Atropo-enantioselective synthesis of an axially chiral C1-symmetric phosphine ligand and its application in the asymmetric hydrosilylation of styrenes

Article abstract of DOI:10.1016/S0957-4166(99)00299-2

The axially chiral monodentate phosphine P-8 was synthesized in enantiomerically pure form, starting from the readily available, configurationally unstable lactone 1. Furthermore, its application as a ligand in the Pd-catalyzed stereoselective hydrosilyla

Full text of DOI:10.1016/S0957-4166(99)00299-2

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3025–3031
Atropo-enantioselective synthesis of an axially chiral
C1-symmetric phosphine ligand and its application in the
asymmetric hydrosilylation of styrenes1
Gerhard Bringmann,a,∗ Andreas Wuzik,a Matthias Breuning,a Petra Henschel,a Karl Peters b
and Eva-Maria Peters b
aInstitut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany
bMax-Planck-Institut für Festkörperforschung, Heisenbergstraße 1, D-70506 Stuttgart, Germany
Received 12 July 1999; accepted 15 July 1999
Abstract
The axially chiral monodentate phosphine P-8 was synthesized in enantiomerically pure form, starting from the
readily available, configurationally unstable lactone 1. Furthermore, its application as a ligand in the Pd-catalyzed
stereoselective hydrosilylation of styrenes was investigated. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
Over the past 20 years, axially chiral 2,20-disubstituted-1,10 -binaphthyls have proved to be most useful
agents in asymmetric synthesis,2 typical examples being BINAL-H in the stereoselective reduction of
ketones3 and BINAP as a ligand for transition metals in asymmetric catalysis.4 However, comparatively
little attention has been paid to the stereoselective preparation of such enantiopure biaryls, in particular
if they are constitutionally unsymmetric and thus C1-symmetric.5 For this attractive goal, we have
developed a novel concept6 which is based on rapidly interconverting lactone-bridged biaryls such as
P-1zM-1 (Scheme 1) as synthetic intermediates. They can be cleaved atropo-enantioselectively using,
for example, chiral hydride transfer reagents, to give the stereochemically stable biaryls 2 with excellent
enantiomeric ratios of up to 98.5:1.5 (97% ee),7 or atropo-diastereoselectively using either metallated
chiral N-nucleophiles such as 1-arylethylamides (drs of up to 95:5, de ≤90%)8 or chiral metal alkoxides,
e.g. derived from menthol (drs of up to 99:1, de ≤98%),9 to give biaryl amides or esters 3.
The potential of the ‘lactone methodology’ has, meanwhile, been demonstrated in the synthesis of
more than 20 natural biaryls6 and axially chiral auxiliaries.10 In this paper, we report on the synthesis
∗
Corresponding author. Tel: +49-931-888-5323; fax: +49-931-888-4755; e-mail: bringman@chemie.uni-wuerzburg.de
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00299-2

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Scheme 1. Alternative pathways to axially chiral biaryls 2 and 3 by atropo-enantio- or -diastereoselective cleavage of 1
of an enantiopure monodentate biaryl phosphine ligand and its application in the enantioselective
hydrosilylation of styrene derivatives.
2. Results and discussion
The catalytic asymmetric hydrosilylation of olefins constitutes an important method for the preparation
of optically active compounds.11 Uozumi and Hayashi12 observed that palladium coordinated to a
chelating bisphosphine such as BINAP did not catalyze the hydrosilylation of 1-alkenes even at 80°C,
while the reaction took place smoothly at 40°C when using monodentate phosphine ligands, instead. In
further efforts they extended the field of application of these ligands to enantioselective hydrosilylation
and allylic alkylation reactions.13,14
Based on these earlier investigations, we envisaged the synthesis of a C1-symmetric monodentate phos-
phine ligand P-8 by the lactone concept: atropo-diastereoselective cleavage of the lactone 1 using lithium
1R-mentholate as a chiral O-nucleophile9 (dr 89:11, 78% de), separation of the diastereomeric menthyl
esters by column chromatography, reduction of the pure major isomer with LiAlH4, and subsequent
benzylic hydroxy–halogen exchange gave the known10 bromo compound M-4 in an enantiomerically
pure form (Scheme 2). By a second reduction step, M-4 was transformed into the (still phenolic) 2-
methyl compound P-5,15 which was then converted into the corresponding triflate P-6 by treatment with
triflic anhydride.
Palladium-mediated phosphinylation of P-6 to the phosphine oxide P-7 and final reductive P-
deoxygenation gave the required axially chiral biaryl phosphine P-8 in 56% overall yield from 1. An
X-ray structural analysis of P-716 confirmed the anticipated constitution. Further, as can be seen, the
array at the configurationally stable biaryl axis is additionally fixed by π-stacking of the distal (i.e.
‘outer’) naphthalene ring to one of the two diastereotopic phenyl substituents on the P-atom (see the
righthand crystal structure in Scheme 2).
For an evaluation of the potential of the phosphine P-8 as a reagent in asymmetric synthesis, we
selected the hydrosilylation of styrenes 9a–d (Scheme 3). In accordance with previous work in the
literature,13 we used [PdCl(π-C3H5)]2 as the catalyst precursor, now with P-8 as the chiral ligand. In our

G. Bringmann et al. / Tetrahedron: Asymmetry 10 (1999) 3025–3031
3027
Scheme 2. Synthesis of the axially chiral phosphine ligand P-8 and crystal structure of its direct precursor, P-7. Reaction
conditions: (a) nBuLi, 1R-menthol, toluene, 0°C; (b) LiAlH4, Et2O, rt; (c) (CCl2Br)2, PPh3, CH2Cl2, 0°C; (d) LiAlH4, Et2O, rt;
(e) Tf2O, DABCO, CH2Cl2, 0°C; (f) Pd(OAc)2, HP(O)Ph2, dppb, iPrNEt2, DMSO, 100°C; (g) HSiCl3, xylene, 120°C
first attempts, the reactions were carried out at room temperature, regioselectively yielding the silanes
10a–d in 84–99% chemical yields after distillation. Oxidation with H2O2 delivered the benzylic alcohols
11a–d, the enantiomeric ratios of which were determined by HPLC on a chiral phase (see experimental).
Scheme 3. Enantioselective hydrosilylation of styrenes 9a–d and oxidation of the resulting silanes 10a–d to the benzylic
alcohols 11a–d
Under these conditions, the best asymmetric inductions were achieved for the alcohol 11d, which gave
an enantiomeric ratio of 62:38 (24% ee) (see Table 1). At 0°C, by contrast, the best results were attained
with 11c, giving an er of up to 75:25 (50% ee). In all these reactions, the S-enantiomeric products were
formed preferentially.
The results obtained are in good agreement with those of Hayashi and co-workers,13 who reported
excellent enantiomeric ratios of up to 98:2 (96% ee) if related binaphthyl-based monodentate phosphine
ligands without a substituent in the 2-position were used, while for Et, CN, CO2Me, and OH substituents
at C-2, the enantiomeric purities of the products decreased to 18, 26, 30, and 34%, respectively.
Presumably, the dihedral angle between the naphthyl and phenyl rings, which is controlled by the size
of the substituent located at C-2, has a decisive influence on the enantioselectivity. In our case, a lower
steric hindrance at the axis, hopefully giving rise to higher asymmetric inductions, might be achieved by
decreasing the steric demand of the alkyl substituent in the phenyl part of P-8, by starting from an analog
of the biaryl lactone precursor 1 in which the methyl groups are missing.

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Table 1
Enantioselective hydrosilylation of styrenes 9a–d
3. Conclusion
The facile atropo-enantioselective synthesis of the new enantiopure monodentate biarylphosphine P-
8 described in this paper, is achieved smoothly and in a very good overall yield of 56% starting from
1. This underlines the efficiency and flexibility of the ‘lactone methodology’, giving rise to virtually
any substitution pattern (here a P-substituent) in the proximity of the biaryl axis. As shown for the Pd-
catalyzed enantioselective hydrosilylation of styrene derivatives (ee ≤50%), the potential of P-8 as a
ligand for catalysts in asymmetric synthesis has been demonstrated.
4. Experimental
Optical rotations were measured with a Perkin–Elmer polarimeter. Melting points were determined in
a Kofler melting point apparatus. The IR spectra were scanned from KBr pellets using a Perkin–Elmer
spectrophotometer model 1420. The NMR spectra were recorded with a Bruker AC 250 (250 MHz)
instrument. Elemental analyses were performed in the Institute of Inorganic Chemistry of the University
of Würzburg using a Leco CHNS-932. Mass spectra were measured on a Finnigan MAT 2000 mass
spectrometer at 70 eV. All reactions were carried out under an Ar atmosphere using freshly dried solvents.
The reagents were of commercial grade and used as supplied. HPLC analyses were carried out using a
combination of a Waters M 510 pump, a Chiralcel OD-H column (Daicel Chem. Ind. Ltd., 4.6×250 mm),
and an ERC-7215 UV-detector. Compound M-4c was prepared as described previously.10 The styrenes
9a–d and the racemic alcohols 11a–d were purchased from Aldrich.
4.1. P-1-(40,60-Dimethyl-20-hydroxyphenyl)-2-methylnaphthalene P-5
To a solution of M-4 (440 mg, 1.29 mmol) in diethyl ether (20 mL), LiAlH4 (196 mg, 5.16 mmol)
was added and the reaction was stirred for 1 h (monitored by TLC). After hydrolysis with H2O and
acidification with 2N HCl, the aqueous phase was extracted with CH2Cl2 (3×30 mL). The combined
organic layers were dried over Na2SO4 and concentrated in vacuo. Purification of the residue by

G. Bringmann et al. / Tetrahedron: Asymmetry 10 (1999) 3025–3031
3029
chromatography on silica gel (eluent: diethyl ether:petroleum ether, 1:2) yielded P-5 as a slightly yellow
solid, which was recrystallized from diethyl ether:petroleum ether as colorless needles (310 mg, 1.27
20
˜
mmol, 92%): mp 88°C; [α]D −58.2 (c 1.0, CHCl3); IR (KBr): ν 3450, 3020, 2930, 2890, 2830, 1600,
1
1550, 1290, 1035, 830, 810, 780, 750; H NMR (250 MHz, CDCl3): δ 1.82 (s, 3H, CH3), 2.22 (s, 3H,
CH3), 2.39 (s, 3H, CH3), 4.36 (s, 1H, OH), 6.76, 6.79 (s, s, 1H each, 30-H and 50-H), 7.35–7.48 (m,
3H, Ar-H), 7.48 (d, J=8.2 Hz, 1H, 4-H), 7.85 (d, J=8.2 Hz, 1H, 3-H), 7.87 (d, J=7.9 Hz, 1H, 8-H); 13
C
NMR (63 MHz, CDCl3): δ 19.56 (CH3), 20.00 (CH3), 21.36 (CH3), 113.3, 121.7, 123.0, 125.0, 125.4,
126.7, 128.1, 128.5, 130.2, 132.5, 132.8, 136.0, 136.1, 137.7, 138.8, 152.9 (Ar-C); MS: m/z (%) 262
(100) [M+], 247 (46) [M+−CH3], 232 (16) [247−CH3], 202 (13) [232−CO]. Anal. calcd for C19H18O
(262.4): C, 86.49; H, 6.92. Found: C, 86.53; H, 6.85.
4.2. P-1-(40,60-Dimethyl-20-trifluoromethylsulfonyloxyphenyl)-2-methylnaphthalene P-6
A solution of the phenol P-5 (240 mg, 914 µmol) and DABCO (204 mg, 1.83 mmol) in CH2Cl2 (8
mL) was cooled to 0°C and stirred for 30 min. Tf2O (230 µl, 1.37 mmol) was added and the reaction
mixture was stirred for 30 min until completion of the reaction (TLC). Removal of the solvent followed
by chromatography on silica gel (eluent: diethyl ether:petroleum ether, 1:2) gave P-6 as a colorless oil
20
˜
(354 mg, 898 µmol, 98%): [α]D +31.4 (c 1.0, CHCl3); IR (KBr): ν 3020, 3000, 2960, 2930, 2900,
1
1610, 1580, 1490, 1400, 1250, 1110, 730; H NMR (250 MHz, CDCl3): δ 1.84 (s, 3H, CH3), 2.11 (s,
3H, CH3), 2.39 (s, 3H, CH3), 7.03, 7.09 (s, s, 1H each, 30-H and 50-H), 7.14 (m, 1H, Ar-H), 7.22–7.34
(m, 2H, Ar-H), 7.35 (d, J=8.2 Hz, 1H, 4-H), 7.75 (d, J=8.2 Hz, 1H, 3-H), 7.77 (m, 1H, 8-H); 13C NMR
(63 MHz, CDCl3): δ 19.71 (CH3), 20.04 (CH3), 21.20 (CH3), 119.4 (q, J=318 Hz, C-F), 120.6, 122.1,
122.6, 124.6, 124.9, 125.0, 126.2, 128.0, 128.4, 129.3, 130.7, 132.0, 132.1, 134.7, 139.4, 147.6 (Ar-C);
MS: m/z (%) 394 (61) [M+], 246 (100) [M+−OSO2CF3], 231 (19) [246−CH3], 216 (5) [231−CH3], 201
(4) [216−CH3]. Anal. calcd for C20H17F3O3S (394.4): C, 60.91; H, 4.34; S, 8.13. Found: C, 61.12; H,
4.37; S, 7.94.
4.3. P-1-(40,60-Dimethyl-20-diphenylphosphanylphenyl)-2-methylnaphthalene P-7
A mixture of the triflate P-6 (200 mg, 507 µmol), HP(O)Ph2 (205 mg, 1.10 mmol), Pd(OAc)2 (5.7
mg, 26 µmol), dppb (10.9 mg, 26 µmol) and (iPr)2NEt (425 µl, 2.6 mmol) in DMSO (5 mL) was heated
to 100°C for 6 h, cooled to room temperature and concentrated in vacuo. After addition of ethyl acetate
(40 mL), the precipitated solid was removed by filtration. The organic layer was extracted with H2O
(3×30 mL), dried over Na2SO4 and the solvent was removed. Chromatography on silica gel (eluent:
hexane:ethyl acetate, 1:1) of the resulting red oil yielded the product P-7. From petroleum ether:ethyl
acetate, the phosphine oxide P-7 was obtained as colorless crystals (194 mg, 434 µmol, 86%): mp
20
˜
195–196°C; [α]D +85.5 (c 1.0, CHCl3); IR (KBr): ν 3020, 2980, 2920, 2900, 2820, 1600, 1570,
1
1420, 1170; H NMR (250 MHz, CDCl3): δ 1.74 (s, 3H, CH3), 2.13 (s, 3H, CH3), 2.37 (s, 3H, CH3),
6.79–7.19 (m, 10H, Ar-H), 7.21–7.64 (8H, Ar-H); 13C NMR (63 MHz, CDCl3): δ 19.75 (CH3), 20.97
(CH3), 21.20 (CH3), 124.1, 125.3, 125.6, 126.9, 127.6, 127.9, 128.0, 128.3, 130.1, 130.2, 130.6, 130.7,
131.0, 131.4, 131.7, 132.2, 132.7, 132.8, 134.3, 134.8, 135.3, 136.7, 138.7, 140.0 (Ar-C); 31P NMR (162
MHz, CDCl3): δ 26.60; MS: m/z (%) 446 (23) [M+], 431 (4) [M+−CH3], 355 (100) [431−C6H4]. Anal.
calcd for C31H27OP (446.5): C, 83.39; H, 6.09. Found: C, 82.99; H, 6.28.

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G. Bringmann et al. / Tetrahedron: Asymmetry 10 (1999) 3025–3031
4.4. P-1-(40,60-Dimethyl-20-diphenylphosphanophenyl)-2-methylnaphthalene P-8
A solution of the phosphine oxide P-7 (100 mg, 224 µmol) and NEt3 (490 µl, 4.46 mmol) in xylene
(5 mL) was cooled to 0°C, treated with HSiCl3 (114 µl, 1.12 µmol), and heated to reflux for 24 h. After
cooling to room temperature, the reaction mixture was hydrolyzed with a saturated NaHCO3 solution.
The obtained residue was separated by filtration over Celite and washed with diethyl ether (3×10 mL).
The combined organic layers were dried over MgSO4 and the solvent was removed. Purification of the
crude product succeeded by chromatography on silica gel (eluent: diethyl ether) to give P-8, which was
recrystallized from diethyl ether:petroleum ether yielding a white powder (94 mg, 218 µmol, 98%): mp
20
˜
134°C; [α]D +104.3 (c 1.0, CHCl3); IR (KBr): ν 3040, 3020, 2930, 2900, 2830, 1620, 1600, 1560,
1
1420, 730, 690; H NMR (250 MHz, CDCl3): δ 1.73 (s, 3H, CH3), 1.82 (s, 3H, CH3), 2.24 (s, 3H,
CH3), 6.85–7.14 (m, 12H, Ar-H), 7.16–7.27 (m, 4H, Ar-H), 7.67–7.72 (m, 2H, 8-H and 4-H); 13C NMR
(63 MHz, CDCl3): δ 19.82, (CH3), 20.95 (CH3), 21.33 (CH3), 124.5, 125.5, 127.4, 127.7, 128.0, 128.1,
128.2, 128.3, 128.9, 131.8, 132.3, 132.7, 133.4, 133.6, 133.9, 134.0, 134.7, 136.9, 137.4, 137.5, 137.7,
137.9, 138.1, 142.4 (Ar-C); 31P NMR (162 MHz, CDCl3): δ −14.25; MS: m/z (%) 430 (27) [M+], 415
(8) [M+−CH3], 400 (34) [415−CH3], 324 (100) [400−C6H4]. Anal. calcd for C31H27P (430.5): C, 86.48;
H, 6.32. Found: C, 86.07; H, 6.06.
4.5. General procedure for the asymmetric hydrosilylation of the styrenes 9a–d
In analogy to the literature14 styrene 9 (3.80 mmol), [PdCl(π-C3H5)]2 (38.0 µmol), and chiral
phosphine P-8 (76.0 µmol) were stirred for 30 min. Then HSiCl3 (4.56 mmol) was added and the
solution stirred until completion of the reaction (TLC). The silane 10 obtained by distillation from the
reaction mixture was dissolved in THF:MeOH (1:1) and treated with KF (22.8 mmol) and KHCO3 (45.6
mmol). After 10 min stirring at room temperature and addition of 30% H2O2 (22.8 mmol), the suspension
was heated under reflux. Upon completion of the oxidation according to TLC, the reaction mixture was
quenched with saturated aqueous Na2S2O3, and the residue was removed by filtration. The combined
organic layers were dried over Na2SO4 and concentrated in vacuo. Column chromatography of the crude
product on silica gel (eluent: diethyl ether:petroleum ether, 1:1) gave a pure material. The ers of the
benzyl alcohols 11 were determined by HPLC on a chiral phase (Daicel Chiralcel OD-H, detection at
i
254 nm, flow rate 0.5 mL/min, eluent: PrOH:hexane, 1:9). The predominant absolute configurations of
all of the products obtained were assigned to be S by the signs of their optical rotations (all negative), as
reported for (S)-11a–d in the literature.17
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (SFB 347 ‘Selektive Reaktionen
Metall-aktivierter Moleküle’) and by the Fonds der Chemischen Industrie (graduate research fellowship
to M.B. and financial support).
References
1. Part 82 in the series Novel Concepts in Directed Biaryl Synthesis; for Part 81, see: Peters, K.; Peters, E.-M.; Wuzik, A.;
Bringmann, G. Z. Kristallogr. NCS, 1999, in press.

G. Bringmann et al. / Tetrahedron: Asymmetry 10 (1999) 3025–3031
3031
2. For reviews, see: (a) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503–517. (b) Shibasaki, M.; Sasai,
H.; Arai, T. Angew. Chem. 1997, 109, 1290–1311; Angew. Chem., Int. Ed. Engl. 1997, 36, 1236–1256. (c) Pu, L. Chem.
Rev. 1998, 98, 2405–2494.
3. Noyori, R. Chem. Soc. Rev. 1989, 18, 187–208, and references cited therein.
4. For a review, see: Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345–350.
5. (a) Suzuki, T.; Hotta, H.; Hattori, T.; Miyano, S. Chem. Lett. 1990, 807–810. (b) Hayashi, T.; Hayashizaki, K.; Kiyoi, T.;
Ito, Y. J. Am. Chem. Soc. 1988, 110, 8153–8156. (c) Uemura, M.; Kamikawa, K. J. Chem. Soc., Chem. Commun. 1994,
2697–2698. (d) Meyers, A. I.; Lutomski, K. A. J. Am. Chem. Soc. 1982, 104, 879–881. (e) Lipshutz, B. H.; Kayser, F.; Liu,
Z.-P. Angew. Chem. 1994, 106, 1962–1964; Angew. Chem., Int. Ed. Engl. 1994, 33, 1842–1844. (f) Quideau, S.; Feldman,
K. S. Chem. Rev. 1996, 96, 475–503.
6. For a review, see: Bringmann, G.; Breuning, M.; Tasler, S. Synthesis 1999, 525–558.
7. (a) Bringmann, G.; Hartung, T. Tetrahedron 1993, 49, 7891–7902. (b) Bringmann, G.; Hartung, T. Angew. Chem. 1992,
104, 782–783; Angew. Chem., Int. Ed. Engl. 1992, 31, 761–762.
8. Bringmann, G.; Breuning, M.; Tasler, S.; Endress, H.; Ewers, C. L. J.; Göbel, L.; Peters, K.; Peters, E.-M. Chem. Eur. J.
1999, in press.
9. Bringmann, G.; Breuning, M.; Walter, R.; Wuzik, A.; Peters, K.; Peters, E.-M. Eur. J. Org. Chem. 1999, in press.
10. Bringmann, G.; Breuning, M. Tetrahedron: Asymmetry 1998, 9, 667–679.
11. For a review, see: Brunner, H.; Nishiyama, H.; Itoh, K. Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York,
1993; pp. 303–317.
12. Uozumi, Y.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 9887–9888.
13. Kitayama, K.; Uozumi, Y.; Hayashi, T. J. Chem. Soc., Chem. Commun. 1995, 1533–1534.
14. Hayashi, T.; Kawatsutra, M.; Uozumi, Y. J. Chem. Soc., Chem. Commun. 1997, 561–562.
15. Due to formal reasons of the CIP-denotion, the stereodescriptor at the biaryl axis changes from M to P.
16. Cell data for 7: C31H27P, orthorhombic, space group P212121, a=962.3(1) pm, b=1488.6(1) pm, c=1739.5(2) pm.
Additional data for this structure have been deposited at the Cambridge Crystallographic Data Centre.
17. Hayashi, T.; Matsumoto, Y.; Ito, Y. Tetrahedron: Asymmetry 1991, 2, 601–612.