A new modular class of easily accessible, inexpensive, and efficient chiral diphosphine ligands for homogeneous stereoselective catalysis

Full text of DOI:10.1021/jo015738t

5940
J . Org. Chem. 2001, 66, 5940-5942
Ch a r t 1
A New Mod u la r Cla ss of Ea sily Accessible,
In exp en sive, a n d Efficien t Ch ir a l
Dip h osp h in e Liga n d s for Hom ogen eou s
Ster eoselective Ca ta lysis
Tiziana Benincori,† Serafino Gladiali,‡
Simona Rizzo,§ and Franco Sannicolo`*,§
Dipartimento di Chimica Organica e Industriale
dell’Universita` e Centro CNR per la Sintesi e
Stereochimica di Speciali Sistemi Organici, Via Golgi 19,
I-20133-Milano, Italy, Dipartimento di Scienze Chimiche,
Fisiche e Matematiche dell’Universita` dell’Insubria,
Via Valleggio, 11, I-22100 Como, Italy, and Dipartimento
di Chimica dell’Universita`, Via Vienna 2,
Ch a r t 2
I-07100 Sassari, Italy
staclaus@icil64.cilea.it
Received May 8, 2001
The search for new chiral ligands capable of high
enantioselectivity in homogeneous catalysis is a current
challenge in applied chemical research. Chelating diphos-
phines supported on stereogenic atropisomeric biaryl
scaffolds are rated as very efficient chiral modifiers in
most stereoselective reactions.1 The electron density at
the donor centers of these ligands is a crucial parameter
controlling both reaction kinetics and stereoselectivity.2
We demonstrated that an accurate tuning can be effected
by exploiting the inherently differentiated electron-
demand or electron-releasing ability of five-membered
aromatic heterocyclic systems in C2-symmetric diphos-
phino biheteroaryls 1,3 which possess high stereoselection
ability and are, in general, synthetically more accessible
than carbocyclic biaromatic systems4 (Chart 1). The
nature of the heterocyclic system constituting the back-
bone and the position of the diphenylphosphino groups
on it strongly influence the electronic properties at
phosphorus, which ranges gradually from very electron
poor to very electron rich situations.3 It is known,
however, that the homotopism of the chelating centers
is not a prerequisite for high enantioselectivity, and
constitutionally and electronically diverse phosphorus
characterize C1 symmetry controllers of high efficiency.5
We considered that the electronic modularity offered by
the five-membered heteroaromatic systems could be
combined with a very easy synthesis in the C1 symmetry
diphosphines 2, having atropisomeric five-membered
heterocyclic-six-membered carbocyclic biaromatic back-
bones (Chart 1).
In these cases, the synthetic approach is merely
reduced to the preparation of aryl-substituted five-
membered heterocycles. The most relevant point of this
design is the possibility to gain entry into an unlimited,
highly modular class of ligands. The electronic density
on the phosphine group on the heterocyclic ring could be
tuned through the same strategy applied for diphosphino
biheteroaryls 1, while that of the phosphine group on the
carbocyclic moiety through tailored substitution on it.
We report here the synthesis of enantiopure diphos-
phine 3a as the prototype of this new class of asymmetric
ligands, and the preliminary data of the application of
their ruthenium, rhodium, and palladium complexes as
homogeneous catalysts in some homogeneous catalysis
experiments (Chart 2).
Structural design for 3a was based on the assumption
that it was desirable to substantially differentiate the
electronic properties of the phosphine groups, to direct
the approach of the substrate to the heterotopic bonding
sites of the catalytic complex along a single, energetically
preferred, path. The use of inexpensive, commercially
available starting materials was also considered as a
project prerequisite.
* To whom correspondence should be addressed. Phone: +39.027-
0635727. Fax: +39.0270636857.
Polyphosphoric acid (PPA)-promoted cyclodehydration
(62% yields) of 1-(2-bromophenyl)-2-(2-naphthylthio)-
ethanone (4), prepared by condensation (90% yields) of
sodium â-naphthalenethiolate with ω,2-dibromoaceto-
phenone, afforded 3-(2-bromophenyl)naphtho[2,1-b]thio-
phene (3c). Simultaneous transmetalation of the aryl
bromide and acid-base lithiation of the thiophene ring,
effected with butyllithium, quenching of the dianion with
2 equiv of chlorodiphenylphosphine, followed by in situ
hydrogen peroxide treatment, gave phosphine oxide (()-
3b (53% yields) (Scheme 1).
† Universita` dell’Insubria.
‡ Dipartimento di Chimica dell’Universita`.
§ Universita` di Milano.
(1) Akutagawa, S. Appl. Catal. A: General 1995, 128, 171.
(2) Schmid, R.; Broger, E. A.; Cereghetti, M.; Crameri, Y.; Foricher,
J .; Lalonde, M.; Mu¨ller, R. K.; Scalone, M.; Schoette, G.; Zutter, U.
Pure Appl. Chem. 1996, 68, 131.
(3) Benincori, T.; Piccolo, O.; Rizzo, S.; Sannicolo`, F. J . Org. Chem.
2000, 65, 8340.
(4) (a) Benincori, T.; Brenna, E.; Sannicolo`, F.; Trimarco, L.;
Antognazza, P.; Cesarotti, E.; Demartin, F.; Pilati, T. J . Org. Chem.
1996, 61, 6244. (b) Benincori, T.; Cesarotti, E.; Piccolo, O.; Sannicolo`,
F. J . Org. Chem. 2000, 65, 2043.
(5) (a) Francio`, G.; Faraone, F.; Leitner, W. Angew. Chem., Int. Ed.
2000, 39, 1428. (b) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.;
Landert, H.; Tijani, A. J . Am. Chem. Soc. 1994, 116, 4062. (c)
Yoshikawa, K.; Yamamoto, N.; Murata, M.; Awano, K.; Morimoto, T.;
Achiwa, K. Tetrahedron Lett. 1996, 37, 5347.
The racemate was resolved by fractional crystallization
of the diastereomeric adducts obtained by reaction with
(+)- and (-)-dibenzoyltartaric acids. Alkaline decomplex-
10.1021/jo015738t CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/28/2001

Notes
J . Org. Chem., Vol. 66, No. 17, 2001 5941
Ta ble 1. Hyd r ogen a tion of F u n ction a lized CdO a n d CdC Bon d s Usin g Liga n d 3a
Sch em e 1
Ch a r t 3
Sch em e 2
ation of the adducts afforded enantiopure phosphine
oxides (+)-3b and (-)-3b, which were reduced to the
corresponding enantiopure diphosphines (+)-3a and (-)-
3a with trichlorosilane.
The electrochemical oxidative potential (E° , V) was
chosen as parameter for evaluating the electronic avail-
ability of the phosphine groups of 3a . Voltammetric
experiments showed a single irreversible oxidation peak
at 0.74 V, attributable to the diphenylphosphine group
located on the phenyl ring. The electrochemical oxidative
potential of the phosphine group on the thiophene moiety
was inferred from the E° value (0.91 V) found for the
3-ph en yl-2-(diph en ylph osph in o)n a ph t h o[2,1-b]t h io-
phene 3d , prepared by reaction of the lithium anion of
known 3-phenylnaphtho[2,1-b]thiophene6 with chloro-
diphenylphosphine. These values confirm that the two
phosphorus atoms of 3a possess very different electronic
properties: the former is a rather electron-rich phosphine
group, while the latter is a quite electron-poor function.
methyl 2-acetamidoacrylate to methyl N-acetylalaninate
and PdII perchlorate complex 5d in Diels-Alder cycload-
dition.
The enantioselection data obtained in these experi-
ments are illustrated in Table 1 and in Scheme 2.
These data, though resulting from unrefined experi-
ments, demonstrate that diphosphine 3a possesses a
quite good stereoselection capacity. Even though the
enantioselection levels found in the hydrogenation of
2-acetamidoacrylate and in the Diels-Alder cycloaddition
are definitely lower than those achievable with chiral
ligands specifically designed for these reactions, the
enantiomeric excesses obtained in â-ketoesters and meth-
yl phenylglyoxylate hydrogenation are fully comparable
to those produced by the most efficient ligands. When
considering that a preliminary cost estimate for enan-
tiopure 3a is less than one tenth of DuPHOS, one-fifth
of BINAP and one-third of tetraMe-BITIOP,4b it appears
that the class of the C1 symmetry diphosphines 2 may
The preliminary catalysis experiments with 3a were
performed in the hydrogenation of substrates that are
in standard use for the evaluation of the catalytic
properties of all new chiral ligands appearing in the
literature (Table 1) and in the Diels-Alder cycloaddition
of cyclopentadyene and N-acryloyloxazolidin-2-one (Scheme
2).
RuII complexes 5a ,b (Chart 3) were applied in the
reduction of the ketonic function of R- and â-oxoesters.
RhI complex 5c was employed in the hydrogenation of
(6) Dann, O.; Kokorudz, M. Chem. Ber. 1958, 91, 172.

5942 J . Org. Chem., Vol. 66, No. 17, 2001
Notes
effected according to known methodologies.4b Enantiopure (+)-
offer a countless multitude of new highly modular and
efficient chiral modifiers for industrial homogeneous
catalysis.
3b gave enantiopure (-)-3a (mp 325 °C dec; [R]25 ) - 185, c )
D
0.39 in C6H6), while enantiopure (-)-3b gave enantiopure (+)-
(3a ) (mp 325 °C dec; [R]25 ) + 172, c ) 0.38 in C6H6).
D
Enantiomeric purity of (+)-3a and (-)-3a was checked after
reoxidation to phosphine-oxides. MS: m/z 443 (M+ - P(C6H5)2).
1H NMR (CDCl3): δ 6.82 (t, 2 H), 6.87 (t, 2 H), 7.0 (t, 2 H), 7.02-
7.17 (m, 5 H), 7.18-7.42 (m, 15 H), 7.45 (t, 1 H); 7.70, 7.77 (dd,
2 H), 7.86 (d, 1 H). 31P NMR (CDCl3): δ -25.0 (s, 1P); -14.0 (s,
1P).
2-D ip h e n y lp h o s p h in o -3-p h e n y ln a p h t h o [2,1-b ]t h io -
p h en e (3d ). Mp: 294 °C (sint. 180 °C). MS: m/z 444 (M+). 1H
NMR (CDCl3): δ 7.17 (t, 1 H), 7.27-7.52 (m, 17 H), 7.71, 7.77
(dd, 2 H), 7.87 (d, 1 H). 31P NMR (CDCl3): δ -24.1 (s).
Meta l Com p lexes 5. Complexes 5a ,4b 5b,4b and 5c8 were
prepared according to already described standard procedures.
Complex 5d was prepared according to the procedure reported
for the analogous BINAP complex.9
Volt a m m et r ic P r oced u r es.10 Voltammetries were per-
formed in a 0.5 × 10-3 M dry acetonitrile solution, in a three-
electrode cell, at 25 °C, under nitrogen, in the presence of 0.1 M
tetraethylammonium perchlorate as a supporting electrolyte.
The working electrode was a Pt microelectrode (0.003 cm2); the
counter electrode was Pt; the reference electrode was Ag/0.1 M
AgClO4 in acetonitrile (0.34 V vs SCE).
Hyd r ogen a tion P r oced u r es. Already described hydrogena-
tion experimental procedures were followed.3 Specific conditions
are reported in Table 1.
Exp er im en ta l Section
1-(2-Br om op h en yl)-2-(2-n a p h th ylth io)eth a n on e (4). Dry
sodium 2-naphthalenethiolate [from naphthalenethiol (10.0 g)
and NaOMe] was rapidly added to a stirred solution of ω,2-
dibromoacetophenone7 (17.3 g) in MeCN (200 mL) at 5 °C.
Standard workup gave 4 as a viscous oil (20.6 g) that was used
in a crude state. 1H NMR (CDCl3): δ 4.37 (s, 2H, CH2), 7.20-
7.32 (m, 3H), 7.40-7.60 (m, 4H, C6H4), 7.69-7.80 (m, 4H).
3-(2-Br om op h en yl)n a p h th o[2,1-b]th iop h en e (3c). A mix-
ture of compound 4 (20.0 g) and PPA (200 g) was heated under
stirring at 100 °C for 1 h, poured onto ice, neutralized with a
20% NH4OH solution, and extracted with CH2Cl2. The organic
layer was dried and filtered on a silica gel cake to give 3c (11.8
g). Mp: 99 °C (hexane). 1H NMR (CDCl3): δ 7.25 (t, 1H), 7.38 (s,
1H), 7.35-7.55 (m, 5H), 7.78 (d, 2H), 7.94 (d, 2H).
(()-3-[2-(Dip h en ylp h osp h in yl)p h en yl]-2-(d ip h en ylp h os-
p h in yl)n a p h th o[2,1-b]th iop h en e [(()-(3b)]. BuLi (2.5 M in
hexane, 20.6 mL) was dropped into a solution of 3c (8.0 g) and
TMEDA (8 mL) in THF (200 mL) at -70 °C. After 1 h at rt,
Ph2PCl (8.8 mL) was added, the solvent removed, and the
residue treated with CH2Cl2 (200 mL) and a 15% H2O2 solution
(60 mL). Standard workup gave 3b (8.3 g). Mp: 303 °C (AcOEt).
MS: m/z 660 (M+); 583 (M+ - C6H5); 459 (M+ - PO(C6H5)2). H
1
NMR (CDCl3): δ 6.83-7.04 (m, 4 H), 7.04-7.20 (m, 4 H), 7.20-
7.90 (m, 22 H); 31P NMR (CDCl3): δ 20.5 (s, 1 P), 28.1 (s, 1 P).
Resolu tion of (()-3b. Crystallization from AcOEt/CHCl3 1:1
of the diastereomeric adducts formed by reaction of (()-3b with
an equimolar amount of (+)-O,O′-dibenzoyl-D-tartaric acid gave
the dextrorotatory diastereoisomer as the less soluble adduct
Ack n ow led gm en t. We thank MURST COFIN pro-
ject 9803153701, CNR, and Chemi S.p.A.
Su p p or tin g In for m a tion Ava ila ble: Elemental analysis
of (()-3a , (()-3b, and 3d : CD spectra (∆ꢀ/ꢀ) of (+)- and (-)-
3a ; voltammetry of 3c; voltammetry of 3a . This material is
available free of charge via the Internet at http://pubs.acs.org.
(mp 268 °C; [R]25 ) +63.6, c ) 0.42 in EtOH). Alkaline
D
treatment gave enantiopure (+)-3b (mp 268 °C (synt. 125 °C);
[R]25D ) -310, c ) 0.38 in C6H6). The mother liquors were treated
with a 0.75 M NaOH solution and the resulting diphosphine
oxide, treated in turn with (-)-O,O′-dibenzoyl-L-tartaric acid,
gave the levorotatory adduct ([R]25D ) - 63.6, c ) 0.42 in EtOH).
Alkaline treatment gave enantiopure (-)-3b (mp 267 °C (sint.
125 °C); [R]25D ) +305.5, c ) 0.37 in C6H6). Enantiomeric purity
of (+)- and (-)-3b was checked by HPLC (Chiracel OD, Daicel
Chem Ind.; hexane/i-PrOH 99.8:0.2).
J O015738T
(7) Rival, Y.; Grassy, G.; Michel, G. Chem. Pharm. Bull. 1992, 40,
1170.
(8) Roucoux, A.; Thieffry, L.; Carpentier, J .-F.; Devocelle, M.; Me`liet,
C.; Agbossou, F.; Mortreux, A. Organometallics 1996, 15, 2440.
(9) Matsumoto, Y.; Hayashi, T. Tetrahedron 1994, 50, 335.
(10) Benincori, T., Brenna, E., Sannicolo`, F., Trimarco, L., An-
tognazza, P., Cesarotti, E., Demartin, F., Pilati, T., Zotti, G. J .
Organomet. Chem. 1997, 529, 445.
(+)- a n d (-)-3-[2-(Dip h en ylp h osp h in o)p h en yl]-2-(d i-
p h en ylp h osp h in o)n a p h th o[2,1-b]th iop h en e [(+)-(3a )] a n d
(-)-3a ]. Reduction of phosphine oxides to phosphines was