2,5-Dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene: First member of the hetero-DuPHOS family

Article abstract of DOI:10.1021/jo050390d

The 2,5-dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene (UlluPHOS), a new thiophene-based analogue of (R,R)-1,2-bis(phospholano)benzene (Me-DuPHOS), was synthesized, geometrically and electronically characterized, and employed as ligand of Rh and Ru in some standard hydrogenation reactions of prostereogenic functionalized carbon-carbon and carbon-oxygen double bonds. The synthesis of UlluPHOS is much easier than that provided for Me-DuPHOS. UlluPHOS and Me-DuPHOS display very similar geometries, while the electronic availability of the former is higher than that exhibited by the latter. The Rh and Ru complexes of UlluPHOS produced excellent enantiomeric excesses (98.9-99.5%) in the hydrogenation of N-acetyl-α-enamino acids and reaction rates higher than those found when employing the analogous complexes of Me-DuPHOS.

Full text of DOI:10.1021/jo050390d

2,5-Dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene:
First Member of the Hetero-DuPHOS Family
Tiziana Benincori,† Tullio Pilati,‡ Simona Rizzo,‡ Franco Sannicolo`,*,‡,§ Mark J. Burk,|
Lorenzo de Ferra, Elio Ullucci, and Oreste Piccolo#
Dipartimento di Scienze Chimiche ed Ambientali, Universita` dell’Insubria, Via Valleggio,
11-22100-Como, Italy;Istituto CNR Scienze e Tecnologie Molecolari, via G. Venezian,
21-20133-Milano, Italy;Dipartimento di Chimica Organica e Industriale, Universita` di Milano, via
Venezian, 21-20133-Milano, Italy; C.I.M.A.I.N.A.sCentro Interdisciplinare Materiali e Interfacce
Nanostrutturati, Via Celoria, 16-20133-Milano, Italy; Diversa Corporation, 4955 Directors Place, San
Diego, California 92121-1609;Chemi S.p.A., via Vadisi, 5-03010-Patrica (Frosinone), Italy; and Studio
di Consulenza Scientifica, via Borno`, 5-23896-Sirtori (Lecco), Italy
staclaus@unimi.it
Received March 2, 2005
The 2,5-dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene (UlluPHOS), a new thiophene-
based analogue of (R,R)-1,2-bis(phospholano)benzene (Me-DuPHOS), was synthesized, geometrically
and electronically characterized, and employed as ligand of Rh and Ru in some standard
hydrogenation reactions of prostereogenic functionalized carbon-carbon and carbon-oxygen double
bonds. The synthesis of UlluPHOS is much easier than that provided for Me-DuPHOS. UlluPHOS
and Me-DuPHOS display very similar geometries, while the electronic availability of the former is
higher than that exhibited by the latter. The Rh and Ru complexes of UlluPHOS produced excellent
enantiomeric excesses (98.9-99.5%) in the hydrogenation of N-acetyl-R-enamino acids and reaction
rates higher than those found when employing the analogous complexes of Me-DuPHOS.
Introduction
or by changing the position of the phosphine group on a
given heterocyclic system. This makes it possible to select
the ligand having the electronic properties that can better
satisfy the requirements imposed by the reaction typology
and by the substrate. For example, electron-rich ligands
have been observed to elevate both stereoselectivity and
rate of hydrogenation reactions involving prostereogenic
carbon-oxygen2 and carbon-carbon functionalized double
bonds. Similar results also were reported for Diels-Alder
[4 + 2]cycloaddition reactions.3 By contrast, certain car-
We previously conceived and demonstrated the utility
of five-membered aromatic heterocycles as multifunc-
tional scaffolds for the phosphorus atoms of chiral
diphosphine ligands.1 The use of heterocyclic aromatic
systems as a ligand scaffold engenders substantial syn-
thetic advantages over carbocyclic aromatic analogues.
In addition, and perhaps more importantly, heteroaro-
matic scaffolds allow fine modulation of the electronic
properties of the chelating functions bound to the het-
erocyclic ring. Electronic tuning at phosphorus can be
performed either by using different aromatic heterocycles
(1) (a) Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco, L.;
Antognazza, P.; Cesarotti, E. J. Chem. Soc. Chem. Commun. 1995,
685-686. (b) Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco, L.;
Antognazza, P.; Cesarotti, E.; Demartin, F.; Pilati, T. J. Org. Chem.
1996, 61, 6244-. (c) Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco,
L.; Antognazza, P.; Cesarotti, E.; Demartin, F.; Pilati, T.; Zotti, G. J.
Organomet. Chem. 1997, 529, 445-453. (d) Benincori, T.; Cesarotti,
E.; Piccolo, O.; Sannicolo`, F. J. Org. Chem. 2000, 65, 2043-2047. (e)
Benincori, T.; Rizzo, S.; Sannicolo`, F. J. Heterocycl. Chem. 2002, 39,
471-485.
* Corresponding author. Tel:
+39.02.50314139.
+39.02.50314174-73. fax:
† Universita` dell’Insubria.
‡ Istituto CNR Scienze e Tecnologie Molecolari.
§ Universita` di Milano and C.I.M.A.I.N.A.
| Diversa Corp.
Chemi S.p.A.
(2) Benincori, T.; Piccolo, O.; Rizzo, S.; Sannicolo`, F. J. Org. Chem.
2000, 65, 8340-8347.
# Studio di Consulenza Scientifica.
10.1021/jo050390d CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/07/2005
5436
J. Org. Chem. 2005, 70, 5436-5441

First Member of the Hetero-DuPHOS Family
SCHEME 1. (R,R)-2,5-Dimethyl-[3,4-bis(2′,5′-
dimethylphosphospholanyl)]thiophene
bon-carbon bond forming reactions are favored by
catalysts resulting from ligands that are relatively
electron-deficient.4
To quantitatively evaluate the electron-donor ability
of ligands, among the many parameters available, we
have chosen the electrochemical oxidation peak potential
(E°p, volt) determined by voltammetry. In some cases, we
have been able to find quantitative relationships between
the E°p values of the free ligands and the catalytic activity
exhibited by their metal complexes.2
The strategy of using five-membered heteroarenes as
scaffolds for different chelating functions (e.g. phosphi-
nooxazoline) has become rather popular in the past few
years, and recent literature has been enriched with many
chiral ligands bearing electron-donor groups supported
by heteroaromatic scaffolds.5 We considered extending
the strategy to the very successful class of DuPHOS
ligands, which bear the five-membered phospholane
moiety as the stereogenic component.6 An academic-
industrial cooperative effort was initiated in 1999 to test
the concept and to design and investigate this new class
of modular ligands containing phospholanes attached to
heteroaromatic backbones.
as C2 symmetric versions.9 (iii) The two methyl groups
in the R- and R′-positions have multiple functions. Since
the construction of the phospholane rings involves double
lithiation at phosphorus of a 3,4-thienylidenenediphos-
phine, the methyl groups guard against possible alterna-
tive R,R′-ring lithiation. Furthermore, they could increase
the electronic availability of the thiophene ring and hence
of the phosphorus atoms. Additional, unpredictable ef-
fects could also result from steric interactions between
the methyl groups and the phospholane units, thus
reducing the conformational mobility of the ligand.
The synthesis of 1, outlined in Scheme 2, follows the
sequence employed for preparing the phospholane rings
of Me-DuPHOS, starting from an o-arylidene diphosphine
and the cyclic sulfate of enantiopure 2,5-hexanediol. The
preparation of the 2,5-thienylene diphosphine (2) takes
advantage of the palladium-mediated reaction of easily
available 3,4-diiodo-2,5-dimethylthiophene10 with triethyl
phosphite, giving diphosphonate 3 in fairly good yields.
This synthesis is easier than that described for o-
phenylenediphosphine, which involves a sequence of
experimentally critical steps: the double metalation of
o-dichlorobenzene with butyllithium, the quenching of the
resulting ortho-dianion with highly reactive and aggres-
sive bis(diethylamino)chlorophosphine, and the reaction
of the product with dry hydrogen chloride.6,11
Results and Discussion
This paper reports the synthesis, structural charac-
terization, and some preliminary applications of (R,R)-
2,5-dimethyl-[3,4-bis(2′,5′-dimethylphospholanyl)]-
thiophene (1, UlluPHOS). This diphosphine is the first
member of a new family of C2 symmetric hetero-DuPHOS
ligands, characterized by the presence of two homo-
morphic chiral 2,5-dimethyl-substituted phospholane
groups, bound to the homotopic ortho positions of a five-
membered aromatic heterocycle.7
The basic guidelines for our design are the following:
(i) We considered as a crucial point that the ligand would
be electron-rich, since, as anticipated, large electronic
availability at phosphorus is a prerequisite for fast
kinetics in certain hydrogenation processes. Thus, we
chose the electron-rich thiophene ring as the scaffold for
the phospholane units. We located the phosphacycles in
the â-positions, which are endowed with much higher
electron density than the R-positions.8 (ii) We considered
that it was a great advantage to maintain the homo-
topism of the phospholane units, since the metal com-
plexes resulting from asymmetric ligands, displaying
phosphine units located in electronically and constitu-
tionally different surroundings, have not proven as
effective at inducing high levels of absolute stereocontrol
To structurally characterize (R,R)-UlluPHOS (1) and
evaluate the geometric properties of this new ligand when
coordinated to a metal center, we have obtained crystals
of the (1,5-cycloctadiene)-rhodium(I)-tetrafluoborate
complex (4a) suitable for single-crystal X-ray diffracto-
metric analysis. An ORTEP diagram displaying a projec-
tion from above the square plane of the complex is shown
in Figure 1a. For comparison, the projection of the
analogous [((S,S)-Me-DuPHOS)Rh(1,5-cycloctadiene)]-
SbF6 complex, is provided in Figure 1b.6
Table 1 summarizes some of the most characteristic
structural data of these complexes.
From these data it can be inferred that the geometries
of the UlluPHOS and Me-DuPHOS stereogenic core in
the solid state are nearly superimposable. Taking the
plane of the aromatic rings as a reference plane, an
identical out-of-plane distortion of the rhodium and
phosphorus atoms is observed in both the complexes.
(3) Celentano, G.; Benincori, T.; Radaelli, S.; Sada, M.; Sannicolo`,
F. J. Organomet. Chem. 2002, 643-644, 424-430.
(4) (a) Tietze, L. F.; Thede, K. J. Chem. Soc. Chem. Commun. 1999,
1811-1812: (b) Tietze, L. F.; Thede, K.; Sannicolo`, F.; Schimpf, R. J.
Chem. Soc. Chem. Commun. 2000, 583-584.
(9) Degussa patented and currently commercializes through Strem
Chemicals, Inc. (Bischheim, 67800, France) a couple of C2 symmetric
bis(phospholane) ligands characterized by nonaromatic, very electron
poor maleic anhydride and maleinimide as scaffolds for the phos-
pholane rings. Patent WO03084971.
(10) ,5-Dimethyl-3,4-diiodothiophene is the starting material em-
ployed to prepare the tetraMe-BITIOP, a chiral biheteroaromatic
ligand,1d currently produced at a kiloscale level at Chemi S.p.A.
(11) Diphosphinobenzene can be also prepared on a scale through
a photochemical reaction between dichlorobenzene and trimethyl
phosphite, followed by reduction with LAH/TMSCl (see: Kyba et al.
Organometallics 1983, 2, 1877-1879).
(5) Tietze, L. F.; Lohmann, J. K. Synlett 2002, 2083-2085.
(6) Burk, J. M.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am.
Chem. Soc. 1993, 115, 10125-10138.
(7) Sannicolo`, F.; Piccolo, O.; Benincori, T.; Sada, M.; Verrazzani,
A.; Tollis, S.; Ullucci, E.; De Ferra, L.; Rizzo, S. Patent WO03074169;
Patent EP1490173.
(8) Some ligands displaying two homomorphic phospholane units
bound to the 2,3-positions of electron-poor thianaphthene have been
prepared by a past co-worker of one of us and patented by Solvias.
These diphosphines are asymmetric, since the two phospholane rings
are located on constitutionally heterotopic carbon atoms.
J. Org. Chem, Vol. 70, No. 14, 2005 5437

Benincori et al.
SCHEME 2. Synthetic Schemes for UlluPHOS (1) and Me-DuPHOS
TABLE 1. Comparison of Some Bond Angles (θi), Bond Lengths (li), and through-Space P-P Distances (d) in the
Me-DuPHOS- and UlluPHOS-(1,5-Cycloctadiene)-Rhodium Complexesa
θ1 (deg)b
P-C-C(-P)
θ2 (deg)b
Rh-P-Car
θ2 (deg)
P-Rh-P
d (Å)
P-P
l1 (Å)
(P-)C-C(-P)
l2 (Å)c
Car-P
l3 (Å)c
Rh-P
l3 (Å)d
Rh-C
[(ligand)Rh(1,5-COD)]X
(S,S)-Me-DuPHOS
(R,R)-UlluPHOS
117.2
117(3)
110.25
109.6(6)
84.72
85.86(2)
3.056
3.103(2)
1.400
1.437(3)
1.812
1.82(3)
2.268
2.278(2)
2.244
2.243(3)
a Average values are reported with rms and single values with esd (only for 4a). b Average value of chemically equivalent angles.
c Average value of the chemically equivalent bond lengths. d Average value of four chemically equivalent (1,5-cycloctadiene)-Rh-carbon
bond lengths.
of UlluPHOS. Voltammetric experiments showed that the
oxidation peak of the new ligand occurred at 0.17 V, much
lower than that exhibited by Me-DuPHOS (E°p ) 0.36
V), indicating that the strategy adopted for producing a
very electron-rich diphosphine was successful.12 Some
differences might be expected, therefore, in the kinetic
behavior of the hydrogenation reactions of carbon-carbon
and carbon-oxygen double bonds, which have been
shown to be sensitive to the electronic availability of the
donor functions of the ligand.
Hydrogenation precatalysts containing the Rh com-
plexes of UlluPHOS and Me-DuPHOS were prepared in
situ by reaction of the ligands with [Rh(COD)2]BF4 and
applied in parallel reactions to assess the relative ef-
fectiveness of these catalysts for carbon-carbon double
bond hydrogenation. Several typical substrates were
screened, namely methyl 2-acetamidoacrylate, 2-aceta-
midocinnamic acid, itaconic acid, and the methyl ester
of the latter. Also the industrially attractive diastereo-
selective hydrogenation of 5 to compound 6, which is a
key intermediate for the preparation of the HIV protease
inhibitor PNU-140690,13 was examined: diastereoselec-
tivities up to 91% with [[(R,R)-UlluPHOS]Rh(1,5-
FIGURE 1. Projections on the plane of the aromatic rings of
[[(R,R)-UlluPHOS]Rh(1,5-cycloctadiene)] cation (4a) (bottom)
and [[(S,S)-Me-DuPHOS]Rh(1,5-cycloctadiene)SbF6] cation (top);
green ) Rh, violet ) P, yellow ) S, black ) C.
cycloctadiene)OTf] (4b) were achieved.
Some experiments also were devoted to compare the
efficiency of the complex [(UlluPHOS)Ru(iodo)(p-
cymene)]iodide (4c) with the same type of complex of Me-
DuPHOS in the hydrogenation of the ketonic carbonyl
double bond of acetoacetic ester, even though the latter
ligand is known not to be the ligand of choice for this
kind of reaction, probably because the bite angle is too
low in its metal complexes.14
Since the geometry of chiral ligands is known to be a
crucial parameter influencing the facial selection of their
metal complexes, similar levels of absolute stereocontrol
could be expected for the catalysts prepared from Ullu-
PHOS and Me-DuPHOS.
It has been amply demonstrated that the electronic
properties of chiral ligands can also greatly influence
stereoselection in metal-based catalysis. We have previ-
ously assessed the electronic characteristics of a range
of phosphine ligands through cyclic voltametric measure-
ments.1c,2 In a similar fashion, we have determined the
electrochemical oxidation peak potential in order to
assess the electronic availability at the phosphorus atoms
(12) We determined the electrochemical oxidative potential of the
2,3-bis[(2R,5R)-2,5-dimethyl-phospholano]thianaphthene (Solvias Buti-
PHOS), cited above, that we had prepared and tested with meager
results in some of the test reactions of Table 2. The choice of electron-
poor thianaphthene as a backbone for the phospholane rings has as a
consequence a net decrease in the electronic richness of both the
phosphorus atoms, in particular of the phospholane unit located in R
position (E°p ) 0.65 V).
(13) Fors, K. S.; Gage, J. R. J. Org. Chem. 1998, 63, 7348-7356.
5438 J. Org. Chem., Vol. 70, No. 14, 2005

First Member of the Hetero-DuPHOS Family
TABLE 2. Comparative Data of Some Hydrogenation Reactions of Standard Substrates Promoted by (R,R)-UlluPHOS
and (R,R)-Me-DuPHOS Metal Complexes
a Determined by chiral HPLC. b Evaluated by 1H NMR spectroscopy with Eu(III)tris[3-(heptafluoropropylhydroxymethylene)-d-
camphorate] as a shift reagent. c Evaluated by 1H NMR spectroscopy on the methyl ester with Eu(III)tris[3-(heptafluoropropylhydroxy-
methylene)-d-camphorate] as a shift reagent. d Determined by HPLC.
The comparative stereoselection data are reported in
Table 2 together with the main experimental parameters.
The analysis of the data reported in Table 2 indicates
that the stereoselection levels observed in the reactions
promoted by the complexes of UlluPHOS are fully
comparable to those produced by the analogous Me-
DuPHOS complexes, with the exception of itaconic acid,
where the enantiomeric excess produced by the Ullu-
PHOS rhodium complex was found to be somewhat lower
than that attained with the Me-DuPHOS complex. This
observation is in agreement with some recent literature
data, demonstrating that the rhodium complexes of
electron-rich diphosphines display an unexplained mod-
est enantioselection ability for this specific substrate.15
As for the kinetic data, we were able to draw compara-
tively significant, even though not absolutely validated,
values for the reaction rate constants.16 In the case of
the hydrogenation of 2-acetamidocinnamic acid, under
identical experimental conditions (entry 1 of Table 2), we
found rate constant values of 8.5 × 10-3 versus 1.1 × 10-3
depending whether the promoter was derived from Ul-
luPHOS or Me-DuPHOS. In agreement with these find-
ings, 94% conversion, reached by employing the Ullu-
PHOS complex, was compared with 59% conversion,
obtained with the Me-DuPHOS complex, after 0.5 h
reaction time, and 99.5% versus 95.6% conversion after
1 h. Analogously, in the hydrogenation of itaconic acid
promoted by the UlluPHOS complex, the conversion was
found to be 26% after 1 h reaction time, while it was 12%
when the Me-DuPHOS Rh complex was employed as
mediator.
Conclusions
The conclusions that can be drawn from the results of
this research are the following: (i) A new C2 symmetric
diphospholane ligand (1, UlluPHOS) containing a thio-
phene ring as the linker between the phospholane units
was synthesized and structurally characterized. (ii) The
synthesis of 1 (and steric homologues) is simpler than
that available for the DuPHOS ligands family. (iii) The
new ligand displays geometric properties (single-crystal
(14) Burk, M. J.; Harper, T. G. P., Kalberg, C. S. J. Am. Chem. Soc.
1995, 117, 4423-4424.
(15) Herseczki, Z.; Gergely, I.; Hegedu¨s, C.; Szo¨llo¨sy, Bakos, J.
Tetrahedron: Asymmetry 2004, 15, 1673-1676.
(16) Repetitive venting of the autoclave for sampling sometimes
produces degradation of the catalyst with consequent rate depression.
J. Org. Chem, Vol. 70, No. 14, 2005 5439

Benincori et al.
Preparation of 2,5-Dimethyl-3,4-bis[(2R,5R)-2,5-di-
methylphospholano]thiophene (1) (UlluPHOS). n-BuLi
(0.79 mL of a 1.6 M solution in hexane) was added to a stirred
solution of 2,5-dimethyl-3,4-bis(diphosphino)thiophene (2) (0.11
g) in THF (12 mL) at room temperature. The solution was left
stirring for 1.5 h and then a THF solution (1.2 mL) of (2S,5S)-
hexanediol cyclic sulfate (0.23 mg) was added. After 2 h of
stirring, n-BuLi (0.87 mL of a 1.6 M solution in hexane) was
added to the mixture at room temperature. The solution was
stirred for 12 h and then MeOH (0.2 mL) was added. The
solvent was removed under reduced pressure and the solid
residue was treated with degassed CH2Cl2 and filtered under
argon atmosphere, and the filtrate was evaporated to dryness
to give a solid which was crystallized from MeOH to give 1
(0.19 g) in a pure state (70% yield): 1H NMR (CDCl3) δ 0.99
(6H, m), 1.15 (6H, m), 1.20-1.52 (4H, m), 1.94-2.2 (4H, m),
2.42 (6H + 2H, s superimposed to a m), 3.02 (2H, m); 13C NMR
(CDCl3) δ 16.5, 18.6, 20.8 (t, J ) 11.5 Hz), 29.6, 34.1 (t, J )
6.1 Hz), 36.1 (t, J ) 3.4 Hz), 37.9, 136.6, 137.9; 31P NMR
(CDCl3) δ 5.6 (s); [R]25D ) + 54.2 (c ) 1, CHCl3); PM (MS) 444.
Anal. Calcd for C18H26P2S: C, 72.95; H, 5.90. Found: C, 73.11;
H, 5.77.
X-ray analysis and theoretical calculations) very similar
to those found for Me-DuPHOS but quite higher elec-
tronic availability at phosphorus (E°p) relative to the
latter ligand. (iv) The facial recognition and enantiose-
lection associated with Rh and Ru complexes of Ullu-
PHOS and Me-DuPHOS were shown to be similarly high
in several typical test hydrogenation reactions. (v) Pre-
liminary data suggest that olefin hydrogenation reactions
promoted by catalysts bearing UlluPHOS are qualita-
tively faster than those using analogous catalysts of Me-
DuPHOS. (vi) The promising results obtained with
UlluPHOS suggest the extension of the hetero-DuPHOS
family by applying this structural design to other electron-
rich heterocycles, pyrrole in particular, for which the
introduction of the phosphorus atoms could be even easier
than that demonstrated in the case of thiophene.7
Experimental Section
Unless otherwise specified, all solvents and reagents were
reagent grade and used without purification. 1H NMR spectra
were recorded as solutions in CDCl3 on 200 or 300 MHz
spectrometers. All reactions were performed using standard
Schlenk-type techniques. For the preparations of the com-
plexes and the hydrogenation reactions, solvents degassed
under argon were employed. Hydrogenation reactions were
carried out in a stirred (550 rpm), 100 mL, hastelloy autoclave,
equipped with a sampling pipe extending to the bottom of the
vessel.
Preparation of 2,5-Dimethyl-3,4-bis(diethoxyphos-
phoryl)thiophene (3). A solution of 2,5-dimethyl-3,4-diiodo-
thiophene10 (4.0 g) in triethyl phosphite (15 mL) was dropped
under a N2 atmosphere in 2 h into a stirred suspension of
palladium acetate (0.98 g) in triethyl phosphite (20 mL) at 140
°C. The reaction was heated at 140 °C for further 3 h and then
excess triethyl phosphite was removed in a vacuum. The oily
residue was extracted with five 10-mL portions of heptane,
and the combined extracts were evaporated to dryness to give
an oil which was chromatographed (eluant, AcOEt/EtOH 9:1)
to give 3 (1.4 g) as a colorless oil (48% yield). A sample was
purified by distillation under reduced pressure (bp 170-175
°C at 3 Torr) to give 3 as a colorless, low-melting solid which
was crystallized from pentane (mp 35 °C): 1H NMR (CDCl3)
δ 1.78 (t, 12H, J ) 53.6 Hz), 3.12 (d, 6H, J ) 1.6 Hz), 4. 58 (m,
8H); 13C NMR (CDCl3) δ 16.4 (t, J ) 6.7 Hz), 53.7, 62.0 (d, J
) 10.6 Hz), 124.9 (d, J ) 18.8 Hz), 128.8 (d, J ) 18.3 Hz),
150.4 (t, J ) 4.8 Hz; 31P NMR (CDCl3) δ 12.5; PM (MS) 384.
Anal. Calcd for C14H26O6P2S: C, 43.75; H, 6.82. Found: C,
43.55; H, 6.99.
Preparation of 2,5-Dimethyl-3,4-bis(phosphino)thio-
phene (2). Trimethylchlorosilane (11.2 mL) was added to a
suspension of LiAlH4 (3.6 g) in THF (80 mL), at -78 °C, under
N2, and the mixture was stirred at room temperature for 2 h.
The solution was cooled to -60 °C and a solution of 3 (5.6 g)
in dry THF (20 mL) was added. The reaction mixture was
stirred at room temperature for 3 h and then water (3.6 mL),
a 15% NaOH solution (3.6 mL), and water (10.8 mL) were
added in sequence. The mixture was left stirring up to the
formation of a precipitate, which was filtered off and washed
with four 20-mL portions of THF. Removal of the solvent from
the filtrate left a residue which was dissolved in toluene (50
mL) and washed twice with water (2 × 20 mL). The organic
phase was filtered on Decalite and evaporated to dryness to
give 2 as a pale-yellow oil (90% yield). A sample was purified
by distillation under reduced pressure (bp 75 °C at 5 Torr) to
give 2 as a colorless oil: 1H NMR (CDCl3) δ 2.96 (6H, s), 3.67
(t, 2H), 4.70 (t, 2H); 13C NMR (CDCl3) δ 15.9 (t, J ) 4.2 Hz),
127.2, 141.6 (t, J ) 10.9 Hz); 31P NMR (CDCl3) δ -154.7 (t, J
) 6 Hz); PM (MS) 176. Anal. Calcd for C6H10P2S: C, 40.91; H,
5.72. Found: C, 40.66; H, 5.88.
-
Preparation of [(COD)Rh(UlluPHOS)]+BF4 (4a). A
mixture of [Rh(COD)2]BF4 (9.7 mg) and 1 (9 mg) in degassed
CH2Cl2 (1.5 mL) was stirred for 2 h. The solvent was
evaporated under vacuum and the orange complex used
without any purification: 31P NMR (CDCl3) 51.1 (d, J ) 146
Hz).
Crystals of the complex suitable for X-ray analysis were
obtained by stirring a solution of 1 (50 mg) and [Rh(COD)2]-
BF4 (59 mg) in degassed CH2Cl2 (5 mL) for 2 h. THF (2.5 mL)
and n-hexane (5 mL) were added and the solvents slowly
evaporated until some crystals precipitated. After 24 h, the
precipitation was complete, and the crystals were washed first
with Et2O and then with THF.
Preparation of [(COD)Rh(UlluPHOS)]+OTf- (4b). A
mixture of [Rh(COD)2]OTf (108.9 mg) and 1 (90 mg) in
degassed CH2Cl2 (10 mL) was stirred for 2 h. The solvent was
evaporated to one-third of its volume, and then THF (6 mL)
and n-hexane (4 mL) were added. The solvent was evaporated
under reduced pressure until crystallization started. The
mixture was kept at -5 °C in a refrigerator and then the
orange solid precipitate was collected, washed with n-hexane
(3 × 4 mL), and dried under vacuum to give the complex (0.1
g): 31P NMR (CDCl3) 49.7 (d, J ) 134 Hz).
Preparation of [(p-Cymene)Ru(UlluPHOS)I]I (4c). A
solution of [(RuI2(p-cymene)2] (0.0014 mmol) and 1 (0.0035
mmol) in degassed CH2Cl2 (25 mL) and MeOH (9 mL) was
refluxed for 2 h. The solvent was evaporated to dryness and
the red complex used without any further purification: 31P
NMR (CDCl3) δ 79. 25 (d, J ) 45.5 Hz), 59.99 (d, J ) 45.5
Hz); PM (ESI positive) 703.1.
X-ray Crystallography: [(COD)Rh(UlluPHOS)]+BF4
-
(4a). X-ray Structure Determination of the [((S,S)-Me-
DuPHOS)Rh(1,5-cycloctadiene)]BF4 Complex. Crystal
data: C26H42P2RhS+ BF4-, 0.2965(C4H8O), 0.2035(CH2Cl2). fw
) 677.04, monoclinic red crystal 0.32 × 0.21 × 0.11 mm3, space
group C2, a ) 14.764(2) Å, b ) 17.671(3) Å, c ) 11.940(2) Å,
â ) 103.858(6)°, V ) 3024.4(8) Å3, Z ) 4, Fcalc ) 1.486 g cm-3
,
µ(Mo KR) ) 0.818 mm-1, 20 633 reflections measured at 90
K, below θ ) 33.05°, 10 291 unique [9047 with I > 2σ(I)], R(ave)
) 0.248, 366 parameters refined on F2 using SHELXL17 code
to final indices R(all) ) 0.0401, wR )0.0836-3, {w ) 1/[σ2(F2)+-
(0.0495P)2], where P ) (Fo + 2Fc2)/3}. The following are the
2
refinement details: the tetrafluoroborate anion is disordered,
but its interpretation and refinement were sufficiently easy
and suitable. Much more difficult was understanding the
nature of the solvent lying on the crystallographic 2-fold axis.
Because the salt was crystallized from CH2Cl2, THF, and Et2O,
(17) Sheldrick, G. M. SHELXL-97. Program for the Refinement of
Crystal Structures; University of Go¨ttingen, Germany.
5440 J. Org. Chem., Vol. 70, No. 14, 2005

First Member of the Hetero-DuPHOS Family
we attempted to introduce each one of the three pure solvent,
time by time, in the refinement, with unsatisfactory results.
The final refined model for the solvent was a mixture of CH2-
Cl2 and THF. Despite the large anisotropy and magnitude of
atomic displacement parameters of the solvent (particularly
for THF) and the correlations between the same, we adopted
this model because it gave the lowest R and wR and the
smallest residues in the solvent cavity, being nearly irrelevant
with respect the remaining refinement parameters. The CCDC
reference number is 264288.
Padova, Italy) is acknowledged for voltammetric experi-
ments. Dr. Tiziana Benincori thanks the Dipartimento
di Chimica Organica e Industriale of Milan University
for its hospitality.
Supporting Information Available: Voltammetric curve
for 1; ESI spectra for complex 4c with experimental and
1
calculated isotopic distribution patterns; H NMR spectra of
complexes 4c and 4a and analogous Me-DuPHOS complexes;
X-ray diffraction data for 4a, including tables of positional and
isotropic thermal parameters, anisotropic thermal parameters,
interatomic bond distances, and intramolecular and torsion
angles. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. Dr. Alessandra Verrazzani and
Dr. Simona Tollis (Chemi S.p.A.) are warmly acknowl-
edged for their contribution in the experimental and
analytical development of this work. Dr. Gianni Zotti
(CNR-Istituto CNR per l’Energetica e le Interfasi,
JO050390D
J. Org. Chem, Vol. 70, No. 14, 2005 5441