Organic Letters
electrophilic aromatic halogenation of azulene occurs at the
16
most electron-rich one-position. There are no reports on the
direct functionalization of azulene at the six-position, whereas a
very lengthy, six-step synthesis of 10 from 2-chlorotropone was
1
7,18
reported.
Our formal C−H borylation of azulene will find
applications in the chemistry of azulene-based functional
molecules.
1
9
The regioselectivity of the monoborylation in Scheme 3
would depend on the following two factors: (1) the
regioselectivity of the initial diborylation, which obeys that of
12
the conventional Birch reduction, and (2) the regioselectivity
of the oxidative deborylation. Although the exact reaction
mechanism for the oxidative deborylation is unclear, the
deborylation is likely to involve the more crowded, more
electron-rich, and thus less stable boryl group in each
intermediate 11 or 12. The situation is more complex in the
case of azulene derivative 13. We speculate that the oxidation
event takes place at the more conformationally constrained
cyclopentadienylboryl group.
Figure 1. 11B NMR spectrum of the reaction mixture.
broad quartet and at −28 ppm as a sharp quartet, respectively.
The broad quartet was assigned to be methoxyborohydride
−
20
[
MeOBH ] according to the literature. Thomas reported
3
The treatment of pyrene under the standard conditions
entry 4 in Table 1) did not afford any conceivable diborylated
that the treatment of pinacolborane (HBpin) with sodium
(
methoxide induces multiple hydride−alkoxide exchanges and
products but afforded 1-borylpyrene 14 in 64% yield without
exposure to DDQ or TEMPO (Scheme 4). To further explore
−
−
results in the formation of [MeOBH ] and [BH ] . We thus
3
4
concluded that HBpin was formed together with 14 in situ
before workup. The sharp quartet at −28 ppm is assignable to
−
21
Scheme 4. Borylation of Pyrene
[
pyrenylBH ] according to the literature.
3
On the basis of these experiments, Scheme 4 shows a
possible reaction mechanism for the borylation of pyrene. The
first one-electron reduction generates the radical anion of
pyrene, which reacts with MeOBpin followed by another one-
electron reduction to yield monoborylated anion 15. From 15,
we are tempted to propose two pathways. Path A includes a
process similar to the reactions in Schemes 2 and 3: The
second borylation of 15 affords 16. The subsequent hydride
shift followed by retro-hydroboration generates 14 with the
concomitant formation of HBpin and with the recovery of
aromaticity. We performed density functional theory (DFT)
11
calculations on the retro-hydroboration from 17 to 14 to
reveal that the computed activation barrier is >50 kcal/mol.
We hence deny the possibility of path A. Path B does not
include the second borylation: The anion 15 has a highly
conjugated π-system and a delocalized electron density.
MeOBpin could not efficiently react with 15, and instead, a
1,2-hydride shift from the borylated carbon to the boron center
would occur to yield aromatized borate 18. The shifted
hydride would be removed by the action of Lewis-acidic
MeOBpin to eventually provide 14, which is in equilibrium
with its methoxy borate 19. The activation energy of the 1,2-
hydride shift was calculated to be 26.6 kcal/mol, which
indicates that the shift is much more likely to occur.
We have examined the reaction of PAHs with MeOBpin
promoted by sodium and have found three different types of
borylation. (1) Anthracene and phenanthrene derivatives: The
corresponding dearomatized diborylated products were
obtained as stable primary products. The remaining aromatic
systems would endow the diborylated products with sufficient
stability even after the dearomatization. (2) Naphthalene-
based smaller π systems: The initial dearomatized diborylated
products are unstable to handle because of the significant loss
of aromaticity and are subjected to oxidation before workup to
afford formal C−H borylation products regioselectively. The
products represent isomers that are not accessible via the Ir-
catalyzed C−H borylation. This method provides by far the
most concise approach to synthetically useful 6-borylazulene.
the unexpectedly smooth formation of monoborylated 14, we
performed a mechanistic study by monitoring the reaction of
1
1
pyrene by B NMR spectroscopy (Figure 1). Along with the
expected signals for the remaining MeOBpin (22 ppm) and its
−
borate [(RO) B] (3 ppm), the borylated pyrene was observed
4
as its neutral form 14 (33 ppm) and its methoxyborate 19 (8
ppm, vide infra) even under an inert atmosphere. More
importantly, two unexpected signals appeared at −9 ppm as a
4
615
Org. Lett. 2021, 23, 4613−4617
Fukazawa, Mizuki
