Type II Anion Relay Chemistry: Exploiting Bifunctional Weinreb Amide Linchpins for the One‐Pot Synthesis of Differentiated 1, 3‐Diketones, Pyrans, and Spiroketals. Issue 1 (20th November 2015)

• Record Type: Journal Article
• Authors: Farrell, Mark; Melillo, Bruno; Smith, Amos B.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 1(2016)
• Page Start: 232
• Page End: 235
• Publication Date: 2015-11-20
• Subjects: anion relay chemistry -- Brook rearrangement -- 1, 3‐diketones -- spiroketals -- Weinreb amides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201509342
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : A highly effective bifunctional linchpin for type II anion relay chemistry has been developed. The mechanistically novel negative‐charge migration that comprises a Brook rearrangement is initiated by a stabilized tetrahedral intermediate that is generated by nucleophilic addition to a Weinreb amide rather than by a simple, epoxide‐derived oxyanion.