Two Directing Groups Used for Metal Catalysed Meta-C-H Functionalisation Only Effect Ortho Electrophilic C-H Borylation

Abstract

Two templates used in meta-directed C-H functionalisation under metal catalysis do not direct meta-C-H borylation under electrophilic borylation conditions. Using BCl₃ only Lewis adduct formation with Lewis basic sites in the template is observed. While combining BBr₃ and the template containing an amide linker only led to amide directed ortho C-H borylation, with no pyridyl directed meta borylation. The amide directed borylation is selective for the ortho borylation of the aniline derived unit in the template, with no ortho borylation of the phenylacetyl ring - which would also form a six membered boracycle - observed. In the absence of other aromatics amide directed ortho borylation on to phenylacetyl rings can be achieved. The absence of meta-borylation using two templates indicates a higher barrier to pyridyl directed meta borylation relative to amide directed ortho borylation and suggests that bespoke templates for enabling meta-directed electrophilic borylation may be required.

Keywords: Boron; Directing groups; Electrophilic substitution; Meta-C−H Functionalisation.

Figure 1

Top, previous work on directed ortho C−H borylation. Middle, directed meta‐C−H functionalisation along with some key features of the templates that enable meta selectivity. Bottom, this study using meta‐C−H functionalisation templates under electrophilic borylation conditions.

Figure 2

Top left, a template (A) successful for metal catalyzed meta‐C−H functionalisation and it's analogue 1. Right, formation of 2 and 3. Inset‐bottom, the structure of 2, ellipsoids at 50 % probability. Select distances (Å) and angles (°): O1−B1=1.485(2); N1−B2=1.594(2); C10−O1=1.289(1); Cl3−B1−Cl1=110.59(7); Cl1−B1−Cl2=110.91(7); Cl2−B1−Cl3=109.31(7).

Figure 3

Top, formation of 4, bottom the structure of 4, ellipsoids at 50 % probability. Distances (Å) and angles (°): N2−B2=1.588(6); O1−B1=1.501(6); O1−C10=1.288(5); Br5−B2−Br4=105.4(3); Br4−B2−Br3=110.7(3); Br3−B2−Br5=114.4(3).

Scheme 1

Attempted borylation of compound 5 with BX₃ (X=Cl or Br).

Figure 4

Inset, the unobserved ortho borylation isomer, B. Right, compounds 6 and 7 used to assess viability of carbonyl directed electrophilic borylation.

Figure 5

Borylation of compound 6 with BBr₃. Bottom, the solid‐state structure of the cationic portion of compound 8 A. Anion and hydrogen atoms not shown for clarity. Ellipsoids at the 50 % probability level. Selected distances (Å) and angles (°): shortest Br_anion−B1_cation=3.474(6); Br1−B1=1.902(6); B1−O1=1.384(7); O1−C8=1.336(6); C1−B1−Br1=124.3(4); Br1−B1−O1=114.4(4); O1−B1−C1=121.3(5).

Figure 6

Variable (10 °C increments) temperature ¹¹B NMR spectra for the product 8 A/8 B. Measured on a 142 mM DCM solution of 8 A/8 B.

Figure 7

Top borylation of 7, (note 9 A exists in equilibrium with 9 B, not shown, but is analogous to that discussed for 8 A/8 B). Bottom, solid‐state structure of 9 A with BBr₄ ⁻ anion and hydrogen atoms omitted for clarity. Ellipsoids at the 50 % probability level. Selected distances (Å) and angles (°): shortest Br_anion−B1_cation=3.487(5); O1−C8=1.336(6); O1−B1=1.378(6); Br1‐B1‐O1=113.8(4); O1−B1−C1=120.8(4); C1−B1−Br1=125.4(4).

Scheme 2

Top, formation of BDan boronates, 10/11 by directed ortho borylation. Bottom, further BDan substrates formed by amide directed C−H borylation.