Regiochemical control of the catalytic asymmetric hydroboration of 1,2-diarylalkenes

Article abstract of DOI:10.1039/b508292g

The hydroboration of stilbenes and related disubstituted alkenes catalysed by QUINAP complexes may proceed with high enantio- and regioselectivity; rhodium and indium catalysts give the same product regioisomer but opposite enantiomers. The Royal Society

Full text of DOI:10.1039/b508292g

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Regiochemical control of the catalytic asymmetric hydroboration of
1,2-diarylalkenes
Antonia Black, John M. Brown* and Christophe Pichon{
Received (in Cambridge, UK) 13th June 2005, Accepted 16th September 2005
First published as an Advance Article on the web 5th October 2005
DOI: 10.1039/b508292g
observed in its thermal reaction to alkene 1, which occurred with
95% regioselectivity. When the corresponding dppb complex was
employed as catalyst, the alternative regioisomer was obtained
preferentially albeit with weak selectivity (Scheme 1).
The hydroboration of stilbenes and related disubstituted
alkenes catalysed by QUINAP complexes may proceed with
high enantio- and regioselectivity; rhodium and iridium
catalysts give the same product regioisomer but opposite
enantiomers.
These initial results encouraged the hydroboration of a range of
unsymmetrical (E)-stilbenes, designed to probe steric and especially
electronic effects. Results are outlined in Table 1.§
The Rh-complex catalysed asymmetric hydroboration of styrenes
with secondary boronate esters may proceed with high enantio-
selectivity, affording a route to benzylic alcohols,1,2 primary or
secondary amines,3 or carboxylic acids.4 Chelating phosphinamine
ligands have shown broader substrate scope than diphosphines
and can be effective at ambient temperature. The 2,29-disubstituted
biaryl P–N moiety introduced with QUINAP,5 has been modified
and more recently extended in this context.6 Although catechol-
borane is most widely used as reagent, good results have been
obtained recently with pinacolborane.7 There is a general, albeit
ligand-dependent,8 favouring of boron delivery to the benzylic
position of a vinylarene. This follows a pattern established for
many related Rh-catalysed X–H additions, including hydrosilyla-
tion and hydroformylation.9 The Spencer–Yu test demonstrates
preferential Rh addition to the benzyl position of b-substituted
styrenes in hydrogenation.10
Not only is the QUINAPRh+ hydroboration far more
regioselective than the corresponding hydroboration with
dppbRh+, but its direction is predictable. The secondary alcohol
arising from C–B oxidation is preferentially formed adjacent to the
more electron-deficient of the two arenes in the QUINAPRh+ case.
A weaker but similar trend in the dppbRh+ reactions is overridden
by the steric effect of o-F substituents; cf. the first and last entries
of Table 1. As in previous studies, the e.e. is highest when the arene
is electron-rich, and much diminished by the presence of strongly
electron-withdrawing groups other than fluorine. This is illustrated
by the results obtained with simple styrenes bearing the same
substituents, shown in Scheme 2.
An interesting example of the interplay between electronic and
steric effects is afforded by the substituted 1,1-diphenylethylene 10.
This gives predominantly the tertiary alcohol 11 with
QUINAPRh+, albeit in low enantiomer excess, whilst the primary
alcohol 12 is clearly preferred in the case of dppbRh+. This further
illustrates the sensitivity of the diphosphine catalyst to steric effects
(Scheme 3).
The Rh-complex catalysed hydroboration/oxidation of (E)- or
(Z)-stilbene can be carried out in good e.e. using QUINAP as
ligand.11 We have been interested in the factors controlling
regiochemistry when the stilbene is unsymmetrical, for synthetic
and mechanistic reasons. The alkene 1 was prepared and reacted
with catecholborane under the conditions of Scheme 1, with
conventional oxidation of the intermediate boronate; the alcohol
product was analysed. Only one regioisomer 2 was detected, as
confirmed from the three-bond CH2 o-ArH coupling observed in
the HMBC spectrum. This was shown to be the (S)-enantiomer{
formed in 77% isolated yield and 88% e.e. by comparison of the
CD spectrum in EtOH with an authentic sample of (S)-1,2-
diphenylethanol prepared by asymmetric hydroboration, of
known absolute configuration.12 A similar level of enantioselec-
tivity had previously been found for either isomer of the parent
alkene stilbene, and compares with e.e. ranges of 53–87 (E), and
59–99 (Z) obtained with the related quinazoline-based ligand
family developed by Guiry and co-workers, the only other
examples of asymmetric stilbene hydroboration reported to occur
in high e.e.6a The same direction of catecholborane addition was
The regiochemical control observed in these reactions encour-
aged a reexamination of the claim that asymmetric hydroboration
with rhodium catalysts proceeds by a different mechanism from
hydroboration with iridium catalysts.14 Iridium catalysts are
known to reverse the stereochemical course, and to account for
this it was suggested that C–B formation precedes C–H formation.
Scheme 1 (i) Catecholborane (1 equiv.), (1) (1 equiv.),
2 mol%
Chemical Research Laboratory, Mansfield Rd., Oxford, UK OX1 3TA.
E-mail: john.brown@chem.ox.ac.uk; Fax: 44 1865 285002;
Tel: 44 1865 275642
{ Present address: LECSO-UMR 7582, Universite´ Paris XII, 2 rue Henri-
Dunant, 94320 Thiais, France.
QUINAPRh+OTf2, RT, 16 h, then 1 mol% catalyst, catecholborane
(0.5 equiv.), 16 h, RT; for Dppb+OTf2, 2 mol% catalyst, 16 h; thermally –
catecholborane (4 equiv.), 70 uC, 5 h. Oxidative workup was with 30% aq.
H2O2 in 1 M NaOH.
5284 | Chem. Commun., 2005, 5284–5286
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Table 1 Hydroboration of unsymmetrical stilbenes with QUINAPRh+
ReactantAr1CHLCHAr2
Major Product
YieldE.e.a
Regioselectivityb
Ar1 5 Ph
Ar2 5 C6F5
55
60
100 (20)
Ar1 5 p-MeOPh
Ar2 5 p-FPh
51
83
83
90
Ar1 5 Ph
Ar2 5 3,5-(CF3)2Ph
49
29
Ar1 5 Ph
Ar2 5 3,4,5-(MeO)3Ph
48
85
90 (60)
Ar1 5 Ph
62
67
80 (63)
75 (60)
100 (45)
Ar2 5 2-naphthylc
Ar1 5 Ph
Ar2 5 2-thiophenyl
72
95
Ar1 5 C6F5
81
83
Ar2 5 2-thiophenyld
a
b
E.e.’s were determined by HPLC (Diacel OD, C6H12/i-PrOH), or by the P(III) method.13 Bracketed values refer to the selectivity towards
the same regioisomer employing dppbRh+. (Z)-Isomer of alkene. See text for discussion of the reaction with QUINAPIr+PF6 which gives
the opposite hand of product 9.
c
d
2
This possibility is effectively ruled out by the direct comparison
between QUINAPRh+ and QUINAPIr+ as catalysts for the
asymmetric hydroboration, both leading to the same regioisomer
9, (the last entry of Table 1). Both the reactivity (40% yield) and
enantioselectivity are lower in the iridium case and the configura-
tion of the product is reversed, an e.e. of 33% (R) being observed.
Success in the regiochemical control of stilbene hydroborations
encouraged us to examine the differentially protected bis-catechol
derivative 13, prepared by intramolecular Heck reaction via
vinylarene 14 (from piperonal) and bromide 15. Asymmetric
hydroboration using QUINAPRh+ proceeded with pleasingly high
regioselectivity and enantioselectivity, such that a single product
was readily isolated from the reaction at 0 uC in ¢ 98%
regioselectivity (Scheme 4). The structure 16 was that expected
from the precedents of boron transfer to the more electron-
deficient carbon of the alkene. The observed specificity demon-
strates clearly just how sensitive is the hydroboration step to
electronic effects.
The high levels of regiochemical control observed, especially in
the QUINAPRh+ case, indicate that the catalyst can actively
function to enhance selectivity. Good enantioselectivity can be
obtained adjacent to an electron-withdrawing arene in the stilbene
but not the styrene case (compare Schemes 1 and 2). In other
asymmetric catalytic reactions arene–arene interactions have been
convincingly proposed to explain observed specificities.15 In the
present case analysis is facilitated by the availability of X-ray
structures for (E)-stilbene diphosphine complexes.16 Model build-
ing based on derived parameters, and existing QUINAPPd
Scheme 3 (i) Conditions as Scheme 1(i); 66% yield in QUINAPRh
Scheme 2 Conditions as Scheme 1(i), yields 69%; 91%.
hydroboration.
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yield the single isomer 1-pentafluorophenyl-2-(3,4,5-trimethoxyphenyl)etha-
nol as analytically pure white crystals (529 mg, 70%), mp 5 135–137 uC. dH
(400 MHz; CDCl3) 6.41 (2H, s, Ar-H), 5.30 (1H, dd, CHOH, J 5 5.8,
8.4 Hz), 3.87 (6H, s, m-CH3 6 2), 3.86 (3H, s, p-CH3), 3.26 (1H, dd,
CH2CHOH, J 5 5.8, 14.1 Hz), 3.03 (1H, dd, CH2CHOH, J 5 8.4, 14.1
Hz), 2.00 (1H, bs, OH); dC (100.6 MHz; CDCl3) 153.3, 137.1, 132.0 (Ar-C),
106.0 (Ar-CH), 67.0 (CHOH), 60.7 (p-CH3), 56.0 (m-CH3 6 2), 43.2
(CH2CHOH); dF (376.5 MHz; CDCl3) 2142.90 (p), 2154.54 (o), 2161.59
(m); nmax/cm21 (Nujol), 3419 (br, s, OH), 2725 (m, OMe), 1460 (s, CLCH),
1128 (s, C–F), 721 (w, C–F); lmax (CH2Cl2) 227 (log e 3.1), 265 (log e 2.3);
HRMS (M+) calculated for C17H16F5O4: 379.0947; found 379.0956.
Repetition with enantiomerically pure (S)-catalyst gave 1-pentafluorophe-
nyl-2-(3,4,5-trimethoxyphenyl)ethanol (537 mg, 71%); 88% (S) by HPLC
(227 nm, cyclohexane : IPA/98 : 2, 1 ml/min, rt 5 19.6 and 23.1); [a]D22 18.5
(c 5 0.2, CH2Cl2).
1 K. Burgess and M. J. Ohlmeyer, J. Org. Chem., 1988, 53, 5178;
T. Hayashi, Y. Matsumoto and Y. Ito, Tetrahedron: Asymmetry, 1991,
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2 Recent reviews: C. M. Crudden and D. Edwards, Eur. J. Org. Chem.,
2003, 4695; A.-M. Carroll, T. P. O’Sullivan and P. J. Guiry, Adv. Synth.
Catal., 2005, 347, 609.
Scheme 4 (i) PdCl2/P(o-tolyl)3, (2 mol%), 14 (1.25 equiv.), 15 (1 equiv.),
Et3N, 100 uC, 85%; (ii) conditions as Scheme 1(i), 0 uC, 78%.
3 E. Fernandez, M. W. Hooper, F. I. Knight and J. M. Brown, Chem.
Commun., 1997, 173; E. Fernandez, K. Maeda, M. W. Hooper and
J. M. Brown, Chem.-Eur. J., 2000, 6, 1840; K. Maeda and J. M. Brown,
Chem. Commun., 2002, 310.
4 A. C. Chen, L. Ren and C. M. Crudden, Chem. Commun., 1999, 611;
A. Chen, L. Ren and C. M. Crudden, J. Org. Chem., 1999, 64, 9704;
L. Ren and C. M. Crudden, Chem. Commun., 2000, 721.
5 N. W. Alcock, J. M. Brown and D. I. Hulmes, Tetrahedron:
Asymmetry, 1993, 4, 743.
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2000, 1333; D. J. Connolly, P. M. Lacey, M. McCarthy, C. P. Saunders,
A. M. Carroll, R. Goddard and P. J. Guiry, J. Org. Chem., 2004, 69,
6572; (b) F. Y. Kwong, Q. C. Yang, T. C. W. Mak, A. S. C. Chan and
K. S. Chan, J. Org. Chem., 2002, 67, 2769.
Scheme 5 Stilbene si-face coordination in asymmetric hydroboration
using (S)-QUINAPRh+ based on the N-trans-alkene model. H atoms are
omitted for clarity.
7 A. M. Segarra, C. Claver and E. Fernandez, Chem. Commun., 2004,
464; A. M. Segarra, E. Daura-Oller, C. Claver, J. M. Poblet, C. Bo and
E. Fernandez, Chem.-Eur. J., 2004, 10, 6456; C. M. Crudden,
Y. B. Hleba and A. C. Chen, J. Am. Chem. Soc., 2004, 126, 9200.
8 S. A. Westcott, H. P. Blom, T. B. Marder and R. T. Baker, J. Am.
Chem. Soc., 1992, 114, 8863.
9 T. Hayashi, S. Hirate, K. Kitayama, H. Tsuji, A. Torii and Y. Uozumi,
J. Org. Chem., 2001, 66, 1441; K. Nozaki, T. Matsuo, F. Shibahara and
T. Hiyama, Adv. Synth. Catal., 2001, 343, 61.
10 J. Q. Yu and J. B. Spencer, J. Am. Chem. Soc., 1997, 119, 5257.
11 H. Doucet, E. Fernandez, T. P. Layzell and J. M. Brown, Chem.-Eur. J.,
1999, 5, 1320.
12 D. S. Noyce, D. R. Hartter and R. M. Pollack, J. Am. Chem. Soc., 1968,
90, 3791; G. Berti, F. Bottari, P. L. Ferrarini and B. Macchia, J. Org.
Chem., 1965, 30, 4091.
structures,17 is informative. When the stilbene is g2-coordinated
trans- to N with (S)-ligand,18 only si-face coordination is sterically
permissible (Scheme 5). This may also lead to favourable face–face
p-stacking between the electron-rich naphthyl and the more
electron-deficient aryl ring of the alkene.
We thank Johnson-Matthey for the loan of Rh and Ir salts,
EPSRC for support (AB) and the EU for funding under HPRT-
2001-RTN-00172.
13 B. L. Feringa, A. Smaardijk and H. Wynberg, J. Am. Chem. Soc., 1985,
107, 4798.
Notes and references
14 A. P. Luna, M. Bonin, L. Micouin and H.-P. Husson, J. Am. Chem.
Soc., 2002, 124, 12098; A. P. Luna, M. A. Ceschi, M. Bonin, L. Micouin,
H. P. Husson, S. Gougeon, G. Estenne-Bouhtou, B. Marabout,
M. Sevrin and P. George, J. Org. Chem., 2002, 67, 3522.
15 A. V. Malkov, A. Mariani, K. N. MacDougall and P. Kocovsky, Org.
Lett., 2004, 6, 2253.
16 T. J. Brunker, N. F. Blank, J. R. Moncarz, C. Scriban, B. J. Anderson,
D. S. Glueck, L. N. Zakharov, J. A. Golen, R. D. Sommer,
C. D. Incarvito and A. L. Rheingold, Organometallics, 2005, 24, 2730;
D. K. Wicht, M. A. Zhuravel, R. V. Gregush, D. S. Glueck, I. A. Guzei,
L. M. Liable-Sands and A. L. Rheingold, Organometallics, 1998, 17,
1412.
{ The configuration of products 2, 3 and 8 was (S), by CD; all exhibited a
positive Cotton effect in the 215–250 nm range.
§ Typical procedure: Freshly prepared rac-(COD)RhQUINAP (32 mg,
0.04 mmol, 2 mol%) was dissolved in THF (2 ml) under an argon
atmosphere. 1,2,3,4,5-Pentafluoro-6-[(E)-2-(3,4,5-trimethoxyphenyl)-vi-
nyl]-benzene (0.720 g, 2 mmol) was dissolved in THF (0.5 ml) and added
to the catalyst, together with freshly distilled catecholborane (220 ml,
2 mmol) and stirred. After 16 h Rh(COD)(¡)QUINAP (16 mg, 0.02 mmol)
and catecholborane (110 ml, 1 mmol) were added to the reaction and stirred
for a further 16 h to yield a brown solution. Analysis of the brown oil by
1
11B and H NMR, after concentration, showed a single regioisomer. The
17 N. W. Alcock, D. I. Hulmes and J. M. Brown, J. Chem. Soc., Chem.
Commun., 1995, 395; J. M. Brown, D. I. Hulmes, J. M. Long,
J.-M. Valk, S. Pearson, D. M. Bayston, A. Goeke, J. E. Muir and
N. W. Alcock, ECTOC Electronic Conference on Trends in
Organometallic Chemistry, 1997, 28 [www.ch.ic.ac.uk/ectoc/ectoc-3/].
18 E. Daura-Oller, A. M. Segarra, J. M. Poblet, C. Claver, E. Fernandez
and C. Bo, J. Org. Chem., 2004, 69, 2669.
reaction was quenched with ethanol (4 ml) and cooled to 0 uC prior to
the addition of H2O2 (30% aq, 4 ml) and NaOH (2 M in H2O, 5 ml). The
reaction was allowed to warm to room temperature and stirred for 16 h
until golden yellow. The reaction was extracted with CH2Cl2 (3 6 20 ml).
The combined organic phases were washed with NaOH (1 M in H2O,
40 ml), water (2 6 20 ml) and brine (30 ml), dried (MgSO4), filtered
through silica to remove the catalyst and the solvent removed in vacuo to
5286 | Chem. Commun., 2005, 5284–5286
This journal is ß The Royal Society of Chemistry 2005