Heterofunctional control of regio- and enantioselectivity in rhodium-catalysed hydroboration of allylic systems

Article abstract of DOI:10.1016/j.tetasy.2006.01.030

Aryl allylic sulfones were reacted with catecholborane (HBcat) in the presence of neutral and cationic Rh complexes modified with bidentate chiral ligands, to produce the branched heteroorganoboronate ester, as the main isomer with moderate enantioselecti

Full text of DOI:10.1016/j.tetasy.2006.01.030

Tetrahedron: Asymmetry 17 (2006) 315–319
Heterofunctional control of regio- and enantioselectivity
in rhodium-catalysed hydroboration of allylic systems
*
´
Vanesa Lillo and Elena Fernandez
`
´
Dpt. Quı´mica Fı´sica i Inorganica, Universitat Rovira i Virgili, C/Marcel.lı Domingo, 43007 Tarragona, Spain
Received 5 December 2005; accepted 30 January 2006
Abstract—Aryl allylic sulfones were reacted with catecholborane (HBcat) in the presence of neutral and cationic Rh complexes modi-
fied with bidentate chiral ligands, to produce the branched heteroorganoboronate ester, as the main isomer with moderate enantio-
selectivity. The relative rate of the formation of the secondary regioisomer seems to be sensitive to the nature of the catalytic system
and the electronic effects of the substrate.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
(Scheme 1, path b). Even more remarkable is the regio-
control provided by the electronic properties of hetero-
atom-containing substrates,5 such as phenyl vinyl
sulfide, which regioselectively adds the boron unit from
catecholborane at the 2-position of the alkene, in the
rhodium-catalysed hydroboration reaction (Scheme 1,
path c).6
The unusual secondary alcohol produced in the rho-
dium-catalysed hydroboration/oxidation of vinylarenes
is believed to arise from metal-stabilisation of the benz-
ylic intermediate during the catalytic cycle (Scheme 1,
path a).1,2 Either catalysed3 or uncatalysed4 hydrobora-
tion/oxidation reactions can also exhibit special control
towards formation of the branched alcohol on perfluoro-
alkenes substrates, probably due to the combined
electronic effects of the borane reagent and the substrate
However, the directing effects, which revealed a trend in
regioisomeric branched organoborane formation, seem
to diminish substantially from vinylic to allylic systems.
Path b
Path a
O
O
B H
B H
O
O
O
O
O
O
RhLn
RhLn
B
B
Ar
LnRh
Fn+1Cn
+1
R = Ar
R = CnFn
R
O
O
RhLn
B H
Path c
R = SPh
O
O
B
PhS
Scheme 1.
*
Corresponding author. Tel.: +34 9 77 558046; fax: +34 9 77 559563; e-mail: elenaf@quimica.urv.es
0957-4166/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.01.030

316
V. Lillo, E. Ferna´ndez / Tetrahedron: Asymmetry 17 (2006) 315–319
RhLn
HBcat
NaOH/H2O2
OH
Ph
Ph
+
+
+
Ph
Ph
OH
Ph
Ph
OH
33%
2%
65%
O
O
HBcat =
B H
Scheme 2.
[RhCl(PPh3)3]
HBcat
O
+
RO2S
B
RO2S
RO2S
B
O
O
O
O
87%
13%
RO2S
[HRh(PPh3)3]
HBcat
RO2S
RO2S
+
N
H
O
N
B
O
N
H
H
B
O
100%
0%
Scheme 3.
Such is the case for the hydroboration/oxidation of
1-phenylprop-2-ene,7 which provided mixtures of
primary and secondary regioisomers (Scheme 2). In
addition this substrate, where the aromatic group is in
b-position to the alkene moiety, can undergo isomerisa-
tion of the double bond, which favours the formation of
1-arylpropanol.
synthetic utility of chiral organosulfurboronate esters in
biological applications,12 we decided to examine the cat-
alytic chiral hydroboration/oxidation of allyl sulfones,
to determine whether it was possible to preferentially
obtain one of the enantiomers of 1-(phenylsulfonyl)-2-
propanol.
Surprisingly, the metal-catalysed hydroboration of some
heteroatom substituted allylic substrates has furnished
the desired branched heteroorganoboronate ester as a
consequence of the nature of the catalyst. Thus, Wilkin-
son’s catalyst precursor [RhCl(PPh3)3] favours the
formation of the secondary boronate ester in the
hydroboration of allyl sulfones8 (Scheme 3), while
[HRh(PPh3)4] does the same for the hydroboration of
allyl sulfonamides9 (Scheme 3).
2. Results and discussion
Hou and Dai’s observations on the catalytic hydrobora-
tion of allyl sulfones8 show that the neutral Rh(I)
precursor of catalyst [RhCl(PPh3)3] favours addition
of the catecholboryl unit at the 2-position of the
terminal alkene. When we re-examined this reactivity,
we first found that the conversion of the substrate
was total and that, as well as the branched and linear
hydroborated/oxidated products, small percentages of
hydrogenated derivatives could be obtained as a
consequence of the partial formation of the metal
The reversed regioselectivity from terminal B–H addi-
tion in aliphatic and unfunctionalised terminal alkenes
to the branched manner in vinylic systems made it pos-
sible to study an asymmetric version of the catalysed
hydroboration/oxidation of vinylarenes10 and more
recently, we explored the case of perfluoroalkenes.11 How-
ever, to the best of our knowledge no work has been
carried out in this respect for heteroatom-containing
allylic substrates.
13
complex RhH2Cl(PPh3)3 (Table 1, entries 1 and 2;
Scheme 4).
In the hydroboration/oxidation of phenyl allyl sulfones,
an excess of hydroborating reagent seemed to be neces-
sary to guarantee a high selectivity (Table 1, entry 3). A
low chemo- and regioselection towards the branched
alcohol was detected when the sterically hindered hydro-
borating reagent pinacolborane was used instead of
catecholborane (Table 1, entry 4). Next, we decided to
study how Rh-neutral and Rh-cationic catalytic systems
affected the activity and selectivity of hydroboration of
organosulfur substituted 1-alkenes. Like Wilkinson’s
In this context and as a result of our ongoing research
into the use of organoboranes for the synthesis of enan-
tiomerically pure organic compounds, we herein report
a direct and simple method for generating enantiomeri-
cally enriched heterofunctionalised alcohols. Due to the

V. Lillo, E. Ferna´ndez / Tetrahedron: Asymmetry 17 (2006) 315–319
Table 1. Rhodium-catalysed hydroboration/oxidation of phenyl allyl sulfone, 1a
317
Entry
Catalytic system
Conversion (%)b
PhO2S
PhO2S
OH
PhO2S
OH
(%)b
(%)b
(%)b
1c
2
[RhCl(PPh3)3]
[RhCl(PPh3)3]
[RhCl(PPh3)3]
[RhCl(PPh3)3]
[Rh(l-Cl)(COD)]2 + 6equiv PPh3
[Rh(l-Cl)(NBD)]2 + 6equiv PPh3
[Rh(COD)2]BF4 + 2equiv PPh3
[Rh(COD)2]BF4 + 2equiv PPh3
83
100
100
100
100
100
100
100
87
86.2
37
42.3
84.2
84.3
54
13
8.2
43
—
5.6
20
39.7
5.7
6
13.2
6
3d
4e
5
18
10.1
9.7
32.8
—
6
7
8f
94
a Standard conditions: substrate/hydroborating reagent HBcat/Rh = 1/3/0.0075; solvent: THF; T: 25 °C; t: 4 h.
b Conversion and selectivity calculated by 1H NMR.
c Ref. 9, where 3 mol % of Rh catalyst is used.
d Hbcat (1 equiv).
e Hydroborating reagent: Hbpin (3 equiv).
f Addition of 3 equiv of BnMe3NCl.
HBcat or HBpin
RhLn
+
RO2S
RO2S
OH
+
RO2S
RO2S
OH
NaOH/H2O2
1 R = Ph
2 R = p-MePh
3 R = p-ClPh
O
O
O
O
B H
HBcat =
HBpin =
B H
Scheme 4.
catalyst precursor, a preferentially secondary insertion
of the alkene into the metal complex formed from
[Rh(l-Cl)(COD)]2/6 equiv PPh3 [Rh(l-Cl)(NBD)]2/
6 equiv PPh3 has was observed (Table 1, entries 5 and
6). These results differ from the preferential primary
insertion of organofluoro substituted 1-alkenes with
neutral catalytic systems.3
P
P
CH3
H3C
H3C
P
P
P
P
(R,R)-BDPP
(S,S)-Chiraphos
(R)-Prophos
As a general behaviour, the catalytic hydroboration of
phenyl allyl sulfones with neutral Rh complexes pro-
vides higher selectivity towards branched organosulfur-
boronate esters than cationic Rh complexes (Table 1,
entry 7). The considerable neutralising influence of chlo-
rine as counterion was confirmed in a new experiment in
which the salt BnMe3NCl was added to the catalytic sys-
tem formed from [Rh(COD)2]BF4/PPh3 (Table 1, entry
8) because the products were distributed in a very simi-
lar way to when the system [Rh(l-Cl)(COD)]2/6 equiv
PPh3 was used.
N
PPh2
PPh2
PPh2
(S)-Quinap
(R)-Binap
Figure 1.
To analyse to what extent the relative activity, regio-
and enantioselectivity are sensitive functions of the
chiral ligand, new catalytic hydroboration/oxidation
reactions of phenyl allyl sulfone were performed with
cationic and neutral Rh complexes modified with
(R)-Prophos, (S,S)-Chiraphos, (R,R)-BDPP, (R)-Binap
and (S)-Quinap. Conversion of the substrate was com-
plete after 4 h but selectivity for the secondary alcohol
was significantly dependent on the nature of the Rh
Taking into account all these preliminary experiments,
we envisaged that chiral bidentate phosphine ligands
might lead to the desired branched boronate ester with
some asymmetric induction. The ligands considered
for this study were those described in Figure 1, which
form five-, six- and seven-membered rings on chelation
with rhodium.

318
V. Lillo, E. Ferna´ndez / Tetrahedron: Asymmetry 17 (2006) 315–319
Table 2. Catalytic asymmetric hydroboration/oxidation of phenyl allyl sulfone with Rh complexes and HBcata
Entry
Catalytic system
Conv. (%)b
Secondary alcohol (%)b
ee (%)c
1
2
3
4
5
6
7
8d
9
10e
11
12
[Rh(COD)2]BF4 + (R)-Prophos
[Rh(l-Cl)(COD)]2 + (R)-Prophos
[Rh(COD)2]BF4 + (S,S)-Chiraphos
[Rh(l-Cl)(COD)]2 + (S,S)-Chiraphos
[Rh(COD)2]BF4 + (R,R)-BDPP
[Rh(l-Cl)(COD)]2 + (R,R)-BDPP
[Rh(COD)2]BF4 + (R)-Binap
100
100
100
100
100
100
100
100
100
100
100
100
90
54
88
69
98
77
74
12
87
87
85
89
8 (S)
3 (S)
17 (S)
11 (S)
30 (S)
33 (S)
22 (S)
39 (S)
38 (S)
38 (S)
12 (R)
12 (R)
[Rh(COD)2]BF4 + (R)-Binap
[Rh(l-Cl)(COD)]2 + (R)-Binap
[Rh(l-Cl)(COD)]2 + (R)-Binap
[Rh(COD)2]BF4 + (S)-Quinap
[Rh(l-Cl)(COD)]2 + (S)-Quinap
a Standard conditions: substrate/catecholborane/Rh = 1/3/0.0075; solvent = THF; T = 25 °C; t = 4 h.
b Conversion and selectivity calculated by 1H NMR.
c Enantiomeric excess determined by GC with a chiral column, as derivative alcohols. Absolute configuration by comparison with Ref. 15.
d Hydroborating reagent HBpin.
e T = À20 °C.
complex and the chiral ligand. Small percentages of
hydrogenated product could be observed. For those
ligands, which chelate with rhodium to form five-
and six-membered rings, (R)-Prophos, (S,S)-Chiraphos,
(R,R)-BDPP, major regioselection was observed for
the secondary alcohol with the cationic rhodium catal-
ytic system (Table 2, entries 1–6). A certain level of
enantioenrichment (ee = 30–33.4%) was attained when
ligand (R,R)-BDPP was involved (Table 2, entries 5
and 6). However, when the atropoisomeric chiral ligand
(R)-Binap chelates with rhodium to form a seven-mem-
bered ring, a change in the dependency of the electronic
nature of the metal complex was detected. Major regio-
selectivity towards the secondary alcohol was associ-
ated with the neutral rhodium catalytic systems, which
were also responsible for the highest ee values obtained
in this preliminary study (Table 2, entries 7–10). The use
of other hydroborating reagents or lower reaction tem-
peratures did not improve these results. In an attempt
to combine the beneficial effects of the atropoisomeric
ligand (R)-Binap and the ability to chelate with rhodium
and form a six-membered ring by (R,R)-BDPP, we next
focused on the atropoisomeric heterotopic chiral ligand
(S)-Quinap, which chelates with Rh to form a six-mem-
bered ring. However, despite the efficiency shown by this
P,N ligand in several enantioselective syntheses,14
we were disappointed to observe that while regioselec-
tivity remained high, enantioselectivity decreased
significatively.
favoured with chiral ligands that form major chelate
rings with rhodium(I) complexes.
We demonstrated the generality of the regio- and enan-
tioselective hydroboration/oxidation reaction of aryl
allyl sulfones as a function of the electronic and steric
properties, by carrying out the catalytic reaction on elec-
tron-rich and electron-deficient substituted phenyl allyl
sulfones. Of the many sulfone synthetic procedures
described in the literature,16 we prepared the p-methyl-
phenyl allyl sulfone, 2, and p-chlorophenyl allyl sulfone,
3, with an efficient and inexpensive protocol, which uses
the bismuth-catalysed coupling of allylic halides with the
corresponding sulfonyl chloride, under mild condi-
tions17 (Scheme 5).
Bi /THF
ArO2S
+
ClSO2Ar
Cl
2 Ar = p-MePh
3 Ar = p-ClPh
Scheme 5.
The results of the Rh-catalysed hydroboration/oxida-
tion of 2 and 3 were similar to the phenyl allyl sulfone.
The data are summarised in Table 3. Almost complete
regioselectivity for the secondary alcohol was achieved
when [Rh(COD)2]BF4/(R,R)-BDPP was used as a catal-
yst precursor (Table 3, entries 1 and 7) and ee values
At this point, we can infer two things from our initial
asymmetric catalytic results. Firstly, regioselectivity for
the secondary alcohol depends upon the electronic prop-
erties of the substrate, but also on the electronic proper-
ties of the metal complex used as the catalyst. To
highlight the importance of this point, we carried out
two catalytic reactions with the analogue neutral com-
plex [Ir(l-Cl)(COD)]2 modified with (R)-Binap and
(S)-Quinap. However, only 23% and 28% of the second-
ary alcohol was observed, respectively, with almost no
ee’s values. Secondly, enantioselectivity seemed to be
1
around 33% were determined from the H NMR spec-
trum in the presence of the chiral shift reagent
Eu(TFC)3. Contrary to the strong electronic influence
of the aryl sulfonyl functional group on the branched
isomer formation, additional beneficial effect by aryl
substitution with electron-withdrawing groups was
detected. The asymmetric induction has not either been
affected by any aryl substitution on the aryl allyl
sulfone.

V. Lillo, E. Ferna´ndez / Tetrahedron: Asymmetry 17 (2006) 315–319
319
Table 3. Catalytic asymmetric hydroboration/oxidation of substituted phenyl allyl sulfone with Rh complexes and HBcata
Entry
Catalytic system
Substrate
Secondary alcohol (%)b
ee (%)c
1
2
3
4
5
6
7
8
[Rh(COD)2]BF4 + (R,R)-BDPP
[Rh(l-Cl)(COD)]2 + (R,R)-BDPP
[Rh(COD)2]BF4 + (R)-Binap
[Rh(l-Cl)(COD)]2 + (R)-Binap
[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 + (R)-Binap
[Rh(l-Cl)(COD)]2 + (R)-Binap
[Rh(COD)2]BF4 + (S)-Quinap
[Rh(l-Cl)(COD)]2 + (S)-Quinap
2
2
2
2
2
2
3
3
3
3
3
3
98
49
74
52
70
76
95
37
73
38
50
38
34 (S)
33 (S)
11 (S)
7 (S)
16 (R)
25 (R)
33 (S)
30 (S)
17 (S)
13 (S)
7 (R)
9
10
11
12
16 (R)
a Standard conditions: substrate/catecholborane/Rh = 1/3/0.0075; solvent = THF; T = 25 °C; t = 4 h.
b Conversion (100% in all cases) and selectivity calculated by 1H NMR.
c Enantiomeric excess determined by 1H NMR in the presence of chiral shift reagent Eu(TFC)3. Absolute configuration by comparison with Ref. 15.
7. Wescott, S. A.; Blom, H. P.; Marder, T. B.; Baker, R. T. J.
Am. Chem. Soc. 1992, 114, 8863.
3. Conclusion
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We can conclude that we have performed the first
example of direct access to enantiomerically enriched
mixtures of 1-phenylsulfonyl-2-propanol, by varying
the catalytic system throughout the hydroboration/
oxidation of aryl allyl sulfones with catecholborane.
Given the importance of sulfur-substituted 2-propanols
as sulfur-containing chiral synthons in asymmetric
organic synthesis,18 we believe these results provide an
unexplored synthetic alternative, via organoborane
chemistry, that deserves further study in the near
future.
Acknowledgements
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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.
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