared by Schreiber-modified Nicholas reaction beginningwith (S)-4-isopropyl-3-propionyloxazolidin-2-oneand the hexacarbonyldicobalt complex of (& PLUSMN;) 3-methoxy-1-(trimethylsilyl)pentynefollowed by transformation of the aldehyde derived therefrom to the1,1-dimethoxymethylcarbonyl motif. The absolute stereochemical configurationof the Schreiber-Nicholas alkylation product was confirmedby single-crystal X-ray diffraction, whereas the BC half (1) by H-1 NMR spectroscopy showed a J valueof 2.9 Hz consistent with the trans-configuration.Taken together, the route provides a key chiral building block forthe synthesis of photosynthetic tetrapyrroles and analogues.