As usual, fluorous bromosilane 1 was employed as a
fluorous-phase label. Treatment of 1 with excess allyl
Grignard reagent afforded fluorous allylsilane 2 in quantita-
tive yield. The dihydroxylation of 2 with N-methylmorpho-
line N-oxide (NMNO) and catalytic osmium tetraoxide in
aqueous acetone provided the desired fluorous diol 3 in
quantitative yield. As the only fluorous product, compound
Table 1. Partition Coefficients of Boronate 4a (K )
D
C(fluorous solvent)/C(organic solvent), at 10 °C)a
organic solvents
KD
organic solvents
KD
acetonitrile
dichloromethane
chloroform
hexane
13.3
7.53
5.43
6.50
ethyl acetate
acetone
toluene
THF
0.88
2.73
7.69
2.91
3
was obtained in high purity by simple extractive workup
(FC-77/aqueous acetone). Subsequent experiments were then
a
The fluorous solvent is FC-77.
conducted to verify the effectiveness of fluorous diol 3 in
immobilizing boronic acid templates. Encouraging results
showed that compound 3 could couple to 1.0 equiv or a slight
excess of arylboronic acids in quantitative yields. Depending
on the solubility of boronic acids, the reaction time may be
varied. Nevertheless, the formation of fluorous boronates 4
was highly favored in anhydrous solvents such as THF, ether,
pentane, or benzotrifluoride (BTF), and total conversion of
tions. As shown in Table 1, boronate 4a behaves as a
fluorous compound” for most solvent pairs. With appropri-
“
D
ate selection of organic solvents, the K values are high
enough for effective fluorous extraction.
A search for hydrolytic cleavage conditions was then
undertaken. Since hydrolysis under neutral conditions re-
quires a prolonged reaction time, an acidic aqueous media
is advisable for the release of free boronic acids. The released
boronic acids were recovered intact by liquid-liquid extrac-
tion in reasonable yields. Meanwhile, the fluorous diol 3,
which was distributed into FC-77, could be recycled without
additional treatment.
3
was achieved with the aid of 4 Å MS. The fluorous
boronates 4, purified by FC-77/CH CN extraction if neces-
3
sary, were provided in high purity without contaminated by
any diol components. As shown in Scheme 1, this reaction
Scheme 1a
As robust and general methods for carbon-carbon bond
formation, the Suzuki reaction has emerged as an important
tool in parallel synthesis and combinatorial chemistry. In
5
consideration of this fact, we sought to plan different
transformations of these boronates in fluorous synthesis and
then carry out the Suzuki reaction as a detagging process.6
In comparison with simple hydrolysis methods to provide
novel boronic acids, we believe such a synthesis should hold
greater interest for the combinatorial chemistry community.
As a significant demonstration of our approach, we focused
our attention on the synthesis of aminomethylbiaryls, which
are of marked interest in biological and pharmaceutical
a
Reagents and conditions: (1) CH
2
dCHCH
2
MgBr (4.0 equiv),
(cat.), NMNO
O 10:1, 8 h, 99%; (3) RB(OH) , 5a-h (1.0-
.1 equiv), 4 Å MS, anhydrous ether, 0.5-12 h, >90%; (4) (a)
O 80:10:10, 2-4 h, 57-70%.
7
research (Scheme 2). The fluorous boronate 4b, produced
Et
(
1
2
O reflux overnight, 98%; (2) 4% aqueous OsO
4
1.2 equiv), acetone/H
2
2
THF/HOAc/H
2
Scheme 2a
is applicable to a wide variety of electron-rich and electron-
poor arylboronic acids. These prepared boronates, which
1
19
were fully characterized by H NMR, F NMR, IR, MS,
4
and EA, are mostly colorless or pale yellow viscous liquids.
Since prolonged exposure of moisture might detach the
fluorous tag by hydrolysis, they were kept in dry vessels
and showed adequate storage stability for long periods of
time.
To assess the fluorous affinity of these boronates, we chose
compound 4a as representative and determined its partition
a
Reagents and conditions: (1) NBS (1.5 equiv), AIBN (cat.),
BTF, reflux, overnight, 67%; (2) morphline (1.2 equiv), (i-Pr)
1.0 equiv), THF, rt, 18 h, 88%; (3) Pd(PPh (2 mol %), 2 M
PO (2.0 equiv), dioxane, PhI (1.0 equiv), 12 h, 75 °C; 76%.
2
NEt
(
K
3 4
)
coefficient K
D
in several fluorous biphasic solvent combina-
3
4
(
3) (a) Hall, D. G.; Tailor, J.; Grave, M. Angew. Chem., Int. Ed. 1999,
3
8, 3064. (b) Carboni, B.; Pourbaix, C.; Carreaux, F.; Deleuze, H.; Maillard,
by the general method of esterification, was treated with NBS
(1.5 equiv) in BTF at reflux. In a radical process, fluorous
benzyl bromide 4i was obtained and purified by repeated
B. Tetrahedron Lett. 1999, 40, 7979. (c) Arimori, S.; Hartley, J. H.; Bell,
M. L.; Oh, C. S.; James, T. D. Tetrahedron Lett. 2000, 4, 10291.
(
4) Compound 4f was a white waxy solid, mp 59-60 °C. Because of
the action of 4 Å MS, it was formed as an anhydride, since no hydroxyl
1
signal was detected in H NMR or IR.
3
FC-77/CH CN extractions. Compound 4i was further treated
1004
Org. Lett., Vol. 4, No. 6, 2002