New planar chiral P,N-ligands containing tricarbonyl(arene)chromium for enantioselective asymmetric hydroboration of styrenes

Article abstract of DOI:10.1016/S0957-4166(99)00005-1

Optically active (1,2-disubstituted arene) chromium tricarbonyl complexes 2A-2D with a pyridyl and a phosphorus group in the two ortho benzylic positions have been stereoselectively synthesized from a commercially available (+)-(4,6-O-benzylidene)methyl-α-D-glucopyranoside. These chromium complexes have been used as chiral ligands in the preparation of rhodium catalysts for the hydroboration of styrene derivatives. High enantioselectivities were observed in the hydroboration of vinylarenes.

Full text of DOI:10.1016/S0957-4166(99)00005-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 347–354
New planar chiral P,N-ligands containing
tricarbonyl(arene)chromium for enantioselective asymmetric
hydroboration of styrenes
Seung Uk Son, Hye-Young Jang, Jin Wook Han, In Su Lee and Young Keun Chung ∗
Department of Chemistry and Center for Molecular Catalysis, College of Natural Sciences, Seoul National University, Seoul
151-742, Korea
Received 20 November 1998; accepted 21 December 1998
Abstract
Optically active (1,2-disubstituted arene) chromium tricarbonyl complexes 2A–2D with a pyridyl and a phos-
phorus group in the two ortho benzylic positions have been stereoselectively synthesized from a commercially
available (+)-(4,6-O-benzylidene)methyl-α-D-glucopyranoside. These chromium complexes have been used as
chiral ligands in the preparation of rhodium catalysts for the hydroboration of styrene derivatives. High enantio-
selectivities were observed in the hydroboration of vinylarenes. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
We recently reported a new and easy method for the asymmetric synthesis of chiral benzaldehyde
complexes modified by a sugar moiety.1 Thus, starting from chiral (benzaldehyde) chromium tricarbonyl
compound, optically active (1,2-disubstituted arene) chromium tricarbonyl complexes with a diamine
and a phosphorus group in the two ortho benzylic positions have been stereoselectively synthesized and
used as chiral P,N-ligands in the hydroboration of styrenes.2 The new chiral ligands have been shown
to afford moderate enantioselectivities (19–81%) at −15°C and to exhibit pronounced effects on the
enantioselectivity depending on the electronic substituent on the styrene. The P,N-ligand represents a
class of chiral auxiliaries that are easily tuned by steric and electronic modification.3 As an extension of
our recent work, we have prepared new planar chiral P,N-arene chromium compounds having chromium
carbonyls, pyridine, and phosphorus and investigated their role as chiral ligands in the rhodium-catalyzed
asymmetric hydroboration of styrenes. Herein we report the results of our investigation.
∗
Corresponding author. Tel: +82-2-880-6662; fax: +82-2-889-1568; e-mail: ykchung@plaza.snu.ac.kr
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00005-1

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2. Results and discussion
2.1. Synthesis of planar chiral (arene)Cr(CO)3 complexes
The planar chiral compounds 2A–2D were synthesized from 1 (Eq. 1). Compound 1 was previously
prepared by us.2
(1)
Treatment of 1 with 2-pyridine lithium at −78°C led to a diastereomeric mixture (de 31%) in 64% yield.
The diastereomeric mixture was easily separated by flash column chromatography. The major (42%
yield) diastereomer shown in Eq. 1 was named 2A and used to make compounds 2B–2D. Compound 2B
was prepared in 73% yield by deprotonation of 2A in THF followed by addition of MeI. In the same
way, compounds 2C and 2D were prepared by the addition of benzyl bromide with a catalytic amount of
tetrabutylammonium iodide and 4-methoxybenzylchloride, respectively, to the deprotonated form of 2A.
From 2A, compounds 2B, 2C, and 2D were obtained in 73%, 69%, and 71% yields, respectively. The
stereochemistries of 2A–2D were confirmed by the X-ray crystal structure determination of 2B. Single
crystals of 2B suitable for X-ray study were grown by slow evaporation of a solution of 2B in CH2Cl2
and hexane (v/v, 1:1) at −20°C. Fig. 1 shows an X-ray crystal structure of 2B with the atomic numbering.
Crystal data and experimental details are shown in Table 1 and selected bond distances and angles are
shown in Table 2.
The pyridine ring is almost upright to the plane of arene coordinated to Cr(CO)3. The nitrogen atom
is located 1.624(6) Å above the plane of arene, and the phosphorus atom is located 0.164(4) Å above the
plane of the arene. The planes of the pyridine ring and the free arene ring (C01–C016) attached to the
phosphorus are roughly parallel (the interplanar angle: 18.3(2)°) and the distance between the centroids
of these two planes is 4.00 Å. The distance between P and N is 3.649(3) Å. The observed average Cr–CO
bond length (1.842 Å) is shorter than the average value of 1.866 Å.4
2.2. Asymmetric hydroboration
Rhodium complexes with 2A–2D have been examined with regard to the catalytic activity and
enantioselectivity in the reaction of vinylarenes with catecholborane (Eq. 2).
(2)
The results are summarized in Table 3. Our standard reaction conditions are as follows: 1.2 equiv. cate-
cholborane, 0.02 equiv. [Rh(COD)2]BF4, 0.024 equiv. of 2A–2D in THF at 0°C for 18 h. Hydroboration
of styrene derivatives followed by oxidation with alkaline hydrogen peroxide gives the corresponding
sec-alcohol. To determine the enantiomeric excess (ee) values, we used (S)-(+)-O-acetyl mandelate as a
chiral derivatizing reagent to convert an enantiomeric mixture to a pair of diastereomers and calculated
the ee by the inspection of 1H NMR spectra of diastereomers.

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349
Figure 1. ORTEP drawing of 2B, with atom-labeling scheme. Thermal ellipsoids are drawn at the 30% probability level
Initially we started to study the hydroboration of 4-methoxystyrene, which otherwise only reacts with
catecholborane at elevated temperatures,5 using 2A as a chiral ligand (entry 1 in Table 3). The result
(45% yield and 14% ee) was quite disappointing.
To improve the value of the ee, we introduced a substituent to the benzylic position of 2A and prepared
2B–2D. When 4-methoxystyrene was hydroborated using 2B as a chiral ligand (entry 2), the ee was
dramatically improved to 84% with a 72% yield. When 2C was used as a chiral ligand (entry 3), the
ee also improved to 82% with 86% yield. When 2D was used as a chiral ligand (entry 4), the ee was
improved to 61%, but the yield was only 39%. As expected, the ee increases as the steric bulk of the
substituent at the benzylic position increases. However, this is not always true as seen in 2D.
Among 2B–2D, we chose 2C as a chiral ligand in the catalytic asymmetric hydroboration of other
styrene derivatives. The results are shown in entries 5–8 in Table 3. The enantioselectivity was slightly
dependent on the reaction temperature: enantiopurities of 1-(4-methoxyphenyl)ethanol obtained for the
hydroboration at 0°C and −15°C were 82% and 84%, respectively (entries 3 and 5). The enantioselectivity
for other styrene derivatives obtained at 0°C were 73–86%. At first we expected that the electronic effect
of the substituent on the styrene ring would affect the ee values. However, the ee values were not very
sensitive to the electronic effect of the substituent on the styrene ring.6 The highest ee value was obtained
for 2,4-dimethylstyrene (entry 8). The difference in ee values between 2,4-dimethylstyrene and other
substrates was only marginal. The steric effect of the substituent on the styrene was not great.
The reaction of 4-methoxystyrene in the presence of 2A as a chiral ligand gives the S alcohol with a
poor enantioselectivity, whereas reactions of styrene derivatives in the presence of 2B–2D afford the R
alcohols with high enantioselectivities formed by the opposite stereoselection. Any intermediates were
not characterized. However, chiral P,N-ferrocenyl chelating ligands similar to our chiral ligands were
synthesized and their rhodium and palladium complexes were structurally characterized.3f,7 Thus, we

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Table 1
Crystal data and structure refinement for 2B
Table 2
Selected bond lengths (Å) and angles (deg) for 2B

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351
Table 3
Catalytic asymmetric hydroboration of styrenes
envisage that the stereochemical outcome may be related to the steric bulkiness at the benzylic position.
For 2A, there may be almost no steric restriction from the hydroxy group and the pyridyl group may be
partly free to rotate (Scheme 1).
Scheme 1.
Consequently a poor stereoselectivity resulted. However, for 2B–2D, there should be some steric
restriction due to the substituent at the benzylic position and the pyridyl group may be fixed (Scheme 1).
Thus, high stereoselectivities would be obtained.
3. Conclusion
We have demonstrated that planar chiral P,N-ligands 2A–2D can be synthesized from the chiral
benzaldehyde chromium complex 1 and have been used as chiral P,N-ligands in the preparation of a
rhodium catalyst for the hydroboration of styrene derivatives. Good enantioselectivities were observed.
4. Experimental
All solvents were purified by standard methods, and all synthetic procedures were performed under a
nitrogen atmosphere. Reagent grade chemicals were used without further purification.
Elemental analyses were carried out at the Chemical Analytic Center, College of Engineering, Seoul
National University or the Chemical Analytic Center. 1H NMR spectra were obtained with a Bruker 300
or a Bruker AMX-500 instrument. Infrared spectra were recorded on a Shimadzu IR-470 spectrometer.
Compound 1 was prepared by the published method.1

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4.1. Synthesis of 2A
A solution of 1 (0.27 g, 0.63 mmol) in 10 mL of Et2O at −78°C was transferred via cannula to the
solution of 2-pyLi (generated in situ by the reaction of 2-bromopyridine (0.09 mL, 0.9 mmol) in 15 mL
of Et2O with n-BuLi (0.35 mL, 2.5 M in hexane, 0.9 mmol) at −78°C). The resulting solution was stirred
at −78°C for 30 min and at 0°C for 30 min and quenched by sat. aq. NH4Cl (10 mL)/Et2O (50 mL). The
ether layer was separated, dried over anhydrous MgSO4, concentrated, and chromatographed on a silica
gel column eluting with hexane and diethyl ether (v/v, 1:1 -→ 1:2). Evaporation of the solvent gave a
yellow solid (0.38 g, 64%) as a mixture of two diastereomers. We named one of the diastereomers (the
second eluting band) as 2A (42% yield). The first eluting band was the other diastereomer (22% yield).
1
Characterization of 2A: mp 130°C (dec.); IR νCO 1954, 1874 cm−1; H NMR (CDCl3): δ 8.23 (d, 4.3
Hz, 1H), 7.37 (m, 5H), 7.26–7.13 (m, 4H), 7.06 (t, 7.4 Hz, 2H), 6.94–6.90 (m, 2H), 6.61 (m, 1H), 5.72
(d, 6.1 Hz, 1H), 5.64 (t, 5.9 Hz, 1H), 5.09 (t, 6.1 Hz, 1H), 4.89 (d, 6.0 Hz, 1H), 3.47 (d, 5.1 Hz, 1H) ppm.
27
Anal. calcd for C27H20CrNO4P: C, 64.16; H, 3.99; N, 2.77. Found: C, 63.84; H, 3.99; N, 2.91. [α]D
+344 (c 0.1, CH2Cl2). Characterization of the other diastereomer: mp 150°C (dec.); IR νCO 1956, 1878
cm−1; H NMR (CDCl3): δ 8.55 (d, 5.0 Hz, 1H), 7.78 (t, 7.6 Hz, 1H), 7.71 (d, 7.7 Hz, 1H), 7.35 (m,
1
10H), 7.28 (m, 1H), 6.33 (dd, 6.4, 7.4 Hz, 1H), 5.25 (m, 2H), 4.84 (d, 7.4 Hz, 1H), 4.74 (m, 2H) ppm.
20
Anal. calcd for C27H20CrNO4P: C, 64.16; H, 3.99; N, 2.77. Found: C, 64.04; H, 4.20; N, 2.71. [α]D
+210 (c 0.11, CH2Cl2).
4.2. Synthesis of 2B
To a solution of 2A (0.12 g, 0.24 mmol) in 5 mL of THF was added NaH (0.023 g, in 50% mineral oil)
at room temperature. The solution was stirred for 30 min, and then MeI (0.03 mL, 0.48 mmol) was added.
After the resulting solution was stirred for 2 h, the solution was quenched by addition of aq. NH4Cl (15
mL) and Et2O (50 mL). The ether layer was separated, dried over anhydrous MgSO4, concentrated, and
chromatographed on a silica gel column eluting with hexane and diethyl ether (v/v, 1:1). Evaporation
of the solvent gave a yellow solid (0.09 g, 73%). Mp 145°C (dec.); IR νCO 1963, 1882 cm−1; 1H NMR
(CDCl3): δ 8.14 (d, 4.4 Hz, 1H), 7.30 (m, 5H), 7.21–7.09 (m, 3H), 7.02 (t, 7.5 Hz, 2H), 6.84–6.73 (m,
3H), 6.05 (d, 5.7 Hz, 1H), 5.89 (m, 1H), 5.68 (t, 12.7 Hz, 1H), 5.05 (t, 6.2 Hz, 1H), 4.81 (d, 6.2 Hz, 1H),
3.50 (s, 3H) ppm. Anal. calcd for C28H22CrNO4P: C, 64.74; H, 4.27; N, 2.70. Found: C, 64.74; H, 4.29;
N, 2.70. [α]D24 +373 (c 0.1, CH2Cl2).
4.3. Synthesis of 2C
Using the same method as the synthesis of 2B except using tetrabutylammonium iodide (0.1 equiv.) and
benzyl bromide (2 equiv.) instead of MeI, the crude product obtained was purified by chromatography
on a silica gel column and eluted with hexane and diethyl ether (v/v, 1:1). Yellow solid; yield: 69%.
Mp 125°C (dec.); IR νCO 1958, 1877 cm−1; 1H NMR (CDCl3): δ 8.11 (d, 4.5 Hz, 1H), 7.35 (m, 10H),
7.18–7.09 (m, 3H), 7.02 (t, 6.3 Hz, 2H), 6.83 (t, 7.2 Hz, 2H), 6.75 (t, 7.2 Hz, 1H), 6.32 (d, 5.7 Hz, 1H),
6.02 (dd, 2.4, 6.1 Hz, 1H), 5.66 (t, 6.4 Hz, 1H), 5.09 (t, 6.3 Hz, 1H), 4.83 (d, 11.2 Hz, 1H), 4.80 (d, 6.1
Hz, 1H), 4.57 (d, 11.2 Hz, 1H) ppm. Anal. calcd for C34H26CrNO4P: C, 68.57; H, 4.40; N, 2.35. Found:
C, 68.56; H, 4.48; N, 2.32. [α]D28 +281 (c 0.1, CH2Cl2).

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353
4.4. Synthesis of 2D
To the solution of 2A (0.15 g, 0.30 mmol) in 2 mL of DMF was added NaH (25 mg, in 50% mineral oil,
5.1 mmol) at 0°C. After the solution was stirred at 0°C for 15 min, 4-methoxybenzylchloride (0.27 mL,
2.0 mmol) was added. The resulting solution was stirred at room temperature for 12 h and quenched by
sat. aq. NH4Cl (10 mL) and Et2O (50 mL). The ether layer was separated, dried over anhydrous MgSO4,
concentrated, and chromatographed on a silica gel column eluting with hexane and diethyl ether (v/v,
1:1). Evaporation of the solvent gave a yellow solid (0.13 g, 71%). Mp 55–58°C; IR νCO 1963, 1883
cm−1; 1H NMR (CDCl3): δ 8.11 (d, 3.3 Hz, 1H), 7.30 (m, 7H), 7.15–7.03 (m, 5H), 7.00–6.75 (m, 5H),
6.30 (d, 5.7 Hz, 1H), 6.00 (m, 1H), 5.65 (t, 6.1 Hz, 1H), 5.09 (t, 6.2 Hz, 1H), 4.79 (d, 6.4 Hz, 1H), 4.76
(d, 10.6 Hz, 1H), 4.52 (d, 10.3 Hz, 1H), 3.80 (s, 3H) ppm. Anal. calcd for C35H28CrNO5P: C, 67.20; H,
4.51; N, 2.24. Found: C, 66.92; H, 4.46; N, 2.19. [α]D24 +230 (c 0.1, CH2Cl2).
4.5. Catalytic asymmetric hydroboration
A typical procedure is given for 4-vinylanisole. A mixture of [Rh(COD)2]BF4 (7 mg, 0.017 mmol)
and 2C (12 mg, 0.20 mmol) in 3 mL of THF was stirred under nitrogen at room temperature for 1.5 h,
and 4-vinylanisole (0.11 mg, 0.82 mmol) was added at 0°C. Catecholborane (0.97 mL in 1 M in THF,
0.97 mmol) was added at 0°C, and the mixture was stirred at 0°C for 18 h and then quenched with
5 mL of ethanol. To the mixture was added 5 mL of 3 M NaOH and 0.5 mL of 35% H2O2, and the
whole was stirred at room temperature for 3 h. Extraction with Et2O followed by chromatography on
a silica gel column eluting with hexane and diethyl ether (v/v, 10:1) gave 107 mg (86%) of (R)-1-(4-
1
methoxyphenyl)ethanol. The regioisomer was not detected by H NMR analysis of the crude reaction
mixture. To determine the enantiomeric excess (ee) values, we used (S)-(+)-mandelic acid as a chiral
derivatizing reagent to convert the enantiomeric mixture to a pair of diastereomers and calculated the ee
by the inspection of 1H NMR spectra of diastereomers.
4.6. X-Ray crystal structure determination of 2B
Crystals of 2B were grown by slow evaporation of a solution of 2B in hexane and methylene chloride
(v/v, 1:1). Diffraction was measured by an Enraf–Nonius CAD4 diffractometer with an ω–2θ scan
method. Unit cells were determined by centering 25 reflections in the approximate 2θ range. Other
relevant experimental details are in the supporting information. The structure was solved by direct method
using SHELXS-86 and refined by full-matrix least squares with SHELXL-93. All atoms were refined with
anisotropic temperature factors. Further details of the crystal structure investigation are available from
the author.
Acknowledgements
This work was supported by the Ministry of Education (BSRI 1998-015-D00165) and KOSEF through
the Center for Molecular Catalysis.
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