1044507-52-9Relevant academic research and scientific papers
Highly Enantioselective, Hydrogen-Bond-Donor Catalyzed Additions to Oxetanes
Strassfeld, Daniel A.,Wickens, Zachary K.,Picazo, Elias,Jacobsen, Eric N.
supporting information, p. 9175 - 9180 (2020/07/13)
A precisely designed chiral squaramide derivative is shown to promote the highly enantioselective addition of trimethylsilyl bromide (TMSBr) to a broad variety of 3-substituted and 3,3-disubstituted oxetanes. The reaction provides direct and general access to synthetically valuable 1,3-bromohydrin building blocks from easily accessed achiral precursors. The products are readily elaborated both by nucleophilic substitution and through transition-metal-catalyzed cross-coupling reactions. The enantioselective catalytic oxetane ring opening was employed as part of a three-step, gram-scale synthesis of pretomanid, a recently approved medication for the treatment of multidrug-resistant tuberculosis. Heavy-atom kinetic isotope effect (KIE) studies are consistent with enantiodetermining delivery of bromide from the H-bond-donor (HBD) catalyst to the activated oxetane. While the nucleophilicity of the bromide ion is expected to be attenuated by association to the HBD, overall rate acceleration is achieved by enhancement of Lewis acidity of the TMSBr reagent through anion abstraction.
Preparation of aryloxetanes and arylazetidines by use of an alkyl-aryl suzuki coupling
Duncton, Matthew A. J.,Estiarte, M. Angels,Tan, Darlene,Kaub, Carl,O'Mahony, Donogh J. R.,Johnson, Russell J.,Cox, Matthew,Edwards, William T.,Wan, Min,Kincaid, John,Kelly, Michael G.
experimental part, p. 3259 - 3262 (2009/05/07)
(Chemical Equation Presented) The oxetan-3-yl and azetidin-3-yl substituents have previously been identified as privileged motifs within medicinal chemistry. An efficient approach to installing these two modules into aromatic systems, using a nickel-mediated alkyl-aryl Suzuki coupling, is presented.
