title: Synthesis of polycyclic benzofused nitrogen heterocycles via a tandem ynamide benzannulation/ring-closing metathesis strategy. Application in a formal total synthesis of (+)-FR900482.
abstract: A two-stage "tandem strategy" for the synthesis of benzofused nitrogen heterocycles is described that is particularly useful for the construction of systems with a high level of substitution on the benzenoid ring. The first stage in the strategy involves a benzannulation based on the reaction of cyclobutenones with ynamides. This cascade process proceeds via a sequence of four pericyclic reactions and furnishes a multiply substituted aniline derivative which can bear a variety of functionalized substituents at the position ortho to the nitrogen. In the second stage of the tandem strategy, ring-closing metathesis generates the nitrogen heterocyclic ring. This two-step sequence provides efficient access to highly substituted dihydroquinolines, benzazepines, benzazocines, and related benzofused nitrogen heterocyclic systems. The application of this chemistry in a concise formal total synthesis of the anticancer agents (+)-FR900482 and (+)-FR66979 is described.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Xiao Yin
authors.initials: XY
authors.lastname: Mak
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Crombie
authors.forename: Rick L
authors.initials: RL
authors.lastname: Danheiser
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D005240:Feasibility Studies; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000480:Alkynes; D000588:Amines; D000970:Antineoplastic Agents; D010078:Oxazines; C053335:FR 900482; C058745:FR 66979