Metal-Free Borylation of Heteroarenes Using Ambiphilic Aminoboranes: On the Importance of Sterics in Frustrated Lewis Pair C–H Bond Activation

Abstract

Two novel frustrated Lewis pair (FLP) aminoboranes, (1-Pip-2-BH-CH) (2; Pip = piperidyl) and (1-NEt-2-BH-CH) (3; NEt = diethylamino), were synthesized, and their structural features were elucidated both in solution and in the solid state. The reactivity of these species for the borylation of heteroarenes was investigated and compared to previously reported (1-TMP-2-BH-CH) (1; TMP = tetramethylpiperidyl) and (1-NMe-2-BH-CH) (4; NMe = dimethylamino). It was shown that 2 and 3 are more active catalysts for the borylation of heteroarenes than the bulkier analogue 1. Kinetic studies and density functional theory calculations were performed with 1 and 2 to ascertain the influence of the amino group of this FLP-catalyzed transformation. The C-H activation step was found to be more facile with smaller amines at the expense of a more difficult dissociation of the dimeric species. The bench-stable fluoroborate salts of all catalysts (1F-4F) have been synthesized and tested for the borylation reaction. The new precatalysts 2F and 3F are showing higher reaction rates and yields for multigram-scale syntheses.

Sequential C−H Borylation and N‐Demethylation of 1,1′‐Biphenylamines: Alternative Route to Polycyclic BN‐Heteroarenes

“…Moreover, 1‐PPh 2 bearing a diphenylphosphino moiety was converted into a phosphonium borohydride zwitterion in 71 % (entry 7). The observation that the C−H borylation was highly sensitive to the N substituents of the substrates was also disclosed by Fontaine and co‐workers, wherein the efficiency was found to be dependent on the identity of the amino groups of the employed reagents …”

Practical and Scalable Synthesis of Borylated Heterocycles Using Bench-Stable Precursors of Metal-Free Lewis Pair Catalysts

“…In our previous preliminary study, we have described the synthetic protocols for four different fluoroborate salts (1F-4F) that have different alkyl substituents on the ammonium nitrogen center. 24,27 Yet, these precatalysts were synthesized only on a smaller scale (2-5 grams) to explore their catalytic activity towards borylation. As the preliminary study showed that the piperidyl precatalyst 2F is more efficient for the borylation and borylative dearomatization of het-eroarenes (vide infra), its synthesis on a 100-gram scale was attempted.…”

“…In these systems it was shown that 2 undergoes two consecutive C-H activation steps which prevents the metathesis reaction to occur, and thus catalytic activity. 24 Despite some heteroarenes and all precatalysts being in the solid state, the liquid HBpin reagent together with the reaction temperatures of 80 -100 Scheme 4. Catalytic borylative dearomatization of arylsulfonyl indoles on 2 gram-scale using HBpin reagent and precatalyst 2F under solvent-free conditions.…”

Direct C−H Bond Borylation of (Hetero)Arenes: Evolution from Noble Metal to Metal Free

“…To solve this problem, air‐ and moisture‐stable difluoroborate salts of tetramethylpiperidinobenzene were developed by the same group in 2016 (Scheme , 37 ) . The importance of the steric hindrance in this kind of catalysts has also been studied . Interestingly, when 1‐tosyl indoles were used as the starting substrates, borylative dearomatization products were obtained (Scheme b) .…”