cis-dihydroxylation of unsaturated potassium alkyl- and aryltrifluoroborates

Article abstract of DOI:10.1021/ol052549e

(Chemical Equation Presented) The cis-dihydroxylation of olefin-containing potassium alkyl- and aryltrifluoroborates proceeds readily in moderate to excellent yields. The resulting diols are efficient coupling partners in Suzuki-Miyaura-type reactions wit

Full text of DOI:10.1021/ol052549e

ORGANIC
LETTERS
2
006
Vol. 8, No. 1
5-78
cis-Dihydroxylation of Unsaturated
Potassium Alkyl- and
7
Aryltrifluoroborates
Gary A. Molander* and Ruth Figueroa
Roy and Diana Vagelos Laboratories, Department of Chemistry,
UniVersity of PennsylVania, Philadelphia, PennsylVania 19104-6323
gmolandr@sas.upenn.edu
Received October 20, 2005
ABSTRACT
The cis-dihydroxylation of olefin-containing potassium alkyl- and aryltrifluoroborates proceeds readily in moderate to excellent yields. The
resulting diols are efficient coupling partners in Suzuki Miyaura-type reactions with both alkenyl and aryl bromides.
−
Organoboron compounds have been widely used in organic
synthesis. The utility of these organometallic reagents as
Our group has focused on expanding the chemistry of
organotrifluoroborates to processes in which the carbon-
boron bond remains intact. The epoxidation of olefin-
containing potassium organotrifluoroborates demonstrated the
tolerance of such organoboron compounds to oxidative
1
synthetic tools is often based on the ability of the carbon-
2
boron bond to be oxidized. It is this characteristic that also
limits the opportunity to perform oxidative transformations
on other functional groups present in the molecule while still
preserving the valuable carbon-boron bond. Common
oxidizing reagents are often too powerful and are not well
tolerated by many organoboron compounds. Only a few
9
conditions such as MCPBA and dimethyldioxirane. These
results led us to consider other oxidative reactions. This paper
describes our initial results toward the cis-dihydroxylation
of olefin-containing potassium organotrifluoroborates. We
also demonstrate that the diols produced through this method
are valuable synthetic intermediates.
3,4
examples of this type of transformation have been reported.
Organotrifluoroborate salts are unique organoboron com-
5
pounds, notable for their stability to moisture and air. They
are powders or crystalline solids that are easy to access and
handle, and these properties have made them attractive
synthetic intermediates. The chemistry of these compounds
has been expanded to various applications, including Su-
5
a
zuki-Miyaura coupling reactions, rhodium-catalyzed 1,4-
The cis-dihydroxylation of olefins is one of the most
widely used reactions for the synthesis of vicinal diols.
6
7
additions, as well as allylation of aldehydes and N-toluene-
10
sulfonylimines.8
(
6) (a) Navarre, L.; Pucheault, M.; Darses, S. Gen eˆ t, J.-P. Tetrahedron
(
1) (a) Cragg, G. M. Organoboranes in Organic Synthesis; Marcel
Lett. 2005, 46, 4247. (b) Pucheault, M.; Darses, S.; Gen eˆ t, J.-P. Eur. J.
Org. Chem. 2002, 3552. (c) Pucheault, M.; Darses, S.; Gen eˆ t, J.-P.
Tetrahedron Lett. 2002, 43, 6155. (d) Batey, R. A.; Thadani, A. N. Org.
Lett. 1999, 1, 1683.
Decker: New York, 1973. (b) Brown, H. C. Organic Syntheses Via Boranes;
Wiley-Interscience: New York, 1975.
(2) Oxidizing and Reducing Agents. In Handbook of Reagents for
Organic Synthesis; Burke, S. D., Danheiser, R. L., Eds.; Wiley: Chichester,
U.K., 1999.
(7) (a) Thadani, A. N.; Batey, R. A. Tetrahedron Lett. 2003, 44, 8051.
(b) Thadani, A. N.; Batey, R. A. Org. Lett. 2002, 4, 3827. (c) Batey, R. A.;
Thadani, A. N.; Smil, D. V. Synthesis 2000, 990. (d) Batey, R. A.; Thadani,
A. N.; Smil, D. V. Tetrahedron Lett. 1999, 40, 4289.
(
3) de Filippis, A.; Morin, C.; Thimon, C. Synth. Commun. 2002, 32,
2
669.
(
(
4) Matteson, D. S. J. Organomet. Chem. 1999, 581, 51.
5) For reviews of organotrifluoroborate salts, see: (a) Molander, G. A.;
(8) Li, S.-W.; Batey, R. A. Chem. Commun. 2004, 12, 1382.
(9) Molander, G. A.; Ribagorda, M. J. Am. Chem. Soc. 2003, 125, 11148.
(10) For a review in dihydroxylation, see: Schr o¨ der, M. Chem. ReV. 1980,
80, 187.
Figueroa, R. Aldrichimica Acta 2005, 38, 49. (b) Darses, S.; Gen eˆ t, J.-P.
Eur. J. Org. Chem. 2003, 4313.
1
0.1021/ol052549e CCC: $33.50
© 2006 American Chemical Society
Published on Web 12/03/2005

Table 1. Dihydroxylation of Potassium Alkyl- and Aryltrifluoroboratesa
a
The reactions were conducted using OsO4 (1.3 mol %), N-methylmorpholine N-oxide (1.0-1.5 equiv), and an acetone/t-BuOH/water mixture (18:1:1)
at room temperature. Solvent ratio was 4.5:1:1. Solvent ratio was 60:1:1. d OsO4 (0.62 mol %). e Isolated yields. Mixture of diastereomers in a 2:1 ratio.
b
c
f
Catalytic OsO
4
and N-methylmorpholine N-oxide (the Up-
or hydroboration of alkenes with the Snieckus reagent14
(diisopropylprenylborane). This was followed by hydrolysis
and subsequent treatment with KHF . The products were
2
powders or crystalline white solids that were stored on the
benchtop without detectable degradation.
As outlined in Table 1, initial studies were directed toward
sterically unhindered organotrifluoroborates containing a
remote monosubstituted olefin. The dihydroxylation of
potassium 9-decenyltrifluoroborate 1a proceeded in very
john process) have been widely applied after the initial
publication of this method.11 This process provides the
advantage of minimizing overoxidation. With these factors
in mind, we explored the use of these reagents to accomplish
the dihydroxylation of unsaturated organotrifluoroborates (eq
10
1). Acetone, t-BuOH, and water are solvents commonly used
1
0
in this reaction, and based on our prior experience with
the epoxidation reaction, we knew that the appropriate
solvent ratio would facilitate isolation of the diol by
good yield using 1.3 mol % of OsO and a 4.5:1:1 acetone:
4
9
precipitation. The required potassium organotrifluoroborate
t-BuOH:water solvent mixture at room temperature (entry
12
salts were prepared following literature protocols involving
transmetalation of Grignard reagents with trimethyl borate
1). The product was easily isolated as an analytically pure
white solid in 75% yield by a simple filtration. The use of
1
3
1
13
19
11
H, C, F, and B NMR as well as elemental analysis
(
11) (a) Upjohn (W. P. Schneider, A. V. McIntosh) US 2.769.824. (b)
VanRheennen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 17,
973.
12) (a) Vedejs, E.; Fields, S. C.; Hayashi, R.; Hitchcock, S. R.; Powell,
corroborated formation of the diol and retention of the
valuable trifluoroborate moiety.
We subsequently investigated the dihydroxylation of
potassium 4-butenyltrifluoroborate 1b (entry 2), in which the
olefin is closer to the electron-rich boron atom. The reaction
1
(
D. R.; Schrimpf, M. R. J. Am. Chem. Soc. 1999, 121, 2460. (b) Garrett, C.
E.; Fu, G. C. J. Org. Chem. 1996, 61, 1, 3224. (c) Pereira, S.; Srebnik, M.
J. Am. Chem. Soc. 1996, 118, 8, 909. (d) Vedejs, E.; Chapman, R. W.;
Fields, S. C.; Lin, S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, 0, 3020. (e)
Kabalka, G. W.; Narayana, C.; Reddy, N. K. Synth. Commun. 1994, 24,
1
019. (f) Burgess, K.; Ohlmeyer, M. J. Chem. ReV. 1991, 91, 1179. (g)
(13) Matteson, D. S. Tetrahedron 1989, 45, 1859.
(14) Kalinin, A. V.; Scherer, S.; Snieckus, V. Angew. Chem., Int. Ed.
2003, 42, 3399.
M a¨ nning, D.; N o¨ th, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878. (h)
Brown, H. C.; Bhat, N. G.; Somayaji, V. Organometallics 1983, 2, 1311.
76
Org. Lett., Vol. 8, No. 1, 2006

proceeded smoothly as expected to give the diol in excellent
yield. Optimization was required only of the solvent ratio to
a mixture of 18:1:1 acetone/t-BuOH/water. This new solvent
mixture became our standard condition because it facilitated
isolation of the diols. In addition, the dihydroxylation of
potassium 4-vinylphenyltrifluoroborate 1c (entry 3) demon-
strated that the same reaction conditions are applicable to
aryltrifluoroborates.
heteroatom â to the boron. Normally, organoboron com-
pounds with an electronegative atom, such as oxygen, at the
â-position eliminate rapidly via tetracoordination to the boron
(eq 2). This elimination process has been attributed to the
thermodynamic stability of the boron-oxygen bond.15 To
4
the best of our knowledge, only limited examples of this
15,17
type of organoboron compound have been reported.
Our next aim was to carry out the dihydroxylation on more
highly substituted olefins. Interestingly, 1,1-disubstituted
alkyltrifluoroborate 1d (entry 4) proved to be sensitive to
the reaction conditions. The apparent low yield reflects the
inability of all of the product to precipitate in pure form from
the reaction mixture. Thus, the majority of the product co-
precipitated with an impurity that could not be separated from
the desired dihydroxytrifluoroborate under several different
In the event, dihydroxylation of potassium allyltrifluo-
roborate, 5, proceeded smoothly under the reaction conditions
described previously (Scheme 2).
1
11
19
isolation protocols. On the basis of H, B, and F NMR,
we suspect cyclized product 3 as the impurity (Scheme 1),
Scheme 2
Scheme 1
Isolation of diol 6 was easily achieved using the cation
18
exchange protocol reported by Batey and Quach. Tetraco-
ordination of the boron atom by fluoride as well as the
strength of the B-F bond prevented oxidative cleavage and
protonolysis of the trifluoroborate moiety in this and our
6
earlier examples; these characteristics have now been
employed to prevent â-elimination as well.
The Suzuki-Miyaura-type coupling of potassium organ-
which would be generated by displacement of a fluoride by
one of the hydroxy groups of the diol. Similar behavior was
also observed in the dihydroxylation of organotrifluoroborate
otrifluoroborates has been the subject of extensive study in
4.
5
a
our group. Dihydroxylated alkyl- and aryltrifluoroborates
were anticipated to be good coupling partners. The presence
of free hydroxy groups was deemed unlikely to present a
problem because the cross-coupling reactions are often run
using alcohols as solvents. Therefore, the diols were sub-
jected to the cross-coupling reactions without the use of
protecting groups. The optimized reaction conditions reported
by our group for the Suzuki-Miyaura-type coupling reaction
between alkyltrifluoroborates and aryl bromides employ
Nevertheless, 1,1-disubstituted olefins can be successfully
dihydroxylated and isolated as shown by aryltrifluoroborate
e (entry 5). Diols from 1,2-disubstituted olefin-containing
organotrifluoroborates were also obtained in good yield
1
(
entries 6 and 7). Trisubstituted olefins are usually challeng-
10,15
ing substrates in cis-dihydroxylation.
This problem has
been attributed to slow hydrolysis of the intermediate osmate-
(
VI) ester, which results in low turnover in the catalytic
10,16
cycle.
The dihydroxylation of potassium 7-methyl-6-
octenyl trifluoroborate 1h, containing a trisubstituted olefin,
was achieved in good yield without the need to facilitate
the hydrolysis process (entry 8).
The lower yields for diols 2e, 2g, and 2h can be attributed
to difficulties associated with isolation. These products did
not precipitate readily.
PdCl
2
(dppf)‚CH
2
Cl
2
(9 mol %) and CsCO
3
(3 equiv) as a
base, heated to reflux in a 10:1 THF:H
2
O mixture.19 Thus,
with the potassium dihydroxytrifluoroborate 2b in hand, we
conducted a cross-coupling reaction with 4-cyanophenyl
bromide under these conditions to afford 4-cyanophenyl-1,2-
butanediol 7 in 65% yield after column chromatography (eq
3).
The dihydroxylation of potassium allyltrifluoroborate was
of particular interest because the diol produced contains a
(
17) Pereira, S.; Srebnik, M. Tetrahedron Lett. 1996, 37, 3283.
(
15) Ray, R.; Matteson, D. S. Tetrahedron Lett. 1980, 21, 449.
(18) Batey, R. A.; Quach, T. D. Tetrahedron Lett. 2001, 42, 9099.
(19) (a) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393. (b) Molander,
G. A.; Yun, C.-S.; Ribagorda, M.; Biolatto, B. J. Org. Chem. 2003, 68,
5534.
(16) (a) Akashi, K.; Palermo, R. E.; Sharpless, B. K. J. Org. Chem. 1978,
4
1
3, 2063. (b) Sharpless, B. K.; Akashi, K. J. Am. Chem. Soc. 1976, 98,
986.
Org. Lett., Vol. 8, No. 1, 2006
77

2 3
(0.5 mol %), K CO (3 equiv), methanol, reflux] to afford
the biaryl 9 in good yield (eq 5).
The cross-coupling of alkyltrifluoroborates with alkenyl
20
bromides is part of ongoing research. The ideal conditions
to date [PdCl (dppf)‚CH Cl (10 mol %), Cs CO (3 equiv),
2
2
2
2
3
In summary, the first cis-dihydroxylation of potassium
alkyl- and aryltrifluoroborates has been achieved. The
reaction is general for both sterically unhindered and hindered
olefins. The olefin-containing organotrifluoroborate salts are
readily available by the Grignard approach or selective
hydroboration of dienes. The diols were isolated as highly
pure solids. Their versatility and value as synthetic units was
also demonstrated. We successfully accomplished Suzuki-
Miyaura-type coupling reactions of the dihydroxylated tri-
fluoroborates. The cross-coupling reactions were carried out
without the need for protecting groups. Studies directed
toward the asymmetric version of this reaction are underway.
toluene/pH 9 buffer (3:1), 90 °C] were used to couple
potassium 3,4-dihydroxybutyltrifluoroborate (2b) with 3-bro-
mo-2-methyl-2-butene, affording the product in good yield
(eq 4). This reaction is particularly relevant because it
provides an efficient alternative to selective dihydroxylation
at a single olefinic site within a diene or polyene system.
Acknowledgment. We thank the National Institutes of
Health (GM 352419), Merck Research Laboratories, and
Amgen for their generous support. Also, Johnson Matthey
is acknowledged for their generous donation of catalysts.
Agilent Technologies and Rakesh K. Kohli at the University
of Pennsylvania are acknowledged for the determination of
high resolution mass spectra of some of the organotrifluo-
roborates.
The Suzuki coupling of aryltrifluoroborates with aryl
bromides has also been successfully developed by our
group. Therefore, potassium 4-(1′,2′-dihydroxyethyl)phen-
yltrifluoroborate, 2c, was reacted with 4-cyanophenyl bro-
21
Supporting Information Available: Full experimental
details. This material is available free of charge via the
Internet at http://pubs.acs.org.
mide under the previously optimized conditions [Pd(OAc)
2
(20) Dave Seapy, unpublished results.
(21) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302.
OL052549E
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