Mechanistic Studies into Amine-Mediated Electrophilic Arene Borylation and Its Application in MIDA Boronate Synthesis

Direct electrophilic borylation using Y2BCl
(Y2 = Cl2 or o-catecholato)
with equimolar
AlCl3 and a tertiary amine has been applied to a wide range
of arenes and heteroarenes. In situ functionalization
of the ArBCl2 products is possible with TMS2MIDA, to afford bench-stable and easily isolable MIDA-boronates in
moderate to good yields. According to a combined experimental and
computational study, the borylation of activated arenes at 20 °C
proceeds through an SEAr mechanism with borenium cations,
[Y2B­(amine)]+, the key electrophiles. For catecholato-borocations,
two amine dependent reaction pathways were identified: (i) With [CatB­(NEt3)]+, an additional base is necessary to accomplish
rapid borylation by deprotonation of the borylated arenium cation
(σ complex), which otherwise would rather decompose to the starting
materials than liberate the free amine to effect deprotonation. Apart
from amines, the additional base may also be the arene itself when
it is sufficiently basic (e.g., N-Me-indole). (ii)
When the amine component of the borocation is less nucleophilic (e.g.,
2,6-lutidine), no additional base is required due to more facile amine
dissociation from the boron center in the borylated arenium cation
intermediate. Borenium cations do not borylate poorly activated arenes
(e.g., toluene) even at high temperatures; instead, the key electrophile
in this case involves the product from interaction of AlCl3 with Y2BCl. When an extremely bulky amine is used, borylation
again does not proceed via a borenium cation; instead, a number of
mechanisms are feasible including via a boron electrophile generated
by coordination of AlCl3 to Y2BCl, or by initial
(heteroarene)­AlCl3 adduct formation followed by deprotonation
and transmetalation.