New insights on the asymmetric hydroboration of perfluoroalkenes

Article abstract of DOI:10.1039/b313991c

Enantioselective access to Markovnikov regioisomeric perfluoroalcohols is achieved in the presence of chiral cationic rhodium complexes and specific hydroborating reagents.

Full text of DOI:10.1039/b313991c

New insights on the asymmetric hydroboration of perfluoroalkenes
Anna M. Segarra, Carmen Claver and Elena Fernandez*
Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Pça. Imperial Tàrraco 1, 43005
Tarragona, Spain. E-mail: elenaf@quimica.urv.es; Fax: 34 977 559563; Tel: 34 977 558046
Received (in Cambridge,UK) 4th November 2003, Accepted 3rd December 2003
First published as an Advance Article on the web 19th January 2004
Enantioselective access to Markovnikov regioisomeric per-
fluoroalcohols is achieved in the presence of chiral cationic
rhodium complexes and specific hydroborating reagents.
(entries 2 and 3). Similar behaviour was attributed to the catalytic
system [Rh(COD)(dppb)]BF (entries 4–6), although in the latter
4
1
case the regioselectivity was almost quantitative. When (R)-BINAP
was used instead of dppb as the chiral ligand, enantiomeric excesses
were between 60 and 65.5%, under those reaction conditions.
In contrast to the cationic catalysts, a preferentially primary
insertion has been detected of the fluoroalkene into the neutral-Rh
The directing effects of electronegative substituents on 2-substi-
tuted-1-alkenes can substantially modify the regioselectivity ex-
1
2,3
pected both in the transition-metal catalysed and uncatalysed
hydroboration reaction. The reversal of the regioselectivity from
Markovnikov “B–H” addition in unfunctionalised terminal olefins
to the anti-Markovnikov manner in perfluoroalkylethylenes,4
makes it possible to add the borane at the 2-position. However,
other factors that must be taken into account for the control of
regioselectivity in the hydroboration of fluoroolefins are the
hydroborating reagents, the reaction temperature and the electronic
nature of the rhodium complex when it is used as a catalyst
precursor, Scheme 1.
2
complex formed from [Rh(m-Cl)(COD)] –2 equiv. (R)-BINAP.
However, it had very little effect on enantioselectivity, as the e.e.
values remained about 60.5% (Table 1, entry 7). The neutralising
influence of chlorine as a coordinated counterion was confirmed in
a new experiment where the salt BnMe
catalytic system [Rh(COD)(R)-(BINAP)]BF
3
NCl was added to the
, and the products
4
were distributed in a very similar way to when the neutral system
was used (Table 1, entry 8). A complete undesired regioselection
towards the primary alcohol was obtained when the sterically
hindered borane pinacolborane was used instead of catecholborane
as the hydroborating reagent in the presence of [Rh(COD)(R)-
The regioselectivity for a series of fluorinated terminal olefins
can be controlled by choosing the appropriate reaction conditions.
This makes it possible to synthesise the suitable anti-Markovnikov
4
(BINAP)]BF (entry 9).
1
fluoroalkylborane isomers. However, this process has not been
The generality of this reaction was demonstrated by carrying out
the hydroboration of 3,3,4,4,5,5,6,6,6-nonafluoro-1-hexene, 2. The
results were similar to those when catecholborane was used as the
hydroborating reagent (Table 1, entry 10). Alkene isomerization
was not observed during the reaction, in contrast to the observed
trend with hydroboration of unfunctionalized alkenes.6
subjected to an asymmetric catalytic version in order to get the
chiral product. Due to the synthetic utility of chiral fluoroorganic
compounds,5 both in biological and analytical applications, we
decided to undertake for the first time a systematic study of the
asymmetrically rhodium-catalysed hydroboration of perfluoroalk-
ylethylenes.
On the basis of the observations by P. V. Ramachandran and H.
C. Brown that cationic Rh( ) complexes are effective for the
I
Markovnikov hydroboration/oxidation of perfluoroalkyl-ethylenes
1
when catecholborane is used as reagent, we decided to examine
how a cationic catalytic system modified with a chiral diphosphine
ligand affected the process (Scheme 2). In order to make a
comparison with previous studies where dppb was used as bidentate
ligand, we chose (R)-BINAP because both ligands make a
Scheme 2
7-membered chelate with rhodium in the complex.
We started by examining the hydroboration/oxidation of a model
Table 1 Rh–BINAP-catalysed enantioselective hydroboration/oxidation of
substrate 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octene, 1, with 1
mol% of [Rh(COD)(R)-(BINAP)]BF and catecholborane (Scheme
). As is shown in Table 1, the reaction was almost complete within
h at room temperature (entry 1). Regioselection on the secondary
perfluoroalkylolefins with catecholboranea
4
2
1
Catalytic
system
Rh(COD)L–L]-
BF
2°-
alcohol was favoured and increased at low reaction temperatures
Yieldb
T/°C (%)
alcoholb
[
b
Entry
4
R
F
(%)
e.e. (%)
1
2
3
(R)-BINAP
B
B
dppb
B
B
C
B
B
B
B
B
B
B
B
6
F
13
20
0
278
20
0
225
20
20
20
0
99
99
23
82
84
89
99
99
99
99
86
70
84
81
72
90
98
46
35
0
62(+)
65.5(+)
60(+)
—
—
—
60.5(+)
50(+)
—
64(+)
19.5g
c
4
c
5
c
6
d
7
(R)-BINAP
e
8
B
B
B
B
f
9
1
1
a
0
1
C
C
4
F
F
9
80
97
6
5
20
Standard conditions: olefin/catecholborane/Rh complex
=
1/1.1/0.01.
Solvent: THF. T: 20 °C. Time: 1 h. b Determined by GC with chiral column
c
FS-Cyclodex B-IP, 50 m 3 0.25 mm. Ref. 1 with 2 mol% of catalyst.
d
e
2
Precursor of catalyst: [Rh(m-Cl)(COD)] /(R)-BINAP. Addition of 0.03
mmol of BnMe
3
NCl. Pinacolborane. g (R) Enantiomer.
f
Scheme 1
4
64
C h e m . C o m m u n . , 2 0 0 4 , 4 6 4 – 4 6 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

Attending to the fact that the steric factors of the catalyst alter as
much as the electronics in the substrate the access to the sterically
hindered 2-perfluoroalkyl-rhodium intermediate, we studied the
into the primary alkyl–rhodium, throughout a b-H elimination
process, which could also be favoured by the steric demand around
the metal. A high and complete degree of the secondary alkyl–
rhodium complex is obtained by using both “(R)-BINAP–Rh” and
“(S)-QUINAP–Rh” complexes, respectively, when catecholborane
is involved in the reaction. In these cases, the lower steric demand
around the reaction site leads to placement of the metal at the most
hindered carbon, as is expected because of the electronic effect
exerted by the fluorinated alkene.
7
influence of the QUINAP derived Rh-catalyst on the regio- and
stereoselectivity of the hydroboration reaction. Using catecholbor-
ane as the hydroborating reagent, 1 and 2 were transformed into
their corresponding alcohols with complete regioselectivity (Table
2, entries 1 and 3). However the induced chirality was lower than
the chirality provided by the analogue (R)-BINAP derived Rh-
catalyst, even at low temperatures (entry 2). We then conducted the
hydroboration of 1 and 2 with the more sterically demanding
hydroborating reagent pinacolborane, and surprisingly we also
obtained the secondary perfluoroalkylborane quantitatively, with
e.e. values up to 55% (entries 4 and 5). Symmetrically internal alkyl
pinacolboronate products could be previously formed in the
To obtain a total picture of the process, it should be mentioned
that the oxidation of the secondary alkyl–rhodium intermediate,
obtained from both chiral complexes, “(S)-QUINAP–Rh” and “(R)-
BINAP–Rh”, provided principally the same (+)-enantiomer. This
contrasts substantially with the trend observed in the hydro-
boration/oxidation of styrene, where the “(S)-QUINAP–Rh” cata-
lyst provided the (S)-1-phenylethanol and the “(R)-BINAP–Rh”
3 2 3
presence of [RhCl(CO)(PPh ) ] and [NiCpCl(PPh )Cl] but not with
8
9
[RhCl(PPh
3
)
3
].
catalyst provided the (R)-enantiomer. The enantiodifferentiation
It should be pointed out that both cationic Rh-catalytic systems
in the case of the vinylarenes has been previously explained by
some intermolecular p–p stacking interaction between the ligand
and the substrate.10 The lack of phenyl groups in the perfluoroalk-
enes 1 and 2 suggests that the coincidence in the main enantiomer
formed could be due to the configuration of the Rh–H fragment
when it is transferred to the coordinated alkenes. This extreme is
confirmed by an additional experiment, where 2A,3A,4A,5A,6A-
pentafluorostyrene was subjected to the hydroboration/oxidation
reaction with catecholborane and both chiral catalytic systems. In
accordance with the regioselective trend observed with the
hydroboration of vinylarenes, the aromatic perfluoroalkene gave
the (S) enantiomer product in presence of the “(S)-QUINAP–Rh”
and the (R) enantiomer with (R)-BINAP (Table 1, entry 11, Table
2, entry 6, respectively).
The consistently moderate e.e. values (55–65%) obtained here in
the hydroboration of aliphatic perfluoroalkenes are even higher
than those observed in the aromatic perfluoroalkenes (18–19.5%),
and in electron-deficient vinylarenes such as 3,5-bis-trifluoro-
methylstyrene (5%), and 2,6-difluorostyrene ( < 15%).
The results show how asymmetry can be induced in the
hydroboration of perfluoroalkenes. The search for new systems to
improve the e.e. is in progress.
behave differently towards the formation of the secondary-alkyl
rhodium complex due principally to the steric properties of the
hydroborating reagent involved in the intermediates. As can be seen
in Scheme 3, the use of pinacolborane provides almost exclusively
the secondary insertion of the perfluoroalkenes on the “(S)-
QUINAP–Rh” catalyst, but the primary insertion of the same
substrates on the “(R)-BINAP–Rh” catalyst. Presumably the most
congested “(R)-BINAP–Rh–pinacolboryl” intermediate could be
the reason for the terminal olefin insertion. However it cannot be
excluded that this product may also be the result of the
isomerization of a plausible secondary alkyl–rhodium intermediate
Table 2 Rh–QUINAP-catalysed enantioselective hydroboration/oxidation
a
of perfluoroalkenes
2
°-
Yieldb alcohol
b
Hydroborating
Entry reagent
b
R
F
T/°C
13 20
(%)
(%)
e.e. (%)
1
2
3
4
5
6
a
catecholborane
B
B
pinacolborane
B
catecholborane
C
B
6
F
99
99
99
99
99
97
99
99
99
99
99
97
20(+)
19(+)
25(+)
55(+)
53.5(+)
0
C
4
C
6
C
4
C
6
F
F
F
F
9
20
13 20
9
20
20
Notes and references
c
5
18
1
2
3
4
P. V. Ramachandran, M. J. Jennings and H. C. Brown, Org. Lett., 1999,
, 1399–1402.
H. C. Brown, G.-M. Chen, M. J. Jennings and P. V. Ramachandran,
Angew. Chem., Int. Ed., 1999, 38, 2052.
Standard conditions: olefin/catecholborane/Rh complex
Solvent: THF. T: 20 °C. Time: 1 h. Determined by GC with chiral column
FS-Cyclodex B-IP, 50 m 3 0.25 mm. c (S) Enantiomer.
=
1/1.1/0.02.
1
b
P. V. Ramachandran and M. J. Jennings, Chem. Commun., 2002,
3
86–387.
(a) B. Barotcha, W. A. G. Graham and F. G. A. Stone, J. Inorg. Nucl.
Chem., 1958, 6, 119; (b) J. R. Phillips and F. G. A. Stone, J. Chem. Soc.,
1
962, 94.
5
P. V. Ramachandran and H. C. Brown, in Enantiocontrolled Synthesis
of Fluoro-Organic Compounds: Stereochemical Challenges and Bio-
medical Targets; V. A. Soloshonok, Ed.; John Wiley and Sons Ltd.,
New York, 1999.
6
7
T. C. Morill and Ch. A. D’Souza, Organometallics, 2003, 22,
1
626–1629.
J. M. Brown, D. I. Hulmes and T. P. Layzell, J. Chem. Soc., Chem.
Commun., 1993, 1673.
8
9
S. Pereira and M. Srebnik, Tetrahedron Lett., 1996, 37, 3283–3286.
(a) T. Hayashi, Y. Matsumoto and Y. Ito, Tetrahedron: Asymmetry,
1
991, 2, 601–612; (b) H. Doucet, E. Fernandez, P. T. Layzell and J. M.
Brown, Chem. Eur. J., 1999, 5, 1320–1330.
1
0 J. M. Brown, H. Doucet, E. Fernandez, H. E. Heeres, M. W. Hooper, D.
I. Hulmes, F. I. Knight, T. P. Layzell and G. C. Lloyd-Jones, in
Organometallics in Organic Synthesis, Transition Metal Catalysed
Reactions. A “Chemistry for the 21st Century” monograph, ed. S. I.
Murahashi and S. G. Davies, Blackwell Science, Oxford, 1999, pp.
465–481.
Scheme 3
C h e m . C o m m u n . , 2 0 0 4 , 4 6 4 – 4 6 5
465