.
Angewandte
Communications
À
Table 3: Generality of iodonium salt formation from (hetero)aryl dibor-
boronate group, like the C H bond cleaved in the reaction,
was located in a para position to the activating oxygen atom.
Thiophene 1 f was also transformed into the desired salt 2 f;
the reaction proceeded at the a position of the thiophene
onates.[a]
ring.[9] This C H transformation was quite straightforward,
À
and the boron-substituted salts obtained were highly stable.
We considered a partial boron–iodine(III) exchange[10] of
aryl diboronates with iodine(III) reagents as an efficient
alternative route to boron-substituted iodonium salts. Such an
approach would expand the range of possible substrates and
enable the control of regioselectivity. However, the aryl
diboronate 1g was unexpectedly inert to PhI(OH)OTs. The
reaction did not proceed in various ordinary solvents (CH2Cl2,
CH3CN, and MeOH)[11] or even in HFIP (Table 2, entry 1).
Upon further investigation, we found that the addition of
acetic acid to HFIP led to the production of 2g (YÀ = TsOÀ)
as the sole product (Table 2, entry 2). Overreaction leading to
Table 2: Synthesis of boron-substituted salts 2g and 2h from aryl
diboronates 1g and 1h.
[a] The yield based on substrate 1 is reported in each case for the pure
product. [b] TFE was used instead of HFIP. [c] A larger amount of
substrate 1n was used (1.2 equiv with respect to PIFA). [d] Pinacol esters
were used instead of neopentylglycol esters, because the neopentylglycol
esters were difficult to synthesize.
Entry
1
IIII reagent
Additive
Product
Yield [%][a]
obtained from the diboronate 1j with complete regioselec-
tivity.[12] The ortho-boronated salt 2k was obtained from
1
2
3
4
1g PhI(OH)OTs none
1g PhI(OH)OTs AcOH
1g PhI(OH)OTs CF3CO2H 2g (Y=OTs)
1g PhI(OH)OTs TsOH
1g PhI(OH)OTs AcOH
1g PhI(OH)OTs none
1g PIFA
1h PhI(OH)OTs AcOH
1h PIFA AcOH
ND
2g (Y=OTs)
52
44
11
13
a
dimethoxy-substituted diboronate 1k. A symmetrical
biphenyl substrate 1l was transformed into the monoiodo-
nium salt 2l without any overreaction. Salts with other
aromatic backbones, such as naphthalene (compound 2m) or
heteroaromatic structures (compounds 2n and 2o), were also
obtained in good yields.
2g (Y=OTs)
2g (Y=OTs)
NR[d]
2g (Y=OCOCF3) 62
2h (Y=OTs) 77
2h (Y=OCOCF3) 89
5[b]
6[c]
7
AcOH
8
9
Although the effect of acetic acid is still unclear, we
propose that the acid activates diboronates 1 by coordination
to the boron atom. This coordination counteracts the
electron-withdrawing resonance effect of the boronate
groups.[4b,c] A competition experiment with a 1:1 mixture of
1h and m-xylene provided support for this hypothesis
(Scheme 1). Under the optimized conditions with acetic
acid, the reaction gave the salt 2h as the major product,
along with a small amount of the m-xylyliodonium salt 3. In
contrast, the reaction in the absence of acetic acid gave 3 as
the sole product. Therefore, the boronate 1h must be
specifically activated by the acid.
[a] Yield of the pure product with respect to substrate 1. [b] TFE was used
instead of HFIP. [c] AcOH was used as the solvent. [d] A large amount of
PhI(OH)OTs (80%) was recovered. ND=not determined, NR=no
reaction.
the bisiodonium salt should be suppressed by the strong
deactivation effect of the introduced electron-withdrawing
iodonium moiety. The much stronger acids CF3CO2H and
TsOH were less effective than acetic acid (Table 2, entries 3
and 4). When TFE was used instead of HFIP, the yield
decreased (Table 2, entry 5). The reaction did not proceed in
acetic acid as the solvent, although acetic acid was not only an
efficient activator in HFIP, but is also the classically used
solvent to promote the formation of iodonium salts (Table 2,
entry 6). This result indicated that both acetic acid and HFIP
play a crucial role in the reaction. The use of PIFA gave
a superior result to that observed with PhI(OH)OTs (Table 2,
entry 7). The selection of the boronate was also important:
the use of the less bulky neopentylglycol ester 1h significantly
improved the yield (Table 2, entries 8 and 9).
To demonstrate the utility of the boron-substituted salts as
precursors to functionalized boronates, we examined their
reactivity with various reaction partners (Scheme 2). We
À
tested synthetically valuable C C bond formation in an SNAr
The optimized conditions were subsequently applied to
other substrates (Table 3). Methyl-substituted 1i was con-
verted into the sterically hindered salt 2i in excellent yield.
The salt 2j with methoxy and chlorine substituents was
Scheme 1. Competitive iodonium-salt formation with substrates 1h
and m-xylene.
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 12555 –12558