J . Org. Chem. 2000, 65, 2043-2047
2043
2,2′,5,5′-Tetr a m eth yl-4,4′-bis(d ip h en ylp h osh in o)-3,3′-bith iop h en e: A
New , Ver y Efficien t, Ea sily Accessible, Ch ir a l Bih eter oa r om a tic
Liga n d for Hom ogen eou s Ster eoselective Ca ta lysis
Tiziana Benincori,*,† Edoardo Cesarotti,*,‡ Oreste Piccolo,*,§ and Franco Sannicolo`*,|
Dipartimento di Chimica Organica e Industriale dell’Universita`, via Golgi 19-20133-Milano, Italy,
Dipartimento di Scienze Chimiche, Fisiche e Matematiche dell’Universita` dell’Insubria, via Lucini
3-22100-Como, Italy, Dipartimento di Chimica Inorganica, Metallorganica e Analitica dell’Universita`,
via Golgi 19-20133-Milano, Italy, and Chemi S.p.A., via dei Lavoratori 54-20092-Cinisello Balsamo, Italy
Received September 30, 1999
The four-step straightforward synthesis of enantiopure (+)- and (-)-2,2′,5,5′-tetramethyl-4,4′-bis-
(diphenylphoshino)-3,3′-bithiophene (tetraMe-BITIOP), a new C2-symmetry chelating ligand for
transition metals, is described, starting from 2,5-dimethylthiophene. The complexes of this electron-
rich diphosphine with Ru(II) and Rh(I) were used as catalysts in some homogeneous hydrogenation
reactions of prostereogenic carbonyl functions of R- and â-ketoesters, of prostereogenic carbon-
carbon double bonds of substituted acrylic acids, and of N-acetylenamino acids. The enantiomeric
excesses were found to be excellent in all the experiments and comparable with the best results
reported in the literature for the same reactions, carried out under similar experimental conditions,
with the metal complexes of the most popular chiral diphosphine ligands as catalysts.
In tr od u ction
formylation, hydrosilylation, and hydrocyanation reac-
tions have also attained sufficient maturity levels. How-
ever, it was found that each reaction (and substrate)
requires that the steric and electronic properties of the
metal complex be tailored according to its needs: electron-
rich diphosphines are known to give very active com-
plexes in carbon-oxygen double-bond hydrogenation,6
while low phosphorus electronic availability is much more
favorable in olefin hydroformylation.7 Small bite angle
values are crucial for attaining high stereoselectivity
levels in the former reaction, while larger values are
preferable in the latter.8
Our previous work on chiral diphosphines character-
ized by an atropisomeric backbone composed of two
interconnected five-membered heteroaromatic rings9 dem-
onstrated that the supporting heterocycle is crucial in
determining phosphorus electronic availability and the
geometric properties of the ligand.
The recent trends in organic reaction development are
oriented toward synthetic efficiency, which is mainly re-
lated to selectivity (chemo-, regio-, and stereoselectivity),
productivity, and atom economy; it goes without saying
that a reaction should be environmentally responsible by
design.
Stereoselective homogeneous catalysis, promoted by
complexes of transition metals with chiral ligands car-
rying electron-donor chelating functions, represents a
methodology that perfectly meets all of these require-
ments.1 In this light, the multitude of new chiral ligands
for transition metals presented in recent literature2 is
amply justified when considering the enormous variety
of reactions that, at least in theory, can be satisfactorily
carried out in a catalytic manner.3 The hydrogenation
reactions of olefinic and carbonyl (Pro)1-chiral and con-
figurationally labile (Pro)0-chiral substrates are today
widely applied even for the preparation of products of
industrial interest.4 Also, the single and cascade stereo-
selective Heck reaction has recently attracted a great deal
of attention due to its versatility and efficiency in
carbon-carbon bond formation.5 Stereoselective hydro-
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tognazza, P.; Cesarotti, E. J . Chem. Soc., Chem. Commun. 1995, 685.
Antognazza, P.; Benincori, T.; Brenna, E.; Cesarotti, E.; Sannicolo`, F.;
Trimarco, L. Eur. Pat. 0770085 to Chemi S.p. A.. Benincori, T.; Brenna,
E.; Sannicolo`, F.; Trimarco, L,; Antognazza, P.; Cesarotti, E.; Demartin,
F.; Pilati, T. J . Org. Chem. 1996, 61, 6244.
† Dipartimento di Scienze Chimiche, Fisiche e Matematiche dell’
Universita` dell’Insubria.
‡ Dipartimento di Chimica Inorganica, Metallorganica e Analitica
dell’Universita` di Milano.
§ Chemi S.p.A.
| Corresponding author. Dipartimento di Chimica Organica e In-
dustriale dell’Universita` di Milano.
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10.1021/jo991533x CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/09/2000