Generation of Benzyne Species from Diphenylphosphoryl Derivatives: Simultaneous Exchange of Three Functional Groups

• Published in: Chemistry : a European journal Vol. 22; no. 25; pp. 8479 - 8482
• Main Authors: Gorobets, Evgueni, Parvez, Masood, Derksen, Darren J., Keay, Brian A.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 13.06.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Ambient temperature; Benzene Derivatives - chemical synthesis; Benzene Derivatives - chemistry; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; benzynes; Butyrates - chemical synthesis; Butyrates - chemistry; Chemistry; Chemistry, Multidisciplinary; coumarin; Coumarins - chemical synthesis; Coumarins - chemistry; Crystallography, X-Ray; Cycloaddition Reaction; decursinol; Derivatives; Dimethylformamide - chemistry; Exchange; Functional groups; Furans; Furans - chemistry; gigasol; Iodides; Methyl alcohol; Molecular Conformation; Oxides; peucedanol; Physical Sciences; Science & Technology; Sodium Compounds - chemistry; peucedanol; gigasol; coumarin; RESOLUTION; MEO-BIPHEP; ARYNES; decursinol; COUMARINS; benzynes; AMIDES
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201601370

Interaction of (2‐diphenylphosphoryl‐3‐iodo‐4‐methoxy‐phenyl) methanol with NaH in DMF at ambient temperature results in the generation of benzyne intermediates that can be trapped by furan or DMF. Trapping with DMF forms 3‐(dimethylaminomethyl)‐2‐hydroxy‐6‐methoxybenzaldehyde demonstrating the simultaneous exchange of three functionalities in a single step. The presence of the alkoxy substituent adjacent to iodine is critical for high regioselectivity addition of DMF. The corresponding bromide or triflate can be used in place of the iodide with equal efficiency. This methodology was used to synthesize the reported structure of gigasol and leading to a structural reassignment of this biscoumarin natural product. Reactive benzyne intermediates can be generated under mild conditions from diphenylphosphine oxide/iodide‐substituted benzyl alcohols. Reactions in the presence of DMF allow for the manipulation of three functional groups in a single step (see scheme). A revised structure and synthesis of gigasol are also reported.