title: Pd-catalyzed ring assembly by vinylation and intramolecular Heck coupling: a versatile strategy towards functionalized azadibenzocyclooctynes.
abstract: A new modular approach based on Pd-catalyzed C-C bond formation is presented for the assembly of a benzannulated azocine scaffold, the key intermediate in the synthesis of functionalized azadibenzocyclooctynes (aza-DIBOs). The intramolecular ring-closing Heck coupling was investigated by variation of the C-X bond. The reaction rate is limited by the initial oxidative addition step and the regiochemistry strongly depends on the auxiliary phosphine. Under optimized conditions, the 8-endo regioisomer was obtained in 71% yield over two steps (with no protecting group chemistry) or in one pot, inclusive of C-N bond formation. The practical generation of the octyne triple bond of a prototypical N-benzoyl aza-DIBO, without the need for chromatographic purification, is also described. The structural features, including those of the ring-strained cyclic octyne, were elucidated by NMR spectroscopy and X-ray crystallographic analysis. The high reactivity of the N-benzoyl aza-DIBO synthesized is demonstrated in a strain-promoted azide-alkyne cycloaddition reaction with an alkyl azide (k=0.38 M(-1)  s(-1)).
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Humboldtstraße 10, 07743 Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Jäger
authors.forename: Helmar
authors.initials: H
authors.lastname: Görls
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Günther
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
mesh_terms: D001372:Aza Compounds / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D034242:Cyclooctanes / Q000737:chemistry*; D003516:Cycloparaffins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*
chemical_list: D001372:Aza Compounds; D034242:Cyclooctanes; D003516:Cycloparaffins; D010165:Palladium