Asymmetric synthesis. Part 29: Asymmetric hydroformylation of styrene catalyzed by chiral spiro diphosphite-rhodium(I) complexes

Article abstract of DOI:10.1016/S0957-4166(98)00339-5

Chiral diphosphite ligands L₁-L₃ were prepared by the reaction of (1S,5S,6R)-(cis,trans)-spiro[4.4]nonane-1,6-diol with chlorophosphites. These ligands were tested in the rhodium catalyzed hydroformylation of styrene and enantioselectivities up to 69% were achieved. High regioselectivities (97%) to 2-phenylpropanal and high yields (98%) were obtained under mild reaction conditions. The influence of reaction conditions is also discussed.

Full text of DOI:10.1016/S0957-4166(98)00339-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 3185–3189
Asymmetric synthesis. Part 29: Asymmetric hydroformylation of
styrene catalyzed by chiral spiro diphosphite–rhodium(I)
complexes
Yaozhong Jiang,a,∗ Song Xue,a Zhi Li,a Jingen Deng,a Aiqiao Mi a and Albert S. C. Chan b
aChengdu Institute of Organic Chemistry, Academia Sinica, Chengdu 610041, China
bHong Kong Polytechnic University, Hong Kong
Received 4 June 1998; accepted 17 August 1998
Abstract
Chiral diphosphite ligands L1–L3 were prepared by the reaction of (1S,5S,6R)-(cis,trans)-spiro[4.4]nonane-1,6-
diol with chlorophosphites. These ligands were tested in the rhodium catalyzed hydroformylation of styrene and
enantioselectivities up to 69% were achieved. High regioselectivities (97%) to 2-phenylpropanal and high yields
(98%) were obtained under mild reaction conditions. The influence of reaction conditions is also discussed. © 1998
Elsevier Science Ltd. All rights reserved.
1. Introduction
Asymmetric hydroformylation is a method for the preparation of homochiral aldehydes, which are
important precursors for the synthesis of pharmaceuticals and food ingredients. Much effort has been
made to develop chiral catalysts, especially in the design of novel chiral ligands, which are expected to
provide high regio- and stereoselectivity in the hydroformylation of olefins. Rh(I)-catalysts containing
chiral phosphine–phosphite or diphosphite have provided 50–94% ee in the hydroformylation of styrene
with excellent chemo- and regioselectivity.1–3
Recently, a bisphosphinite containing a spiro backbone has been found to be an efficient chiral ligand
for the catalytic asymmetric hydrogenation of enamides in our laboratory.4 Since phosphite–Rh(I) com-
plexes often show high catalytic activity in hydroformylation,5,6 and the phosphites are easily prepared
∗
Corresponding author. E-mail: clf@mail.sc.cninfo.net
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00339-5

3186
Y. Jiang et al. / Tetrahedron: Asymmetry 9 (1998) 3185–3189
from spiro-diol, we have synthesised diphosphites derived from (1S,5S,6R)-(cis,trans)-spiro[4.4]nonane-
1,6-diol 1 and investigated them in the asymmetric hydroformylation of styrene.
2. Results and discussion
The chiral phosphites were readily prepared by the reaction of (1S,5S,6R)-(cis,trans)-diol 1 with the
corresponding chlorophosphites 2a–c, which were formed in situ according to the literature procedure,6
in benzene in the presence of pyridine. Compounds L1–3 are stable in air and can be easily purified by
flash column chromatography using toluene as the eluent.
The catalyst species were prepared in situ by simply mixing Rh(acac)(CO)2 and diphosphites. The
results of the asymmetric hydroformylation of styrene are given in Table 1. In run 1, the substrate was
immediately added after the autoclave had been heated to the desired reaction temperature and a low
6,7
yield of aldehyde resulted. Since an incubation period is necessary for the formation of RhH(L)(CO)2
from Rh(acac)(CO)2 and diphosphite, the catalyst was prepared under typical conditions [40°C, 10 atm
of syn gas (CO:H2=1:1), 10 h] before the substrate was added. Little influence on the enantioselectivity
was observed on varying the pressure of syn gas (runs 2–6), however, the yield of product decreased
markedly when the pressure of syn gas was increased. This catalyst was also tested at low pressure,
even at atmospheric pressure of syn gas and 98% yield of aldehyde was obtained at 5 atm of syn gas
with 61% ee (run 6). It is noteworthy that only 47% ee was obtained at 1 atm of syn gas with moderate
yield (77%, run 7). Moreover, the reaction rate decreased dramatically when the complex was incubated
under the conditions (40°C, 1 atm of syn gas, 10 h) with the same reaction conditions (run 8 versus 7)
and the result implies that the intermediates RhH(L)(CO)2 can be partially formed at an atmospheric
pressure of syn gas. Thus, to achieve high yield, a higher pressure of syn gas (10 atm) is necessary for
the efficient formation of RhH(L)(CO)2 while the catalyst was prepared. When the reaction temperature
was decreased from 40 to 25°C, the enantiomeric excess was slightly increased, but yield of product
decreased markedly (run 2 versus 9). An increase of the ee value was achieved by using a small excess of
diphosphite (run 2 versus 12). However, the enantiometric excess did not improve and the yield of product
decreased when the ratio of P/Rh was increased to 5. High b/n ratios were obtained in this reaction (runs
1–6, 9–14) and this might be attributed to the presence of the spiro backbone and large bulky substituents
on the bis(phenol) group of the catalyst.8
Compounds L1–2 were also evaluated under the typical hydroformylation reaction conditions (40°C,
20 atm of syn gas, 10 h). Compound L2 showed relatively high catalytic activity and 92% yield was
found with up to 59% ee (run 15). Compound L1 with no substituents on the ortho and para positions
of the biaryl moiety showed very low catalytic activity and only gave very low enantioselectivity (run

Y. Jiang et al. / Tetrahedron: Asymmetry 9 (1998) 3185–3189
3187
Table 1
Asymmetric hydroformylation of styrene catalyzed by diphosphite–Rh(I) complexesa
16). These results demonstrate that the enantioface discriminating ability of this type of catalyst may be
steered by a bulky phenol moiety.9
In conclusion, novel chiral diphosphites L2–3 derived from (1S,5S,6R)-(cis,trans)-spiro[4.4]nonane-
1,6-diol 1 are good ligands in the rhodium-catalyzed hydroformylation of styrene providing high regio-
and chemoselectivity for branched aldehydes, and moderate enantioselectivity.
3. Experimental
3.1. General
All reactions were carried out in oven-dried glassware using Schlenk techniques under pure nitrogen.
Benzene and toluene were distilled from sodium–benzophenone, pyridine from CaH2. PCl3 and styrene
were distilled before use and stored under pure nitrogen. 2,20-Dihydroxybiphenyl was purchased from
Sigma Chemical Co. 4,40,6,60-Tetra-tert-butyl-2,20 -bis(phenol) and 6,60-di-tert-butyl-4,40 -dimethoxy-
2,20-bis(phenol) were prepared according to literature procedures.10,11 Melting points were determined
on a Southend SS25PH apparatus and are uncorrected. Elemental analyses were recorded on a Carlo
Erba-1106 instrument. Gas chromatographic analyses were performed by SC-7 gas chromagraphy. 31P-
NMR spectra were obtained on a Varian FT-80A using H3PO4 (85%) as an internal standard and
1H-NMR spectra on a Bruker 300 spectrometer. Optical rotations were measured on a Perkin–Elmer
241 polarimeter. Enantiomeric excesses were measured after Jones oxidation of the aldehyde to the
corresponding acids on a SC-7 gas chromatograph with a Chrompack β-236M, 0.25×25 m chiral
capillary column. Hydroformylation reactions were carried out in a laboratory-made stainless-steel
autoclave (40 ml).

3188
Y. Jiang et al. / Tetrahedron: Asymmetry 9 (1998) 3185–3189
3.2. Preparation of 1,6-bis(2,20-bisphenoxyphosphinoxy)spiro[4.4]nonane, L1
2,20-Dihydroxybiphenyl (600 mg, 3.2 mmol) dried under reduced pressure at 80°C for 30 min was
dissolved in benzene (10 ml) and pyridine (0.5 ml). This solution was added dropwise to a cooled
solution (0°C) of PCl3 (0.3 ml) and pyridine (0.5 ml). The reaction mixture was stirred for 6 h at 60°C.
The solvent and excess of PCl3 were removed under vacuum. The last trace of PCl3 in the residue
was removed by benzene (3 ml) under reduced pressure and this procedure was repeated three times.
Compound 2a formed in situ was dissolved in benzene (10 ml) and pyridine (1.0 ml). (1S,5S,6R)-
(cis,trans)-Spiro[4.4]nonane-1,6-diol (210 mg, 1.3 mmol) dissolved in benzene was added dropwise to
the solution of compound 2a at 0°C. The reaction mixture was stirred overnight at room temperature.
The resulting pyridine salts were filtered off. Evaporation of the solvent gave a white plaster which
was purified by flash column chromatography using toluene as eluent. A white foam (460 mg, 58%)
was obtained. [α]D20=−8.4 (0.35, CH2Cl2); mp=58–59°C; 31P-NMR (CD3COCD3, δ) 145.72, 140.69
ppm; 1H-NMR (CD3COCD3, δ) 7.56–7.20 (m, 16H), 4.97 (m, 1H), 4.38 (m, 1H), 2.07–1.47 (m, 12H).
Elemental analysis, calcd: C, 67.82; H, 5.14. Found: C, 67.71; H, 5.15.
3.3. Preparation of 1,6-bis(4,40,6,60-tetra-tert-butyl-2,20 -bisphenoxyphosphinoxy)spiro[4.4]nonane, L2
Treatment of 4,40,6,60-tetra-tert-butyl-2,20 -bis(phenol) (950 mg, 2.3 mmol) and (1S,5S,6R)-(cis,trans)-
spiro[4.4]nonane-1,6-diol (120 mg, 0.77 mmol) as described for compound L1 afforded compound L2
(380 mg, 48%). [α]D20=−15.6 (0.52, CH2Cl2); mp=139–140°C; 31P-NMR (CD3COCD3, δ) 146.59,
144.90 ppm; 1H-NMR (CD3COCD3, δ) 7.50–7.45 (m, 4H), 7.23–7.17 (m, 4H), 4.92 (m, 1H), 4.39 (m,
1H), 1.71–0.83 (m, 84H). Elemental analysis, calcd: C, 75.33; H, 9.07. Found: C, 75.59; H, 9.17
3.4. Preparation of 1,6-bis(6,60-di-tert-butyl-4,40 -dimethoxy-2,20-bisphenoxyphosphinoxy)spiro[4.4]-
nonane, L3
Treatment of 6,60-di-tert-butyl-4,40 -dimethoxy-2,20-bis(phenol) (900 mg, 2.5 mmol) and (1S,5S,6R)-
(cis,trans)-spiro[4.4]nonane-1,6-diol (130 mg, 0.83 mmol) as described for compound L1 afforded
compound L3 (510 mg, 66%). [α]D20=+13.8 (0.44, CH2Cl2); mp=81–82°C; 31P-NMR (CD3COCD3,
δ) 145.83, 144.81 ppm; 1H-NMR (CD3COCD3, δ) 6.96–6.93 (m, 4H), 6.83–6.76 (m, 4H), 4.93 (m, 1H),
4.41 (m, 1H), 3.84 (s, 6H), 3.82 (s, 6H), 1.82–0.83 (m, 48H). Elemental analysis, calcd: C, 68.52; H,
7.29. Found: C, 69.22; H, 7.64.
3.5. General procedure for the asymmetric hydroformylation
The autoclave filled with Rh(acac)(CO)2 (0.0085 mmol) and diphosphite (0.025 mmol) was purged
three times with syn gas (CO:H2=1:1), then toluene (1.5 ml) was added and pressurised to 10 atm of syn
gas. The reaction mixture was stirred for 10 h at 40°C to form the active catalyst. Styrene (4.25 mmol) and
toluene (1 ml) were placed in the autoclave and the syn gas was introduced until the desired pressure was
reached. After the desired reaction time, the autoclave was cooled to room temperature and depressurised.
cis-Decahydronaphthalene as an internal standard was added. The mixture was filtered on silica gel and
the filtrate was analysed by GC for the yield and regioselectivity. A sample of the filtrate was oxidised to
acid by Jones oxidation and analysed by GC for determination of the enantiomeric excess.

Y. Jiang et al. / Tetrahedron: Asymmetry 9 (1998) 3185–3189
3189
Acknowledgements
We are grateful for the financial support of the Natural Science Foundation of China (29790124)
References
1. Sakai, N.; Mano, S.; Nozaki, K.; Takaya, H. J. Am. Chem. Soc. 1993, 115, 7033–7034.
2. Babin, J. E.; Whiteker, G. T. WO 93/03839, U.S. Pat. US 911518, 1992 [C.A. 1994, 119, 159872].
3. Nozaki, K.; Sakai, N.; Nanno, T.; Higashijima, T.; Mano, S.; Horiuchi, T.; Takaya, H. J. Am. Chem. Soc. 1997, 119,
4413–4423.
4. Chan, A. S. C.; Hu, W. H.; Jiang, Y. Z.; Mi, A. Q. J. Am. Chem. Soc. 1997, 119, 9570–9571.
5. van Leeuwen, P. W. N. M.; Roobeek, C. F. J. Organomet. Chem. 1983, 258, 343–350.
6. Buisman, G. J. H.; Vos, E. J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. J. Chem. Soc., Dalton Trans. 1995, 409–417.
7. Van Rooy, A.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Goubitz, K.; Fraanje, J. Organometallics 1996, 15, 835–847.
8. Buisman, G. J. H.; Martin, M. E.; Vos, E. J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Tetrahedron: Asymmetry 1995, 6,
719–738.
9. Buisman, G. J. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Tetrahedron: Asymmetry 1993, 4, 1625–1634.
10. Kushioka, K. J. Org. Chem. 1984, 49, 4456–4459.
11. Jongsma, T.; Fossen, M.; Challa, G.; van Leeuwen, P. W. N. M. J. Mol. Catal. 1993, 83, 17–35.