Catalytic asymmetric hydroboration of heterofunctional allylic substrates: an efficient heterogenized version

Article abstract of DOI:10.1016/j.tetasy.2007.03.031

The hydroboration of heterofunctional allylic systems with catecholborane (HBcat) using neutral and cationic rhodium complexes modified with P-P and P-N bidentate chiral ligands has been described in order to produce the secondary heteroorganoboronate ester as a major product with moderate enantioselectivity. The immobilization of cationic chiral rhodium complexes onto clays has beneficial effects on the recyclability and reuse of the catalytic system in particular for the hydroboration of allyl aryl sulfones.

Full text of DOI:10.1016/j.tetasy.2007.03.031

Tetrahedron: Asymmetry 18 (2007) 911–914
Catalytic asymmetric hydroboration of heterofunctional allylic
substrates: an efficient heterogenized version
*
´
Vanesa Lillo, Elena Fernandez and Anna M. Segarra
`
´
Dpt. Quı´mica Fı´sica i Inorganica, Universitat Rovira i Virgili, C/MarcelÆlı Domingo, 43007 Tarragona, Spain
Received 1 March 2007; accepted 29 March 2007
Abstract—The hydroboration of heterofunctional allylic systems with catecholborane (HBcat) using neutral and cationic rhodium
complexes modified with P–P and P–N bidentate chiral ligands has been described in order to produce the secondary heteroorgano-
boronate ester as a major product with moderate enantioselectivity. The immobilization of cationic chiral rhodium complexes onto clays
has beneficial effects on the recyclability and reuse of the catalytic system in particular for the hydroboration of allyl aryl sulfones.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
this study to the catalytic hydroboration of heterofunc-
tional allylic substrates, in order to see the influence of
the electronic properties of the O, N, and S heteroatoms
on the regiocontrol, and in the stereocontrol. In these cases
where the catalytic system provides an efficient and selec-
tive route to the corresponding secondary organoboronate
product, we explored the recovery and recycling of the
active metal species involved. The immobilization of chiral
rhodium-complexes onto clays had provided clear advanta-
ges in the past toward the asymmetric hydroboration of
vinylarenes,12 such as an improved stability of the metal
species under air, easy separation from the reaction mix-
ture by simple filtration and recycling for consecutive runs
without the loss of activity, regio- and stereoselectivity.
Indeed, there are few examples of recovery of the catalyst
in hydroboration reactions,13 but even less on the recycling
capability. The most recent work by Leitner et al. using the
biphasic IL/scCO2 methodology is one of the few exam-
ples.14 It is also noteworthy that none of these previous
attempts13,14 for recycling the catalytic system was studied
under the asymmetric version.
Regiochemical control in the hydroboration reaction of
vinylarenes can be assessed by a catalytic system, providing
suitable access to secondary organoboronate compounds.1
Alternatively, the electronic properties of heterofunctional
vinylic substrates, such as perfluoroalkenes2 and aryl vinyl
sulfides,3 allow strong regiocontrol toward the secondary
isomer formation, in the catalytic hydroboration with cate-
cholborane (HBcat, cat = 1,2-O2C6H4). This particular
electronic influence from heteroatom-containing substrates
has also been observed in the catalyzed hydroboration of
aryl allyl sulfones (PhSO2CH2CH@CH2)4 and allyl sulfon-
amides (ArSO2NRCH2CH@CH2; R = H, Ph, Bz)5 using
the precursors [RhCl(PPh3)3] and [HRh(PPh3)3] as cata-
lysts; this is in contrast to the catalytic hydroboration of
1-phenylprop-2-ene where mixtures of linear and branched
product were formed simultaneously.6
The regioselectivity toward the secondary regioisomer has
permitted the study of the asymmetric version of the cata-
lyzed hydroboration/oxidation of vinylarenes.7 However,
to the best of our knowledge, the asymmetric version of
the catalytic hydroboration reaction of heteroatom-con-
taining substrates has only been carried out in the case of
perfluoroalkenes8 and aryl allyl sulfones9 by our group.
Since heteroorganoboronate esters are extensively applied
in medicine10 and organic synthesis,11 we wanted to extend
2. Results and discussion
The use of ionic Rh(I) compounds modified with chiral
ligands such as (R,R)-BDPP and (S)-QUINAP (Fig. 1)
has already been demonstrated to catalyze aryl allyl sulf-
ones with a total conversion and high regioselectivity but
moderate enantiomeric excesses.9 This previous work,
was in agreement with Wescott’s5 observations on the hyd-
roboration of allyl sulfonamides, as far as the requirement
*
Corresponding author. Tel.: +34 977 559575; fax: +34 977 559563;
e-mail: anamaria.segarra@urv.cat
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.03.031

912
V. Lillo et al. / Tetrahedron: Asymmetry 18 (2007) 911–914
H
S
N
N
P
N
1
2
5
3
P
O
O
PPh2
O
S
S
O
O
(S)-QUINAP
(R,R)-BDPP
6
4
Figure 1.
Figure 2.
of an excess of hydroborating reagent is concerned, to keep
the catalytic activity high enough.
hydroboration of ArSO2N@CHCH2CH3 provided the
hydrogenation product.
When the catalytic hydroboration/oxidation (Scheme 1)
was performed on a series of heterofunctional allylic sub-
strates (Fig. 2) using cationic Rh complexes modified with
(R,R)-BDPP and an excess of HBcat as a hydroborating
reagent, conversion of the substrates was completed after
1 h (Table 1).
The hydroboration/oxidation of phenyl allyl ether 4 with
neutral and ionic rhodium complexes, showed a similar
activity and selectivity to N-allyl-N-methylaniline 3 (Table
1, entries 15–18). We observed that in both cases, the mod-
ification of rhodium complexes with (S)-QUINAP pro-
vided larger percentages of the secondary alcohol than
with (R,R)-BDPP as the chiral ligand.
The regiocontrol of the hydroboration/oxidation reaction
seems to depend on the electronic influence of the hetero-
functional group which plays a decisive role in obtaining
the desired branched product. As a general behavior, the
sulfone group of substrates 5 and 6 selectively induced
the Markovnikov alcohol product (Table 1, entries 1 and
3). However, the analogue sulfide substrate 1 showed a
lower regiocontrol giving a few percentage of the secondary
alcohol but linear and hydrogenated product instead
(Table 1, entry 5). When the cationic rhodium-complex
was modified with (S)-QUINAP, the percentage of the
branched organoboronate product was slightly improved
upon. In the case of substrates N-allylaniline 2 and N-
allyl-N-methylaniline 3, with both cationic and neutral
complexes, the regiocontrol was only moderate, although
the hydrogenated byproduct was almost not observed
(Table 1, entries 7–14). This is in contrast with Wescott’s5
observations on the catalytic hydroboration of allyl sulfon-
amides which show a competing isomerization reaction as
the main reason for the branched isomer formation in high
yields. In fact, they proposed a tandem isomerization/
hydroboration catalytic reaction whereby a rhodium-
hydride complex could be involved in the in situ transfor-
mation of allyl sulfonamides to the N-prop-1-en-1-yl
sulfonamide ArSO2NHCH@CHCH3 and N-propylidene
sulfonamide ArSO2N@CHCH2CH3. While the secondary
heteroorganoboronate was explained as the main product
of the hydroboration of ArSO2NHCH@CHCH3, the
The enantioselectivities obtained were moderate and were
determined either from the H NMR spectra in the pres-
1
ence of the chiral shift reagent Eu(TFC)3 or by CG with
a chiral column. Contrary to the electronic influence of
the heterofunctional group on the branched isomer forma-
tion, the enantioselectivity was not affected. When the
catalytic system was [Rh(COD)2]BF4/(R,R)-BDPP the ee
values were found to be between 22% and 32% for the sec-
ondary alcohol obtained from substrates 1–6. However,
lower ee values could be obtained for the same substrates
with the catalytic system [Rh(COD)2]BF4/(S)-QUINAP.
For the allyl phenyl ether substrate 4, the use of neutral
and ionic complexes modified with (S)-QUINAP afforded
higher asymmetric induction than cationic complex
[Rh(COD)2]BF4, modified with (R,R)-BDPP (Table 1,
entries 15 and 18).
In order to perform the heterogenized version of the cata-
lytic asymmetric hydroboration of heterofunctional allylic
systems, we selected the Rh(I) catalytic system that showed
the highest activity and selectivity. We tested the long-term
stability of [Rh(COD)2]BF4/(R,R)-BDPP and its recovery
and reuse in consecutive runs by its immobilization in the
smectita clay montmorillonite MK-10 (MK-10), previously
treated at 100 °C for 24 h. To immobilize the ionic rhodium
complex into the MK-10, the colored solution of the metal
OH
O
X
OH
X
H
B
X
[Rh],
X
*
O
+
+
R
EtOH/NaOH/H2O2
R
R
R
R= H; X= S, SO2, NH, NCH3, O
R= CH3; X= SO2
Scheme 1.

V. Lillo et al. / Tetrahedron: Asymmetry 18 (2007) 911–914
913
Table 1. Homogeneous asymmetric hydroboration/oxidation of aryl allyl systems with neutral and cationic rhodium catalytic precursora
Entry Catalytic system
Substrate Secondary alcoholb (%) eec (%)
Linear alcoholb (%) Hydrogenated productb (%)
1
[Rh(COD)2]BF4/(R,R)-BDPP
5
5
6
6
1
1
2
2
2
2
3
3
3
3
4
4
4
4
99
85
98
70
7f
32 (S)
12 (R)
34 (S)
16 (R)
—
1
15
—
30
67
30
33
35
39
23
59
88
49
42.5
60
76
39
32
—
—
2
—
25
40
—
3
2e
3
[Rh(COD)2]BF4/(S)-QUINAP
[Rh(COD)2]BF4/(R,R)-BDPP
[Rh(COD)2]BF4/(S)-QUINAP
[Rh(COD)2]BF4/(R,R)-BDPP
[Rh(COD)2]BF4/(S)-QUINAP
[Rh(COD)2]BF4/(R,R)-BDPP
[Rh(l-Cl)(COD)]2/(R,R)-BDPP
[Rh(COD)2]BF4/(S)-QUINAP
[Rh(l-Cl)(COD)]2/(S)-QUINAP
[Rh(COD)2]BF4/(R,R)-BDPP
[Rh(l-Cl)(COD)]2/(R,R)-BDPP
[Rh(COD)2]BF4/(S)-QUINAP
[Rh(l-Cl)(COD)]2/(S)-QUINAP
[Rh(COD)2]BF4/(R,R)-BDPP
[Rh(l-Cl)(COD)]2/(R,R)-BDPP
[Rh(COD)2]BF4/(S)-QUINAP
[Rh(l-Cl)(COD)]2/(S)-QUINAP
4e
5
6
7
8
9
10
11
12
13
14
15
16
17
18
30f
67
62
60
74
41
22
51
57.5
40
24
61
68
—
23 (S)
12 (S)
20 (R)
23 (R)
22 (S)
23 (S)
26 (R)
22 (R)
15 (S)d
22 (S)d
23 (R)d
25 (R)d
1
3
—
—
—
—
—
—
—
—
a Standard conditions: substrate/HBcat/Rh precursor = 1:3:0.0075, solvent: THF, T: 25 °C; t: 1 h. Oxidative workup with EtOH/NaOH/H2O2.
b Conversion, selectivities calculated by 1H NMR in CDCl3. Characterization was made in comparison with pure products, Refs. 16 and 17.
c Enantiomeric excess of the branched alcohol determined by 1H NMR in the presence of chiral shift reagent Eu(TFC)3. Absolute configuration was
assigned by comparison with Ref. 15.
d Enantiomeric excess of the branched alcohol was determined by GC with a chiral column, on derivative alcohols. Absolute configuration was assigned by
comparison with Ref. 15.
e Ref. 9.
f Branched organoboronate products.
Table 2. Heterogenized asymmetric hydroboration/oxidation of aryl allyl sulfonesa
Entrya
Catalytic system
Substrate
Run
Conversionb (%)
Branchedb (%)
eec (%)
Linearb (%)
1
[Rh((R,R)-BDPP)(COD)2]BF4/MK-10
5
1
2
3
4
100
100
100
89.5
93
98
94
97
32 (S)
34 (S)
36 (S)
29 (S)
7
2
6
3
2
[Rh((R,R)-BDPP)(COD)2]BF4/MK-10
6
1
2
3
100
100
100
>99
>99
>99
30 (S)
28 (S)
25 (S)
—
—
—
a Standard conditions: substrate/HBcat = 1:3 and 1.5% of catalytic precursor immobilized in 250 mg of MK-10, solvent: THF, T: 25 °C; t: 2 h. Oxidative
work-up with EtOH/NaOH/H2O2.
b Conversion, selectivities calculated by 1H NMR in CDCl3. Characterization was made in comparison with pure products, Ref. 17.
c Enantiomeric excess of the branched alcohols was determined by 1H NMR in the presence of chiral shift reagent Eu(TFC)3. Absolute configuration was
assigned by comparison with Ref. 15.
compound in anhydrous dichloromethane with MK-10
was stirred for 24 h at room temperature, under nitrogen,
following a solvent-impregnation methodology.12,18 The
high superficial area of the montmorillonite allows an
immobilization via adsorption of the cationic complex
and thus permitting an easy accessibility of the substrate
to the immobilized complex.
the first run and were maintained during four consecutive
runs (Table 2). Leaching of the catalyst was not observed.
These results show the capability of the [Rh((R,R)-
BDPP)(COD)]BF4/MK-10 catalytic system to be recovered
and reused in the asymmetric catalytic hydroboration/oxi-
dation reaction of allyl aryl sulfone for more than four
runs, obtaining the secondary alcohol as the major product
with moderate enantiomeric excess.
The experiments with the heterogenized rhodium catalytic
system [Rh((R,R)-BDPP)(COD)2]BF4/MK-10 were carried
out using the previously optimized conditions for the
homogeneous version in the hydroboration/oxidation of
both allyl phenyl sulfone 5 and allyl aryl sulfone 6 with
HBcat. The results are shown in Table 2.
3. Conclusion
We can conclude that the regioselectivity toward the sec-
ondary heteroorganoboronate ester in the hydroboration
of heterofunctional allylic substrates, is controlled by the
nature of the heteroatom, following the order:
SO2 > NH > N(CH3) ꢀ O ꢁ S. However, the enantioselec-
The activities, selectivities, and enantioselectivities were
similar to those of the homogeneous catalytic system from

914
V. Lillo et al. / Tetrahedron: Asymmetry 18 (2007) 911–914
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P.; Guiry, P. J. Adv. Synth. Catal. 2005, 347, 609–631.
tivity seems to be controlled by the chiral ligand and the
nature of the complex giving in all the cases moderated
enantiomeric excess. The cationic rhodium complex modi-
fied with (R,R)-BDPP was immobilized in MK-10 and
employed in the heterogenized hydroboration/oxidation
reaction of the allyl aryl sulfones showing an efficient
recovery and reuse of the catalytic system without the loss
of activity and selectivity.
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Acknowledgments
The authors want to thank the financial support from the
CICYT of Spain (CTQ2004-04412/BQU) and V.L. thanks
the MEC for a fellowship.
11. Fu, G. C. Transition Metals for Organic Synthesis Building
Blocks and Fine Chemicals; Wiley-VCH: New York, 1998;
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