Ronald L. Reyes, Miyu Sato, Tomohiro Iwai
Dec 10, 2019
Citations
0
Influential Citations
38
Citations
Journal
Journal of the American Chemical Society
Abstract
α-Aminoboronic acids, isostructural boron analogues of α-amino acids, have received much attention because of the important biomedical applications implicated for compounds containing this structure. Additionally, the inherent versatility of α-aminoboronic acids as synthetic intermediates through diverse carbon-boron bond transformations make the efficient synthesis of these compounds highly desirable. Here, we present a Rh-monophosphite chiral catalytic system that enables a highly efficient enantioselective borylation of N-adjacent C(sp3)-H bonds for a range of substrate classes including 2-(N-alkylamino)heteroaryls and N-alkanoyl or aroyl-based secondary or tertiary amides, some of which are pharmaceutical agents or related compounds. Various stereospecific transformations of the enantioenriched α-aminoboronates including Suzuki-Miyaura coupling with aryl halides and the Rh-catalyzed reaction with an isocyanate derivative of α-amino acid affording a new peptide chain elongation method have been demonstrated. As a highlight of this work, the borylation protocol was successfully applied to the catalyst-controlled site- and stereoselective C(sp3)-H borylation of an unprotected dipeptidic compound allowing remarkably streamlined synthesis of the anti-cancer drug molecule bortezomib, offering a straightforward route for the synthesis of privileged molecular architectures.