Study of conditions for streamlined assembly of a model bacteriochlorophyll from two dihydrodipyrrin halves

• Published in: New journal of chemistry Vol. 45; no. 2; pp. 569 - 581
• Main Authors: Nguyen, Khiem Chau, Wang, Pengzhi, Lindsey, Jonathan S
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 18.01.2021; Royal Society of Chemistry
• Subjects: Acetic acid; Acetonitrile; Acids; Byproducts; Chemistry; Chemistry, Multidisciplinary; Chromophores; Closures; NMR; Nuclear magnetic resonance; Photosynthesis; Physical Sciences; Piperidine; Room temperature; Science & Technology; Substitution reactions; MAGNESIUM; ACID CATALYSTS; KNOEVENAGEL; LIGANDS; DE-NOVO SYNTHESIS; CATALYTIC NAZAROV CYCLIZATION; YTTERBIUM TRIFLATE; CHLOROPHYLL SERIES; DERIVATIVES; PRINCIPLES
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d0nj04855k

A long-term goal is to gain synthetic access to native photosynthetic bacteriochlorophylls. A recently developed route entails Knoevenagel condensation of an AD dihydrodipyrrin ( I , bearing a carboxaldehyde attached to pyrroline ring D) and a BC dihydrodipyrrin ( II , bearing a β-ketoester attached to pyrrole ring C) to form the Z / E -enone. Acid-mediated double-ring closure of the E -enone III- E (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol) affords the bacteriochlorophyll skeleton BC-1 containing the isocyclic ring (ring E), a trans -dialkyl group in ring D, and a gem-dimethyl group in ring B. Prior work established the synthesis and the integrity of the resulting trans -dialkyl groups and bacteriochlorin chromophore. The counterpart report here concerns an in-depth study of conditions for the double-ring closure: catalyst/solvent surveys; grid search including time courses of [ III- E ] versus [acid] concentrations emphasizing equimolar, inverse molar, and variable acid lines of inquiry; and chlorin byproduct quantitation. Key findings are that (1) the double-ring closure can be carried out in 4 h ( t 1/2 ∼ 40 min) instead of 20 h, affording ∼1/5th the chlorin byproduct (0.16%) while maintaining the yield of BC-1 (up to 77%); (2) the separate Z / E -enones of III have comparable reactivity; (3) sub-stoichiometric quantities of acid are ineffective; (4) the Knoevenagel condensation (40 mM, room temperature, piperidine/acetic acid in acetonitrile) and the acid-mediated double-ring closure (0.20 mM, 80 °C, Yb(OTf) 3 in acetonitrile) can be carried out in a two-step process; and (5) zinc insertion to form ZnBC-1 is straightforward. Together, the results enable streamlined conversion of dihydrodipyrrin reactants to the bacteriochlorophyll model compounds. Knoevenagel condensation followed by double-ring closure (Nazarov cyclization, electrophilic aromatic substitution, elimination of methanol) and optional zinc insertion smoothly afford models of the native bacteriochlorophylls.