Amides as modifiable directing groups in electrophilic borylation

• Published in: Chemical science (Cambridge) Vol. 14; no. 14; pp. 3865 - 3872
• Main Authors: Iqbal, Saqib A, Uzelac, Marina, Nawaz, Ismat, Wang, Zhongxing, Jones, T. Harri, Yuan, Kang, Millet, Clement R. P, Nichol, Gary S, Chotana, Ghayoor Abbas, Ingleson, Michael J
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 05-04-2023; The Royal Society of Chemistry
• Subjects: Amides; Aromatic compounds; Boron; Carbazoles; Carbonyls; Cations; Chemistry; Nitrogen; Polycyclic aromatic hydrocarbons; Substrates
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d2sc06483a

Amide directed C-H borylation using ≥two equiv. of BBr
3
forms borenium cations containing a R
2
N(R′)C&z.dbd;O→B(Ar)Br unit which has significant Lewis acidity at the carbonyl carbon. This enables reduction of the amide unit to an amine using hydrosilanes. This approach can be applied sequentially in a one-pot electrophilic borylation-reduction process, which for phenyl-acetylamides generates
ortho
borylated compounds that can be directly oxidised to the 2-(2-aminoethyl)-phenol. Other substrates amenable to the C-H borylation-reduction sequence include mono and diamino-arenes and carbazoles. This represents a simple method to make borylated molecules that would be convoluted to access otherwise (
e.g. N
-octyl-1-BPin-carbazole). Substituent variation is tolerated at boron as well as in the amide unit, with diarylborenium cations also amenable to reduction. This enables a double C-H borylation-reduction-hydrolysis sequence to access B,N-polycyclic aromatic hydrocarbons (PAHs), including an example where both the boron and nitrogen centres contain functionalisable handles (N-H and B-OH). This method is therefore a useful addition to the metal-free borylation toolbox for accessing useful intermediates (ArylBPin) and novel B,N-PAHs.
A sequence of amide-directed borylation followed by amide to amine reduction furnishes useful organoboranes that are otherwise convoluted to access.