An established route to the bacteriochlorophyll skeleton from two dihydrodipyrrin halves has been extended to accommodate several substituents characteristic of the native bacteriochlorophyll a.

Native chlorophylls and bacteriochlorophylls share a common trans-substituted pyrroline ring D (17-propionic acid, 18-methyl), whereas diversity occurs in ring A particularly at the 3-position. Two dihydrodipyrrins equipped with native-like D-ring substituents and tailorable A-ring substituents have been synthesized. The synthesis relies on a Schreiber-modified Nicholas reaction to construct the stereochemically defined precursor to ring D, a dialkyl-substituted pent-4-ynoic acid. The carboxylic acid group of the intact propionic acid proved unworkable, whereupon protected propionate (−CO2 tBu) and several latent propyl ethers were examined. The tert-butyldiphenylsilyl-protected propanol substituent proved satisfactory for reaction of the chiral N-acylated oxazolidinone, affording (2S,3S)-2-(3-((tert-butyldiphenylsilyl)­oxy)­propyl)-3-methylpent-4-ynoic acid in ∼30% yield over 8 steps. Two variants for ring A, 2-tert-butoxycarbonyl-3-Br/H-5-iodo-4-methylpyrrole, were prepared via the Barton–Zard route. Dihydrodipyrrin formation from the pyrrole and pentynoic acid entailed Jacobi Pd-mediated lactone formation, Petasis methenylation, and Paal–Knorr-type pyrroline formation. The two AD-dihydrodipyrrins bear the D-ring methyl and protected propanol groups with a stereochemical configuration identical to that of native (bacterio)­chlorophylls, and a bromine or no substitution in ring A corresponding to the 3-position of (bacterio)­chlorophylls. The analogous β-position of a lactone–pyrrole intermediate on the path to the dihydrodipyrrin also was successfully brominated, opening opportunities for late-stage diversification in the synthesis of (bacterio)­chlorophylls.

Challenges to the de novo synthesis of bacteriochlorophyll a (BChl a ), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the trans-dialkyl substituents in both pyrroline rings (B and D). A known route to a model bacteriochlorophyll with a gem-dimethyl group in each pyrroline ring has been probed for utility in the synthesis of BChl a by preparation of a hybrid macrocycle (BC-1), which contains a trans-dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2S,3S)-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the trans-dialkyl-substituted AD dihydrodipyrrin. Knoevenagel condensation of the latter and a gem-dimethyl, β-ketoester-substituted BC dihydrodipyrrin afforded the enone (E, 70%; Z, 3%); subsequent double-ring cyclization of the E-enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave BC-1 (53% yield) along with a trace of chlorin byproduct (1.4% relative to BC-1 upon fluorescence assay). BC-1 exhibited the desired trans-dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 132-carbomethoxy substituent. The strategy wherein trans-dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.

N‐heterocyclic carbenes (NHCs) have emerged as catalysts for the construction of C−C bonds in the synthesis of substituted ketones under single‐electron processes. Despite these recent reports, there still remains a need to increase the utility and practicality of these reactions by exploring new radical coupling partners. Herein, we report the synthesis of γ‐aryloxyketones via combined NHC/photoredox catalysis. In this reaction, an α‐aryloxymethyl radical is generated via oxidation of an aryloxymethyl potassium trifluoroborate salt, which is then added into styrene derivatives to provide a stabilized benzylic radical. Subsequent radical‐radical coupling reaction with an azolium radical affords the γ‐aryloxy ketone products.

Eleven bacteriochlorins have been prepared for surface attachment, bioconjugation, water-solubilization, vibrational studies, and elaboration into multichromophore arrays.