Strain-release 2-azaallyl anion addition/borylation of [1.1.1]propellane: synthesis and functionalization of benzylamine bicyclo[1.1.1]pentyl boronates

• Published in: Chemical science (Cambridge) Vol. 12; no. 2; pp. 766 - 772
• Main Authors: Shelp, Russell A, Ciro, Anthony, Pu, Youge, Merchant, Rohan R, Hughes, Jonathan M. E, Walsh, Patrick J
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 14.04.2021; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Imines; Nitrogen; Organic compounds; Physical Sciences; Science & Technology; Substrates; Synthesis
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d1sc01349a

We report a 3-component reaction between N -benzyl ketimines, [1.1.1]propellane, and pinacol boronates to generate benzylamine bicyclo[1.1.1]pentane (BCP) pinacol boronates. These structures are analogous to highly sought diarylmethanamine cores, which are common motifs in bioactive molecules. We demonstrate the versatility of the boronate ester handle via downstream functionalization through a variety of reactions, including a challenging Pd-catalyzed (hetero)arylation that exhibits a broad substrate scope. Together, these methods enable the synthesis of high-value BCP benzylamines which are inaccessible by existing methods. Furthermore, we demonstrate the successful application of these newly developed (hetero)arylation conditions to a variety of challenging tertiary pinacol boronates, including nitrogen-containing heterocycles, 1,1-disubstituted cyclopropanes, and other BCP cores. We report a 3-component reaction between N -benzyl ketimines, [1.1.1]propellane, and pinacol boronates to generate benzylamine bicyclo[1.1.1]pentane (BCP) pinacol boronates.