C2-symmetric diphosphinite ligands derived from carbohydrates. The strong influence of remote stereocenters on asymmetric rhodium-catalyzed hydrogenation.

Article abstract of DOI:10.1021/jo0496502

Modular ligands of C(2) symmetry (13a-e, 14a,b,d, and ent-9), systematically modified at positions 2 and 5, were easily prepared from d-glucosamine, D-glucitol, and tartaric acid, respectively. The application of these ligands in the rhodium-catalyzed hyd

Full text of DOI:10.1021/jo0496502

C2-Sym m etr ic Dip h osp h in ite Liga n d s Der ived fr om
Ca r boh yd r a tes. Th e Str on g In flu en ce of Rem ote Ster eocen ter s on
Asym m etr ic Rh od iu m -Ca ta lyzed Hyd r ogen a tion
Mohamed Aghmiz, Ali Aghmiz, Yolanda D´ıaz,* Anna Masdeu-Bulto´, Carmen Claver, and
Sergio Castillo´n*
Departament de Quı´mica Analı´tica i Qu´ımica Orga`nica, Facultat de Qu´ımica,
Universitat Rovira i Virgili, Pl. Imperial Tarraco 1, 43005 Tarragona, Spain, and
Departament de Quı´mica Fı´sica i Inorga`nica, Facultat de Quı´mica, Universitat Rovira i Virgili,
Pl. Imperial Tarraco 1, 43005 Tarragona, Spain
ydiaz@quimica.urv.es; castillon@quimica.urv.es
Received March 2, 2004
Modular ligands of C2 symmetry (13a -e, 14a ,b,d , and en t-9), systematically modified at positions
2 and 5, were easily prepared from D-glucosamine, D-glucitol, and tartaric acid, respectively. The
application of these ligands in the rhodium-catalyzed hydrogenation of methyl acetamidoacrylate,
methyl acetamidocinnamate, and dimethyl itaconate shows that both the configuration and the
substituents at positions 2 and 5 of the tetrahydrofuran backbone have a strong influence on the
enantioselectivty of the processes.
In tr od u ction
In recent decades, carbohydrates have been widely
used as chiral synthons for the synthesis of enantiomeri-
cally pure compounds.1 A variety of structures can be
obtained from carbohydrates, mainly pyranoses and
furanoses, through well-established procedures. Because
hydroxyl groups are present, phosphinite, phosphonite,
and phosphite functional groups are easily introduced so
that they can be used as ligands in metal-catalyzed
reactions.2 The first reports on the use of carbohydrates
as chiral frameworks for preparing chiral ligands date
back to the 1970s when Cullen3 and Thompson4 reported
the synthesis of diphosphinites 1 and 2 with pyranose
and furanose structures, respectively (Figure 1).
Selke5 systematically studied different modifications
of diphosphinite 2 and found that diphosphinite 3 pro-
vided the best enantioselectivity in the hydrogenation of
enamido acids. He also proved that the corresponding
ligand with unprotected hydroxyl groups at positions 4
and 6 also provided excellent enantiomeric excesses when
water was used as the solvent.6 Other ligands have
recently been prepared with this purpose and have
proven to be highly efficient.7,8
F IGURE 1. Relevant phosphorus ligands with C1 and C2
symmetries derived from carbohydrates.
(1) Hollinsworth, R. I.; Wang, G. Chem. Rev. 2000, 100, 4267-4282.
(2) (a) Steiborn, D.; J unicke, H. Chem. Rev. 2000, 100, 4283. (b)
RajanBabu, T. V.; Casalnuovo, A. L.; Ayers, T. A. In Advances in
Catalytic Processes; Doyle, M. P., Ed.; J AI Press: Greenwich, CT, 1998;
Vol. 2. p 1.
(3) Cullen, W. R.; Sugi, Y. Tetrahedron Lett. 1978, 1635-1636.
(4) J ackson, R. W.; Thompson, D. J . J . Organomet. Chem. 1978, 159,
C29-C31.
(5) (a) Selke, R.; Pracejus, H. J . Mol. Catal. 1986, 37, 213-225. (b)
Selke, R.; Schwarze, M.; Baudisc, H.; Grassert, I.; Michalik, M.; Oehme,
G.; Stoll, N.; Costisella, B. J . Mol. Catal. 1993, 84, 223-237.
(6) Kadyrov, R.; Se´ller, R.; Selke, R. Tetrahedron: Asymmetry 1998,
9, 329.
(7) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. J .
Org. Chem. 1999, 64, 5593-5598.
RajanBabu subsequently improved the efficiency of
these ligands by modifying the electronic properties of
the aryl groups bonded to the phosphorus atoms.9 These
ligands were successfully used in the rhodium-catalyzed
hydrogenation of enamido acids10 and in the nickel-
catalyzed hydrocyanation of alkenes.11
(8) Shin, S.; RajanBabu, T. V. Org. Lett. 1999, 1, 1229-1232.
(9) RajanBabu, T. V.; Casalnuovo, A. L. J . Am. Chem. Soc. 1992,
114, 6265-6266.
10.1021/jo0496502 CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/30/2004
7502
J . Org. Chem. 2004, 69, 7502-7510

C2-Symmetric Diphosphinite Ligands
F IGURE 2. (+)-Diphin, diop, and bdpcp ligands with a five-
membered ring in their structures.
One of the limitations of the ligands prepared from the
chiral pool is that only one enantiomer is accessible.
Ligand 4, however, proved to function as a pseudoenan-
tiomer of 3, and in fact, it provides the opposite enanti-
omer in the asymmetric hydrogenation of prochiral
olefins.12
Although ligand 1 is one of the first reported ligands
derived from carbohydrates, there are only a few ex-
amples of ligands with a furanose structure. Ligand 5
provided high enantioselectivity in the nickel-catalyzed
hydrocyanation of alkenes.13
Our group has prepared ligands with a furanose
structure, such as 6 and other similar structures, and
they have proven to be efficient in rhodium-catalyzed
hydrogenation14,15 and hydroformylation16,17 and pal-
ladium allylic alkylation.18
Ligands with C2 symmetry have also been prepared
from carbohydrates, mainly from mannitol. Notable
examples are the duphos analogues 719 and 820 where the
phospholane ring was prepared from D-mannitol. These
ligands are water soluble and behave like duphos.
Recently, a diop analogue, which provides excellent
enantioselectivity in asymmetric hydrogenation,21 has
also been prepared from mannitol.
F IGURE 3. (a) Structural modifications in the modular
ligands of 12. (b) Tetrahydrofuran-derived diphosphinite ligands
without (en t-9) and with substituents of different configura-
tions (13 and 14) at positions 2 and 5.
derivative (11)22,23 provided enantiomeric excesses of 55
and 43%, respectively. This indicates that small struc-
tural changes in the ligand can induce significant changes
in the enantioselectivity.
In this context, we decided to prepare a series of new
modular ligands with a tetrahydrofuran backbone, such
as 12 (Figure 3), which can be modified by changing the
phosphorus function, the nature of substituents, and the
configuration at positions 2 and 5. In this paper, we
report the synthesis of diphosphinites 13, 14, and en t-
9, which are related to 9, in which the substituents and
configuration at positions 2 and 5 have been systemati-
cally varied. We also report their rhodium complexes. We
show that the presence of these additional stereocenters
has a dramatic influence on the enantioselectivity of the
rhodium-catalyzed hydrogenation of enamidoesters.
As far as ligands with a tetrahydrofuran structure are
concerned, J ackson22 reported that diphosphinite 9
(Figure 2), which was obtained from diethyl tartrate,
provided an enantiomeric excess of 20% in the rhodium-
catalyzed hydrogenation of enamido acids. However, the
closely related ligand diop (10)22 and the cyclopentane
Resu lts a n d Discu ssion
Syn th esis of Liga n d s a n d Com p lexes. Ligands 13
and 14 can be easily prepared from the corresponding
2,5-bis-hydroxymethyl tetrahydrofuran-3,4-diol deriva-
tives, which in turn can be prepared from D-glucosamine
and D-glucitol, respectively, in a straightforward manner
(Schemes 1 and 2).
(10) RajanBabu, T. V.; Ayers, T. A.; Casalnuovo, A. L. J . Am. Chem.
Soc. 1994, 116, 4101-4102.
(11) Casalnuovo, A. L.; RajanBabu, T. V.; Ayers, T. A.; Warren, T.
H. J . Am. Chem. Soc. 1994, 116, 9869-9882.
Thus, the treatment of D-glucosamine with sodium
nitrite followed by reduction with sodium borohydride
provided tetrol 15 in 82% yield24 (Scheme 1). To study
the effect of the groups at positions 2 and 5, we protected
the primary alcohol in 15 by reaction with TrCl, TBDP-
SCl, and TIPSCl to afford diols 16a ,25 16b, and 16e,
respectively. We were also interested in determining the
effect of a methyl group at positions 2 and 5. To this end,
tetrol 15 was selectively ditosylated to give 16c,25 which
was treated with LiAlH4 to afford compound 16d .25
Compounds 16a -e were treated with chlorodiphenyl-
phosphine to obtain the diphosphinites 13a -e in 60-
80% yield.
(12) (a) RajanBabu, T. V.; Ayers, T. A.; Halliday, G. A.; You, K. K.;
Calabrese, J . C. J . Org. Chem. 1997, 62, 6012-6028. (b) RajanBabu,
T. V.; Radeich, B.; You, K. K.; Ayers, T. A.; Casalnuovo, A. L.;
Calabrese, J . C. J . Org. Chem. 1999, 64, 3429-3447.
(13) (a) RajanBabu, T. V.; Casalnuovo, A. L. Pure Appl. Chem. 1994,
66, 1535-1542. (b) RajanBabu, T. V.; Casalnuovo, A. L. J . Am. Chem.
Soc. 1996, 118, 6325-6326.
(14) (a) Pa`mies, O.; Die´guez, M.; Net, G.; Ruiz, A.; Claver, C. Chem.
Commun. 2000, 12, 2383-2384. (b) Pa`mies, O.; Die´guez, M.; Net, G.;
Ruiz, A.; Claver, C. J . Org. Chem. 2001, 66, 8364-8369.
(15) Die´guez, M.; Ruiz, A.; Claver, C. J . Org. Chem. 2002, 67, 3796-
3801.
(16) (a) Die´guez, M.; Pa`mies, O.; Ruiz, A.; Castillo´n, S.; Claver, C.
Chem.sEur. J . 2001, 7, 3086-3094. (b) Die´guez, M.; Pa`mies, O.; Ruiz,
A.; Catillo´n, S.; Claver, C. Chem. Commun. 2000, 1607-1608.
(17) Die´guez, M.; Pa`mies, O.; Ruiz, A.; Claver, C. New J . Chem.
2002, 26, 826-833.
(18) Die´guez, M.; J ansat, S.; Go´mez, M.; Ruiz, A.; Muller, G.; Claver,
C. Chem. Commun. 2001, 1132-1133.
(19) (a) Bayer, A.; Mursat, P.; Tewalt, U.; Rieger, B. Eur. J . Inorg.
Chem. 2002, 2614-1624. (b) RajanBabu, T. V.; Yan, Y.-Y.; Sin, S. J .
Am. Chem. Soc. 2001, 123, 10207-10213. (c) Li, W.; Zhang, Z.; Xiao,
D.; Zhang, X. J . Org. Chem. 2000, 65, 3489-3496. (d) Li, W.; Zhang,
Z.; Xiao, D.; Zhang, X. Tetrahedron Lett. 1999, 40, 6701-6704.
(20) Holz, J .; Stu¨rmer, R.; Schmidt, U.; Drexler, H.-J .; Heller, D.;
Krimmer, H.-P.; Bo¨rner, A. Eur. J . Org. Chem. 2001, 63, 4621-4624.
(21) Yan, Y. Y.; RajanBabu, T. V. Org. Lett. 2000, 2, 4137-4140.
(22) J ackson, W. R.; Lovel, C. G. Aust. J . Chem. 1982, 35, 2069-
2075.
Tetrol 17 was obtained from D-glucitol following a
reported procedure (Scheme 2).26 The yield was only 5%,
(23) Hayashi, T.; Tanaka, M.; Ogata, I. Tetrahedron Lett. 1977, 18,
295-296.
(24) (a) Horton, D.; Philips, K. D. Methods Carbohydr. Chem. 1976,
7, 68-70. (b) Otero, D. A.; Simpson, R. Carbohydr. Res. 1984, 128,
79-86. (c) Claustre, S.; Bringaud, F.; Aze´ma, L.; Baron, R.; Pe´rie´, J .;
Willson, M. Carbohydr. Res. 1999, 315, 339-344.
(25) Guthrie, R. D.; J enkins, I. D.; Watters, J . J .; Wright, M. W.;
Yamasaki, R. Aust. J . Chem, 1982, 35, 2169-2173.
J . Org. Chem, Vol. 69, No. 22, 2004 7503

Aghmiz et al.
SCHEME 1
14a ,b,d , and en t-9, respectively. All of the complexes
were isolated as colored solids and were stable in air.
[Rh(cod)2]BF4 + 13a -e f [Rh(cod)(13a -e)]BF4 (1)
[Rh(cod)2]BF4 + 14a ,b,d f [Rh(cod)(14a ,b,d )]BF4
(2)
[Rh(cod)2]BF4 + en t-9 f [Rh(cod)(en t-9)]BF4 (3)
Ligands 13a -e, 14a ,b,d , and en t-9, as well as their
1
alcohol precursors, showed very simple H and 13C NMR
spectra, characteristic of compounds with a C2 symmetry.
The 31P NMR spectrum of 13a -e, 14a ,b,d , and en t-9
showed only one signal between 112 and 119 ppm,
characteristic of a phosphinite function.
SCHEME 2
NMR spectra of complexes [Rh(cod)(13a -e)]BF4, [Rh-
(cod)(14a ,b,d )]BF4, and [Rh(cod)(en t-9)]BF4 at 25 °C
show they have C2 symmetry in solution. In the 31P NMR
spectrum, only one signal appeared between 120 and
129.7 ppm (J P-Rh ) 164.8-170.8 Hz). The chemical shift
and coupling constant values are in agreement with those
observed for structurally related cationic diphosphinite
rhodium complexes.11a The mononuclearity of complexes
was confirmed by FAB and L-SIMS spectra, which in all
of the cases showed molecular ions corresponding to the
cation [Rh(cod)L]+.
The crystal structure of complex [Rh(cod)(14d )]BF4 was
obtained by slow diffusion of hexane into a CH2Cl2
solution of the complex. Two cationic units only differing
slightly in the relative disposition of the phenyl rings
were detected, but only one of them is discussed here.
The cationic rhodium complex consists of discrete mono-
nuclear units, [Rh(cod)(14d )]+, in the solid state, where
the diphosphinite ligand acts as a chelate, and there is
no interaction between the counterion and Rh. As ex-
pected, the complex is square planar and the P1-Rh-
P2 angle is around 90°. Cyclooctadiene (cod) is disordered
in two different conformations. Selected bonds and angles
are listed in Figure 4.
The determination of the conformation of the metalo-
cycle in the solid state is of interest since it has been
shown that there is a good correlation between this
conformation and the sense of the enantioinduction of the
catalyst in the hydrogenation of enamidoesters, the
conformation λ leading preferentially to the S enanti-
omer, and the δ conformer leading to the R (Figure 5).29
As it is shown in Figure 4, the complex is not C2
symmetric in the solid state, and the aryl substituents
are in a nonalternating pseudoaxial-pseudoequatorial
array providing an achiral environment around Rh.
Comparing the structures of complexes [Rh(14d )(cod)]-
BF4 and 20,12b which has (1S,2S)-bis-diphenylphosphi-
noxycyclohexane as a chiral ligand (Figure 5), we ob-
served several differences. (a) The cyclohexane ring in
20 has a chair conformation, while the tetrahydrofuran
ring in [Rh(14d )(cod)]BF4 has an envelope conformation.
(b) The seven-membered chelate has a twist-chair con-
formation in 20 and a distorted boat conformation in [Rh-
(14d )(cod)]BF4, as deduced from the parameters R, â, R′,
SCHEME 3
similar to previously reported yields, but this procedure
allows 17 to be easily obtained from a very accessible
nonexpensive starting material in a multigram scale.
Primary alcohols were also protected by reaction with
TrCl and TBDPSCl to give compounds 18a and 18b. The
2,5-dimethyl derivative 18d was obtained by selective
ditosylation of 17 to give 18c and further reduction with
LiAlH4.
Treatment of 18a , 18b, and 18d with Ph2PCl in basic
medium afforded the ligands 14a , 14b, and 14d , respec-
tively, with yields higher than 80%. Ligand 14c was not
prepared.
Since the configuration of stereocenters bonded to the
phosphinite moiety in ligand 9 is opposite to those of
ligands 13 and 14, we prepared enantiomer en t-9 for the
purpose of comparison. Thus, diol 1927 reacted with Ph2-
PCl to give en t-9 in 60% yield (Scheme 3).
Rhodium complexes [Rh(cod)(13a -e)]BF4, [Rh(cod)-
(14a ,b,d )]BF4, and [Rh(cod)(en t-9)]BF4 (eqs 1-3) were
prepared by reacting [Rh(cod)2]BF4 with ligands 13a -e,
(26) (a) Rafka, R. J .; Morton, B. J . Carbohydr. Res. 1994, 260, 155-
158. (b) Cassel, S.; Debaig, C.; Benvegnu, T.; Chaimbault, P.; Lafosse,
M.; Plusquellec, D.; Rollin, P. Eur. J . Org. Chem. 2001, 875-896.
(27) Terfort, A. Synthesis 1992, 951-953.
(28) Farrugia, L. J . ORTEP-3 for Windows. J . Appl. Crystallogr.
1997, 30, 565-566.
(29) See ref 12b and references therein.
7504 J . Org. Chem., Vol. 69, No. 22, 2004

C2-Symmetric Diphosphinite Ligands
TABLE 1. An gles (r-δ a n d r′-δ′) a n d Dih ed r a l An gles (ω a n d ω′) for Rh Com p lexes [Rh (cod )(14d )]BF 4 a n d 20a ,b
entry
1
complex
R
â
R′
â′
γ
δ
γ′
δ′
ω
ω′
[Rh(cod)(14d )]BF4
cation 1
9.9(f)
72.5(r)
70.4(r)
11.2(f)
21.7
86.0
84.1
22.8
52.7
-53.2
2
3
20 (L ) NBD, boat)c
20 (L ) cod, chair λ)c
8.3(f)
75(r)
72(r)
47(f)
64(-)
90(r)
54(-)
31(f)
15
41
58
29
37
48
31
21
7
-19
-57
-36
a
b
In degrees. For definitions of parameters see Figure 1 in the Supporting Information. Position: f ) front, r ) rear, - ) position
uncertain. c From ref 12b.
TABLE 2. Hyd r ogen a tion of 21 w ith th e Ca ta lytic
System [Rh ]/13a a
entry solvent substrate/Rh ratio time (min) conv (%) % ee
1
2
3
4
5
6
7
CH2Cl2
CH2Cl2
THF
toluene
MeOH
MeOH
acetone
100
500
500
500
500
100
500
5
35
15
15
15
5
100
93
36
14
63
67(R)
67(R)
63(R)
41(R)
73(R)
73(R)
75(R)
100
99
15
a
Conditions: solvent ) 15 mL, [Rh] ) 15 × 10-6 mol, L/Rh )
1.05, room temperature, P(H2) ) 1 bar.
as δ and δ′, are similar (entry 3, Table 1); furthermore,
ω and ω′ values have an identical sign. By contrast, in
complex [Rh(14d )(cod)]BF4, correlations exist between
angles R and â′, R′ and â, δ and γ′, and δ′ and γ. Moreover,
angles ω ) 52.69° and ω′ ) -53.25° are of opposite sign
(Table 1). These data correlate better with values of entry
2 and consequently with a boat conformation.
Ca ta lysis. Complexes [Rh(cod)13a -e]BF4, [Rh(cod)-
14a ,b,d ]BF4, and [Rh(cod)en t-9]BF4, as well as in situ
catalysts formed by adding ligands 13a -e, 14a ,b,d , and
en t-9 to [Rh(cod)2]BF4, were used as catalyst precursors
in asymmetric hydrogenation. We initially studied the
effect of the solvent on the hydrogenation of methyl
acetamidoacrylate (21) with the catalytic system Rh/13a
in an attempt to find the best conditions for a compara-
tive study of ligands.
F IGURE 4. ORTEP28 representation of the crystal structure
of complex [Rh(cod)(14d )]BF4. Counterions, solvates, and H
atoms are omitted (a; front view) for clarity, and (b; front,
bottom view) cyclooctadiene is also omitted in order to see the
conformations of tetrahydrofuran and chelate rings. Selected
distances and angles: Rh-P(6) ) 2.288(2) Å, Rh-P(1) )
2.309(2) Å, P(6)-Rh-P(1) ) 93.83(9)°, C(11)-Rh-P(6) )
91.1(2)°, C(7)-Rh-P(6) ) 92.4(3)°, C(7)-Rh-C(10) ) 77.9(4)°,
and C(14)-Rh-P(1) ) 89.2(3)°.
Table 2 shows that this catalytic system is active in
the hydrogenation of enamidoester 21 in very mild
conditions. It mainly affords enantiomer R. When the
reaction was carried out in dichloromethane with a
substrate/Rh ratio ) 100, the conversion was complete
in 5 min, and reached 93% in 35 min when this ratio was
500. In both cases, the enantiomeric excess was 67%
(entries 1 and 2, Table 2). When the experiment was
carried out using THF or toluene, both the conversion
and the enantiomeric excessess were lower (entries 3 and
4). Although these types of ligands can hydrolyze in
alcohol, we performed the experiment with MeOH at
different substrate/Rh ratios and found that at substrate/
Rh ) 500, the enantiomeric excess attained 73%, but
conversion stopped at 63% (entry 5). However, at sub-
strate/Rh ) 100, the conversion was complete in 5 min,
which suggests that in the former case the catalyst
F IGURE 5. Conformations, λ (a) and δ (b), of seven-membered
cationic chelates. Conformation of complexes 20 (c) and
[Rh(14d )(cod)]BF4 (d) in the solid state.
(30) Pavlov, V. A.; Klabunowskii, E. I.; Struchkov, Y. T.; Voloboev,
A. A.; Yanovsky, A. I. J . Mol. Catal. 1988, 44, 217-243.
(31) Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.; Hunziker,
D.; Petter, W. Helv. Chim. Acta 1992, 75, 2171-2209.
â′, γ, δ, γ′, δ′, ω, and ω′ (entry 1, Table 1), determined
after Paulov30 and Seebach.31 In the chair conformation,
values for angles R and R′, â and â′, and γ and γ′, as well
J . Org. Chem, Vol. 69, No. 22, 2004 7505

Aghmiz et al.
TABLE 3. Hyd r ogen a tion of 21 w ith th e Ca ta lytic
System s [Rh ]/13a -e, 14a ,b,d , a n d en t-9 a n d Com p lexes
[Rh (cod )(13a -e)]BF 4, [Rh (cod )(14a ,b,d )]BF 4, a n d
TABLE 4. In flu en ce of Tem p er a tu r e a n d P r essu r e on
th e Hyd r ogen a tion of 21 w ith th e Ca ta lytic System s
[Rh ]/13b a n d 13ea
a
[Rh (cod )(en t-9)]BF 4
entry ligand P (bar) T (°C) time (min) conv (%) ee (%)
[Rh(cod)2]BF4/L
(% ee)
[Rh(cod)L]BF4
(% ee)
1
2
3
4
13bb
13bb
13bb
13bb
13bb
13bb
13ec
13ec
1
1
1
rt
0
5
5
100
100
100
95
85(R)
88(R)
91(R)
91(R)
83(R)
78(R)
87(R)
93(R)
entry
L
1
2
3
4
5
6
7
8
9
13a b
13bc
13c
75(R)
85(R)
82(R)
79(R)
87(R)
5(R)
59(R)
26(R)
16(R)
76(R)
85(R)
80(R)
78(R)
87(R)
5(R)
59(R)
26(R)
18(R)
-25
-40
rt
50
rt
20
150
30
50
5
1
5c
6c
7
10
10
1
98
13d c
13e
100
100
100
14a
14b
14d
en t-9
8
1
-25
30
a
Conditions: solvent ) 15 mL, [Rh] ) 15 × 10-6 mol, L/Rh )
1.05, substrate/Rh ) 100, room temperature, P(H2) ) 1 bar.
Acetone/CH2Cl2, 13:2. c Acetone.
b
Conditions: solvent ) acetone, 15 mL, [Rh] ) 15 × 10-6 mol,
a
L/Rh ) 1.05, substrate/Rh ) 100, room temperature, P(H2) ) 1
As far as the substituents at C2 and C5 are concerned,
results were best with tert-butyldiphenylsilyloxymethyl
and triisopropylsilyloxymethyl chains (entries 2, 5, and
7), while trityloxymethyl chains led to the lowest enan-
tiomeric excesses (entries 1 and 6). On the other hand,
the less-bulky methyl derivatives (entries 4 and 8)
provided intermediate enantiomeric excess values. Figure
6 shows the relative influence of these factors on the
enantioselectivity.
bar, 100% conversion. Substrate/Rh ) 500, 15 min. c Solvent )
b
acetone/CH2Cl2, 13:2.
The effects of pressure and temperature on the enan-
tioselectivity of the reduction of 21 were studied next.
Ligands 13b,e, which had provided the best results, were
selected. Initially, we tried the catalytic system Rh/13b
at 0 °C and maintained all of the other reaction condi-
tions. The conversion was also complete in 5 min, and
the enantiomeric excess increased slightly to 88% (entries
1 and 2, Table 4). Because the activity was maintained,
we decreased the temperature to -25 °C and achieved a
91% ee in 20 min (entry 3). When the temperature was
decreased to -40 °C, the enantiomeric excess did not
improve and the activity decreased (entry 4). Performing
the experiment at 10 bar at room temperature decreased
the enantiomeric excess and the conversion (entry 5).
When the temperature was increased to 50 °C and the
pressure was increased to 10 bar, there was an additional
decrease in the enantiomeric excess (entry 6). When the
catalytic system Rh/13e was used at -25 °C and 1 bar,
the enantiomeric excess reached 93%.
We next studied the reduction of methyl R-acetamido-
cinnamate 23 with the catalytic systems Rh/L (L ) 13a -
e, 14a ,b,d , and en t-9). The results are listed in Table 5.
The influence of the different parameters on the enan-
tioselectivity was similar to that observed for the reduc-
tion of substrate 21. Thus, the synergy among additional
stereocenters at C2, C5, and X groups in ligands 13a -e
was also observed in this substrate (entries 1-5).
These ligands form more efficient catalytic systems
than ligands 14a ,b,d (entries 6-8), although in general
both are more enantioselective than en t-9 (entry 9). The
effect of substituents in the lateral chains also showed a
similar trend, and the silyloxymethyl chains provided the
best results in ligands 13 (entries 2 and 5) and ligands
14 (entry 7). In this case, ligand 14a also provided a very
low enantiomeric excess, which confirms that the struc-
tural elements are particularly mismatched in this ligand
(entry 6).
F IGURE 6. Influence of substituent configuration at C2 and
C5 (a) and of the nature of substituents (b) on the enantio-
selectivity of the hydrogenation of 21.
decomposes, probably by ligand solvolysis (entry 6).
Ligands were stable in other solvents, and the best result
was obtained in acetone, with the enantiomeric excess
being 75% (entry 7).
Rhodium catalytic systems formed in situ from [Rh-
(cod)2]BF4 and ligands 13a -e, 14a -c, and en t-9 were
then used in the hydrogenation of 21 in acetone. Ligands
13b,d were not soluble in acetone, and the experiment
was carried out with an acetone/dichloromethane
mixture. The results are listed in Table 3.
In the presence of rhodium, all of the ligands gave
catalytic systems that were active in the hydrogenation
of 20. Experiments carried out by catalytic systems
formed in situ provided essentially the same enantio-
selectivity values as those obtained from preformed
complexes (Table 3). On the other hand, preformed
complexes made it possible to carry out catalytic experi-
ments in methanol without apparent solvolysis.
A comparison of the results provided by ligand en t-9
(entry 9) and ligands 13a -e (entries 1-5) and 14a ,b,d
(entries 6-8) shows that the enantioselectivity is strongly
influenced by (a) the presence of additional stereogenic
centers at positions 2 and 5 of the tetrahydrofuran ring
and (b) the steric effect of groups X (see Schemes 1 and
2). It can also be concluded that there is a synergy (match
effect) among stereocenters 3,4 and 2,5 in ligands 13a -e
and an antagonism (mismatch effect) in ligands 14a ,b,d ,
which is modulated by groups X.
The main enantiomer obtained in the hydrogenation
was always R. This suggests that chirality is determined
by the stereocenters at C3 and C4, which are bonded to
the coordinating atoms. Figure 6 summarizes the effect
of the stereogenic centers at C2 and C5 on the en-
antioselectivity.
A comparison of Tables 2 and 4 shows that the
behavior of these catalytic systems toward the reduction
of substrates 21 and 23 is similar. In general terms,
7506 J . Org. Chem., Vol. 69, No. 22, 2004

C2-Symmetric Diphosphinite Ligands
TABLE 5. Hyd r ogen a tion of 23 w ith th e Ca ta lytic
en t-9 provides a value that is the average. It is not easy
to rationalize these results, although the fact that
substrate 25 behaves differently from substrates 20 and
22 may be related to the different coordination of these
substrates to the metal.
System s [Rh ]/13a -e, 14a ,b,d , a n d en t-9a
When the phenyl groups in the PPh2 were modified by
introducing groups such as p-OMe of p-CF3, ligand 13b
did not improve the enantioselectivity of reduction of 20
and 22.
entry
L
conv (%)
ee (%)
1
2
3
4
5
6
7
8
9
13a
95
96
73(R)
81(R)
77(R)
75(R)
86(R)
18(R)
59(R)
32(R)
27(R)
13bb
13c
Concerning the origin of the enantioselectivity, it has
been seen before that complex [Rh14d (cod)]BF4 has
practically an achiral structure in the solid state, which
may account for the modest enantioselectivity obtained
with this complex in the hydrogenation of substrates 21,
23, and 25, but does not allow one to find a relation
between the conformation and the sense of the enantio-
selectivity. However, comparing the configuration of the
main enantiomer obtained in hydrogenation of enami-
doesters and dimethylitaconate using complex 2012b and
related complexes,5-12 which give the S enantiomer, and
[Rh14d (cod)]BF4, which gives the R enantiomer (see
Tables 3, 5, and 6), one can conclude that the sense of
the enantioinduction is determined by the configuration
of carbons of the tetrahydrofuran frame attached to the
phosphinoxy groups. In parts c and d of Figure 5, it can
be seen that the carbons bonded to the phosphinoxy
groups have opposite configuration in complexes 20 and
[Rh14d (cod)]BF4. This conclusion can be extended to the
complexes with ligands 13 and 14 (see Tables 2-6),
which show a similar trend.
Despite our efforts, we were unable to obtain crystals
of a complex with ligands 13 and en t-9 that would allow
us to gain information about the influence of the lateral
chain in the conformation of complexes in the solid state.
It is well-known that five-membered rings are very
flexible, and that the presence of substituents in the ring
increases the energy for the conformational changes. On
the other hand, the limitation of flexibility usually
increases the enantioselectivity.32 In this context, the
influence of substituents at positions 2 and 5 of ligands
13 and 14 in the level of asymmetric induction may be
related to restrictions of the conformational mobility in
the tetrahydrofuran ring and, consequently, in the seven-
membered quelate ring.33 The different sense of optical
induction for catalysts having close structures (see entries
1 and 8, Table 6) has also been observed by other authors
and attributed to changes of the metal-ligand chelate
conformation.32 Mechanistic studies in order to prove
these facts are in progress.
100
100
100
100
100
100
100
13d b
13e
14a
14b
14d
en t-9
Conditions: solvent ) acetone, 15 mL, [Rh] ) 15 × 10-6 mol,
a
L/Rh ) 1.05, substrate/Rh ) 100, room temperature, P(H2) ) 1
b
bar, t ) 5 min. Acetone/CH2Cl2, 13:2.
TABLE 6. Hyd r ogen a tion of 25 w ith th e Ca ta lytic
System s [Rh ]/13a -e, 14a ,b,d , a n d en t-9a
entry
L
solvent
CH2Cl2
CH2Cl2
acetone/CH2Cl2
CH2Cl2
CH2Cl2
acetone/CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
time (min)
ee (%)
1
2
3
4
5
6
7
8
9
13a
13b
13b
13c
13d
13d
13e
14a
14b
14d
en t-9
5
5
75
5
5
60
5
5
5
5
5
48(S)
48(S)
29(S)
54(S)
53(S)
63(S)
51(S)
53(R)
9(R)
b
b
10
11
CH2Cl2
CH2Cl2
19(R)
4(R)
Conditions: solvent ) 15 mL, [Rh] ) 15 × 10-6 mol, L/Rh )
a
1.05, substrate/Rh ) 100, room temperature, P(H2) ) 1 bar, 100%
b
conversion. Acetone/CH2Cl2, 13:2.
ligands 13 are superior to 14, and ligand en t-9 results
in the poorest enantiomeric excess.
The catalytic systems Rh/L (L ) 13a -e, 14a ,b,d , and
en t-9) were also very active in the hydrogenation of
dimethyl itaconate 25 (Table 6). However, the hydroge-
nation of this substrate was very different than those of
substrates 21 and 23. With regard to the solvent, the
reaction rate in acetone was slower. Furthermore, the
enantioselectivity in acetone was also much lower, with
the exception of ligands 13d and 14d . In general, the
catalytic systems Rh/13a -e (entries 1-7) provided better
enantioselectivities than Rh/14a ,b,d and Rh/en t-9 (en-
tries 8-11). Curiously, ligand 14a , which provided very
low enantioselectivities with substrates 21 and 23, gives
better enantioselectivity than 14b,d in the hydrogenation
of 25, and values similar to those of ligands 13a -e.
Furthermore, a noteworthy difference is that the config-
uration of the main isomer of hydrogenated compound
26 depends on the configuration of stereogenic centers
at C2 and C5. Ligands 13a -e preferably give the isomer
S; ligands 14a ,b,d give isomer R, and en t-9 gives no
enantiomeric excess. Interestingly, in some cases, for
instance 13a and 14a , the enantiomeric excess values
obtained are similar but of opposite sign, while ligand
Con clu sion
New families of ligands 13a -e, 14a ,b,d , and en t-9,
which have a tetrahydrofuran backbone, were easily
prepared from D-glucosamine, D-glucitol, and (2S,3S)-
diethyl tartrate, respectively. These ligands were used
to prepare catalyst precursors of the general formula [Rh-
(cod)L]BF4 (L ) 13a -e, 14a ,b,d , and en t-9). The cata-
lytic systems obtained from [Rh(cod)L]BF4 or [Rh(cod)2]-
BF4/L were active in the hydrogenation of enamidoesters
(32) Li, W.; Waldkirch, J . P.; Zhang, X. J . Org. Chem. 2002, 67,
7618-7623.
(33) Kagan, H. B. In Comprehensive Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon Press:
NewYork, 1982; Vol. 8, p 463.
J . Org. Chem, Vol. 69, No. 22, 2004 7507

Aghmiz et al.
over Na2SO4, and the evaporation of the solvent provided a
residue that was purified by column chromatography with
hexane/ethyl acetate (4:1) to render 1.28 g (72%) of 18b as
21 and 23 and of diester 25. The results showed that in
the hydrogenation of 21 and 23, the configuration of the
main enantiomer obtained is determined by the config-
uration of C3 and C4, which support the coordinative
heteroatoms. However, the enantiomeric excess values
are strongly influenced by the configuration of the remote
stereogenic centers at C2 and C5 and the steric effect of
substituents. These effects are synergic for ligands 13,
which provide the best results. In contrast, in the
hydrogenation of 25, the sense of asymmetric induction
is determined by the configuration at positions 2 and 5.
Ligands 13 lead to enantiomer S, while ligands 14 lead
to enantiomer R.
white crystals: mp ) 122-123 °C; [R]25 -12.61° (CHCl3, c
D
1.19); 1H NMR (CDCl3, 400 MHz) δ 1.06 (s, 18 H), 3.98 (d, J )
3.2 Hz, 2 H), 4.04 (dd, J 1′,2 ) 3.6, 11.2 Hz, 2 H), 4.07 (dd, J )
4.4, 11.2 Hz, 2 H), 4.26 (m, 2 H), 4.38 (t, J ) 3.2 Hz, 2 H),
7.25-7.80 (m, 20 H); 13C NMR (CDCl3, 100.6 MHz) δ 19.2, 26.8,
63.7, 78.9, 79.7, 127.7-135.5. Anal. Calcd for C38H48O5Si2: C,
71.21; H, 7.55. Found: C, 70.92; H, 7.55.
1,6-Di-O-(p-tolu en su lfon yl)-2,5-a n h yd r o-L-id itol (18c).
To a cold solution (0 °C) of 17 (0.98 g, 5.97 mmol) in 40 mL of
dry pyridine was added 2.62 g (13.74 mmol) of p-toluensulfonyl
chloride under an inert atmosphere. The resulting mixture was
stirred for 48 h at room temperature, diluted with CH2Cl2, and
washed with an aqueous solution of 1 N HCl (100 mL × 3).
The combined aqueous layer was extracted with CH2Cl2. The
combined organic layer was washed with an aqueous solution
of NaHCO3 and H2O, dried over Na2SO4, and concentrated.
Chromatography on silica gel with hexane/ethyl acetate (1:1)
yielded 31.7 g (60%) of 18c as a white solid: mp ) 147-148
°C; [R]25D +7.95° (THF, c 1.065); 1H NMR (CDCl3, 400 MHz) δ
2.44 (s, 6 H), 2.59 (s, 2 H), 4.03 (dd, J ) 4.6, 8.6 Hz, 2 H),
4.28-4.21 (m, 6 H), 7.75 (d, J ) 8.4 Hz, 4 H), 7.33 (d, J ) 8.4
Hz, 4 H); 13C NMR (CDCl3, 100.6 MHz) δ 21.8, 67.2, 76.5, 77.8,
127.9-145.1. Anal. Calcd for C20H24O9S2: C, 50.84; H, 5.12;
S, 13.57. Found: C, 51.02; H, 5.13; S, 13.57.
Exp er im en ta l Section
1,6-Di-O-(ter t-bu tyld ip h en ylsilyl)-2,5-a n h yd r o-D-m a n -
n itol (16b). tert-Butyldiphenylsilyl chloride (3 mL, 11.66
mmol) was added dropwise to a solution of 15 (0.87 g, 5.3
mmol) and imidazole (1.5 g, 22.28 mmol) in 12 mL of dry DMF
at 0 °C. The reaction mixture was left to warm to room
temperature and stirred for 25 h. The solvent was then
removed in vacuo, and the residue was dissolved in CH2Cl2
and washed with water. The organic layer was dried with Na2-
SO4, concentrated, and purified by column chromatography
(hexane/ethyl acetate, 4:1) to afford 1.36 g (40%) of 16b as a
1,6-Did eoxy-2,5-a n h yd r o-L-id itol (18d ). To a solution of
1.69 g (3.57 mmol) of 18c in 10 mL of dry THF was added
0.407 g (10.7 mmol) of LiAlH4. The resulting suspension was
heated to reflux for 2 h. After the mixture was cooled to room
temperature, Arberlite IR-120(H+) was carefully added, and
the mixture was stirred continuously until the evolution of H2
could no longer be observed. The mixture was filtered through
a Celite pad and washed with THF. The solvent was then
removed and the crude product chromatographed over silica
gel in CH2Cl2/MeOH (12:1) to render 0.36 g (77%) of 18d as a
white syrup: mp ) 90-91 °C; [R]25 +19.66° (CHCl3, c 1.15);
D
1H NMR (CDCl3, 400 MHz) δ 1.06 (s, 18 H), 3.75 (dd, J ) 2.4,
11.1 Hz, 2 H), 3.86 (dd, J ) 3.6, 11.1 Hz, 2 H), 4.03 (d, J ) 9
Hz, 2 H), 4.17 (m, 2 H), 4.25 (m, 2 H), 7.25-7.80 (m, 20 H);
13C NMR (CDCl3, 75.4 MHz) δ 19.0, 26.7, 65.5, 79.7, 87.1,
127.8-135.7. Anal. Calcd for C38H48O5Si2: C, 71.21; H, 7.55.
Found: C, 70.92; H, 7.54.
1,6-Di-O-(t r iisop r op ylsilyl)-2,5-a n h yd r o-D-m a n n it ol
(16e). Silylation was carried out from 0.687 g (4.18 mmol) of
15, 1.19 g (17.48 mmol) of imidazole, and 1.94 mL (9.16 mmol)
of triisopropylchlorosilane in 9.5 mL of dry DMF for 48 h. The
crude oil of the reaction was purified by column chromatog-
white solid: mp ) 75-76 °C; [R]25 +24.94° (THF, c 1.15); 1H
D
NMR (CDCl3, 300 MHz) δ 1.17 (d, J ) 6.6 Hz, 6 H), 3.90 (d, J
) 3.0 Hz, 2 H), 4.22 (qd, J 2,3 ) 3.0, 6.6 Hz, 2 H), 4.87 (s, 2 H);
13C NMR (CDCl3, 75.4 MHz) δ 14.7, 77.3, 79.7. Anal. Calcd
for C6H12O3: C, 54.53; H, 9.15. Found: C, 54.70; H, 9.14.
raphy with hexane/ethyl acetate (5:1) to give 16e (1.4 g, 70%)
1
as a colorless syrup: [R]25 +14.78° (CHCl3, c 1.11); H NMR
D
(CDCl3, 400 MHz) δ 1.05-1.20 (m, 42 H), 3.83 (dd, J ) 10.8,
2.4 Hz, 2 H), 3.91 (dd, J ) 10.8, 2.8 Hz, 2 H), 4.10 (d, J ) 10.4
Hz, 2 H), 4.14 (m, 2 H), 4.60 (d, J ) 10.4 Hz, 2 H); 13C NMR
(CDCl3, 100.6 MHz) δ 11.7, 17.7, 17.7, 65.3, 79.6, 88.2. Anal.
Calcd for C24H52O5Si2: C, 60.45; H, 10.99. Found: C, 60.42;
H, 11.00.
Gen er a l P r oced u r e for Syn th esizin g Dip h osp h in ites
fr om th e Cor r esp on d in g Diols. To a solution of the diol (1
mmol) in dry and degassed CH2Cl2 or THF (5 mL) was added
dry Et3N (4.4 mmol). After the mixture was cooled to -15 °C,
a solution of chlorophosphine (2.2 mmol) in 3 mL of dry and
degassed CH2Cl2 was slowly added. The mixture was then
stirred, and the temperature gradually increased. Completion
of the reaction was monitored by TLC. The mixture was then
diluted with ether in order to precipitate Et3N‚HCl. The solids
were filtered off through a Celite pad, and the filtrate was
concentrated to dryness. The crude product was purified by
chromatographic techniques.
1,6-Di-O-(tr ip h en ylm eth yl)-2,5-a n h yd r o-L-id itol (18a ).
A solution of 17 (0.51 g, 3.1 mmol) and trityl chloride (1.92 g,
6.88 mmol) in 8 mL of dry pyridine was heated at 100 °C for
72 h. The mixture was then diluted with CH2Cl2 and washed
successively with 0.03 M aqueous HCl (3 × 50 mL), with a
saturated aqueous solution of NaHCO3, and with H2O. The
organic phase was dried over Na2SO4 and concentrated to
dryness. The purification of the resulting residue by column
chromatography with hexane/ethyl acetate (3:1) gave 1.17 g
3,4-Bis-O-(d ip h e n ylp h osp h in o)-1,6-d i-O-(t r ip h e n yl-
m eth yl)-2,5-a n h yd r o-D-m a n n itol (13a ). The synthesis of
13a was carried out in accordance with the general procedure
from 0.40 g (0.61 mmol) of 16a , 3 mL of dry and degassed CH2-
Cl2, 378 mL (2.71 mmol) of dry Et3N, and 243 mL (1.35 mmol)
of Ph2PC, dissolved in 1.5 mL of CH2Cl2. After 15 min, the
reaction was complete, and the residue obtained was purified
by column chromatography in hexane/ethyl acetate (4:1) to
afford 0.5 g (80%) of 13a as a white foam: mp ) 64-65 °C;
(58%) of 18a as a white foam: mp ) 92-93 °C; [R]25 -8.75°
D
(CHCl3, c 0.93); 1H NMR (CDCl3, 400 MHz) δ 3.23 (s, 2 H),
3.40 (dd, J ) 3.8, 9.8 Hz, 2 H), 3.48 (dd, J ) 5.4, 9.8 Hz, 2 H),
4.25 (d, J ) 2.8 Hz, 2 H), 4.41 (m, 2 H), 7.0-7.0 (m, 30 H); 13
C
NMR (CDCl3, 100.6 MHz) δ 62.8, 78.6, 78.8, 87.2, 127.0-143.2.
Anal. Calcd for C44H40O5: C, 81.46; H, 6.21. Found: C, 81.19;
H, 6.19.
[R]25 +0.36° (CHCl3, c 1.04); 1H NMR (CDCl3, 400 MHz) δ
D
1,6-Di-O-(ter t-b u t yld ip h en ylsilyl)-2,5-a n h yd r o-L-id i-
tol (18b). tert-Butyldiphenylsilyl chloride (1.6 mL, 6.15 mmol)
was added dropwise to a cold suspension (0 °C) of 17 (0.45 g,
2.74 mmol) and imidazole (0.8 g, 11.75 mmol) in 6.5 mL of
dry DMF under an argon atmosphere. The mixture was left
to warm to room temperature and stirred for 48 h. The solvent
was then removed in vacuo. The crude oil obtained was diluted
in CH2Cl2 and washed with water, and the aqueous phase
extracted with CH2Cl2. The combined organic layer was dried
3.17 (dd, J ) 5.6, 10.8 Hz, 2 H), 3.19 (dd, J ) 5.6, 10.8 Hz, 2
H), 4.28 (m, 2 H), 4.62 (md, J ) 8.8 Hz, 2 H), 7.10-7.50 (m,
aromatic, 50 H); 13C NMR (CDCl3, 100.6 MH) δ 64.2, 83.5 (m),
86.1 (m), 86.6, 126.8-144.0; 31P NMR (CDCl3, 161.97 MHz) δ
115.63 (s). Anal. Calcd for C68H58O5P2: C, 80.30; H, 5.75.
Found: C, 79.99; H, 5.73.
3,4-Bis-O-(d ip h e n ylp h osp h in o)-1,6-d i-O-(t er t -b u t yl-
d ip h en ylsilyl)-2,5-a n h yd r o-D-m a n n itol (13b). The title
7508 J . Org. Chem., Vol. 69, No. 22, 2004

C2-Symmetric Diphosphinite Ligands
compound was prepared in accordance with the general
method from 0.58 g (0.9 mmol) of 16b. The reaction was
complete after 15 min, and the residue obtained was purified
by column chromatography with hexane/ethyl acetate (4:1) to
afford 0.75 g (81%) of the diphosphinite 13b as a white syrup:
141.8; 31P NMR (CDCl3, 161.97 MHz) δ 114.12 (s). Anal. Calcd
for C68H58O5P2: C, 80.30; H, 5.75. Found: C, 79.97; H, 5.76.
3,4-Bis-O-(d ip h en ylp h osp h in o)-1,6-d i-O-(ter t-bu tyld i-
p h en ylsilyl)-2,5-a n h yd r o-L-id itol (14b). This compound was
prepared in accordance with the general method from 0.40 g
(0.62 mmol) of diol 18b. The reaction was controlled by TLC
in hexane/ethyl acetate (3:2) as eluent. The reaction was
complete after 1.5 h. Chromatography on silica gel with
[R]25 +9.9° (CHCl3, c 1.8); 1H NMR (CDCl3, 400 MHz) δ 1.01
D
(s, 18 H), 3.62 (dd, J ) 4.6, 11.0 Hz, 2 H), 3.75 (dd, J ) 5.2,
11.0 Hz, 2 H), 4.18 (m, 2 H), 4.88 (md, J ) 8.4 Hz, 2 H), 7.19-
7.63 (m, aromatic, 40 H); 13C NMR (CDCl3, 100.6 MHz) δ 19.2,
26.8, 63.8, 84.2 (m), 85.5 (m), 127.6-142.1; 31P NMR (CDCl3,
161.97 MHz) δ 115.51 (s). Anal. Calcd for C62H66O5P2Si2: C,
73.78; H, 6.59. Found: C, 73.65; H, 6.57.
hexane/ethyl acetate (3:2) yielded 0.56 g (91%) of 14b as a
1
white syrup: [R]25 -17.8° (CHCl3, c 0.88); H NMR (CDCl3,
D
400 MHz) δ 0.94 (s, 18 H), 3.72 (dd, J ) 5.8, 10.0 Hz, 2 H),
3.85 (dd, J ) 7.4, 10.0 Hz, 2 H), 4.20 (m, 2 H), 4.51 (dd, J )
2.8, 8.0 Hz, 2 H), 7.15-7.65 (m, 30 H); 13C NMR (CDCl3, 100.6
MHz) δ 19.2, 26.9, 61.7, 80.7 (m), 83.1 (m), 127.4-135.5; 31P
NMR (CDCl3, 161.97 MHz) δ 115.73 (s). Anal. Calcd for
3,4-Bis-O-(d ip h en ylp h osp h in o)-1,6-d i-O-(p -t olu en su l-
fon yl)-2,5-a n h yd r o-D-m a n n itol (13c). This compound was
sythesized from 0.51 g (1.09 mmol) of diol 16c in 3 mL of THF,
669 mL (4.8 mmol) of Et3N, and a solution of 431 mL (2.4
mmol) of Ph2PCl in 2 mL of THF. The reaction, which was
monitored by TLC with the system hexane/ethyl acetate
(1:2), was complete in 30 min. Chromatography on silica using
the system hexane/ethyl acetate yielded 0.64 g (71%) of 13c
C
62H66O5P2Si2: C, 73.78; H, 6.59. Found: C, 73.99; H, 6.57.
3,4-Bis-O-(d ip h en ylp h osp h in o)-1,6-d id eoxy-2,5-a n h y-
d r o-L-id itol (14d ). This ligand was prepared in accordance
with the general procedure described above from 0.33 g (2.49
mmol) of diol 18d in 5 mL of THF, 1.53 mL (10.97 mmol) of
Et3N, and a solution of 0.98 mL (5.45 mmol) of Ph2PCl in 2.5
mL of THF. The reaction, which was controlled by TLC in CH2-
Cl2/MeOH (3:1), was complete in l.75 h. The crude oil was
purified by column chromatography using the hexane/ethyl
acetate (3:1) system to render 0.98 g (79%) of 14d as a white
as a white syrup: [R]25 +15.48° (CHCl3, c 1.13); 1H NMR
D
(CDCl3, 400 MHz) δ 2.39 (s, 6 H), 3.87 (dd, J ) 5.6, 10.4 Hz,
2 H), 3.92 (dd, J ) 4.4, 10.4 Hz, 2 H), 4.01 (m, 2 H), 4.38 (md,
J ) 8.8 Hz, 2 H), 7.23 (d, J ) 8.0 Hz, 4 H), 7.66 (d, J ) 8.0 Hz,
4 H), 7.27-7.34 (m, aromatic, 20 H); 13C NMR (CDCl3, 100.6
MHz) δ 21.6, 68.4, 81.2 (m), 84.1 (m), 128.0-144.8; 31P NMR
syrup: [R]25 -34.37° (CHCl3, c 0.98); 1H NMR (CDCl3, 400
D
(CDCl3, 161.97 MHz) δ 119.17 (s). Anal. Calcd for C44
42O9P2S2: C, 62.85; H, 5.03; S, 7.63. Found: C, 62.94; H, 5.01;
S, 7.60.
-
MHz) δ 1.20 (d, J ) 6.4 Hz, 6 H), 4.23 (dd, J ) 3.2, 9.2 Hz, 2
H), 4.35 (qd, J ) 3.2, 6.4 Hz, 2 H), 7.45-7.20 (m, 20 H); 13C
H
NMR (CDCl3, 100.6 MHz) δ 15.2, 76.0, 85.0, 128.1-141.9; 31
P
NMR (CDCl3, 161.97 MHz) δ 114.04 (s). Anal. Calcd for
3,4-Bis-O-(d ip h en ylp h osp h in o)-1,6-d id eoxy-2,5-a n h y-
d r o-D-m a n n itol (13d ). This ligand was prepared in ac-
cordance with the general method from 0.84 g (6.35 mmol) of
diol 16d in 13 mL of THF, 3.92 mL (28.09 mmol) of Et3N, and
a solution of 2.52 mL (14.04 mmol) of Ph2PCl in 6.5 mL of THF.
The reaction, which was controlled by TLC using CH2Cl2/
MeOH (3:1), was complete in l.7 h. The reaction crude product
was purified by column chromatography using hexane/ethyl
acetate (4:1) as eluent to render 2.6 g (80%) of 13d as a
colorless syrup: [R]25D -20.4° (CHCl3, c 1.04); 1H NMR (CDCl3,
400 MHz) δ 1.21 (d, J ) 6.4 Hz, 6 H), 4.12 (m, 2 H), 4.26 (md,
J ) 8.8 Hz, 2 H), 7.2-7.5 (m, aromatic, 20 H); 13C NMR (CDCl3,
100.6 MHz) δ 19.1, 78.3 (m), 90.7 (m), 128.0-141.9; 31P NMR
(CDCl3, 161.97 MHz) δ 114.38 (s). Anal. Calcd for C30H30O3P2:
C, 71.99; H, 6.04. Found: C, 72.22; H, 6.06.
C
30H30O3P2: C, 71.99; H, 6.04. Found: C, 72.27; H, 6.02.
(3R,4R)-(-)-3,4-Bis(d ip h en ylp h osp h in oxy)tetr a h yd r o-
fu r a n (en t-9). The title compound was prepared in accordance
with the general procedure beginning with 0.28 g (2.68 mmol)
of 19, 1.69 mL (12.12 mmol) of dry Et3N, and a solution of
1.10 mL (6.12 mmol) of Ph2PCl, dissolved in 3.5 mL of THF.
The reaction, which was controlled by TLC in CH2Cl2/MeOH
(4:1), was complete in 30 min. The crude oil was purified by
column chromatography using the hexane/ethyl acetate (3:1)
system to give 0.82 g (63%) of en t-9 as a white solid: mp )
1
60-61 °C; [R]25 -71.68° (CHCl3, c 1.055); H NMR (CDCl3,
D
400 MHz) δ 3.92 (d, J ) 9.8 Hz, 2 H), 4.05 (dd, J ) 3.4, 9.8
Hz, 2 H), 4.05 (dd, J ) 3.4, 9.8 Hz, 2 H), 4.51 (dd, J ) 3.4, 8.8
Hz, 2 H), 7.20-7.45 (m, 20 H); 13C NMR (CDCl3, 100.6 MHz)
δ 72.9, 83.7, 128.2-141.3; 31P NMR (CDCl3, 161.97 MHz) δ
112.43 (s). Anal. Calcd for C28H26O3P2: C, 71.18; H, 5.55.
Found: C, 71.18; H, 5.52.
3,4-Bis-O-(d ip h en ylp h osp h in o)-1,6-d i-O-(tr iisop r op yl-
silyl)-2,5-a n h yd r o-D-m a n n itol (13e). The title compound
was synthesized from 0.457 g (0.95 mmol) of diol 16e. The
reaction, which was monitored by TLC using hexane/ethyl
acetate (3:2), was complete in 2 h. The residue obtained was
purified by column chromatography using the system hexane/
ethyl acetate (4:1) to give 0.48 g (60%) of 13e as a colorless
P r ep a r a t ion of R h Com p lexes [R h (cod )(L)]BF 4, L )
Dip h osp h in ite: Gen er a l P r oced u r e. The complexes were
prepared by adding a solution of 0.088 mmol of diphosphinite
in 3 mL of CH2Cl2 to a solution of 0.030 g (0.073 mmol) of [Rh-
(cod)2]BF4 in 10 mL of CH2Cl2. The mixture was then stirred
for 30 min, and the solvent was removed in vacuo. The residue
was washed with dry hexane first and then with dry ether in
order to remove the excess diphosphinite and free cycloocta-
diene.
syrup: [R]25 +8.34° (CHCl3, c 1.11); 1H NMR (CDCl3, 400
D
MHz) δ 1.10-0.98 (m, 42 H), 3.67 (dd, J ) 5.2, 10.4 Hz, 2 H),
3.74 (dd, J ) 5.6, 10.4 Hz, 2 H), 4.15 (m, 2 H), 4.71 (md, J )
8.8 Hz, 2 H), 7.20-7.47 (m, aromatic, 20 H); 13C NMR (CDCl3,
100.6 MHz) δ 11.8, 17.9, 17.9, 63.7, 84.8 (m), 85.6 (m), 130.6-
142.2; 31P NMR (CDCl3, 161.97 MHz) δ 115.13 (s). Anal. Calcd
for C48H70O5P2Si2: C, 68.21; H, 8.35. Found: C, 67.96; H, 8.35.
[Rh (cod )(13a )]BF 4. Beginning with 0.030 g (0.073 mmol)
of [Rh(cod)2]BF4 in 10 mL of CH2Cl2 and 0.090 g (0.088 mmol)
of diphosphinite 13a and following the general procedure, we
obtained 0.042 g (43%) of complex [Rh(cod)(13a )]BF4 as a
yellow solid: MS (FAB positive) m/z 1227.4 [M]+, 1119.3 [M
3,4-Bis-O-(d ip h e n ylp h osp h in o)-1,6-d i-O-(t r ip h e n yl-
m eth yl)-2,5-a n h yd r o-L-id itol (14a ). This compound was
prepared following the general method from 0.61 g (0.94 mmol)
of 18a , 5 mL of dry CH2Cl2, 578 mL (4.14 mmol) of dry Et3N,
and 372 mL (2.07 mmol) of Ph2PCl, dissolved in 1.5 mL of CH2-
Cl2. The reaction was monitored by TLC in hexane/ethyl
acetate (3:2). After 1.5 h, the reaction was complete, and the
residue obtained was purified by column chromatography
using the hexane/ethyl acetate (3:2) system to give 0.8 g (83%)
1
- (cod)]+; H NMR (CDCl3, 400 MHz) δ 2.15-2.32 (m, CH2,
cod, 8 H), 3.16 (dd, J ) 3.2, 10.8 Hz, 2 H), 3.58 (dd, J ) 2.6,
10.8 Hz, 2 H), 4.46 (m, 2 H), 4.70 (s, 4 H), 5.36 (s, 2 H), 7.00-
7.50 (m, 50 H); 13C NMR (CDCl3, 100.6 MHz) δ 30.2, 30.3, 63.3,
82.4 (m), 82.7, 87.0, 104.1 (m), 106.0 (m), 127.3-143.6; 31P
NMR (CDCl3, 161.97 MHz) δ 122.60 (d, J Rh,P ) 166.1 Hz).
of 14a as a white solid: mp ) 119-120 °C; [R]25 +9.53°
[Rh (cod )(13b)]BF 4. Beginning with 0.050 g (0.12 mmol)
of [Rh(cod)2]BF4 in the minimum quantity of CH2Cl2 and 138
mg (0.136 mmol) of diphosphinite 13b and following the
general procedure, we obtained 0.132 g (68%) of complex [Rh-
(cod)(13b)]BF4 as an orange solid: MS (FAB positive) m/z
D
1
(CHCl3, c 1.025); H NMR (CDCl3, 400 MHz) δ 3.18 (dd, J )
5.8, 9.4 Hz, 2 H), 3.47 (dd, J ) 6.6, 9.4 Hz, 2 H), 4.37 (dd, J )
3.0, 8.0 Hz, 2 H), 4.30 (m, 2 H), 7.25-7.10 (m, 50 H); 13C NMR
(CDCl3, 100.6 MHz) δ 62.8, 79.6 (m), 82.6 (m), 86.8, 126.6-
J . Org. Chem, Vol. 69, No. 22, 2004 7509

Aghmiz et al.
1219.4 [M]+, 1111.3 [M - (cod)]+; 1H NMR (CDCl3, 400 MHz)
δ 1.09 (s, 18 H), 2.60-2.20 (m, 8 H), 3.69 (dd, J ) 3.2, 11.6
Hz, 2 H), 3.85 (dd, J ) 2.2, 11.6 Hz, 2 H), 4.18 (s, 2 H), 4.66 (s,
2 H), 4.76 (bs, 2 H), 5.24 (s, 2 H), 7.20-7.80 (m, 40 H); 13C
NMR (CDCl3, 100.6 MHz) δ 19.4, 26.9, 29.9, 30.8, 63.1, 81.2,
82.5 (m), 104.4, 106.2, 127.6-135.5; 31P NMR (CDCl3, 161.97
MHz) δ 125.13 (d, J Rh,P ) 167.9 Hz).
[Rh (cod )(13c)]BF 4. Complex [Rh(cod)(13c)]BF4 (130 mg,
92%) was prepared as a yellow solid from 0.050 g (0.123 mmol)
of [Rh(cod)2]BF4, dissolved in the minimum quantity of CH2-
Cl2, and 0.108 g (0.128 mmol) of diphosphinite 13c in 3 mL
of CH2Cl2: HRMS (L-SIMS) calcd for [C52H54O9P2S2Rh]+
1051.173957; found 1051.173930; 1H NMR (CDCl3, 400 MHz)
δ 2.44 (s, 6 H), 2.25-2.60 (m, 8 H), 3.90 (dd, J ) 2.4, 11.2 Hz,
2 H), 4.01 (m, 2 H), 4.07 (dd, J ) 4, 11.2 Hz, 2 H), 4.72 (m, 2
H), 4.88 (m, 2 H), 5.06 (m, 2 H), 7.34 (d, J ) 8 Hz, 4 H), 7.71
(d, J ) 8 Hz, 4 H), 7.47-7.66 (m, 20 H); 13C NMR (CDCl3,
100.6 MHz) δ 21.7, 29.8, 30.7, 68.1, 78.3 (m), 79.2, 104.7 (m),
104.9 (m), 127.9-145.7; 31P NMR (CDCl3, 161.97 MHz) δ
127.81 (d, J Rh,P ) 169.4 Hz).
[Rh (cod )(13d )]BF 4. The general procedure was followed
as 50 mg (0.12 mmol) of [Rh(cod)2]BF4, dissolved in the
minimum quantity of CH2Cl2, was treated with 74 mg (0.147
mmol) of diphosphinite 13d in 3 mL of CH2Cl2 to afford 54
mg (55%) of complex [Rh(cod)(13d )]BF4 as an orange solid: MS
(FAB positive) m/z 711.1 [M]+, 603 [M - (cod)]+; 1H NMR
(CDCl3, 400 MHz) δ 1.13 (d, J ) 6 Hz, 6 H), 2.20-2.60 (m,
CH2, cod, 8 H), 3.91 (m, 2 H), 4.39 (m, 2 H), 4.63 (m, 2 H),
4.73 (m, 2 H), 7.40-7.80 (m, 20 H); 13C NMR (CDCl3, 100.6
MHz) δ 18.6, 30.0, 30.5, 75.7 (m), 85.7, 104.1 (m), 105.6 (m),
128.8-132.6; 31P NMR (CDCl3, 161.97 MHz) δ 127.39 (d, J Rh,P
) 169.4 Hz).
(84%) of complex [Rh(cod)(14d )]BF4 as an orange solid:
HRMS (L-SIMS) calcd for [C38H42O3P2Rh]+ 712.169 780, found
712.170 007; 1H NMR (CDCl3, 400 MHz) δ 1.28 (d, J ) 6.4
Hz, 6 H), 2.20-2.60 (m, 8 H), 4.55 (q, J ) 6.4 Hz, 2 H), 4.77
(s, 4 H), 5.08 (m, 2 H), 7.25-7.60 (m, 20 H); 13C NMR (CDCl3,
100.6 MHz) δ 15.1, 30.5, 30.5, 73.8 (m), 84.1, 103.7 (m), 104.7
(m), 128.7-131.8; 31P NMR (CDCl3, 161.97 MHz) δ 121.97 (d,
J Rh,P ) 166.0 Hz).
[Rh (cod )(14d )]BF 4. X-r a y Cr ysta llogr a p h y. Crystals of
[Rh(cod)(14d )]BF4 were obtained by slow diffusion of hexane
into a solution of [Rh(cod)(14d )]BF4 in dichloromethane.
Crystal data:
C38H42O3P2RhBF4‚2(CH2Cl2), orange blocks.
Empirical formula: C80H92B2Cl8F8O6P4Rh2. FW ) 968.23. T
) 125.0(1) K. λ ) 0.710 73 Å. Crystal system: monoclinic.
Space group: P21. Unit cell dimensions: a ) 11.0767(19) Å,
b ) 20.018(4) Å, c ) 19.139(3) Å, R ) 90°, â ) 94.683(3)°, γ )
90°. Volume ) 4229.6(13) Å3; Z ) 2. Density (calculated) )
1.521 mg/m3. Absorption coefficient ) 0.787 mm-1. F(000) )
1976. Crystal size ) 0.6 × 0.17 × 0.14 mm3. θ range for data
collection ) 1.07-28.27°. Index ranges ) -14 r h r 14, 0 r
k r 26, 0 r l r 25. Reflections collected: 30 560. Independent
reflections: 10 448 [R(int) ) 0.0385]. Completeness to θ )
28.27°, 96.7%. Absorption correction: semiempirical from
equivalents. Maximum and minimum transmission ) 1.000
and 0.811. Refinement method: full-matrix least-squares on
F2. Data/restraints/parameters: 10448/1/992. Goodness of fit
on F2 ) 1.090. Final R indices [I > 2σ(I)]: R1 ) 0.0447, wR2
) 0.1026. R indices (all data): R1 ) 0.0635, wR2 ) 0.1120.
Absolute structure parameter ) 0.09(4). Largest differential
peak and hole ) 0.965 and -0.851 e Å-3
.
The asymmetric unit consists of two independent cations,
-
with two BF4 counterions and four dichloromethane solvate
[Rh (cod )(13e)]BF 4. According to the standard procedure,
50 mg (0.12 mmol) of [Rh(cod)2]BF4, dissolved in the minimum
quantity of CH2Cl2, was treated with 109 mg (0.128 mmol) of
diphosphinite 13e in 3 mL of CH2Cl2 to render 138 mg (98%)
of complex [Rh(cod)(13e)]BF4 as a yellow solid: HRMS (L-
SIMS) calcd for [C56H82O5P2Si2Rh]+ 1055.423113, found
molecules. Cyclooctadiene is disordered in two different con-
formations.
[Rh (cod )(en t-9)]BF 4. This complex was prepared in ac-
cordance with the general procedure using 350 mg (0.123
mmol) of [Rh(cod)2]BF4, dissolved in CH2Cl2, and 61 mg (0.129
mmol) of diphosphinite en t-9 to afford 77 mg (82%) of complex
[Rh(cod)(en t-9)]BF4 as a yellow solid: HRMS (L-SIMS) calcd
for [C36H38O3P2Rh]+ 683.135 125, found 683.135 336; 1H NMR
(CDCl3, 400 MHz) δ 2.25-2.45 (m, 4 H), 2.45-2.65 (m, 4 H),
3.86 (dd, J ) 6.0, 10.0 Hz, 2 H), 4.31 (dd, J ) 6.6, 10.0 Hz, 2
H), 4.78 (s, 4 H), 5.13 (m, 2 H), 7.20-7.80 (m, 20 H); 13C NMR
(CDCl3, 100.6 MHz) δ 30.4, 30.6, 72.2 (m), 82.8, 103.5 (m),
104.3 (m), 128.5-131.8; 31P NMR (CDCl3, 161.97 MHz) δ
122.75 (d, J Rh,P ) 164.8 Hz).
Gen er a l P r oced u r e for th e Rh -Ca ta lyzed Hyd r ogen a -
tion of CdC. In a typical experiment, a dichloromethane
solution (15 mL) of [Rh(cod)2]BF4 (6.1 mg, 0.015 mmol), the
corresponding ligand (0.016 mmol), and the substrate (1 mmol)
under nitrogen were transferred into a Schlenk flask and
purged three times with vacuum and hydrogen. The reaction
mixture was then shaken under H2 (1 atm) at room temper-
ature, unless otherwise stated. Conversion and enantiomeric
excesses were determined by gas chromatography.
1
1055.423167; H NMR (CDCl3, 400 MHz) δ 1.01-1.13 (m, 42
H), 2.35-2.51 (m, 8 H), 3.77 (dd, J ) 3.0, 11.4 Hz, 2 H), 3.90
(dd, J ) 2.6, 11.4 Hz, 2 H), 4.12 (m, 2 H), 4.69 (m, 2 H), 4.81
(m, 2 H), 5.25 (m, 2 H), 7.25-7.60 (m, 20 H); 13C NMR (CDCl3,
100.6 MHz) δ 11.9, 17.9, 18.0, 29.9, 30.7, 62.7, 81.2, 82.6 (m),
104.9 (m), 105.4 (m), 128.0-132.2; 31P NMR (CDCl3, 161.97
MHz) δ 124.97 (d, J Rh,P ) 167.8 Hz).
[Rh (cod )(14a )]BF 4. The general procedure was followed as
37.7 mg (0.092 mmol) of [Rh(cod)2]BF4, dissolved in 2 mL of
CH2Cl2, was treated with 99 mg (0.097 mmol) of diphosphinite
14a to give 110 mg (90%) of complex [Rh(cod)(14a )]BF4 as a
yellow solid: HRMS (L-SIMS) calcd for [C76H70O5P2Rh]+
1227.375 356, found 1227.375 310; 1H NMR (CDCl3, 400 MHz)
δ 2.20-2.50 (m, 8 H), 3.14 (dd, J ) 3.6, 10.4 Hz, 2 H), 3.47
(dd, J ) 4.4, 10.4 Hz, 2 H), 4.72 (s, 4 H), 4.99 (m, 2 H), 5.44
(m, 2 H), 7.00-7.50 (m, 50 H); 13C NMR (CDCl3, 100.6 MHz)
δ 30.2, 30.7, 63.7, 78.4, 83.2, 87.7, 103.9, 104.6, 126.9-143.4;
31P NMR (CDCl3, 161.97 MHz) δ 122.03 (d, J Rh,P ) 164.8 Hz).
[Rh (cod )(14b)]BF 4. This complex (184 mg, 95%) was
prepared as an orange solid from 0.060 g (0.148 mmol) of [Rh-
(cod)2]BF4, dissolved in the minimum quantity of CH2Cl2, and
0.159 g (0.157 mmol) of the diphosphinite [Rh(cod)(14b)]BF4
in 3 mL of CH2Cl2: HRMS (L-SIMS) calcd for [C70H78O5P2Si2-
Rh]+ 1219.391 813, found 1219.391 784; 1H NMR (CDCl3, 400
MHz) δ 0.90 (s, 18 H), 2.20-2.60 (m, 8 H), 3.61 (dd, J ) 2,
11.2 Hz, 2 H), 3.75 (dd, J ) 3.6, 11.2 Hz, 2 H), 4.61 (s, 4 H),
4.70 (m, 2 H), 5.26 (m, 2 H), 7.20-7.85 (m, 40 H); 13C NMR
(CDCl3, 100.6 MHz) δ 19.0, 26.8, 30.3, 30.4, 63.2, 78.0, 81.0,
102.3 (m), 107.81 (m), 127.61-135.48; 31P NMR (CDCl3, 161.97
MHz) δ 129.74 (d, J Rh,P ) 170.8 Hz).
Ack n ow led gm en t. Financial support from DGESIC
BQU2002-01188 and BQU2001-0656 (Ministerio de
Ciencia y Tecnolog´ıa, Spain) is acknowledged. Technical
assistance from the Servei de Recursos Cientifics (URV)
is acknowledged. Authors thank Prof. P.W.N.M. van
Leeuwen (University of Amsterdam) for helpful discus-
sions.
Su p p or tin g In for m a tion Ava ila ble: General methods,
atomic coordinates, thermal parameters, and a complete list
of bond lengths and angles of compound [Rh(cod)(14d )]BF4.
This material is available free of charge via the Internet at
http://pubs.acs.org.
[Rh (cod )(14d )]BF 4. The general procedure was followed
as 58 mg (0.144 mmol) of [Rh(cod)2]BF4, dissolved in the
minimum quantity of CH2Cl2, was treated with 76 mg (0.150
mmol) of diphosphinite 14d in 3 mL of CH2Cl2 to give 97 mg
J O0496502
7510 J . Org. Chem., Vol. 69, No. 22, 2004