1,3-Aza-Brook Rearrangement of Aniline Derivatives: In Situ Generation of 3-Aminoaryne via 1,3-C-(sp²)-to-N Silyl Migration

Abstract

The design, synthesis, and validation of 3-aminobenzyne precursors induced by C-(sp2)-to-N 1,3-aza-Brook rearrangement have been achieved, allowing access to diverse aniline derivatives. Through crossover experiments, we demonstrated the intramolecular mechanism of 1,3-C-to-N silyl transfer. To gain insight into the regioselectivity observed in the reactions, we performed density functional theory calculations. Finally, the method was applied to the synthesis of xylanigripones A in five linear steps in an overall yield of 30%.

Regioselective Arylation of Amidoaryne Precursors via Ag‐Mediated Intramolecular Oxy‐Argentation

“…[3a,13] Recently, we demonstrated novel 3-amino-2-(trialkylsilyl)phenyl triflates as aminobenzyne precursors. [14] These are base-activated aminoaryne precursors induced via an 1,3-aza-Brook rearrangement, and the resulting aminoaryne intermediates were used for nucleophilic addition and cycloadditions to furnish various aniline derivatives. Interestingly, when the reaction was performed using an amidoaryne precursor and NaH in N-methyl-2-pyrrolidone (NMP) at 40 °C, O-silylimidate was obtained from the imidobenzyne intermediate formed through 1,5-Brook rearrangement (Figure 1B-f).…”

An umpolung mechanism of B(pin)-mediated Cu/B rearrangement and origin of regioselectivity for NHC-Cu-catalyzed allylation of imines

“…In our previous study on the copper-catalyzed reductive coupling of benzaldehyde and benzophenone, we revealed the mechanism of the Brook rearrangement, which is mediated by organobases (Li/Na/KO t Bu). 8 We also examined in detail the mechanisms of both the aza-Brook rearrangement 9 and the bora-Brook rearrangement. 10 The common mechanism characteristic of these Brook rearrangements is the deprotonation of nitrogen (or removal of a metal ion from oxygen) to form the corresponding anion (Scheme 1b).…”

Regiocontrol Using Fluoro Substituent on 3,6-Disubstituted Arynes

“…[1][2][3][4][5] However, the use of unsymmetrically substituted arynes in these reactions is limited because of low regioselectivity. In general, the regiocontrol of such reactions can be achieved by introducing a directing group at the 3-position of arynes [6][7][8][9][10][11][12][13][14][15][16][17][18] (Fig. 1).…”