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. 2023 Mar 15;14(14):3865-3872.
doi: 10.1039/d2sc06483a. eCollection 2023 Apr 5.

Amides as modifiable directing groups in electrophilic borylation

Saqib A Iqbal  1 , Marina Uzelac  1 , Ismat Nawaz  1   2 , Zhongxing Wang  1 , T Harri Jones  1 , Kang Yuan  1 , Clement R P Millet  1 , Gary S Nichol  1 , Ghayoor Abbas Chotana  2 , Michael J Ingleson  1
Affiliations

Amides as modifiable directing groups in electrophilic borylation

Saqib A Iqbal et al. Chem Sci. .

Abstract

Amide directed C-H borylation using ≥two equiv. of BBr3 forms borenium cations containing a R2N(R')C[double bond, length as m-dash]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.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. (Top) Three possible fates of DGs post directed borylation. (Bottom) A rare example of a modifiable DG in directed electrophilic borylation to make a B-doped PAH.
Fig. 2
Fig. 2. Previous work on: Lewis acid catalysed amide reduction (top); amide directed borylation (middle); and this work (bottom) combining amide directed electrophilic borylation and amide reduction to make novel borylated compounds.
Fig. 3
Fig. 3. HIA at boron and the carbonyl carbon of [1]+.
Fig. 4
Fig. 4. Formation of amine-borane 2a using silanes via hemi-aminal 3.
Fig. 5
Fig. 5. (Left) Formation of amine borane 5. (Right) The solid-state structure of 5, ellipsoids at the 50% probability and hydrogens omitted for clarity.
Scheme 1
Scheme 1. (Top) Borylation reduction tolerating both electron donating and withdrawing groups and substituents at ortho, meta and para positions in the starting material (isolated yields in parentheses). (Bottom) Conversion of N,N-Me2-phenylacetylamide into 2-(2-Me2N-ethyl)phenol 6.
Scheme 2
Scheme 2. Proposed pathway for the reduction of [1]+ to 2avia3, 3-O and C.
Scheme 3
Scheme 3. Formation of boron-enolate 7 from 3.
Scheme 4
Scheme 4. Reduction of [8][BBr4] to form compound 9.
Fig. 6
Fig. 6. Top, reduction of [10][BBr4]. Bottom left, additional substrates isolated as Dan derivatives. Inset, substrate 14 used in Zn catalysed amide reduction, and 15 one of the products from that process.
Fig. 7
Fig. 7. The C1 borylation–reduction of N-acyl carbazoles.
Scheme 5
Scheme 5. (i) Borylation with BBr3 followed by protection at boron; (ii) borylation with BBr3, reduction with SiHEt3 and then protection.
Fig. 8
Fig. 8. Lewis acidity of diaryl-borane derived cations.
Fig. 9
Fig. 9. Double borylation–reduction–hydrolysis to form B,N-containing PAHs 29-THQ and 29-Me. Right, solid state structures, ellipsoids at 50% probability and most hydrogens omitted for clarity.
Fig. 10
Fig. 10. Top, the solid-state structure of the cationic portion of 27-Me, ellipsoids at 50% probability, most hydrogens omitted for clarity. Bottom, select metrics.
See this image and copyright information in PMC

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