S. J. Burke et al. / Tetrahedron Letters 56 (2015) 5500–5503
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Table 2
Sequential,
Comparison of potassium haloalkyltrifluoroborate salt syntheses via
sequential procedure versus one-pot sequential procedure
a
two-pot
one-pot synthesis
1) BCl3, Et3SiH, -78 °C; 2) H2O, Et2O, 0 °C;
3) KHF2, H2O, Et2O
Br
Compound
Br(CH2)2+nBF3K
n
Two-pot sequential
One-pot sequential
KF3B
Br
procedure yielda (%)
procedure yielda (%)
n
n
65-92% overall yield
n = 1, 2, 3
4a c
-
1a-c
4a
4b
4c
1
2
3
74
80
60
65
70
92
R
B
KHF2, H2O
Et2O
Hydroboration
Br
R
n
a
Hydroboration was conducted with dichloroborane, prepared in situ from tri-
2a c
- , R=OH
ethylsilane and boron trichloride. The sequential procedures take the unpurified
hydroboration product immediately forward to the potassium haloalkyltrifluorob-
orate salt synthesis.
3a
(n=1), R=pinacol
18-71% overall yield (2 steps)
Scheme 1. The reported high yielding, sequential synthesis of potassium haloalkyl-
trifluoroborate salts (top) compared to a lower yielding, two-step procedure where
the boron intermediates are isolated (bottom).
via partitioning, recrystallization, or column chromatography. Low
yields were caused by
a rarely mentioned hydroboration
byproduct: 1,1,1,3,3,3-hexaethyldisiloxane, or (Et3Si)2O. It was
observed that the boronic acid and ester products were soluble in
this byproduct, making purification challenging. In only one case
was an acceptable yield of the hydroboration product obtained,
boronic acid 2c (Table 1). Here the crude mixture of the boronic
acid and the (Et3Si)2O byproduct was dissolved in water with
heat, and the boronic acid was recrystallized to obtain
significantly higher yields than were achieved with 2a and 2b. The
longer alkyl chain (n = 3) may have resulted in decreased
solubility of 2c in water compared to 2a and 2b, allowing the
recrystallization to occur. As expected, treatment of 2a–c and 3a
with potassium hydrogen difluoride as previously related by
Vedejs13 and Molander7a (Scheme 1) proceeded without difficulty
in moderate to high yields (Table 1).
The hydroboration complications using in situ prepared
dichloroborane led to the examination of a sequential two-pot pro-
cedure that carried the crude hydroboration products forward
through the potassium haloalkyltrifluoroborate salt synthesis
(Table 2). The (Et3Si)2O byproduct was expected to be inert under
the subsequent reaction conditions of potassium hydrogen difluo-
ride in ether and water. Additionally, (Et3Si)2O would be easily
removed from the reaction product via trituration due to its high
ether solubility, contrary to the potassium haloalkyltrifluoroborate
salts. The sequential haloalkyltrifluoroborate salt synthesis worked
better than expected for boronic acids 2a and 2b (Table 2), with the
overall yield being notably higher than when the boronic acid was
first purified (Table 1). Unfortunately this two-step sequential pro-
cedure gave a relatively unimpressive yield of 4c, 60%. While a
modest yield was obtained with unpurified pinacol ester 3a as
the intermediate (65% for the two steps), further studies on the
pinacol ester were not attempted due to the lower atom economy
of this process. Note that a similar procedure to synthesize
haloalkyl MIDA boronates was not fruitful.
unpurified products to potassium hydrogen difluoride (Scheme 1,
top). To illustrate their synthetic utility as boron building blocks,
we present example substitution reactions with potassium
haloalkyltrifluoroborate salts 4a–c. Additionally, we report
a
reversible, one-step conversion of the substitution products to
MIDA boronates (Tables 3 and 4), overcoming the purification
limitations of the potassium organotrifluoroborate salts.
Results and discussion
Initial synthetic studies explored various hydroboration proce-
dures with commercially available haloalkenes (allyl bromide, 4-
bromo-1-butene, and 5-bromo-1-pentene, 1a–c, respectively).
Reactions with Wilkinson’s catalyst and pinacolborane10 resulted
in decomposition, likely caused by poor catalyst chemoselectivity.
Success was realized with [Ir(cod)Cl]2 and pinacolborane,9h but
high cost and modest yields discouraged further consideration.
Additionally, use of catecholborane as the hydroboration
reagent4b afforded good yields of the hydroboration product.
However, hydrolysis or transesterification with pinacol presented
catechol and benzoquinone contamination, which have been
widely reported in the literature. Finally, use of commercially
available dichloroborane dioxane11 and dibromoborane dimethyl
sulfide12 complexes resulted in low yields and mixtures of prod-
ucts. Both the desired boronic acid and a borinic acid byproduct
were observed. As previously discussed by Brown,11a the borinic
acid byproducts are caused by disproportionation of the
dihaloborane complexes.
Due to the difficulties encountered using standard hydrobora-
tion protocols with haloalkenes 1a–c, dichloroborane was next
examined as the hydroboration reagent. To avoid the disproportion-
ation problems previously observed, dichloroborane was prepared
in situ from BCl3 and Et3SiH (dichloroborane is also more reactive
than the commercially available dihaloborane complexes).9b This
reagent provided moderate to low yields of boronic acids 2a–c or
pinacol ester 3a (Table 1) after aqueous work-up and purification
With the success achieved carrying the crude hydroboration
materials forward, it was postulated that a one-pot synthesis
might be feasible. Here the hydroboration reaction was performed
as previously described, but instead of an aqueous workup, the
Table 1
Dichloroborane hydroboration of haloalkenes 1a–c (with purification of the resulting boronic acids 2a–c and ester 3a) and subsequent synthesis of
potassium haloalkyltrifluoroborate salts 4a–c
Compound
n
R
Br(CH2)2+nBR2 yielda (%)
Compound
Br(CH2)2+nBF3K yieldb (%)
Overall yieldc (%)
2a
2b
2c
3a
1
2
3
1
OH
OH
OH
Pinacol
27
22
79
51
4a
4b
4c
4a
65
62
90
66
18
14
71
34
a
Hydroboration was performed with dichloroborane, prepared in situ from triethylsilane and boron trichloride. Quenching was conducted with
water or pinacol, and the products were purified.
b
Reaction was conducted on the purified boronic acid or ester.
Overall yield of the two-step sequence.
c