Type II Anion Relay Chemistry: Exploiting Bifunctional Weinreb Amide Linchpins for the One-Pot Synthesis of Differentiated 1,3-Diketones, Pyrans, and Spiroketals

Angew Chem Int Ed Engl. 2016 Jan 4;55(1):232-5. doi: 10.1002/anie.201509342. Epub 2015 Nov 20.


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.

Keywords: 1,3-diketones; Brook rearrangement; Weinreb amides; anion relay chemistry; spiroketals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemistry*
  • Anions / chemical synthesis
  • Anions / chemistry
  • Ketones / chemical synthesis*
  • Ketones / chemistry
  • Molecular Structure
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry


  • Amides
  • Anions
  • Ketones
  • Pyrans
  • Spiro Compounds