Investigation of the factors controlling the regioselectivity of the hydroboration of fluoroolefins

Article abstract of DOI:10.1039/b108389a

Either Markovnikov or anti-Markovnikov regioselectivity can be achieved at will during the hydroboration-oxidation of perfluoroalkyl(aryl)ethylenes by varying the hydroborating agent.

Full text of DOI:10.1039/b108389a

Investigation of the factors controlling the regioselectivity of the
hydroboration of fluoroolefins
P. Veeraraghavan Ramachandran* and Michael P. Jennings
Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, West
Lafayette, IN, USA 47907-1393. E-mail: chandran@purdue.edu; Fax: 765-494-0239; Tel: 765-494-5303
Received (in Corvallis, OR, USA) 25th September 2001, Accepted 13th November 2001
First published as an Advance Article on the web 30th January 2002
Either Markovnikov or anti-Markovnikov regioselectivity
can be achieved at will during the hydroboration–oxidation
of perfluoroalkyl(aryl)ethylenes by varying the hydroborat-
ing agent.
the formation of the 1°-ol in 94 and 95% regioselectivities in 80
and 85% yields, respectively.
Clearly, the dihaloboranes might be exhibiting a special case
of Markovnikov hydroboration–oxidation with fluoroolefins
due to a combined electronic effects of the reagent and the
subtrate. Interestingly, variants of HBCl2 provided a mixture of
regioisomeric products revealing a trend dependent on both the
alkyl moiety and the Lewis acidity of the borane reagents.
Monochloroborane (ClBH2) provided a majority of the 2°-ol
(84%).3 The exchange of a halogen atom for a cyclohexyl
moiety also led to 80% of 2°-ol. The moderately electrophilic
Dihaloboranes (Br2BH and Cl2BH) are unique hydroborating
agents. For example, dibromoborane preferentially hydro-
borates 2-substituted-1-alkenes in the presence of unsubstituted
terminal olefins.1 In comparison, diisoamylborane, (Sia2BH)
furnishes the complementary product from the latter alkenes.1
Again, Br2BH chemoselectively hydroborates an internal
acetylene in the presence of a terminal alkene, whereas a
dialkylborane, 9-borabicyclo[3.3.1]nonane (9-BBN), provides
the complementary product from the hydroboration of the olefin
moiety.2
7
and sterically hindered boranes, ChxBH2 and thexylborane
(ThxBH2), readily hydroborated 1a within 1 h at rt to afford a
1+1 regioisomeric mixture after oxidation [eqn. (1)].
Recently we reported the reaction of dihaloboranes with
fluorinated olefins, followed by oxidation providing Markovni-
kov hydration products, whereas the lone dialkylborane tested,
9-BBN, is inert to such alkenes.3 We had surmised that this is
entirely due to the effect of the fluorine atoms. Herein we have
demonstrated that the reagent also plays an important role in
determining the regioselectivity for the hydroboration of
fluoroolefins.
(1)
A careful examination of the kinetics and mechanism of
hydroboration suggested that 9-BBN might have been an
improper reagent to hydroborate perfluoroalkylethylenes.
Brown and coworkers have shown that the kinetic rate
expressions and thus the mechanistic pathways of hydro-
boration with dialkylboranes depend on the reagent and
substrate used. For example, with less nucleophilic olefins, the
reaction sequence with (9-BBN)2 expressed a three-halves
order kinetic rate (2d[(9-BBN)2]/dt = K3/2[(9-BBN)2]1/2[alk-
ene]) in which the rate-determining step is the olefin hydro-
boration and not the dimer dissociation. However, it has been
confirmed that (Sia2BH)2 reacts by means of a second order
kinetic rate (2d[(Sia2BH)2]/dt = K1[(Sia2BH)2][alkene]) re-
gardless of alkene reactivity.4 Contrary to that of 9-BBN, the
kinetic evidence supported a direct attack of the substrate on the
dimer, and not a prior dissociation followed by hydro-
boration.4
Additional support for the above hypothesis that the re-
gioselectivities observed in the hydroboration of perfluoroalk-
ylethylenes with dihaloboranes are due to combined effects of
the substrate and the reagent was obtained by probing the
hydroboration of fluoroolefins with inserted methylene spacers.
Thus, hydroboration of 4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoro-
non-1-ene8 (1d) with HBCl2, followed by alkaline H2O2
oxidation provided a 1+1 mixture of 1°- and 2°- regioisomers9
in 89% yield [eqn. (2)]. However, the dialkylborane provided
pure 1°-alcohol. Thus, homologation of 1a by a methylene
entity significantly diminished the electron withdrawing effect
of the perfluoroalkyl group when hydroborated with a dihalo-
borane.
On the basis of the above rate expressions, we envisaged that
(Sia2BH)2 might reveal different reactivity toward perfluoroalk-
ylethylenes. Indeed, the reaction of 3,3,4,4,5,5,6,6,7,7,8,8,8-tri-
decafluoro-1-octene (1a) with (Sia2BH)2 proceeded to comple-
tion within 14 h at rt, as revealed by 11B NMR spectroscopy.
Alkaline H2O2 oxidation provided a 3+2 regioisomeric mixture
favoring the anti-Markovnikov alcohol. In all probability, the
lack of regioselectivity might be due to the disproportionation
of the borane as it is unstable at rt for long periods of time (vide
infra for regioselectivities with monoalkylboranes).5 This
prompted us to examine the relatively stable dicyclohexylbor-
ane (Chx2BH).6 As anticipated, the hydroboration was complete
within 16 h at rt and oxidation furnished essentially pure 1°-ol!
The generality of the anti-Markovnikov hydration of fluorinated
olefins with sterically demanding Chx2BH was further demon-
strated by the reaction with 3,3,3-trifluoropropene (1b) and
3,3,4,4,5,5,6,6,6-nonafluoro-1-hexene (1c), which resulted in
(2)
Introducing a second methylene spacer between the alkene
and the perfluoroalkyl entity10 restored the anti-Markovnikov
regioselectivity for hydroboration–oxidation with dichlorobor-
ane [eqn. (3)]. Hydroboration–oxidation of both 1d and 1e with
Sia2BH furnished essentially regiopure 1°-ol.11
(3)
386
CHEM. COMMUN., 2002, 386–387
This journal is © The Royal Society of Chemistry 2002

The results from the hydroboration–oxidation of 1a–e with
sterically and electronically diverse borane reagents are summa-
rized in Table 1.
In order to delineate the effect of the pentafluorophenyl
group, as performed previously with the aliphatic olefins, the
regioselectivity of 3-(2A,3A,4A,5A,6A-pentafluorophenyl)-1-pro-
pene (1g) was examined under the standard HBCl2and Sia2BH
conditions. Hydroboration of 1g with HBCl2, followed by
alkaline peroxide oxidation provided an 86% yield of a regio-
isomeric mixture of 94+6 favoring the 1°-ol.12 As expected,
Sia2BH also furnished the 1°-ol exclusively [eqn. (5)]. Ob-
viously the effect of the pentafluorophenyl group is dependent
on the conjugation of the olefin to the aromatic ring in that just
by removing the perfluoroaryl group by one carbon the effect
ceased almost entirely. The results for the hydroboration of 1f
and 1g are also summarized in Table 1.
The hydroboration–oxidation of perfluoroarylethylenes is
even more fascinating. 2,3,4,5,6-Pentafluorostyrene (1f) pro-
vided the Markovnikov product exclusively with HBCl2 or
HBBr2.3 In contrast to the inertness of 1a toward 9-BBN, 1f
reacted within 96 h and furnished 92% of the 1°-ol (anti-
Markovnikov product). The hydroboration of 1f with Chx2BH
readily proceeded within 1 h at rt and provided 85% of the
1°-regioisomer. By utilizing (Sia2BH)2, enhanced regioselectiv-
ities were observed (94%, 1°-ol) within 0.75 h at 0 °C under
identical conditions [eqn. (4)].
(5)
(4)
In summary, we have observed a rare example of complete
regioselective control for a series of fluorinated terminal olefins
by a judicious choice of borane reagent. By investigating the
hydroboration of these olefins, a dramatic difference in
reactivity between similar dialkylboranes, 9-BBN, Chx2BH,
and Sia2BH has been observed. With Chx2BH the hydro-
boration–oxidation of perfluoroalkyl(aryl)ethylenes readily
proceeds to provide predominantly the anti-Markovnikov
isomer, in contrast to the procedure involving HBCl2. Conse-
quently, it is now possible to conveniently synthesize either
regioisomer of fluoroalkylboranes from the corresponding
olefins by selecting the appropriate borane reagent. We are
testing the limits of this selectivity and utilizing these
intermediates in fluoroorganic syntheses.
Table 1 Hydroboration–oxidation of 1a–1g with representative borane
reagents
Product alcohol
Olefin Reagent
Solvent
Time/h Yield (%) 2°-ola 1°-ol
We thank the Herbert C. Brown Center for Borane Re-
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1e
1e
1f
1f
1f
1f
1f
1f
1f
1g
1g
BCl2H
BBr2H
BClH2
Hexane
Hexane
Et2O
inst.
inst.
24
1
1
1
16
16
96
inst.
inst.
16
inst.
inst.
16
inst.
10
inst.
4
inst.
inst.
1
1
1
90
90
86
82
78
81
82
86
0
82
82
80
84
84
85
81
83
88
79
90
90
73
82
82
52
86
78
88
99
99
84
80
51
50
40
5
NR
99
99
6
99
99
5
50
3
1b
1b
16
20
49
50
60
95
search13 and Eastman Kodak Co. for financial assistance.
ChxBClH Hexane
ChxBH2
ThxBH2
Sia2BH
Chx2BH
9-BBN
BCl2H
BBr2H
Chx2BH
BCl2H
BBr2H
Chx2BH
BCl2H
Chx2BH
BCl2H
Chx2BH
BBr2H
THF
THF
THF
THF
Notes and references
1 (a) H. C. Brown and N. Ravindran, J. Am. Chem. Soc., 1977, 99, 7097;
(b) H. C. Brown and J. B. Campbell, J. Org. Chem., 1980, 45, 389.
2 H. C. Brown and J. Chandrasekharan, J. Org. Chem., 1983, 48, 644.
3 H. C. Brown, G.-M. Chen, M. P. Jennings and P. V. Ramachandran,
Angew. Chem., Intl. Ed., 1999, 38, 2052.
4 H. C. Brown, J. Chandrasekharan and K. K. Wang, Pure and Appl.
Chem., 1983, 55, 1387.
THF
Hexane
Hexane
THF
Hexane
hexane
THF
Hexane
THF
Hexane
THF
1b
1b
94
1b
1b
5 H. C. Brown and A. W. Moerikofer, J. Am. Chem. Soc., 1961, 83,
3417.
95
50
97
99
99
6 G. Zweifel, N. R. Ayyangar and H. C. Brown, J. Am. Chem. Soc., 1963,
85, 2072.
7 H. C. Brown and S. K. Gupta, J. Am. Chem. Soc., 1971, 94, 4062.
8 S. Matsubara, M. Mitani and K. Utimoto, Tetrahedron Lett., 1987, 28,
5857.
9 (a) N. O. Brace, L. W. Marshall, C. J. Pinson and G. Wingerden, J. Org.
Chem., 1984, 49, 2361; (b) N. O. Brace, J. Fluorine Chem., 1982, 20,
313.
10 W. A. Herrmann, W. Wagner, U. N. Flessner, U. Volkhardt and H.
Komber, Angew. Chem., 1991, 103, 1704.
11 M. Kotora, M. Hajek, B. Ameduri and B. Boutevin, J. Fluorine. Chem.,
1994, 68, 49.
12 G. M. Brooke and D. I. Wallis, J. Chem. Soc., Perkin Trans. 1, 1981,
1659.
13 Contribution No. 15 from the Herbert C. Brown Center for Borane
Research.
1
1
Hexane
Hexane
94
92
70
50
15
8
6
6
1
6b
8b
30
BCl2H
ChxBClH Hexane
ThxBH2
CHx2BH
9-BBN
Sia2BH
BCl2H
THF
THF
THF
THF
Hexane
THF
50
85
92
94
94
99
96
0.75
inst.
0.75
Sia2BH
a Determined by a combination of 1H NMR, 19F NMR, and GC analysis.
b From ref. 3.
CHEM. COMMUN., 2002, 386–387
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