Synthesis of Functionalized Aromatic Oligomers from a Versatile Diphenylmethane Template

• Published in: Journal of organic chemistry Vol. 62; no. 15; pp. 5174 - 5190
• Main Authors: Bruno, J. G, Chang, M. N, Choi-Sledeski, Y. M, Green, D. M, McGarry, D. G, Regan, J. R, Volz, F. A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.07.1997; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; AURINTRICARBOXYLIC ACID; LIBRARIES; TRANSFORMATION; PEPTIDES; SOLID-PHASE SYNTHESIS; POLYAROMATIC ANIONIC COMPOUNDS; DRUG DISCOVERY; INHIBITORS; HEPARIN; BINDING
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo970596h

An efficient synthesis of the functionalized diphenylmethane system 1 is described. Selective unmasking of the latent phenol groups on 1 allowed the introduction of various appendages onto the diphenylmethane scaffold via simple alkylation, Mitsunobu etherification, and transition-metal-mediated C−C bond formation. Conversion of 1 to iodide 18 and benzylic zinc reagent 28 followed by palladium(0)-mediated coupling of these derivatives provided homologue 29. Repetitive application of this homologation protocol was used to prepare oligomers of chain length up to 16. Several examples of functional group manipulations on these higher order oligomers are presented. Diphenylmethane 1 was also employed as a key building block in the synthesis of the elastase inhibitor 67. The potential application of extended aromatic oligomers to the field of drug discovery is discussed.