Synthesis of a new class of functionalized chiral bisphospholane ligands and the application in enantioselective hydrogenations

Full text of DOI:10.1021/jo980960s

J . Org. Chem. 1998, 63, 8031-8034
8031
Du Pont de Nemours & Company, which has seen also
application in other asymmetric reactions.6
Syn th esis of a New Cla ss of F u n ction a lized
Ch ir a l Bisp h osp h ola n e Liga n d s a n d th e
Ap p lica tion in En a n tioselective
Hyd r ogen a tion s
J ens Holz,*,† Michael Quirmbach,† Ute Schmidt,†
Detlef Heller,† Rainer Stu¨rmer,‡ and Armin Bo¨rner*,†
Institut fu¨r Organische Katalyseforschung an der
Universita¨t Rostock e.V., Buchbinderstrasse 5/ 6,
D-18055 Rostock, Germany, and BASF Aktiengesellschaft,
Hauptlaboratorium - ZHF/ D, Feinchemikalien,
D-67056 Ludwigshafen, Germany
Received May 20, 1998
In tr od u ction
The enantioselective hydrogenation of prochiral olefins
or ketones with phosphine-metal complexes represents
an extremely useful and versatile reaction.1 Over the last
years it has seen broad application in lab-scale organic
synthesis as well as in the industrial scale for the
production of fine chemicals.2 Due to the increasing
importance there is an ongoing interest focused on the
design of new ligands and metal complexes.3
One of the most powerful classes of ligands associated
to rhodium(I) hydrogenation catalysts constitutes chiral
C2-symmetric bis-phospholanes, e.g., 1,2-bis(2,5-dimeth-
ylphospholanyl)benzene (1a , DuPHOS), 1,2-bis(2,5-di-
methylphospholanyl)ethane (1b , BPE),4 and related
ligands,5 originally developed by Burk and co-workers at
The synthesis of these chiral phospholanes entails as
key steps the asymmetric hydrogenation of â-keto esters
affording the corresponding chiral hydroxy esters, fol-
lowed by an electrochemical coupling procedure of the
chiral units (Kolbe reaction). Due to this preparative
protocol the self-made synthesis requires additional
experience and equipment not always available in each
laboratory. Inspection of the literature reveals that some
alternatives for the construction of the chiral phospholane
framework exist including stoichiometric asymmetric
reactions as well as the employment of enzymatic
methods.7-10 However, none of the procedures delivers
functionalized phospholanes, although the effect of ad-
ditional functional groups in phosphine metal complexes
is well documented. In particular ether functions known
from the high efficiency of DIPAMP-Rh(I)-complexes11
can advantageously contribute to the enantioface-dis-
criminating ability of the catalyst.12
* Corresponding author. Tel: +49-381-4669310/50. Fax: +49-
381-4669324. E-mail: armin.boerner@ifok.uni-rostock.de.
† Institut fu¨r Organische Katalyseforschung.
‡ BASF.
(1) (a) Koenig, K. E. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: Orlando, 1985; Vol. 5, Chapter 3, p 71. (b) Takaya,
H.; Ohta, T.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I.,
Ed.; VCH: Weinheim, 1993; Chapter 1, p 1. (c) Seyden-Penne, J . Chiral
Auxiliaries and Ligands in Asymmetric Synthesis; J ohn Wiley &
Sons: New York, 1995; Chapter 7, p 367.
(2) (a) Akutagawa, S. In Chirality in Industry; Collins, A. N.,
Sheldrake, G. N., Crosby, J ., Eds.; J ohn Wiley & Sons: Chichester,
1992; Chapter 17, p 325. (b) Sheldon, R. A. Chirotechnology; Marcel
Dekker: New York, 1993, Chapter 8, p 285. (c) Kumobayashi, H. Rec.
Trav. Chim. Pay-Bas 1996, 115, 201. (d) Blaser, H.-U.; Spindler, F.
Chimia 1997, 51, 297. (e) Imwinkelried, R. Ibid. 1997, 51, 300. (f)
Crameri, Y.; Foricher, J .; Hengartner, U.; J enny, C.-J .; Kienzle, F.;
Ramuz, H.; Scalone, M.; Schlageter, M.; Schmid, R.; Wang, S. Ibid.
1997, 51, 303. (g) Bo¨rner, A.; Holz, J . In Transition Metals for Organic
Synthesis; Beller, M., Bolm, C., Eds; Vol. 2, VCH: Weinheim, 1998;
Chapter 1.1.1, p 3.
(3) For recent publications see: (a) Pye, P. J .; Rossen, K.; Reamer,
R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J . J . Am. Chem. Soc. 1997,
119, 6207. (b) Robin, F.; Mercier, F.; Ricard, L.; Mathey, F.; Spagnol,
M. Chem. Eur. J . 1997, 3, 1365. (c) Langer, F.; Pu¨ntener, K.; Stu¨rmer,
R.; Knochel, P. Tetrahedron: Asymmetry 1997, 8, 715. (d) Enev, V.;
Ewers, C. L. J .; Harre, M.; Nickisch, K.; Mohr, J . T. J . Org. Chem.
1997, 62, 7092. (e) Zhu, G.; Cao, P.; J iang, Q.; Zhang, X. J . Am. Chem.
Soc. 1997, 119, 1799. (f) Imamoto, T.; Watanabe, J .; Wada, Y.; Masuda,
H.; Yamada, H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J . Am.
Chem. Soc. 1998, 120, 1635.
(4) (a) Burk, M. J . J . Am. Chem. Soc. 1991, 113, 8518. (b) Burk, M.
J .; Feaster, J . E.; Harlow, R. L. Tetrahedron: Asymmetry 1991, 2, 569.
(c) Burk, M. J .; Feaster, J . E.; Nugent, W. A.; Harlow, R. L. J . Am.
Chem. Soc. 1993, 115, 10125. (d) Burk, M. J .; Feng, S.; Gross, M. F.;
Tumas, W. J . Am. Chem. Soc. 1995, 117, 8277. (e) Burk, M. J .; Gross,
M. F.; Harper, T. G. P.; Kalberg, C. S.; Lee, J . R.; Martinez, J . P. Pure
Appl. Chem. 1996, 68, 37. (f) Albrecht, J .; Nagel, U. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 407.
Considering these features, we decided to disclose a
new and simple pathway to enantiopure and function-
alized bis-phospholane ligands 3a ,b and 4a starting from
(6) (a) Barnhart, R. W.; McMorran, D. A.; Bosnich, B. Chem.
Commun. 1997, 589. (b) Alexakis, A.; Burton, J .; Vastra, J .; Mangeney,
P. Tetrahedron: Asymmetry 1997, 8, 3987.
(7) (a) Fiaud, J .-C.; Legros, J .-Y. Tetrahedron Lett. 1991, 32, 5089.
(b) Nagai, H.; Morimoto, T.; Achiwa, K. Synlett 1994, 289. (c) Morimoto,
T.; Ando, N.; Achiwa, K. Ibid. 1996, 1211. (d) Longeau, A.; Durand,
S.; Spiegel, A.; Knochel, P. Tetrahedron: Asymmetry 1997, 8, 987. (e)
Hume, S. C.; Simpkins, N. S. J . Org. Chem. 1998, 63, 912.
(8) For related ligands based on the chiral phosphetane framework
see: Marinetti, A.; Kruger, V.; Buzin, F. X. Tetrahedron Lett. 1997,
38, 2947.
(9) Quite recently, the synthesis of the bis-phospholane-based ligand
PennPHOS, being highly efficient in ketone hydrogenation, was
reported: J iang, Q.; J iang, Y.; Xiao, D.; Cao, P.; Zhang, X. Angew.
Chem., Int. Ed. 1998, 37, 1100.
(10) One of the referees informed us that at the time the requisite
chiral 1,4-diols for the synthesis of DuPHOS-type ligands at ChiroTech
(Cambridge, UK) are derived from an enzymatic approach.
(11) Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J .; Bachmann,
G. L.; Weinkauff, D. J . J . Am. Chem. Soc. 1977, 99, 5946.
(12) (a) Horner, L.; Siegel, H.; Buthe, H. Angew. Chem., Int. Ed.
Engl. 1968, 7, 942. (b) J ohnson, C. R.; Imamoto, T. J . Org. Chem. 1987,
52, 2170. (c) Burgess, K.; Ohlmeyer, M. J .; Whitmire, K. H. Organo-
metallics 1992, 11, 3588. (d) Nagel, U.; Krink, T. Angew. Chem., Int.
Ed. Engl. 1993, 32, 1052. (e) Nagel, U.; Krink, T. Chem. Ber. 1993,
126, 1091. (f) Yang, H.; Alvarez, M.; Lugan, N.; Mathieu, R. J . Chem.
Soc., Chem. Commun. 1995, 1721. (g) Nagel, U.; Krink, T. Chem. Ber.
1995, 128, 309.
(5) Burk, M. J .; Gross, M. F. Tetrahedron Lett. 1994, 35, 9363.
10.1021/jo980960s CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/08/1998

8032 J . Org. Chem., Vol. 63, No. 22, 1998
Notes
the “chiral pool”.13 The new phosphines bear ether
groups in position 3 and 4 of the heterocycle. Already in
1987, Brunner reported the synthesis of bis-phospholane
2 employing (R,R)-tartaric acid as starting material.14
However, due to the remote position of the chiral centers
from the metal, asymmetric induction in the rhodium-
(I)-catalyzed hydrogenation of a prochiral test olefin was
disappointingly low. In contrast to these results, our new
family of ligands named “RoPHOS”15 combines structural
motifs of both ligand types and matches the high ef-
ficiency of DuPHOS-type complexes in asymmetric hy-
drogenations.
Sch em e 1a
Resu lts a n d Discu ssion
The starting material of our approach is the com-
mercially available and inexpensive D-mannitol, which
has been selectively converted into the 1,2;5,6-di-O-
isopropylidene derivative by a known protocol.16 O-
Benzylation of the remaining alcoholic groups afforded
3,4-di-O-benzyl ether 5.17 Acidic cleavage of the acetal
protective groups yielded the tetrol 6.17a,18 Both primary
hydroxymethyl groups in turn were converted via tosyl-
ation (7)19 and subsequent reduction with LiAlH4 into
methyl groups (8).20 Esterification of the hydroxy groups
with thionyl chloride and in situ oxidation of the inter-
mediate sulfite with catalytic amounts of RuO4 gave the
cyclic sulfate 9. The latter could be also used for a change
of the O-protective groups. Thus, hydrogenolysis of the
benzyl groups employing catalytic amounts of palladium
on charcoal afforded alcohol 10. Treatment of the hy-
droxy groups with isobutylene furnished O-tert-butyl-
substituted sulfate 11. Sulfates 9 and 11 were individu-
ally reacted with 1,2-diphosphinoethane in the presence
of n-BuLi to give bis-phospholanes 3a ,b. For the purpose
of purification the highly air-sensitive trialkylphosphines
were converted in situ into the corresponding phosphine-
borane adducts 12a ,b by treatment with an 1 M THF
solution of BH3.21 After flash chromatography the phos-
phines were liberated with 1,4-diazabicyclo[2.2.2]octane
(DABCO)22 in toluene to afford the aspired phosphines
3a ,b. Alternatively, sulfate 9 was reacted with 1,2-
diphosphinobenzene to give bis-phospholane 4a . The
latter was much less sensitive to air than 3a ,b and could
be therefore simply purified by flash chromatography
without prior conversion into its borane adduct.23
a
Key: (a) acetone, ZnCl2, rt; (b) BnBr, NaOH, THF; (c) 70% aq
HOAc, rt; (d) TsCl, pyridine, 0 °C; (e) LiAlH4, THF; (f) (1) SOCl2,
(2) RuCl3, NaIO4, CH3CN, H2O, CCl4; (g) H2, Pd/C, MeOH, rt; (h)
isobutylene, H2SO4, CH2Cl2, 5 d, rt; (i) BuLi, 1,2-H2P(CH2)2PH2,
THF; (j) BH3-THF; (k) DABCO, toluene, 40 °C, 48 h; (l) BuLi,
1,2-H2PC6H4PH2, THF, rt.
Sch em e 2a
a
Key: (m) [Rh(COD)2]BF4, THF, -10 °C.
(1J Rh-P ) 152.6 Hz) (Scheme 2). It is noteworthy that
the undesired formation of catalytically inactive Rh(I)
complexes bearing two chelating diphosphine ligands
could be averted when the reaction was run below 0 °C.
The new complexes were tested in the hydrogenation
of different prochiral olefins. As listed in Table 1 the
catalysts tolerate a range of several functional groups
attached to the double bond. In all cases, even in the
hydrogenation of the unsaturated phosphonate,24 enan-
tioselectivities between 92.6 and 99.1% were achieved.
Although the catalytic differences between ethylene- and
phenylene-bridged phospholanes as well as the influence
of the different O-protective groups upon the intrinsic
enantioselectivity of the 2,4-dimethylphospholane com-
plex are small, the effect is significant. Thus, by the
proper choice of these structural features fine-tuning of
the catalyst toward the special requirements of each
substrate is possible.
Complexation reactions of the new ligands with [Rh-
(COD)2]BF4 formed the expected five-membered cis-
chelates [Rh(3a )(COD)]BF4 (1J Rh-P ) 148.8 Hz), [Rh(3b)-
(COD)]BF4 (1J Rh-P ) 148.4 Hz) and [Rh(4a )(COD)]BF4
(13) Bo¨rner, A.; Holz, J.; Voss, G.; Stu¨rmer, R. DE 48 084 (18.06.1997).
(14) Brunner, H.; Sievi, R. J . Organomet. Chem. 1987, 328, 71.
(15) The name is derived from the city of Rostock where the institute
is situated.
(16) Tipson, R. S.; Cohen, A. Carbohydrate Res. 1968, 7, 232.
(17) (a) J urczak, J .; Bauer, T.; Chmielewski, M. Carbohydrate Res.
1987, 164, 493. (b) Gurjar, M. K.; Pawar, S. M. Indian J . Chem. Sect.
B 1987, 26, 55. (c) Zou, W.; Szarek, W. A. Carbohydr. Res. 1994, 254,
25.
(18) Kong, X.; Grindley, T. B. Can. J . Chem. 1994, 72, 2396.
(19) (a) Fitremann, J .; Dure´ault, A.; Depezay, J .-C. Tetrahedron Lett.
1994, 35, 1201. (b) Fitremann, J .; Dureault, A.; Depezay, J .-C.
Tetrahedron 1995, 51, 9581.
(20) See also Kagan, H. B.; Fiaud, J .-C.; Hoornaert, C.; Meyer, D.;
Polin, J .-C. Bull. Soc. Chim. Belg. 1979, 88, 923.
(21) For a review on the use of phosphine-boranes for the synthesis
of chiral phosphine ligands, compare: Ohff, M.; Holz, J .; Quirmbach,
M.; Bo¨rner, A. Synthesis, in press.
(22) Brisset, H.; Gourdel, Y.; Pellon, P.; Le Corre, M. Tetrahedron
Lett. 1993, 34, 4523.
(23) It is noteworthy that by the effect of BH3-THF only the mono-
borane adduct was produced, obviously due to the steric hindrance in
the o-phenylenediphosphine unit. See also: Schmidbaur, H.; Pascha-
lidis, C.; Steigelmann, O.; Wilkinson, D. L.; Mu¨ller, G. Chem. Ber. 1989,
122, 1857 and ref 8.
(24) Schmidt, U.; Oehme, G.; Krause, H.-W. Synth. Commun. 1996,
26, 777.

Notes
J . Org. Chem., Vol. 63, No. 22, 1998 8033
Ta ble 1. Asym m etr ic Hyd r ogen a tion s w ith Rh
Com p lexes of RoP HOS Typ ea
in THF (100 mL) under stirring at ambient temperature. After
1 h stirring, the suspension was heated for 2 h under reflux.
After cooling the mixture to room temperature, the excess of
LiAlH4 was decomposed by careful addition of water (2.25 mL),
15% aqueous NaOH (2.25 mL), and water (6.75 mL). Then, the
inorganic compounds were filtered off, and the residue was
extracted with CH2Cl2 by means of a Soxhlet. The combined
extracts were evaporated, and the residue was purified by flash
chromatography (n-hexane:AcOEt ) 1:2; Rf ) 0.45) to provide
time for 50%
conversion
(min)
eeb (%)/
config
ligand R1
R2
Ph NHAc
Ph NHAc
R3
8 as a white solid (3.6 g, 73%): mp 46-50 °C; [R]26 ) -4.7 (c
D
0.990, CHCl3); 1H NMR (CDCl3) δ 7.40-7.25 (m, 10H), 4.65 (AB,
J ) 11.3 Hz, 2H), 4.64 (AB, J ) 11.3 Hz, 2H), 4.09 (m, 2H), 3.53
(m, 2H), 2.96 (br, exchangeable with D2O, 2H), 1.25 (d, J ) 6.4
Hz, 6H); 13C NMR (CDCl3) δ 137.4, 128.5, 128.2, 128.0, 81.5,
73.3, 67.3, 19.7; IR (KBr) 3417, 3287 cm-1; MS (70 eV, m/z) 331
[M+ + H] (1). Anal. Calcd for C20H26O4: C, 72.70; H, 7.93.
Found: C, 72.79; H, 7.94.
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
4a
4a
4a
4a
4a
COOH
COOMe
COOH
62
52
24
93.5 (S)
97.5 (S)
98.0 (R)
98.9 (R)
95.4 (R)
96.8 (S)
98.4 (S)
96.7 (R)
99.1 (R)
98.8 (R)
93.0 (S)
96.0 (S)
97.5 (R)
98.0 (R)
92.6 (R)
H
H
CH2COOH
CH2COOMe COOMe
9
Ph NHBz
Ph NHAc
Ph NHAc
P(O)(OMe)2
COOH
COOMe
COOH
780
115
125
11
8
500
75
48
10
28
600
H
CH2COOH
(4R ,5S ,6S ,7R )-5,6-Bis(b e n zyloxy)-4,7-d im e t h yl[1,3,2]-
d ioxa th iep a n e 2,2-Dioxid e (9). A suspension of diol 8 (4.75
g, 14.4 mmol) and SOCl2 (1.3 mL) in CCl4 (20 mL) was heated
under reflux for 1.5 h. After cooling the mixture to room
temperature, the solvent was removed under vacuum. The
residue was dissolved in a mixture of CCl4 (10 mL), acetonitrile
(10 mL), and water (15 mL). The solution was cooled to 0 °C,
and RuCl3‚3H2O (0.021 g, 0.08 mmol) and sodium periodate (6.2
g, 29.0 mmol) were successively added. After 1 h of stirring,
water (75 mL) was added and the solution extracted with diethyl
ether (4 × 100 mL). The combined extracts were washed with
brine, dried (Na2SO4), and filtered through silica gel. The
ethereal solution was evaporated and the residue purified by
flash chromatography (n-hexane:AcOEt ) 9:1, Rf ) 0.25) to give
the sulfate 9 as colorless crystals (3.4 g, 60%): mp 90-94 °C;
H
CH2COOMe COOMe
Ph NHBz
Ph NHAc
Ph NHAc
P(O)(OMe)2
COOH
COOMe
COOH
H
CH2COOH
H
CH2COOMe COOMe
Ph NHBz
P(O)(OMe)2
a
Condition of the hydrogenation: 1.0 atm overall pressure over
the solution. The experiments were carried out under standard
conditions with 0.01 mmol of precatalyst and 1.0 mmol of prochiral
b
olefin in 15 mL of solvent. For the determination of the %ee, see
Experimental Section.
In summary, we have prepared a new class of chiral
functionalized chelating diphosphines by a convenient
and simple synthetic sequence starting from D-manni-
tol.25 The corresponding rhodium complexes are highly
effective in the hydrogenation of a range of functionalized
olefins.
[R]23 ) -2.8 (c 1.012, CHCl3); 1H NMR (CDCl3) δ 7.32-7.18
D
(m, 10H), 4.79 (AB, J ) 10.7 Hz, 2H), 4.64 (AB, J ) 10.8 Hz,
2H), 4.60 (m, 2H), 3.48 (m, 2H), 1.46 (d, J ) 6.4 Hz, 6H); 13C
NMR (CDCl3) δ 137.1, 128.6, 128.1, 127.7, 84.2, 79.4, 76.2, 17.9;
MS (70 eV, m/z): 392 [M+] (1). Anal. Calcd for C20H24O6S: C,
61.21; H, 6.16; S, 8.17. Found: C, 61.20; H, 6.24; S, 8.08.
(4R ,5S ,6S ,7R )-5,6-D i h y d r o x y -4,7-d i m e t h y l[1,3,2]-
d ioxa th iep a n e 2,2-Dioxid e (10). A solution of dibenzyl ether
9 (8.60 g, 21.9 mmol) in MeOH (150 mL) was stirred in the
presence of 10% Pd/C (300 mg) under a H2 atmosphere (1 atm
H2 pressure) at room temperature. After completion of the
hydrogen consumption, the mixture was filtered off and the
solvent removed under vacuum. The residue was subjected to
flash chromatography (n-hexane:AcOEt ) 1:2, Rf ) 0.4) to give
10 as colorless crystals (3.90 g, 84%): mp 118-123 °C (dec);
Exp er im en ta l Section
Gen er a l. All reagents were obtained from Aldrich and
Merck. Solvents were dried and freshly distilled under argon
before use. Reactions using phosphines and organometallic
compounds were performed under an Ar atmosphere by using
standard Schlenk techniques. Thin-layer chromatography was
performed on precoated TLC plates (silica gel 60 F254, Merck).
Flash chromatography was carried out with silica gel 60 (particle
size 0.040-0.063 mm, Merck). Melting points are corrected.
NMR spectra were recorded at the following frequencies: 400.13
MHz (1H), 100.63 MHz (13C), 161.98 MHz (31P). Chemical shifts
of 1H and 13C NMR spectra are reported in ppm downfield from
TMS as internal standard. Chemical shifts of 31P NMR spectra
are referred to H3PO4 as external standard. Signals are quoted
as s (singlet), d (doublet), br (broad), and m (multiplett).
Hydrogenation experiments have been carried out under
normal pressure and isobaric conditions with an automatically
registrating gas measuring device (1.0 atm overall pressure over
the solution). The experiments were performed with 0.01 mmol
precatalyst and 1.0 mmol of prochiral olefin in 15 mL of solvent
at 25 °C. The conversion of the prochiral dehydroamino acids
and the %ee were determined by GC. The acids were esterified
with (trimethylsilyl)diazomethane before the GC-measure-
ments: FID, Carrier gas: Ar: 1 mL/min; methyl N-acetylphen-
ylalaninate: fused silica, 10 m, XE-60-L-valin-tert-butylamide,
i.d. 0.2 mm; oven temperature: 150 °C; dimethyl methylsucci-
nate: fused silica, Lipodex E (Machery and Nagel), 25 m, i.d.
0.25 mm, oven temperature: 85 °C. The conversion to the
saturated phosphonate and its %ee were determined by HPLC:
stationary phase: Chiralcel OD-H, eluent: n-hexane/ethanol.
(2R,3R,4R,5R)-3,4-Di-O-b en zylh exa n e-2,3,4,5-t et r ol (8).
A solution of ditosylate 7 (10 g, 14.9 mmol) in THF (30 mL) was
added dropwise to a suspension of LiAlH4 (2.25 g, 59.6 mmol)
[R]23 ) -24.5° (c 1.028, CH3OH); 1H NMR (CD3OD) δ 4.36 (m,
D
2H), 3.15 (m, 2H), 1.31 (d, J ) 6.0 Hz, 6H); 13C NMR (CD3OD)
δ 81.4, 77.8, 18.3; IR (KBr) 3452, 3375 cm-1; MS (CI, m/z) 269
[M+ + C4H9]. Anal. Calcd for C6H12O6S: C, 33.96; H, 5.70; S,
15.11. Found: C, 34.13; H, 5.56; S, 14.87.
(4R,5S,6S,7R)-5,6-Bis(ter t-bu tyloxy)-4,7-d im eth yl[1,3,2]-
d ioxa th iep a n e 2,2-Dioxid e (11). A pressure vessel was fitted
with a solution of alcohol 10 (3.61 g, 17.0 mmol) in CH2Cl2 (70
mL). After cooling the mixture to -78 °C, isobutylene (70 mL)
and concentrated sulfuric acid (0.2 mL) were successively added.
The vessel was closed and the solution stirred for 5 days at room
temperature. Then, the solution was cooled to -78 °C and the
excess of isobutylene carefully liberated. The remaining solution
was washed with water (2 × 25 mL) and dried (Na2SO4). After
filtration and removal of the solvent, the residue was subjected
to flash chromatography (n-hexane:AcOEt ) 4:1, Rf ) 0.35) to
afford 11 as colorless crystals (1.83 g, 33%): mp 112-117 °C;
[R]24 ) 21.5° (c 0.998, CHCl3). Anal. Calcd for C14H28O6S: C,
D
51.83; H, 8.70; S, 9.88%; Found: C, 51.91; H, 8.78; S, 9.72.
BH3 Ad d u ct of 1,2-Bis[(2S,3S,4S,5S)-3,4-bis(ben zyloxy)-
2,5-d im eth ylp h osp h ola n yl]eth a n e (12a ). To a stirred solu-
tion of 1,2-diphosphinoethane (0.396 g, 4.21 mmol) in THF (70
mL) was added n-BuLi (1.6 M n-hexane solution, 5.26 mL, 8.42
mmol) dropwise via
a syringe at room temperature. The
resulting yellow solution was stirred for further 2 h. When a
solution of sulfate 9 (3.30 g, 7.92 mmol) dissolved in THF (15
mL) was added, a change of the color from yellow to brown
occurred. After 4 h of stirring, n-BuLi (1.6 M hexane solution,
5.79 mL, 9.26 mmol) was added and the solution kept for 16 h
at room temperature. Then 2.2 equiv of BH3-THF complex (1
(25) Dr. J . M. Brown (Oxford, UK) kindly informed us that his group
recently succeeded in the synthesis of a DIPAMP-BPE hybrid ligand
also starting from D-mannitol.

8034 J . Org. Chem., Vol. 63, No. 22, 1998
Notes
M solution in THF, 9.26 mL, 9.26 mmol) was added at 0 °C.
After 2 h the solvents were removed under reduced pressure.
To the residue was added water (20 mL) and the aqueous
solution extracted with CH2Cl2 (3 × 30 mL). The combined
organic layers were dried (Na2SO4) and concentrated to afford
the crude phospholane-borane as a colorless syrup. Purification
was accomplished by flash chromatography (n-hexane:AcOEt )
4:1, Rf ) 0.25) to give 12a as a colorless syrup (750 mg, 25%):
1H NMR (CDCl3) δ 7.38-7.20 (m, 20H), 4.55-4.42 (m, 8H), 3.90
(m, 4H), 2.58 (m, 2H), 2.24 (m, 2H), 2.00-1.64 (m, 4H), 1.20-
1.11 (m, 12H), 0.90-0.05 (b, 6H); 13C NMR (CDCl3) δ 137.8,
137.5, 128.5-127.4, 84.0, 82.3, 72.5, 72.3, 34.5 (d, J ) 33.4 Hz),
34.0 (d, J ) 31.5 Hz), 17.8, 10.0, 8.1; 31P NMR (CDCl3) δ 39.2.
Anal. Calcd for C42H58O4B2P2: C, 71.00; H, 8.23. Found: C,
71.42; H, 8.33.
pressure. The residue was dissolved in CH2Cl2 (50 mL), washed
with water (20 mL), and dried (Na2SO4). After filtration and
removal of the solvent, the crude phosphine was purified by flash
chromatography (n-hexane:AcOEt ) 9:1, Rf ) 0.2) to give 4a as
a colorless syrup (0.46 g, 16%). 1H NMR (CDCl3) δ 7.55-7.19
(m, 24H), 4.63 (AB, J ) 12.0 Hz, 2H), 4.59 (AB, J ) 12.0 Hz,
2H), 4.58 (s, 4H), 4.05 (m, 4H), 2.98-2.82 (m, 4H), 1.29 (m, 6H),
0.84 (m, 6H); 13C NMR (CDCl3) δ 142.3, 138.7, 131.7, 128.1-
127.4, 84.4, 84.2, 72.0, 71.9, 31.9, 31.4, 14.3, 12.8; 31P NMR
(CDCl3) δ -4.3; MS (FDpos) 731 [M+ + H] (100). Anal. Calcd
for C46H52O4P2: C, 75.60; H, 7.17. Found: C, 75.98; H, 7.42.
[Rh (3a )(COD)]BF 4. A solution of diphospholane 3a (180 mg,
0.26 mmol) in THF (1.5 mL) was slowly added to [Rh(COD)2]-
BF4 (107 mg, 0.26 mmol) dissolved in THF (1.5 mL) at -10 °C.
The solution was stirred for 15 min at room temperature. After
addition of diethyl ether (12 mL), a brownish oil was formed.
Decantation and repeated washing with diethyl ether (3 × 5 mL)
converted the oil into a solid. It was dried under vacuum to
give the complex as orange-brown powder (134 mg, 52%). 1H
NMR (CDCl3) δ 7.38-7.27 (m, 20H), 5.30 (m, 2H), 5.17 (m, 2H),
4.61-4.43 (m, 8H), 4.09-3.93 (m, 4H), 2.60-1.70 (m, 16H) 1.37-
1.20 (m, 12H); 13C NMR (CDCl3) δ 137.6, 137.2, 128.7-127.5,
101.8, 95.5, 83.8, 83.5, 73.0, 72.6, 41.9, 33.5, 31.3, 28.6, 25.6,
14.5, 8.8; 31P NMR (CDCl3) δ 72.7 (d, J Rh-P ) 148.8 Hz); MS
(FDpos) 892 [M+ - BF4] (100). Anal. Calcd for C50H64O4P2-
RhBF4: C, 61.24; H, 6.58. Found: C, 61.55; H, 6.26.
BH 3 Ad d u ct of 1,2-Bis[(2S,3S,4S,5S)-3,4-b is(ter t-b u t yl-
oxy)-2,5-d im eth ylp h osp h ola n yl]eth a n e (12b). Analogously
as described for the preparation of 12a starting from 1,2-
diphosphinoethane (0.352 g, 3.74 mmol) and sulfate 11 (2.43 g,
7.48 mmol). Purification of the phosphine-borane was finally
carried out by flash chromatography (n-hexane:AcOEt ) 9:1, Rf
) 0.30) to give 12b as a colorless syrup (310 mg, 14%): mp 200-
210 °C; [R]24 ) 27.3° (0.565, CHCl3); 31P NMR (CDCl3) δ 39.1;
D
MS (EI, m/z) 573 [M+ - H]. Anal. Calcd for C30H66O4P2B2: C,
62.73; H, 11.58. Found: C, 63.13; H, 11.86.
1,2-Bis[(2S,3S,4S,5S)-3,4-bis(ben zyloxy)-2,5-dim eth ylph os-
p h ola n yl]eth a n e (3a ). A solution consisting of phosphine-
borane adduct 12a (290 mg, 0.41 mmol) and 4 equiv of DABCO
(183 mg, 1.64 mmol) in toluene (6 mL) was stirred for 48 h at
40 °C. The conversion was followed by TLC (n-hexane:AcOEt
) 4:1, Rf of the phosphine ) 0.3). After full conversion, the
solution was passed through a short column. The toluene was
removed under reduced pressure to give the phosphine (210 mg,
75%). 1H NMR (CDCl3) δ 7.37-7.15 (m, 20H), 4.54-4.34 (m,
8H), 3.96-3.78 (m, 4H), 2.53 (m, 2H), 2.10 (m, 2H), 1.73-1.50
(m, 4H), 1.30-1.05 (m, 12H); 13C NMR (CDCl3) δ 138.7, 138.5,
128.3-127.3, 86.8, 85.1, 72.2, 71.9, 33.5, 22.6, 14.1, 9.4; 31P NMR
(CDCl3) δ -1.5. Due to the high sensitivity of the phosphine to
oxidation, it was immediately chelated to Rh(I).
[Rh (3b)(COD)]BF 4. Analogously as described for the prepa-
ration of [Rh (3a )(COD)]BF 4 starting from diphospholane 3b
(95 mg, 0.173 mmol) and [Rh(COD)2]BF4 (72 mg, 0.173 mmol)
to give the complex as orange powder (110 mg, 75%). 31P NMR
(CDCl3) δ 74.3 (d, J Rh-P ) 148.4 Hz). Anal. Calcd for C38H72O4P2-
RhBF4: C, 54.04; H, 8.59. Found: C, 54.57; H, 8.61.
[Rh (4a )(COD)]BF 4. Analogously as described for the prepa-
ration of [Rh (3a )(COD)]BF 4 starting from diphospholane 4a
(300 mg, 0.41 mmol) and [Rh(COD)2]BF4 (167 mg, 0.41 mmol)
to give the complex as brown powder (200 mg, 47%). 31P NMR
(CDCl3) δ 76.1 (d, J Rh-P ) 152.6 Hz); MS (FDpos) 941 [M+
-
BF4] (10). Anal. Calcd for C54H64O4P2RhBF4: C, 63.05; H, 6.27.
Found: C, 62.58; H, 6.18.
1,2-Bis[(2S,3S,4S,5S]-3,4-b is(ter t-b u t yloxy)-2,5-d im et h -
ylp h osp h ola n yl]eth a n e (3b). Analogously as described for the
preparation of 3a starting from the borane adduct 12b (130 mg,
0.23 mmol) and 4 equiv of DABCO (101 mg, 0.92 mmol). After
stirring for 48 h at 40 °C and workup by flash chromatography
(n-hexane:AcOEt ) 2:1, Rf of the phosphine 0.60) the extremely
air-sensitive phosphine was obtained as a colorless syrup (95
mg, 77%). 31P NMR (CDCl3) δ -0.5. Due to the high sensitivity
of the phosphine to oxidation, it was immediately chelated to
Rh(I).
1,2-Bis[(2S,3S,4S,5S)-3,4-bis(ben zyloxy)-2,5-dim eth ylph os-
p h ola n yl]ben zen e (4a ). To a stirred solution of 1,2-diphos-
phinobenzene (0.564 g, 3.96 mmol) in THF (70 mL) was added
n-BuLi (1.6 M hexane solution, 4.95 mL, 7.93 mmol) at room
temperature. The resulting yellow solution was stirred for
further 2 h. Then a solution of sulfate 9 (3.11 g, 7.92 mmol)
dissolved in THF (15 mL) was added. A change of the color from
yellow to brown occurred. After 4 h of stirring n-BuLi (1.6 M
hexane solution, 5.45 mL, 8.71 mmol) was added and the solution
kept for another 16 h at room temperature. After addition of
methanol (3 mL), the solvents were evaporated under reduced
Ack n ow led gm en t. We thank Mrs G. Voss and Mrs
C. Pribbenow for skilled technical assistance. Acknowl-
edgment is given to Mrs. K. Kortus and Dr. Ch. Fischer
for the analysis of the hydrogenation products. It is a
pleasure to thank the BASF AG (Ludwigshafen) for
financial support of this work, the Deutsche Fors-
chungsgemeinschaft for a grant given to M. Q., and the
Fonds der Chemischen Industrie. We thank Prof. Dr.
R. Selke for helpful discussion.
Su p p or tin g In for m a tion Ava ila ble: A complete list of
all IR and MS spectra, 1H and 13C NMR spectra of 11, 12b,
3b, [Rh (3b)(COD)]BF 4, and [Rh (4a )(COD)]BF 4 (2 pages).
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