title: Type II Anion Relay Chemistry: Exploiting Bifunctional Weinreb Amide Linchpins for the One-Pot Synthesis of Differentiated 1,3-Diketones, Pyrans, and Spiroketals.
abstract: The design, synthesis, and validation of new highly effective bifunctional linchpins for type II anion relay chemistry (ARC) has been achieved. The mechanistically novel negative-charge migration that comprises the Brook rearrangement is now initiated by a stabilized tetrahedral intermediate, which is generated by nucleophilic addition to a Weinreb amide, rather than by a simple oxyanion that is generated from an epoxide. As a result, the linchpin preserves the carbonyl functionality in the ARC adducts, thus permitting access to functionally complex systems in a single flask without the need for further chemical manipulations. This tactic was validated with the one-pot preparation of monoprotected 1,3-diketones as well as pyran and spiroketal scaffolds, depending on the choice of nucleophile, electrophile, and work-up conditions.
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104 (USA).
authors.forename: Mark
authors.initials: M
authors.lastname: Farrell
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104 (USA).
authors.forename: Bruno
authors.initials: B
authors.lastname: Melillo
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104 (USA). smithab@sas.upenn.edu.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
mesh_terms: D000577:Amides / Q000737:chemistry*; D000838:Anions / Q000138:chemical synthesis / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000577:Amides; D000838:Anions; D007659:Ketones; D011714:Pyrans; D013141:Spiro Compounds
keywords: 1,3-diketones; Brook rearrangement; Weinreb amides; anion relay chemistry; spiroketals