Northern–Southern Route to Synthetic Bacteriochlorins

A new
route to bacteriochlorins via Northern–Southern (N-S)
self-condensation of a dihydrodipyrrin–acetal complements a
prior Eastern–Western (E-W) route. Each bacteriochlorin was
prepared in five steps from an α-halopyrrole and a 2,2-dimethylpent-4-ynoic
acid. The first three steps follow Jacobi’s synthesis of dihydrodipyrrins:
Pd-mediated coupling to form a lactone–pyrrole, Petasis reagent
treatment for methenylation, and Paal–Knorr type ring closure
to form the 1,2,2-trimethyl-substituted dihydrodipyrrin. Subsequent
steps entail conversion of the 1-methyl group to the 1-(dimethoxymethyl)
unit and acid-catalyzed self-condensation of the resulting dihydrodipyrrin–acetal.
The essential differences between the N-S and E-W routes lie in (1)
the location of the gem-dimethyl group (with respect
to the 1-acetal unit) at the 2- versus 3-position in the dihydrodipyrrin–acetals,
respectively, (2) the method of synthesis of the dihydrodipyrrins,
and consequently (3) access to diverse substituted bacteriochlorins
including those with substituents at the meso-positions. Ten new bacteriochlorins
bearing 0–6 total aryl, alkyl, and carboethoxy substituents
at the β-pyrrole and/or meso-positions have been prepared, with
yields of macrocycle formation of up to 39%. Four single-crystal X-ray
structures (two intermediates, two bacteriochlorins) were determined.
The bacteriochlorins exhibit characteristic bacteriochlorophyll-like
absorption spectra, including a Qy band
in the region 713–760 nm.