title: Asymmetric synthesis of dihydroindanes by convergent alkoxide-directed metallacycle-mediated bond formation.
abstract: A convergent synthesis of highly substituted and stereodefined dihydroindanes is described from alkoxide-directed Ti-mediated cross-coupling of internal alkynes with substituted 4-hydroxy-1,6-enynes (substrates that derive from 2-directional functionalization of readily available epoxy alcohol derivatives). In addition to describing a new and highly stereoselective approach to bimolecular [2 + 2 + 2] annulation that delivers products not available with other methods in this area of chemical reactivity, evidence is provided to support annulation by way of regioselective alkyne-alkyne coupling, followed by metal-centered [4 + 2] rather than stepwise alkene insertion and reductive elimination. Overall, the reaction proceeds with exquisite stereochemical control and defines a convenient, convergent, and enantiospecific entry to fused carbocycles of great potential value in target-oriented synthesis and medicinal chemistry.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Greszler
authors.forename: Holly A
authors.initials: HA
authors.lastname: Reichard
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Micalizio
mesh_terms: D000480:Alkynes / Q000737:chemistry; D003500:Cyclization; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D013237:Stereoisomerism; D014025:Titanium / Q000737:chemistry*
chemical_list: D000480:Alkynes; D007189:Indans; D009942:Organometallic Compounds; D010087:Oxides; D014025:Titanium