Critical role of catalysts and boranes for controlling the regioselectivity in the rhodium-catalyzed hydroboration of fluoroolefins

Article abstract of DOI:10.1021/ol9909583

(formula presented) Catalytic hydroboration of perfluoroalkylethylenes (R_FCH=CH₂) with cationic and neutral rhodium complexes allows for selective access to either regioisomeric alcohol after hydroboration with catechol- and pinacolboranes, followed by oxidation with alkaline hydrogen peroxide.

Full text of DOI:10.1021/ol9909583

ORGANIC
LETTERS
1999
Vol. 1, No. 9
1399-1402
Critical Role of Catalysts and Boranes
for Controlling the Regioselectivity in
the Rhodium-Catalyzed Hydroboration of
Fluoroolefins
P. Veeraraghavan Ramachandran,* Michael P. Jennings, and Herbert C. Brown*
H.C. Brown and R.B. Wetherill Laboratories of Chemistry, Purdue UniVersity,
West Lafayette, Indiana 47907-1393
chandran@purdue.edu
Received August 18, 1999
ABSTRACT
Catalytic hydroboration of perfluoroalkylethylenes (R CHdCH ) with cationic and neutral rhodium complexes allows for selective access to
F
2
either regioisomeric alcohol after hydroboration with catechol- and pinacolboranes, followed by oxidation with alkaline hydrogen peroxide.
The introduction of fluorine in place of hydrogen often
improves the biological properties of organic molecules.1
Furthermore, fluorinated compounds are increasingly being
used in analytical, materials, and polymer chemistry due to
their unique properties.1 Accordingly, many effective meth-
ods for fluoroorganic synthesis have been reported.2 How-
ever, organoboranes have not been pursued in this respect
until recently,3 although they are routinely used in many
synthetic laboratories. The Markovnikov hydroboration of
perfluoroalkylethylenes, such as 3,3,3-trifluoropropene, has
been known for four decades.4 We reexamined the hydro-
boration of 3,3,3-trifluoropropene and observed that HBCl2
and HBBr2 provide Markovnikov products more selectively
than previously reported for BH3.5 In continuation of our
research on the utilization of organoboranes for the synthesis
of fluoroorganic compounds,6 we desired a simple, direct
method for selective access to the anti-Markovnikov isomer
as well. However, these 1°-fluoroalkyl boranes could not be
(1) (a) For several recent reviews, see: Biomedical Frontiers of Fluorine
Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; ACS Symposium
Series 639; American Chemical Society: Washington, DC, 1996. (b) Welch,
J. T. Tetrahedron 1987, 43, 3123. (c) Biochemistry InVoVlVing Carbon-
Fluorine Bonds; Filler, R., Ed.; ACS Symposium Series 28; American
Chemical Society: Washington, DC, 1976. (d) Smith, F. A. CHEMTECH.
1973, 422. (e) Filler, R. CHEMTECH. 1973, 752. (f) Biomedical Aspects
of Fluorine Chemistry; Filler, R., Kobayashi, Y., Eds.; Elsevier Biomedi-
cal: Amsterdam, 1982. (g) Kiselyov, A. S.; Strekowski, L. Org. Prep. Proc.
Int. 1996, 28, 289. (h) Harper, D. B.; O’Hagan, D. Nat. Prod. Rep. 1994,
123.
(2) (a) Asymmetric Fluoro-organic Chemistry: ACS Symposium Series
746; Ramachandran, P. V., Ed.; American Chemical Society: Washington,
DC, 1999, in press. (b) Kitazume, T.; Yamazaki, T. Experimental Methods
in Organic Fluorine Chemistry; Gordon and Breach Science: Amsterdam,
1998. (c) Burton, D. J.; Yang, Z.-Y.; Qiu, W. Chem. ReV. 1996, 96, 1641.
(d) Ojima, I. Chem. ReV. 1988, 88, 1011.
(3) (a) Ichikawa, J.; Hamada, S.; Sonoda, T.; Kobayashi, H. Tetrahedron
Lett. 1992, 33, 3779 and references therein. (b) Ramachandran, P. V.;
Teodorovic’, A. V.; Brown, H. C. Tetrahedron 1993, 49, 1725. (c)
Ramachandran, P. V.; Gong, B.; Teodorovic’, A. V.; Brown, H. C.
Tetrahedron: Asymmetry 1994, 5, 1061. (d) Ibid. 1994, 5, 1075. (e)
Ramachandran, P. V.; Gong, B.; Brown, H. C. J. Org. Chem. 1995, 60, 61.
(4) (a) Barotcha, B.; Graham, W. A. G.; Stone, F. G. A. J. Inorg. Nucl.
Chem. 1958, 6, 119. (b) Phillips, J. R.; Stone, F. G. A. J. Chem. Soc. 1962,
94.
(5) Brown, H. C.; Chen, G.-M.; Jennings, M. P.; Ramachandran, P. V.
Angew. Chem. Int. Ed. Engl. 1999, 38, 2052.
(6) Ramachandran, P. V.; Brown, H. C. Enantiocontrolled Synthesis of
Fluoro-Organic Compounds: Stereochemical Challenges and Biomedical
Targets; Soloshonok, V. A., Ed.; John Wiley and Sons Ltd.: 1999.
10.1021/ol9909583 CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/07/1999

produced by uncatalyzed hydroboration due to the low
reactivity of these fluorinated olefins toward sterically
hindered hydroborating reagents such as 9-BBN and Sia2BH.
Since the pioneering discovery by Ma¨nning and No¨th that
rhodium catalysts facilitate the hydroboration of alkenes with
catecholborane,7 there have been notable developments of
both achiral and chiral versions of this reaction with variation
in the catalysts, substrates, and boranes.8 It has been shown
that transition-metal-catalyzed and uncatalyzed hydroboration
reactions proceed via different mechanisms, periodically
resulting in opposite regiochemical outcomes.9 Sneddon and
co-workers had previously reported, as part of their extensive
study, the first rhodium-catalyzed hydroboration of 3,3,3-
trifluoropropene with borazine for use in materials chemis-
try.10 With this background, we decided to undertake a
systematic study of the rhodium-catalyzed hydroboration of
fluoroolefins to complement the uncatalyzed procedure.
Herein, we wish to report the critical importance of rhodium
catalysts and boranes in achieving high levels of selectivity
for both regioisomers.
The generality of this reaction was demonstrated by carrying
out the hydroboration of 3,3,3-trifluoropropene (1b) and
3,3,4,4,5,5,6,6,6-nonafluoro-1-hexene (1c) which provided
similar results. The hydroboration of 1d produced optimal
results (g97% 2°-product) at room temperature. The results
are summarized in Table 1.
Table 1. [Rh(COD)(dppb)]+BF4--Catalyzed Hydroboration of
Perfluoroalkyl(aryl)ethylenes with CBH in THF
no.
RF
T, °C
time (h)
yield (%)a
2°-ol
1°-ol
1a
1a
1a
1a
1a
1b
1c
1d
1d
C6F13
C6F13
C6F13
C6F13
C6F13
CF3
20
20
0
-25
-25
-25
-25
20
0.25
0.25
0.50
0.75
0.75
0.75
0.75
0.25
0.25
82 (71)
84 (72)
84 (74)
89 (77)
87 (74)
87
84 (73)
89 (80)
91 (82)
72
75
90
98
98
97
99
97
97
28
25
10
2
2
3
1
3
3
b
b
C4F9
C6F5
b
C6F5
20
As previously reported by Evans and co-workers, cationic
rhodium complexes were the most active for the hydro-
boration of alkenes.11 We chose these types of catalysts due
to the intrinsic lower reactivity of the electron deficient
fluoroolefins. To enhance the convenience of isolation, we
selected 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octene (1a)
and 2′,3′,4′,5′,6′-pentafluorostyrene (1d), as representative
examples of an aliphatic and aromatic perfluoroethylene
(RFCHdCH2).
The hydroboration of 1a at room temperature with 1 mol
% of [Rh(COD)(dppb)]+BF4- (2) and catecholborane (CBH)
in THF was complete in 0.25 h (11B δ 34.5). Alkaline H2O2
oxidation furnished the product alcohols in 71% isolated
yield. Gas chromatography (GC) revealed a moderate excess,
72%, of the 2°-alcohol with 28% of the 1°-alcohol (Scheme
1). Decreasing the reaction temperature to 0 °C increased
-
a GC (isolated). b Rh(NBD)(dppb)+BF4 used as catalyst.
We surmised that altering the electronics and sterics of
the catalyst could impede secondary and impose selective
primary insertion of the fluoroalkene into the rhodium
complex. Accordingly, we selected Wilkinson’s catalyst
(Rh(PPh3)3Cl (3) due to the metal coordinated anion and large
cone angle of the PPh3 ligands.
The hydroboration of 1a with 1 mol % of 3 and 1.5 equiv
of CBH in THF was complete in 0.5 h (11B NMR δ 34.5
ppm). Alkaline H2O2 oxidation provided an excess of the
1°-alcohol (76% vs 24%) in 60% isolated yield. Contrary to
the cationic catalysts, lowering the temperature had very little
effect on selectivity. Hydroboration was also performed with
1b and 1c, and we observed a modest effect of the RF chain
length on the regioselectivity (Scheme 2).
Scheme 1
Scheme 2
the regioselectivity to 9:1. Subsequent lowering of the
temperature to -25 °C produced essentially pure 2°-alcohol.
However, hydroboration of 1d still provided the Markov-
nikov product (79%) which improved to >99% upon the
addition of excess PPh3. The results are compiled in Table
2.
(7) Ma¨nnig, D.; No¨th, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 879.
(8) For the most recent comprehensive review, see: Beletskaya, I.; Pelter,
A. Tetrahedron 1997, 53, 4957.
(9) (a) Hayashi, T.; Matsumoto, Y.;. Ito, Y. Tetrahedron: Asymmetry
1991, 2, 601. (b) Evans, D. A.; Fu, G. C.; Hoyveda, A. H. J. Am. Chem.
Soc. 1988, 110, 6917. (c) Evans, D. A.; Fu, G. C.; Anderson, B. A. J. Am.
Chem. Soc. 1992. 114, 6679.
(11) Evans, D. A.; Fu, G. C.; Hoyveda, A. H. J. Am. Chem. Soc. 1992,
114, 6671.
(10) Frazen, P. J.; Sneddon, L. G. Organometallics 1994, 13, 2867.
1400
Org. Lett., Vol. 1, No. 9, 1999

Table 2. Rh(PPh3)3Cl (1 mol %) Catalyzed Hydroboration of
Perfluoroalkyl(aryl)ethylenes with CBH
no.
RF
T, °C
time (h)
yield (%)a
2°-ol
1°-ol
1a
1a
1a
1b
1b
1c
1d
1d
C6F13
C6F13
C6F13
CF3
20
20
0
20
20
20
20
20
0.5
3
1
1
1
1
0.5
0.5
71 (60)
74 (64)
79 (67)
71
24
31
36
47
45
38
79
>99
76
69
64
53
55
62
21
<1
b
c
CF3
73
C4F9
C6F5
C6F5
74 (62)
79 (70)
81 (72)
c
Figure 1.
a GC (isolated) yield. b 0.1 mol % of catalyst. c 2 equiv of PPh3.
Gratified by the partial success achieved, we chose to study
the effect of variation in the hydroborating reagents. Wilkin-
son’s catalyst (3) had previously been reported to accelerate
the hydroboration of simple olefins and acetylenes with
pinacolborane (PBH).12 On the basis of this result, we
envisaged that a bulkier borane might lead to the desired
anti-Markovnikov product. Indeed, the hydroboration of 1a
(1.5 equiv) with PBH in the presence of 2 mol % of 3
provided the 1°-product in 71% isolated yield and 97%
regioisomeric purity! Having attained our goal, we examined
other perfluoroalkylethylenes 1b and 1c, and the results were
similar (Scheme 3).
cationic rhodium catalyst 2 preferentially forms the sterically
hindered 2°-alkyl rhodium complex due to the electronic
effect exerted by the RF groups (pathway B). In addition,
reductive elimination must be more facile than a â-H
elimination (C) followed by a primary reinsertion sequence
(A). However, similar to that of styrene, the catalyst binds
as a more stable η-3 complex with 1d, and the corresponding
reductive elimination provides the Markovnikov product
exclusively.
Upon the reaction of 3 and CBH, olefins 1a-c presumably
undergo both 1°- and 2°-insertions (pathways A and B).
Reductive elimination of the hindered 2°-alkyl complex may
procee at a rate comparable to or even faster than that of
pathway C, to account for the production of 2°-alcohol. For
the hydroboration with PBH, there are two distinct possibili-
ties. A highly selective (>92%) primary insertion takes place
due to the steric hindrance of the rhodium-borane complex
(path A), followed by elimination providing the 1°-product.
However, we cannot discount the possibility of an initial
olefin insertion pattern similar to CBH, followed by a rapid
isomerization of the very sterically congested 2°-alkyl
complex placing the metal on the least hindered carbon
(pathway C and then A). Subsequent reductive elimination
would yield the 1°-product in high regioselectivity.
Scheme 3
In conclusion, we have realized our goal of preparing anti-
Markovnikov perfluoroalkyl boranes via neutral Rh-mediated
catalytic hydroboration with pinacolborane.13 In addition, we
have also shown that the Markovnikov products can be
obtained via cationic Rh-catalyzed hydroboration with cat-
echolborane at low temperatures. Thus we have discovered
the first example of direct access to either regioisomer for
the catalytic hydroboration of aliphatic olefins by varying
the catalyst and borane. Given the importance of fluorine-
The hydroboration of 1d produced a majority (60 vs 25%)
of the 1°-boronate ester along with 15% of a â-styrenyl
boronate ester side product. The results are summarized in
Table 3.
Table 3. Rh(PPh3)3Cl (2 mol %) Catalyzed Hydroboration of
Perfluoroalkyl(aryl)ethylenes with PBH at Room Temperature
no.
RF
time (h)
yield (%)a,b
2°-ol
1°-ol
(12) Pereira, S.; Srebnik, M. J. Am. Chem. Soc. 1996, 118, 909.
(13) A typical experimental procedure for the hydroboration of fluoro-
alkenes with Wilkinson’s catalyst and PBH is as follows. Wilkinson’s
catalyst (2 mol %) was placed and weighed in a 50-mL round-bottom flask
under argon followed by 3 mL of dry THF. Pinacolborane (3 mmol) was
then added to this solution and maintained at room temperature. After 5
min, 1a (4.5 mmol) was added slowly and the solution was stirred until the
reaction was complete by 11B NMR (δ 33.4). The boronate ester was then
oxidized by adding 3 mL of 3 M NaOH and 3 mL of 30% H2O2, slowly.
The crude product was analyzed by GC to give 97% of the 1°-alcohol and
3% of the 2°-alcohol with a combined isolated yield of 71%.
1a
1b
1c
1d
C6F13
CF3
C4F9
2.5
2
2.5
2.5
76 (71)
73
74 (68)
70 (61)
3
8
4
97
92
96
60
c
C6F5
25
a GC (isolated) yield. b Yield based on PBH. c Isolated as boronate esters.
(14) Brown, H. C. Organic Syntheses Via Boranes; Wiley-Interscience:
New York, 1975. Reprinted edition, Vol. 1. Aldrich Chemical Co. Inc.,
Milwaukee, WI, 1997. Chapter 9.
On the basis of previous mechanistic studies,9c we offer
the following rationale for our observations (Figure 1). The
Org. Lett., Vol. 1, No. 9, 1999
1401

containing molecules in agricultural, medicinal, and materials
chemistry, we believe these results will lead to the synthesis
of various fluoroorganic molecules via established organo-
borane chemistry.14
Acknowledgment. We thank the Purdue Borane Research
Fund for financial assistance.
OL9909583
1402
Org. Lett., Vol. 1, No. 9, 1999