Phosphorus-Chiral Analogues of 1,1′-Bis(diphenylphosphino)ferrocene: Asymmetric Synthesis and Application in Highly Enantioselective Rhodium-Catalyzed Hydrogenation Reactions

Article abstract of DOI:10.1021/jo982481z

Five new ferrocene ligands 1a-e (1 = 1,1′-bis(aryl-phenylphosphino)ferrocene with aryl residues a = 1-naphthyl, b = 2-naphthyl, c = 2-anisyl, d = 2-biphenylyl, and e = 9-phenanthryl) bearing stereogenic phosphorus atoms have been prepared in enantiomerica

Full text of DOI:10.1021/jo982481z

3996
J . Org. Chem. 1999, 64, 3996-4004
P h osp h or u s-Ch ir a l An a logu es of
1,1′-Bis(d ip h en ylp h osp h in o)fer r ocen e: Asym m etr ic Syn th esis a n d
Ap p lica tion in High ly En a n tioselective Rh od iu m -Ca ta lyzed
Hyd r ogen a tion Rea ction s
Ulrike Nettekoven,† Paul C. J . Kamer,† Piet W. N. M. van Leeuwen,*,† Michael Widhalm,*,‡
Anthony L. Spek,§ and Martin Lutz§
Institute of Molecular Chemistry, Universiteit van Amsterdam, Nieuwe Achtergracht 166,
1018 WV Amsterdam, The Netherlands, Institute of Organic Chemistry, University of Vienna,
Wa¨hringer Strasse 38, 1090 Vienna, Austria, and Bijvoet Center for Biomolecular Research,
Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
Received December 21, 1998
Five new ferrocene ligands 1a -e (1 ) 1,1′-bis(aryl-phenylphosphino)ferrocene with aryl residues
a ) 1-naphthyl, b ) 2-naphthyl, c ) 2-anisyl, d ) 2-biphenylyl, and e ) 9-phenanthryl) bearing
stereogenic phosphorus atoms have been prepared in enantiomerically pure form via an asymmetric
synthesis protocol. The use of (+)- or (-)-ephedrine as the optically active auxiliary during
subsequent nucleophilic displacement reactions at borane-protected phosphorus centers gave rise
to the title compounds in 41-65% overall yield. The absolute configuration of the ferrocenyldiphos-
phines was confirmed by crystal structure analysis of 1a , 1b, and 1d . Their efficiency as chiral
ligands was demonstrated in rhodium-catalyzed asymmetric hydrogenation reactions of R-(acyl-
amino)cinnamic acid derivatives. While low reactivity or enantiomeric discrimination were observed
when employing ligands 1b and 1d , the in situ formed catalysts prepared from diphosphines 1a ,
1c, or 1e effected complete conversion and enantioselectivities of up to 98.7% ee.
In tr od u ction
involving lithium-sparteine-mediated enantioselective
metalation of alkyldimethylphosphine boranes8 and tert-
butylphenylphosphine boranes9 open a practicable access
to optically active mono- and diphosphines.
Among the chiral ligands that have brought about the
success of asymmetric transition metal catalysis, biden-
tate phosphines have played a dominant role.1 Landmark
discoveries such as BINAP2 and DIOP3 promoted the
synthesis and application of a vast variety of new, carbon-
chiral diphosphines in numerous enantioselective trans-
formations.4 Considerably less attention, however, has
been paid to ligand structures bearing asymmetrically
substituted phosphorus donors. Although the use of its
most prominent member, Dipamp,5 in the enantioselec-
tive hydrogenation of a L-Dopa precursor had been
commercialized in the late 1970’s,6 further developments
within the class of phosphorus-chiral ligands suffered
from synthetic difficulties and tedious resolution proce-
dures.7 Only very recently did the elegant approaches
Within our continuous interest in the design and
synthesis of “tailor-made“ ligand structures for specified
applications,10 we wanted to explore the catalytic behav-
ior of C2-symmetrical phosphorus-chiral diphosphine
ligands bearing three aryl substituents. Upon coordina-
tion of such a ligand to a transition metal the stereogenic
phosphorus atoms are positioned in utmost proximity of
the metal center, giving rise to conformationally rigid
complexes. Structural unambiguity as well as pronounced
dissymmetric interaction resulting thereof are assumed
to improve asymmetric induction in different types of
enantioselective reactions.11
Since the above-mentioned protocols do not seem to be
amenable to the preparation of P-chiral triarylphos-
phines, we focused our attention on a synthetic procedure
describing stepwise stereodefined introduction of differ-
ent alkyl as well as aryl residues to a phosphorus center.
As reported by J uge´ et al., this approach avoided an
optical resolution procedure and established the first
asymmetric synthesis of (RP)- and (SP)-anisylmethylphen-
ylphosphine, which were subsequently transformed into
enantiopure Dipamp via ipso-coupling.12 The stereospeci-
* To whom correspondence should be addressed. E-mail:
(P.W.N.M.v.L.)
felix.orc.univie.ac.at.
pwnm@anorg.chem.uva.nl;
(M.W.)
miwi@
† Universiteit van Amsterdam.
‡ University of Vienna.
§ Utrecht University.
(1) For representative reviews, see, for example: (a) Noyori R.
Asymmetric Catalysis in Organic Synthesis; J ohn Wiley: New York,
1994. (b) Ojima, I., Ed. Catalytic Asymmetric Synthesis; VCH Publish-
ers: Weinheim, 1993.
(2) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345.
(3) Kagan, H. B.; Dang, T.-P. J . Am. Chem. Soc. 1972, 94, 6429.
(4) Brunner, H., Zettlmeier, W., Eds. Handbook of Enantioselective
Catalysis; VCH Publishers: Weinheim, 1993.
(5) (a) Knowles, W. S.; Sabacky, M. J .; Vineyard, B. D. J . Chem.
Soc., Chem. Commun. 1972, 10. (b) Vineyard, B. D.; Knowles, W. S.;
Sabacky, M. J .; Bachman, G. L.; Weinkauff, D. J . J . Am. Chem. Soc.
1977, 99, 5946.
(8) (a) Muci, A. R.; Campos, K. R.; Evans, D. A. J . Am. Chem. Soc.
1995, 117, 9075. (b) Imamoto, T.; Watanabe, J .; Wada, Y.; Masuda,
H.; Yamada, H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J . Am.
Chem. Soc. 1998, 120, 1635.
(9) Wolfe, B.; Livinghouse, T. J . Am. Chem. Soc. 1998, 120, 5116.
(10) (a) Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J .;
van Leeuwen, P. W. N. M. Organometallics 1995, 14, 3081. (b)
Widhalm, M.; Wimmer, P.; Klintschar, G. J . Organomet. Chem. 1996,
523, 167.
(6) Knowles, W. S.; Sabacky, M. J .; Vineyard, B. D. US Patent 4
005.127, 1977.
(7) (a) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375.
(b) Kolodiazhnyi, O. I. Tetrahedron: Asymmetry 1998, 9, 1279.
(11) Halpern, J . Science 1982, 217, 401.
10.1021/jo982481z CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/06/1999

Rhodium-Catalyzed Hydrogenation Reactions
J . Org. Chem., Vol. 64, No. 11, 1999 3997
F igu r e 1. Possible synthetic pathways to (mono)- and (bis)-
triarylphosphines utilizing the J uge´-Geneˆt approach (R )
aryl).
ficity of this method is marked by the use of (+)- or (-)-
ephedrine as chiral auxiliary and the protection of the
phosphorus centers as their borane complexes. Despite
the possibilities of steric overcrowding and insufficient
chiral discrimination, we envisaged that the stereoselec-
tive attachment of three different arylsubstituents to a
phosphorus atom should be feasible. Furthermore, we
anticipated that nucleophilic attack of a dilithiated aryl
species would result in compounds bearing two stereo-
genic phosphorus moieties (Figure 1).
Resu lts a n d Discu ssion
Liga n d Syn th esis. The required P-chiral precursor,
oxazaphospholidine borane 2, was readily prepared from
bis(diethylamino)phenylphosphine, (+)- or (-)-ephedrine
and BH3‚dimethyl sulfide.12 The stereospecific character
of this condensation reaction results in the formation of
a single diastereoisomer ((2RP,4S,5R)-2 or (2SP,4R,5S)-
2, depending on the enantiomer of ephedrine used).
Complexation of phosphorus prevented oxidation and
contributed to a stereocontrolled course of the subsequent
nucleophilic displacement sequence 2 f 4 f 5 f 6 f 1
(Scheme 1).
Treatment of 2 with aryllithium reagents 3a -e at -78
°C afforded the phosphine amide boranes 4a -e in 85-
94% yield. In the case of 2-anisyllithium (3c), this
reaction was proposed to proceed via a cyclic pentacoor-
dinate intermediate followed by stereopermutation with
overall retention of configuration at phosphorus. The
latter was confirmed by crystal structure analysis,16 and
therefore, we assume that the same holds for structurally
related reagents 3a ,b,d ,e. Introduction of several di-
lithioaryl species at this stage of the synthesis was also
attempted, but this led to the formation of monosubsti-
tuted products or mixtures of diastereomers. (Using 1,1′-
dilithioferrocene a mixture of (RP,RP)- and (RP,SP)-bis-
(phosphine amide boranes) in a 65:35 ratio was obtained).
Considering the mechanism,16 interference of the in-
creased steric bulk imposed by a neighboring phosphine
amide moiety with the second nucleophilic attack or
stereorearrangements might account for the observed
results.
In this context, we regarded the 1,1′-substituted fer-
rocene unit to be a suitable chelate backbone. Since dppf
(1,1′-bis(diphenylphosphino)ferrocene) is one of the most
frequently used phosphorus donors in organometallic
chemistry and catalysis,13 it seemed appealing to create
chiral derivatives of this successful ligand. In the follow-
ing we describe our synthetic efforts based on the
mentioned strategy. The intermediate phosphine amide
boranes incorporating the ephedrine unit as well as the
phosphinite boranes may serve as useful enantiomeri-
cally pure organophosphorus building blocks.14 The sub-
sequent reaction of 1,1′-dilithioferrocene with optically
active phosphinites gave rise to the new phosphorus-
chiral dppf analogues 1a -e.15
(12) J uge´, S.; Stephan, M.; Laffitte, J . A.; Geneˆt, J . P. Tetrahedron
Lett. 1990, 31, 6357.
(13) (a) Gan, K.-S.; Hor, T. S. A. In Ferrocenes; Togni, A.; Hayashi,
T., Eds.; VCH Publishers: Weinheim, 1995. (b) For examples of
nonracemic ferrocene derivatives applied in asymmetric synthesis,
see: Richards, C. J .; Locke, A. J . Tetrahedron: Asymmetry 1998, 9,
2377 and references therein.
(14) (a) Compounds 4a , 4c, 5a , and 5c were first described in ref
12. (b) Brown, J . M.; Laing, J . C. P. J . Organomet. Chem. 1997, 529,
435. (c) Stoop, R. M.; Mezzetti, A.; Spindler, F. Organometallics 1998,
17, 668.
(15) (a) The synthesis of ligands 1a (BPNF) and 1c (BPAF) as well
as their application in asymmetric allylic alkylation reactions has been
communicated: Nettekoven, U.; Widhalm, M.; Kamer, P. C. J .; van
Leeuwen, P. W. N. M. Tetrahedron: Asymmetry 1997, 8, 3185. (b) An
optically active methylphenylphosphine analogue of dppf has been
prepared utilizing a different synthetic approach: Kaloun, E. B.;
Merde`s, R.; Geneˆt, J . P.; Uziel, J .; J uge´, S. J . Organomet. Chem. 1997,
529, 455.
(16) J uge´, S.; Stephan, M.; Merde`s, R.; Geneˆt, J . P.; Halut-Desportes,
S. J . Chem. Soc., Chem. Commun. 1993, 531.

3998 J . Org. Chem., Vol. 64, No. 11, 1999
Nettekoven et al.
Sch em e 1
F igu r e 2. Molecular plot of (R,R)-1a .
Compounds 4a -e were subjected to acidic methanoly-
sis from which the methyl phosphinite borane complexes
5a -e were isolated after column chromatography in 66-
94% yield. Due to the SN2-type character of this nucleo-
philic substitution, inversion of configuration took place
at the stereogenic phosphorus atoms.12,14c The enantio-
meric purity of the products was checked by chiral HPLC
and found to be at least 98% ee, which rendered extensive
recrystallization procedures unnecessary.
From the viewpoint of stereochemical unambiguity, the
subsequent reaction of 1,1′-dilithioferrocene with 5a -e
proved to be crucial. To obtain complete configurational
inversion at phosphorus, various reaction conditions were
applied. We found that addition of a suspension of 1,1′-
dilithioferrocene to the phosphinite borane solution at
-40 °C, warming to room temperature over a period of
15 h, followed by aqueous workup yielded the desired C2-
symmetrical diphosphine boranes, accompanied by minor
amounts (∼10%) of monosubstituted byproduct. Only in
the case of phosphinite borane 5d did we detect small
amounts of (R,S)-meso-diphosphine diborane in the crude
product (4% with respect to the total yield of diphosphine
diborane). Tentatively, we ascribe the incomplete enan-
tiomeric discrimination to the sterically encumbering and
flexible nature of the biphenyl moiety. At temperatures
above 0 °C, the presence of TMEDA (released from 1,1′-
dilithioferrocene‚TMEDA complex) caused slow decom-
plexation of BH3 from the products in the reaction
mixture (up to 30% as judged from 31P NMR). A similar
deprotection of the starting phosphinite boranes 5 was
not observed and can therefore be excluded as racemiza-
tion pathway for 6d . Purification of chiral 6d was
nevertheless easily achieved by column chromatography
and subsequent recrystallization.
F igu r e 3. Molecular plot of (S,S)-1b.
of the different phosphinites seem to surpass that of the
oxazaphospholidine borane substrate (vide infra).17
Decomplexation of (crude) borane complexes 6a -e was
achieved by stirring in diethylamine at 50 °C for several
hours, at which point the stereochemical integrity of the
phosphorus centers was preserved.18 After evaporation
of solvent and chromatographic purification, the phos-
phorus-chiral diphosphine ligands 1a -e were obtained
in 72-81% yield and enantiomeric excesses of >98% ee.
Cr ysta l Str u ctu r es a n d Assign m en t of Absolu te
Con figu r a tion . Clarification regarding the stereochem-
ical outcome of the dilithioferrocene attack on phosphin-
ites 5 was gained by means of crystal structure deter-
mination of ligands 1a , 1b, and 1d (Figures 2-4). As
outlined in Scheme 1, the use of (SP,4R,5S)-2 (prepared
(17) These findings are in agreement with previously made observa-
tions; see ref 14b.
(18) The deboronation step is reported to proceed without loss of
enantiomeric purity: Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto,
T.; Sato, K. J . Am. Chem. Soc. 1990, 112, 5244. Stirring at reflux
temperature for longer reaction times, however, has been observed to
cause minor racemization: ref 14c.
Summarizing, it turned out that introduction of a bulky
diaryl species is best performed as the last substitution
step, since stereodiscrimination abilities and reactivity

Rhodium-Catalyzed Hydrogenation Reactions
J . Org. Chem., Vol. 64, No. 11, 1999 3999
tion with the column material (Chiralcel OD, n-hexane/
2-propanol/acetic acid ) 97:2.8:0.2 or Chiralcel OJ ,
heptane/ethanol ) 85:15).
An alternative method, which proved to be faster and
more general, was the use of chiral NMR shift reagents,
especially N-(3,5-dinitrobenzoyl)-1-phenylethylamine.
While it was originally developed by Kagan et al. for the
determination of enantiomeric purity of sulfoxides,20a this
reagent also efficiently interacts with (racemic) phosphine
oxide functionalities, giving rise to well-resolved signals
of (diastereomeric) complexes.20b
Oxidation of ligands 1a -e by H2O2 in acetone yielded
configurationally unchanged diphosphine dioxides 7a -
e.21 Upon addition of 2 equiv of (S)-(+)-N-(3,5-dinitroben-
zoyl)-1-phenylethylamine to racemic or enantiomerically
enriched samples of 7a -e, splitting of signals of the
ferrocenylprotons occurred that allowed easy determina-
tion of enantiomeric purity by integration (error (2%).
In the corresponding 31P NMR spectrum, a significant
downfield shift was observed upon complexation of the
phosphine oxide moiety with the shift reagent. Complete
separation of signals, however, could only be obtained
after addition of 3 equiv of Kagan’s reagent and perform-
ing measurements at low temperature (233 K). On the
contrary, in samples of diphosphine dioxides 7a -e,
prepared from ligands 1a -e by stereospecific oxidation,
we could not detect any trace of the second enantiomer
within the error range of NMR integration.
Asym m etr ic Hyd r ogen a tion Rea ction s. The cata-
lytic performance of the new ligands was readily explored
in enantioselective rhodium-catalyzed hydrogenation
reactions.22 Cinnamic acid derivatives 8a -c were hydro-
genated at 2 bar of initial H2 pressure in the presence of
catalysts formed in situ from [Rh(nbd)2]ClO4 and the
respective ligand (eq 1).
F igu r e 4. Molecular plot of the first molecule of (R,R)-1d .
from (1S,2R)-(+)-ephedrine) as starting material should
give rise to intermediates (RP,1S,2R)-4 and (S)-5. If
inversion took place during the subsequent nucleophilic
substitution, followed by retention of configuration upon
decomplexation,18 (R,R)-configurated diphosphines should
be obtained. The crystal structures of 1a , 1b and 1d were
determined in chiral space groups, and their absolute
structure was confirmed by refinement of the Flack x
parameter.19 According to our expectations, the ligands
1a and 1d showed the (R,R)-configuration at phosphorus
atoms. For diphosphine 1b, however, the synthesis was
started employing (1R,2S)-(-)-ephedrine as auxiliary.
The stereochemistry of the sequence thus became re-
versed, ending up with the opposite enantiomer of the
diphosphine, (S,S)-1b.
The molecular plots of these structures are shown in
Figures 2-4. The crystals of 1d consist of two crystallo-
graphically independent molecules, which mainly differ
in the torsion angles within the biphenyl groups and in
the torsion angles along the P-Cbiphenyl bonds. The
geometries at the phosphorus atoms are quite similar in
all structures with CPC angle sums of 301.8-307.6° and
distances P-Cphenyl ) 1.821(9)-1.843(4) Å, P-Cferrocenyl
)
1.797(6)-1.820(3) Å, P-Cnaphthyl ) 1.823(5)-1.842(7) Å,
and P-Cbiphenyl ) 1.845(3)-1.851(4) Å. The conforma-
tions of the ferrocenyl groups in structure 1a and both
molecules of 1d are rather similar with C1-Centr.-
Centr.′-C1′ torsion angles of 123.1(3)-128.6(2)°; in
structure 1b this torsion angle is 158.5(3)°. There is no
obvious intramolecular reason for this conformation
change so that we assume crystal packing effects as a
cause.
With the exception of the catalyst containing ligand
1d , all reactions proceeded smoothly and were completed
within 2-6 h; the results are summarized in Table 1.
The disappointing performance of diphosphine 1b
might be explained by its structural properties. Bearing
Deter m in a tion of En a n tiom er ic Excess. After con-
ducting reactions 5 f 6 no signals originating from the
meso-(R,S)-forms of the diphosphine diboranes could be
detected in the NMR spectra of the crude products (with
exception of compound 6d , vide supra), which seems to
support a highly stereoselective course of the nucleophilic
substitution. Nevertheless, experimental evidence con-
cerning the enantiomeric purity of the ligands was sought
and prompted us to perform chiral HPLC measurements.
Sufficient enantioseparation, however, could only be
obtained for the diborane complex 6c, in which the
methoxy functionalization is believed to facilitate interac-
(20) (a) Desmukh, M.; Dunach, E.; J uge´, S.; Kagan, H. B. Tetrahe-
dron Lett. 1984, 25, 3467. (b) Dunach, E.; Kagan, H. B. Tetrahedron
Lett. 1985, 26, 2649.
(21) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.; Na-
gashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi, M.;
Yamamoto, K.; Kumada, M. Bull. Chem. Soc. J pn. 1980, 53, 1138.
(22) (a) For a review on asymmetric hydrogenation of R-(N-acylami-
no)acrylic acid derivatives, see: Koenig, K. E. In Asymmetric Synthesis;
Morrison, J . D., Ed.; Academic Press: New York, 1985; Vol. 5. For more
recent developments, see, for example: (b) Burk, M. J .; Feaster, J . E.;
Nugent, W. A.; Harlow, R. L. J . Am. Chem. Soc. 1993, 115, 10125. (c)
RajanBabu, T. V.; Ayers, T. A.; Halliday, G. A.; You, K. K.; Calabrese,
J . C. J . Org. Chem. 1997, 62, 6012. (d) Zhu, G.; Cao, P.; J iang, Q.;
Zhang, X. J . Am. Chem. Soc. 1997, 119, 1799. (e) Pye, P. J .; Rossen,
K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J . J . Am.
Chem. Soc. 1997, 119, 6207. (f) Sawamura, M.; Kuwano, R.; Ito, Y. J .
Am. Chem. Soc. 1995, 117, 9602. (g) Robin, F.; Mercier, F.; Ricard, L.;
Mathey, F.; Spagnol, M. Chem. Eur. J . 1997, 3, 1365.
(19) Flack, H. D. Acta Crystallogr. 1983, A39, 876.

4000 J . Org. Chem., Vol. 64, No. 11, 1999
Nettekoven et al.
complex species displaying larger bite angles10a and thus
allowing more effective shielding of diagonal quadrants
by the sterically demanding aryl groups might account
for the observed results.25 Employment of catalysts
incorporating the smaller anisyl-functionalized ligand 1c
gave rise to slightly lower ee values in comparison to 1a
and 1e. To what extent this behavior can be ascribed to
steric effects only remains unclear.26 Action of the meth-
oxy group as a hemilabile intramolecular oxygen donor
has been observed previously in alkylhydride catalytic
intermediates,27 but the influence of such a coordination
on the enantioselectivity-determining step is still a
matter of debate. Our results as well as the ones obtained
by Imamoto et al.8b suggest, however, that, on providing
a suitable backbone framework, marked steric differences
between the alkyl or aryl residues on phosphorus are
more important with respect to stereodifferentiation than
possible cooperative effects attributed to the methoxy
functionalization.
Summarizing, regarding the excellent enantioselec-
tivities of up to 98.7% ee obtained in asymmetric hydro-
genations of R-acylamino cinnamic acid derivatives, we
feel that a promising new class of C2-symmetrical phos-
phorus-chiral ligands has been disclosed. Having a range
of diphosphines with differing steric and electronic
properties available, tuning of ligand structures becomes
possible and we expect further successful applications in
other types of hydrogenation reactions.
Ta ble 1. En a n tioselectivities in Hyd r ogen a tion
Rea ction s Usin g in Situ F or m ed [Rh (1a -e)]ClO4
Ca ta lysts
entrya
substrate
ligand L*
% ee (abs config)b
1
2
3
4
5
6
7
8
9
10
11
12
13
8a
8a
8a
8a
8a
8b
8b
8b
8b
8c
8c
8c
8c
(S,S)-1a
(S,S)-1b
(R,R)-1c
(R,R)-1d
(R,R)-1e
(S,S)-1a
(S,S)-1b
(R,R)-1c
(R,R)-1e
(R,R)-1a
(S,S,-1b
(R,R)-1c
(R,R)-1e
98.2 (R)
21.0 (S)
95.4 (S)
c
98.5 (S)
94.8 (R)
11.0 (S)
92.0 (S)
95.5 (S)
97.3 (S)
7.6 (S)
95.1 (S)
98.7 (S)
a
Reactions were conducted at 25 °C using 0.01 mmol of
[Rh(nbd)2]ClO4, 0.011 mmol of ligand, 1 mmol of substrate in 14
b
mL of methanol under an initial H2 pressure of 2 bar. Determi-
nation of ee values was performed by chiral GC analysis (Chirasil-
Val) after conversion of 9a and 9b into the corresponding methyl
esters. Assignments of absolute configurations were made by
comparing signs of optical rotations with those of authentic
samples. c Conversion was found to be <10%; increasing the H2
pressure to 20 bar did not give a significant improvement.
substituents only in the meta position of the aryl moiety,
the steric environment of the active [Rh-1b] complex
resembles the one created by the achiral dppf chelate.
Modeling of the outer coordination sphere of the catalyst
by the far-reaching 2-naphthyl substituent not only has
a deleterious effect on enantiodiscrimination but also
causes inversion of the chirality of the product.
The low reactivity of catalyst systems incorporating
ligand 1d , however, was not anticipated. Tentatively, we
assume that intramolecular coordination23 of one of the
o-phenyl groups of the biphenyl moieties prevents effec-
tive substrate complexation.24
On the contrary, the performance of ligands 1a , 1c,
and 1e and the obtained enantioselectivities as high as
98.7% correspond well to results reported for other
phosphorus-chiral ligands such as Dipamp5b or the
recently introduced tetramethylsilanebis(1-naphthyl-
phenylphosphine)14c (96% and 97.7% ee, respectively, for
the hydrogenation of 8c). The absolute configuration of
the hydrogenation products being opposite to that of the
diphosphine is also in agreement with observations made
employing the two latter mentioned ligands. Apparently,
in the case of the methyl (R-acetamido)cinnamate sub-
strate, a change in the backbone structure from ethylene
or carbosilane bridges to the less flexible ferrocene
influences reactivity and enantiomeric discrimination
only to a small extent. In hydrogenation reactions of free
acids, high enantioselectivities are retained, contrasting
the results observed for Dipamp in analogous experi-
ments.5b By using ligands 1a , 1c, and 1e, reduction of
R-benzamidocinnamic acid 8b afforded the N-benzoylphe-
nylalanine product in up to 95.5% ee, and the acetamido
derivative 8a was hydrogenated with comparatively high
or even higher ee values as obtained for 8c.
Con clu sion s
We have developed a versatile and efficient route for
the preparation of optically active (bis)triarylphosphines
bearing a ferrocene moiety. The synthetic pathway is
characterized by its tolerance toward bulky aryl substit-
uents as well as excellent enantio- and diastereoselec-
tivity. The possibility and necessity of steric tuning was
demonstrated by the synthesis of five phosphorus-chiral
ferrocenyldiphosphines 1a -e and their application in
rhodium-catalyzed asymmetric hydrogenation reactions.
Ligands 1a and 1e, creating sterically pretentious rigid
complexes, or ligand 1c, offering the possibility of hemi-
labile or secondary interaction by means of the methoxy
functionalization, have been identified as valuable tools
for the reduction of cinnamic acid derivatives. The
structural similarity with the well-known Dipamp is also
mirrored in catalysis results, giving ee values of up to
98.7% for N-acylphenylalanine products. The disappoint-
ing performance of ligands 1b and 1d is assumed to
originate from a too low or too high a degree of steric
interaction, respectively, with the substrate during hy-
drogenation reactions.
Extension of this investigation toward electronic varia-
tions of ligand structures and exploration of ligand per-
formance in other asymmetric transformations is cur-
rently under progress and will be reported in due course.
Exp er im en ta l Section
Gen er a l P r oced u r es. Melting points are uncorrected.
NMR spectra were recorded on 250, 300, and 400 MHz
instruments; CDCl3 was used as solvent if not mentioned
For all three substrates tested, the highest asymmetric
inductions were achieved using the bulky 9-phenanthryl-
substituted ligand 1e, followed closely by the structurally
related 1-naphthyl analogue 1a . Creation of very rigid
(25) Knowles, W. S. Acc. Chem. Res. 1983, 16, 106.
(26) Imamoto, T.; Tsuruta, H.; Wada, Y.; Masuda, H.; Yamaguchi,
K. Tetrahedron Lett. 1995, 36, 8271.
(23) Landis, C. R.; Halpern, J . Organometallics 1983, 2, 840.
(24) Landis, C. R.; Halpern, J . J . Am. Chem. Soc. 1987, 109, 1746.
(27) Ramsden, J . A., Claridge, T. D. W., Brown, J . M. J . Chem. Soc.,
Chem. Commun. 1995, 2469 and references therein.

Rhodium-Catalyzed Hydrogenation Reactions
J . Org. Chem., Vol. 64, No. 11, 1999 4001
otherwise. Assignments of 13C-carbon multiplicities were made
by means of spin-echo-Fourier transform (SEFT) and two-
dimensional (1H,13C-COSY) experiments. Phosphorus-carbon
coupling constants (J CP) were identified by comparison of 13C
spectra measured at different magnetic field strengths. Phos-
phorus-boron coupling constants (J PB) were determined be-
tween the central peaks of the nonbinomial quartets. Optical
rotations were measured in a thermostated polarimeter with
l ) 1 dm. Mass spectra were recorded on a J EOL J MS SX/
SX102A four-sector mass spectrometer; 3-nitrobenzyl alcohol
was used as matrix for FAB-MS. Elemental analyses were
obtained using an Elementar Vario EL apparatus. Chiral GC
separations were conducted with a Chirasil-L-Val capillary
column (0.25 mm × 25 m). Chiral HPLC analyses were carried
out using a Daicel Chiralcel-OD column (0.46 × 25 cm).
(br, m, 3H); 1.27 (d, 3H, J ) 6.7 Hz); 1.87 (s, 1H); 2.52 (d, 3H,
J HP ) 7.8 Hz); 4.35 (m, 1H); 4.84 (d, 1H, J ) 6.3 Hz); 7.17-
7.63 (m, 13H), 7.81-7.89 (m, 3H); 8.09 (br, d 1H, J ) 12.2 Hz)
ppm. 13C NMR (100.62 MHz): δ 13.48 (d, CH3, J CP ) 1.1 Hz);
30.57 (d, CH3, J CP ) 3.8 Hz); 58.18 (d, CH, J CP ) 10.3 Hz);
78.74 (d, CH, J CP ) 5.8 Hz); 126.71 (d, CH, J CP ) 3.3 Hz);
126.72 (CH); 127.61 (CH); 127.73 (d, CH, J CP ) 1.8 Hz); 127.73
(CH); 127.88 (d, CH, J CP ) 3.8 Hz); 128.08 (d, CH, J CP ) 9.9
Hz); 128.29 (d, C, J CP ) 60.3 Hz); 128.34 (d, CH, J CP ) 10.4
Hz); 128.55 (CH); 128.78 (CH); 130.65 (d, C, J CP ) 68.1 Hz);
130.71 (d, CH, J CP ) 2.2 Hz); 132.05 (d, CH, J CP ) 9.9 Hz);
132.60 (d, C, J CP ) 11.4 Hz); 133.84 (d, CH, J CP ) 9.9 Hz);
134.31 (d, C, J CP ) 1.9 Hz); 142.45 (C) ppm. 31P NMR (121.50
MHz): δ 71.40 (br, q, J PB ) 82 Hz) ppm. [R]20 ) +61.1 (c )
D
0.524; CH2Cl2). HRMS (FAB+): m/z calcd for C26H27NOP
([MH]+ - BH3) 400.1830, obsd 400.1827. Anal. Calcd for
Ma ter ia ls. If not otherwise stated, reactions were per-
formed under argon atmosphere using standard Schlenk
techniques. THF and diethyl ether were distilled from sodium
benzophenone ketyl, CH2Cl2 and acetonitrile were distilled
from CaH2, and toluene and methanol were distilled from
sodium wire under nitrogen. Except for the compounds given
below, all reagents were purchased from commercial suppliers
and used without further purification. Diethylamine was
distilled from KOH under argon. 2-Bromoanisole and 1-bro-
monaphthalene were distilled prior to use. 1,1′-dilithiofer-
rocene was synthesized following a procedure given by Bishop
et al.28 (2SP,4R,5S)-(-)-3,4-Dimethyl-2,5-diphenyl-1,3,2-oxaza-
phospholidine borane 2 and its enantiomer were prepared
according to the method of J uge´ et al.12
Syn th esis of P h osp h in a m id es 4a -e (Typ ica l P r oce-
d u r e). A degassed 0.5 M solution of the aryl bromide RBr (with
R ) 1-naphthyl, 2-naphthyl, 2-methoxyphenyl, 2-biphenylyl,
or 9-phenanthryl) (11.5 mmol) in diethyl ether was cooled to
-78 °C and n-butyllithium (12 mmol) was added via syringe.
The reaction mixture was kept at this temperature for 2 h and
then warmed to -20 °C to ensure complete lithiation. The
resulting aryllithium suspension 3 was added slowly via Teflon
cannula to a precooled (-78 °C) 1 M solution of oxazaphos-
pholidine borane 2 (10 mmol) in THF. The reaction mixture
was warmed to room temperature over a period of 15 h and
then quenched with water. Solvent was evaporated, and the
residue was extracted with CH2Cl2, washed with water, and
dried (MgSO4). After removal of the solvent in vacuo, the crude
product was subjected to column chromatography (SiO2,
toluene/ethyl acetate ) 95:5) to give diastereomerically pure
amides 4 as white, slightly air-sensitive crystals.
C
26H29BNOP: C, 75.55; H, 7.08; N, 3.39. Found: C, 75.68; H,
7.01; N, 3.32.
(SP ,1R,2S)-(+)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -
2-yl-P -(2-m eth oxyp h en yl)-P -(p h en yl)p h osp h in a m id e bo-
1
r a n e, 4c. Yield: 93%. Mp: 115 °C. H NMR (400.13 MHz): δ
0.51-1.73 (br, m, 3H); 1.22 (d, 3H, J ) 6.7 Hz); 2.03 (d, 1H, J
) 4.1 Hz); 2.54 (d, 3H, J HP ) 8.0 Hz); 3.56 (s, 3H); 4.33 (m,
1H); 4.87 (d, 1H, J ) 5.6 Hz); 6.90 (br, dd, 1H, J ) 4.1, 8.3
Hz); 7.01 (m, 1H); 7.17-7.40 (m, 8H); 7.42-7.51 (m, 3H); 7.58
(ddd, 1H, J ) 1.7, 7.6, 12.7 Hz) ppm. 13C NMR (100.61 MHz):
δ 12.50 (br, CH3); 30.90 (d, CH3, J CP ) 3.8 Hz); 55.00 (CH3);
58.06 (d, CH, J CP ) 10.7 Hz); 78.77 (d, CH, J CP ) 5.5 Hz);
111.51 (d, CH, J CP ) 4.6 Hz); 118.60 (d, C, J CP ) 57.2 Hz);
120.78 (d, CH, J CP ) 10.6 Hz); 126.52 (CH); 127.51 (CH);
127.87 (d, CH, J CP ) 10.7 Hz); 128.28 (CH); 129.85 (d, CH,
J CP ) 2.2 Hz); 130.84 (d, CH, J CP ) 10.4 Hz); 132.23 (d, C, J CP
) 71.1 Hz); 133.20 (d, CH, J CP ) 1.6 Hz); 134.90 (d, CH, J CP
) 10.8 Hz); 142.56 (C); 161.06 (d, C, J CP ) 2.5 Hz) ppm. 31P
NMR (121.50 MHz): δ 69.18 (br, q, J PB ) 71 Hz) ppm. [R]20
D
) +38.1 (c ) 0.360; CH2Cl2). HRMS (FAB+): m/z calcd for
C
23H30BNO2P ([MH]+) 394.2107, obsd 394.2112. Anal. Calcd
for C23H29BNO2P: C, 70.24; H, 7.44; N, 3.56. Found: C, 70.04;
H, 7.22; N, 3.48.
(SP ,1R,2S)-(+)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -
2-yl-P -(2-bip h en ylyl)-P -(p h en yl)p h osp h in a m id e bor a n e,
1
4d . Yield: 85%. Mp: 100-101 °C. H NMR (400.13 MHz): δ
0.55-1.65 (br, m, 3H); 0.71 (d, 3H, J ) 6.9 Hz); 2.38 (s, 1H);
2.59 (d, 3H, J HP ) 7.2 Hz); 3.97 (m, 1H); 4.88 (d, 1H, J ) 2.8
Hz); 7.16-7.52 (m, 17H); 7.67-7.75 (m, 2H) ppm. 13C NMR
(100.58 MHz): δ 9.87 (d, CH3, J CP ) 6.9 Hz); 31.72 (d, CH3,
J CP ) 3.8 Hz); 58.04 (d, CH, J CP ) 10.7 Hz); 78.78 (CH); 125.62
(CH); 126.75 (d, CH, J CP ) 9.9 Hz); 127.11 (CH); 127.32 (d,
CH; J CP ) 4.6 Hz); 127.34 (CH); 128.10 (CH); 128.10 (d, CH,
J CP ) 9.9 Hz); 128.81 (d, C, J CP ) 66.6 Hz); 129.64 (CH); 130.46
(d, CH, J CP ) 2.3 Hz); 130.51 (d, CH, J CP ) 2.3 Hz); 132.18 (d,
CH, J CP ) 9.9 Hz); 132.67 (d, CH, J CP ) 8.4 Hz); 133.39 (d, C,
J CP ) 58.1 Hz); 134.08 (d, CH, J CP ) 9.9 Hz); 141.35 (d, C, J CP
) 3.1 Hz); 142.47 (C); 147.37 (d, C, J CP ) 9.9 Hz) ppm. 31P
(SP ,1R,2S)-(+)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -
2-yl-P -(1-n aph th yl)-P -(ph en yl)ph osph in am ide bor an e, 4a.
Yield: 94%. Mp: 113 °C. 1H NMR (400.13 MHz): δ 0.72-2.00
(br, m, 3H); 1.32 (d, 3H, J ) 7.0 Hz); 1.83 (d, 1H, J ) 4.0 Hz);
2.66 (d, 3H, J HP ) 7.5 Hz); 4.47 (m, 1H); 5.00 (br, t, 1H, J )
4.0 Hz); 7.22-7.54 (m, 12H); 7.56-7.63 (m, 2H); 7.85 (br, d,
1H, J ) 8.0 Hz); 7.94 (br, d, 1H, J ) 8.0 Hz); 8.23 (br, d, 1H,
J ) 8.5 Hz) ppm.13C NMR (100.58 MHz): δ 11.55 (d, CH3, J CP
NMR (121.50 MHz): δ 70.95 (br, q, J PB ) 64 Hz) ppm. [R]20
D
) 3.8 Hz); 31.48 (d, CH3, J CP ) 3.1 Hz); 58.13 (d, CH, J CP
)
) +64.9 (c ) 0.297; CH2Cl2). HRMS (FAB+): m/z calcd for
9.9 Hz); 79.18 (d, CH, J CP ) 2.9 Hz); 124.62 (d, CH, J CP ) 10.7
Hz); 126.05 (CH); 126.22 (CH); 126.32 (CH); 127.10 (d, C, J CP
) 61.2 Hz); 127.27 (d, CH, J CP ) 6.1 Hz); 127.50 (CH); 128.36
(CH); 128.49 (d, CH, J CP ) 9.9 Hz); 128.85 (d, CH, J CP ) 1.4
Hz); 130.89 (d, CH, J CP ) 2.3 Hz); 132.22 (d, CH, J CP ) 9.9
Hz); 132.38 (d, CH, J CP ) 2.3 Hz); 132.38 (d, C, J CP ) 62.0
Hz); 132.74 (d, CH, J CP ) 7.6 Hz); 133.39 (d, C, J CP ) 11.1
Hz); 134.06 (d, C, J CP ) 8.4 Hz); 142.54 (C) ppm. 31P NMR
(121.50 MHz): δ 71.42 (br, q, J PB ) 75 Hz) ppm. [R]20D ) +97.8
(c ) 0.680; CH2Cl2). HRMS (FAB+): m/z calcd for C26H27NOP
([MH]+ - BH3) 400.1830, obsd 400.1827. Anal. Calcd for
C
28H29NOP ([MH]+ - BH3) 426.1987, obsd 426.1958. Anal.
Calcd for C28H31BNOP: C, 76.54; H, 7.12; N, 3.19. Found: C,
76.80; H, 7.22; N, 3.06.
(RP ,1S,2R)-(-)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -
2-yl-P -(9-p h en a n t h r yl)-P -(p h en yl)p h osp h in a m id e b o-
1
r a n e, 4e. Yield: 86%. Mp: 135 °C. H NMR (400.13 MHz): δ
0.83-2.01 (br, m, 3H); 1.36 (d, 3H, J ) 6.9 Hz); 2.36 (s, 1H),
2.70 (d, 3H, J HP ) 7.4 Hz); 4.54 (m, 1H); 5.06 (d, 1H, J ) 3.9
Hz); 7.13-7.86 (m, 16H); 8.37 (d, 1H, J ) 8.3 Hz); 8.67 (d, 1H,
J ) 8.3 Hz); 8.72 (d, 1H, J ) 8.4 Hz) ppm. 13C NMR (100.58
MHz): δ 11.48 (d, CH3, J CP ) 4.2 Hz); 31.47 (d, CH3, J CP
)
C
26H29BNOP: C, 75.55; H, 7.08; N, 3.39. Found: C, 75.74; H,
3.2 Hz); 58.11 (d, CH, J CP ) 10.4 Hz); 79.13 (d, CH, J CP ) 2.3
Hz); 122.51 (CH); 122.97 (CH); 125.99 (d, C, J CP ) 60.3 Hz);
126.00 (CH); 126.33 (CH); 126.91 (CH); 127.43 (CH); 128.19
(d, CH, J CP ) 7.2 Hz); 128.29 (CH); 128.41 (d, CH, J CP ) 24.4
Hz); 128.52 (d, CH, J CP ) 16.6 Hz); 128.97 (CH); 129.56 (CH);
130.19 (d, C, J CP ) 11.0 Hz); 130.79 (d, C, J CP ) 7.4 Hz); 130.83
(d, C, J CP ) 11.3 Hz); 130.94 (d, CH, J CP ) 1.9 Hz); 131.75 (d,
C, J CP ) 1.8 Hz); 132.18 (d, C, J CP ) 62.4 Hz); 132.29 (d, CH,
7.15; N, 3.26.
(SP ,1R,2S)-(+)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -
2-yl-P -(2-n aph th yl)-P -(ph en yl)ph osph in am ide bor an e, 4b.
Yield: 89%. Mp: 133 °C. 1H NMR (400.13 MHz): δ 0.69-1.77
(28) Bishop, J . J .; Davison, A.; Katcher, M. L.; Lichtenberg, D. W.;
Merrill, R. E.; Smart, J . C. J . Organomet. Chem. 1971, 27, 241.

4002 J . Org. Chem., Vol. 64, No. 11, 1999
Nettekoven et al.
J CP ) 10.0 Hz); 135.52 (d, CH, J CP ) 7.2 Hz); 142.28 (C) ppm.
31P NMR (121.50 MHz): δ 72.50 (br, q, J PB ) 50 Hz) ppm.
[R]20D ) -101.0 (c ) 0.243; CH2Cl2). HRMS (FAB+): m/z calcd
for C30H29NOP ([MH]+ - BH3) 450.1987, obsd 450.1971. Anal.
Calcd for C30H31BNOP: C, 77.76; H, 6.75; N, 3.02. Found: C,
77.40; H, 6.98; N, 2.78.
Syn th esis of P h osp h in ite Bor a n es 5a -e (Typ ica l P r o-
ced u r e). The phosphinamide borane 4 (11.5 mmol) was
dissolved in 100 mL of methanol, degassed, and cooled in an
ice bath. Concentrated sulfuric acid (11.5 mmol) was added
dropwise, and the solution was stirred for 20 h at room
temperature. After removal of solvent, the residue was purified
by column chromatography (SiO2; hexane/ethyl acetate ) 95:
5). Phosphinites 5a -e were obtained as white crystalline
products that proved to be largely air-stable. The enantiomeric
composition was determined by chiral HPLC and found to be
>98% ee. Eventually, recrystallization from hexane yielded
enantiopure products.
(S)-(+)-Meth yl (2-Bip h en ylyl)p h en ylp h osp h in ite Bo-
r a n e, 5d . Yield: 87%. Enantiomeric purity: 98.1% ee.
HPLC: Chiralcel OD, hexane/2-propanol ) 99.5:0.5, tR [(S)-
5c] ) 13.0 min, tR [(R)-5c] ) 14.5 min. Recrystallization from
hexane yielded enantiopure product. Mp: 120 °C. 1H NMR
(400.14 MHz): δ 0.32-1.50 (br, m, 3H); 3.57 (d, 3H, J HP
)
10.6 Hz); 6.89-6.94 (m, 2H); 7.08-7.14 (m, 2H); 7.18-7.26 (m,
4H); 7.29-7.39 (m, 3H); 7.47-7.57 (m, 2H); 8.06 (ddd, 1H, J
) 1.6, 7.5, 12.6 Hz) ppm. 13C NMR (100.62 MHz): δ 53.43 (d,
CH3, J CP ) 1.1 Hz); 126.84 (d, CH, J CP ) 11.3 Hz); 126.97 (CH);
127.00 (d, CH, J CP ) 5.1 Hz); 127.86 (d, CH, J CP ) 10.8 Hz);
129.37 (CH); 130.04 (d, C, J CP ) 59.9 Hz); 130.72 (d, CH, J CP
) 11.4 Hz); 130.88 (d, CH, J CP ) 2.3 Hz); 131.32 (d, CH, J CP
) 2.0 Hz); 131.47 (d, CH, J CP ) 7.7 Hz); 132.08 (d, C, J CP
64.8 Hz); 133.32 (d, CH, J CP ) 14.9 Hz); 140.17 (d, C; J CP
)
)
3.2 Hz); 146.47 (d, C, J CP ) 7.4 Hz) ppm. 31P NMR (121.50
MHz): δ 109.78 (br, q, J PB ) 83 Hz) ppm. [R]20 ) + 17.4 (c )
D
0.945, CH2Cl2). HRMS (FAB+): m/z calcd for C19H18OP ([MH]+
- BH3) 293.1095, obsd 293.1114. Anal. Calcd for C19H20BOP:
C, 74.54; H, 6.59. Found: C, 74.50; H 6.60.
(S)-(+)-Met h yl (1-Na p h t h yl)p h en ylp h osp h in it e Bo-
r a n e, 5a . Yield: 84%. Enantiomeric purity: >99.5% ee.
HPLC: Chiralcel OD, heptane/2-propanol ) 99.5:0.5, tR [(R)-
5a ] ) 20.9 min, tR [(S)-5a ] ) 22.3 min. Mp: 82-83 °C. 1H NMR
(S)-(-)-Meth yl (9-P h en a n th r yl)p h en ylp h osp h in ite Bo-
r a n e, 5e. Yield: 64%. Enantiomeric purity: >99.5% ee.
HPLC: Chiralcel OD, hexane/2-propanol ) 98:2, tR [(R)-5e] )
26.1 min, tR [(S)-5e] ) 29.6 min. Mp: 140 °C. 1H NMR (400.13
MHz): δ 0.60-1.75 (br, m, 3H); 3.81 (d, 3H, J HP ) 12.2 Hz);
7.34-7.49 (m, 4H); 7.61 (ddd, 1H, J ) 1.1, 7.1, 8.2 Hz); 7.65-
7.71 (m, 3H); 7.78 (ddd, 1H, J ) 1.3, 7.0, 8.3 Hz); 8.05 (dd,
1H, J ) 1.0, 7.7 Hz); 8.14 (br, d, 1H, J ) 8.3 Hz); 8.62-8.75
(400.14 MHz): δ 0.49-1.76 (br, m, 3H); 3.74 (d, 3H, J HP
)
12.2 Hz); 7.32-7.50 (m, 5H); 7.52-7.68 (m, 3H); 7.86 (br, d,
1H, J ) 8.1 Hz); 8.03 (br, d, 1H, J ) 8.3 Hz); 8.11 (br, d, 1H,
J ) 8.5 Hz); 8.25 (ddd, 1H, J ) 0.9, 7.2, 15.0 Hz) ppm. 13C
NMR (100.62 MHz): δ 53.98 (d, CH3, J CP ) 1.9 Hz); 124.73
(d, CH, J CP ) 13.7 Hz); 126.30 (CH); 126.32 (d, CH, J CP ) 5.1
Hz); 126.57 (d, C, J CP ) 55.1 Hz); 127.10 (CH); 128.57 (d, CH,
J CP ) 10.6 Hz); 129.06 (d, CH, J CP ) 0.9 Hz); 130.87 (d, CH,
J CP ) 11.1 Hz); 131.58 (d, CH, J CP ) 2.2 Hz); 132.20 (d, C, J CP
(m, 3H) ppm. 13C NMR (100.58 MHz): δ 54.04 (d, CH3, J CP
)
1.9 Hz); 122.58 (CH); 123.22 (CH); 125.20 (d, C, J CP ) 53.3
Hz); 126.95 (d, CH, J CP ) 7.4 Hz); 127.26 (CH); 127.34 (d, CH,
J CP ) 4.7 Hz); 128.61 (d, CH, J CP ) 10.6 Hz); 129.35 (CH);
129.91 (d, C, J CP ) 4.3 Hz); 130.04 (d, C, J CP ) 14.6 Hz); 130.22
(CH); 130.68 (d, C, J CP ) 6.7 Hz); 130.69 (CH); 130.80 (CH);
131.55 (d, CH, J CP ) 2.2 Hz); 132.10 (d, C, J CP ) 68.5 Hz);
132.32 (d, C, J CP ) 1.9 Hz); 138.91 (d, CH, J CP ) 18.1 Hz) ppm.
31P NMR (121.50 MHz): δ 111.53 (br, q, J PB ) 84 Hz) ppm.
) 67.5 Hz); 132.63 (d, C, J CP ) 5.1 Hz); 133.71 (d, CH, J CP
)
2.4 Hz); 133.74 (d, C, J CP ) 6.8 Hz); 135.24 (d, CH, J CP ) 17.2
Hz) ppm. 31P NMR (121.50 MHz): δ 111.50 (br, q, J PB ) 81
Hz) ppm. [R]20 ) +14.9 (c ) 0.808, CH2Cl2). HRMS (FAB+):
D
m/z calcd for C17H16OP ([MH]+ - BH3) 267.0939, obsd 267.0945.
Anal. Calcd for C17H18BOP: C, 72.89; H, 6.48. Found: C, 73.11;
H, 6.48.
[R]20 ) -78.1 (c ) 0.702, CH2Cl2). HRMS (FAB+): m/z calcd
D
for C21H18OP ([MH]+ - BH3) 317.1095, obsd 317.1081. Anal.
Calcd for C21H20BOP: C, 76.39; H, 6.11. Found: C, 76.53; H,
6.12.
(R)-(+)-Met h yl (2-Na p h t h yl)p h en ylp h osp h in it e Bo-
r a n e, 5b. Yield: 94%. Enantiomeric purity: >99.5% ee.
HPLC: Chiralcel OD, hexane/2-propanol ) 99.5:0.5, tR [(R)-
5b] ) 17.6 min, tR [(S)-5b] ) 19.2 min. Mp: 85-86 °C. 1H NMR
Syn th esis of F er r ocen yld ip h osp h in es 1a -e (Typ ica l
P r oced u r e). The respective phosphinite 5 (10 mmol) was
dissolved in 10 mL of THF, degassed, and cooled to -40 °C. A
suspension of 1,1′-dilithioferrocene (5 mmol) in 40 mL of
diethyl ether and 5 mL of THF was cooled and slowly added
to the phosphinite solution via Teflon cannula. The reaction
mixture was allowed to reach room temperature over a period
of 15 h and was then quenched with water. After evaporation
of solvent, the residue was extracted with CH2Cl2. The
combined organic layers were washed with water, dried
(MgSO4), and concentrated. The crude borane complex 6 was
suspended in 50 mL of diethylamine, degassed, and stirred at
50 °C for 5 h. After treatment, the solvent was evacuated and
the product diphosphine was purified by column chromatog-
raphy (SiO2; hexane/CH2Cl2 ) 3:1 for 1a -d ; hexane/CH2Cl2
) 2:1 for 1e). Minor amounts of monophosphine byproduct
were eluted first, followed by diphosphines 1a -e, which were
obtained as yellow to orange crystals. Recrystallization from
CH2Cl2/hexane afforded analytically pure products.
(400.14 MHz): δ 0.53-1.68 (br, m, 3H); 3.77 (d, 3H, J HP
)
12.1 Hz); 7.42-7.60 (m, 5H); 7.66 (dt, 1H, J ) 1.5, 8.7 Hz);
7.73-7.79 (m, 2H); 7.83-7.93 (m, 3H); 8.36 (br, d, 1H, J )
12.7 Hz) ppm. 13C NMR (100.58 MHz): δ 54.12 (d, CH3, J CP
)
1.8 Hz); 125.92 (d, CH, J CP ) 9.7 Hz); 126.94 (CH); 127.82
(CH); 128.25 (CH); 128.55 (d, CH, J CP ) 9.8 Hz); 128.67 (d,
CH, J CP ) 10.5 Hz); 128.69 (d, C, J CP ) 63.0 Hz); 128.92 (CH);
131.26 (d, CH, J CP ) 11.3 Hz); 131.76 (d, C, J CP ) 64.7 Hz);
131.90 (d, CH, J CP ) 2.3 Hz); 132.52 (d, C, J CP ) 12.3 Hz);
133.42 (d, CH, J CP ) 13.3 Hz); 134.74 (d, C, J CP ) 2.1 Hz) ppm.
31P NMR (161.98 MHz): δ 108.84 (br, q, J PB ) 68 Hz) ppm.
[R]20 ) +44.9 (c ) 1.29; CH2Cl2). HRMS (FAB+): m/z calcd
D
for C17H16OP ([MH]+ - BH3) 267.0939, obsd 267.0951. Anal.
Calcd for C17H18BOP: C, 72.89; H, 6.48. Found: C, 72.80; H,
6.49.
(S)-(+)-Meth yl (2-Meth oxyp h en yl)p h en ylp h osp h in ite
Bor a n e, 5c. Yield: 85%. Enantiomeric purity: 99.3% ee.
HPLC: Chiralcel OD, hexane/2-propanol ) 99.5:0.5, tR [(R)-
(R,R)-(-)-1,1′-Bis(1-n a p h t h ylp h en ylp h osp h in o)fer r o-
1
1
5c] ) 20.7 min, tR [(S)-5c] ) 21.8 min. Oil. H NMR (400.14
cen e, 1a . Yield: 74%. Mp: 176 °C. H NMR (400.13 MHz): δ
MHz): δ 0.61-1.60 (br, m, 3H); 3.58 (s, 3H); 3.71 (d, 3H, J HP
) 12.1 Hz); 6.84 (dd, 1H, J ) 4.3, 8.3 Hz); 7.06 (dt, 1H, J )
1.8, 7.4 Hz); 7.36-7.50 (m, 4H); 7.69-7.84 (m, 3H) ppm. 13C
NMR (100.61 MHz): δ 53.80 (d, CH3, J CP ) 3.6 Hz); 55.45
(CH3), 111.65 (d, CH, J CP ) 4.9 Hz); 119.16 (d, C, J CP ) 61.6
Hz); 120.75 (d, CH, J CP ) 11.0 Hz); 128.07 (d, CH, J CP ) 10.8
Hz); 131.01 (d, CH, J CP ) 11.5 Hz); 131.29 (d, CH, J CP ) 2.1
Hz); 131.97 (d, C, J CP ) 65.8 Hz); 133.80 (d, CH, J CP ) 11.1
Hz); 134.16 (br, CH); 160.95 (d, C, J CP ) 3.1 Hz) ppm. 31P NMR
3.70 (m, 2H); 4.25 (m, 2H); 4.32 (m, 2H); 4.36 (m, 2H); 7.11-
7.16 (m, 2H); 7.19-7.28 (m, 6H); 7.30-7.43 (m, 10H); 7.75-
7.81 (m, 4H); 8.33-8.37 (m, 2H) ppm. 13C NMR (100.61
MHz): δ 72.47 (br, CH); 72.95 (d, CH, J CP ) 6.9 Hz); 73.06 (d,
CH, J CP ) 3.0 Hz); 75.25 (d, CH, J CP ) 25.9 Hz); 76.50 (d, C,
J CP ) 5.3 Hz); 125.22 (d, CH, J CP ) 1.5 Hz); 125.73 (br, CH);
125.94 (d, CH, J CP ) 2.3 Hz); 126.02 (d, CH, J CP ) 25.9 Hz);
128.13 (d, CH, J CP ) 7.6 Hz); 128.50 (br, CH); 128.81 (CH);
129.09 (CH); 131.41 (br, CH); 133.33 (d, C, J CP ) 4.6 Hz);
133.83 (d, CH, J CP ) 20.6 Hz); 134.71 (d, C, J CP ) 21.4 Hz);
136.68 (d, C, J CP ) 14.5 Hz); 137.10 (d, C, J CP ) 8.4 Hz) ppm.
(121.50 MHz): δ 106.96 (br, q, J PB ) 80 Hz) ppm. [R]20
)
D
+26.2 (c ) 0.565; CH2Cl2). HRMS (FAB+): m/z calcd for C14H19
BO2P ([MH+]) 261.1216, obsd 261.1206. Anal. Calcd for C14H18
BO2P: C, 64.65; H, 6.98. Found: C, 64.45; H, 6.91.
-
-
31P NMR (161.98 MHz): δ -30.39 (s) ppm. [R]20 ) -197.2 (c
D
) 0.251; CHCl3). HRMS (EI+): m/z calcd for C42H32FeP2

Rhodium-Catalyzed Hydrogenation Reactions
J . Org. Chem., Vol. 64, No. 11, 1999 4003
654.1329, obsd 654.1342. Anal. Calcd for C42H32FeP2: C, 77.07;
H, 4.93. Found: C, 76.98; H, 5.02.
0.649 Å-1. The structures were solved with the program
DIRDIF-9729 and refined by a full-matrix least-squares refine-
ment against F2 with the program SHELXL-97.30 For confir-
mation of the absolute structure the Flack x parameter was
included in the refinement.19 Hydrogen atoms were introduced
in calculated positions and refined as rigid groups. Structure
graphics and checking for higher symmetry were performed
with the program PLATON.31
(R,R)-(-)-1,1′-Bis(1-n a p h t h ylp h en ylp h osp h in o)fer r o-
cen e, 1a : C42H32FeP2, Mr ) 654.47, orthorhombic, P212121 (No.
19), a ) 9.4685(19) Å, b ) 13.6848(19) Å, c ) 24.721(4) Å, V )
3203.2(9) Å3, Z ) 4, Fcalcd ) 1.357 g/cm3. Red-brown plate, 0.45
× 0.32 × 0.18 mm3. Absorption correction with DE-LABS
(PLATON, 0.77-0.90 transmission). 4612 measured reflec-
tions, 4476 unique reflections, 407 parameters. R1(F) [I > 2σI]
) 0.0665, wR2(F2) [all data] ) 0.2008.
(S,S)-(-)-1,1′-Bis(2-n a p h t h ylp h en ylp h osp h in o)fer r o-
1
cen e, 1b. Yield: 78%. Mp: 87 °C. H NMR (400.13 MHz): δ
4.04 (m, 4H); 4.28 (m, 4H); 7.23-7.35 (m, 12H); 7.41-7.49 (m,
4H); 7.63 (br, d, 2H, J ) 8.4 Hz); 7.70-7.83 (m, 6H) ppm. 13C
NMR (100.61 MHz): δ 72.51 (m, 2CH); 73.77 (d, CH, J CP
)
3.0 Hz); 73.91 (d, CH, J CP ) 3.8 Hz); 76.58 (d, C, J CP ) 7.6
Hz); 126.16 (CH); 126.49 (CH); 127.49 (d, CH, J CP ) 6.1 Hz);
127.67 (CH); 128.04 (CH); 128.15 (d, CH, J CP ) 6.9 Hz); 128.53
(CH); 129.81 (d, CH, J CP ) 16.0 Hz); 133.00 (d, C, J CP ) 8.4
Hz); 133.20 (C); 133.44 (d, CH, J CP ) 19.0 Hz); 133.64 (d, CH,
J CP ) 23.0 Hz); 136.27 (d, C, J CP ) 9.9 Hz); 138.70 (d, C, J CP
) 9.9 Hz) ppm. 31P NMR (161.98 MHz): δ -17.77 (s) ppm.
[R]20 ) -15.3 (c ) 0.261; CHCl3). HRMS (EI+): m/z calcd for
D
C
42H32FeP2 654.1329, obsd 654.1298. Anal. Calcd for C42H32-
FeP2: C, 77.07; H, 4.93. Found: C, 76.91; H, 5.30.
(S,S)-(-)-1,1′-Bis(2-n a p h t h ylp h en ylp h osp h in o)fer r o-
cen e, 1b: C42H32FeP2‚CH2Cl2, Mr ) 739.45, monoclinic, P21
(No. 4), a ) 8.8921(5) Å, b ) 21.0173(12) Å, c ) 9.6078(12) Å,
â ) 90.724(4)°, V ) 1795.4(3) Å3, Z ) 2, Fcalcd ) 1.368 g/cm3.
Orange block, 0.5 × 0.5 × 0.5 mm3. No absorption correction
considered necessary. The electron density contribution of the
disordered solvent molecules was added to the calculated F2
values via back-Fourier transformation. This calculation was
performed with the routine CALC SQEEZE as implemented
in the PLATON package. The diffuse electron density corre-
sponds to one crystallographic independent CH2Cl2 molecule.
4719 measured reflections, 4209 unique reflections, 407 pa-
rameters. R1(F) [I > 2σI] ) 0.0473, wR2(F2) [all data] ) 0.1250.
(R,R)-(-)-1,1′-Bis(2-b ip h en ylylp h en ylp h osp h in o)fer -
r ocen e, 1d : C46H36FeP2, Mr ) 706.54, monoclinic, P21 (No.
4), a ) 9.2755(8) Å, b ) 14.0054(11) Å, c ) 27.6627(13) Å, â )
96.275(6)°, V ) 3572.1(4) Å3, Z ) 4, Fcalcd ) 1.314 g/cm3. Orange
block, 0.5 × 0.5 × 0.5 mm3. No absorption correction considered
necessary. 10102 measured reflections, 8491 unique reflec-
tions, 884 parameters. R1(F) [I > 2σI] ) 0.0362, wR2(F2) [all
data] ) 0.0825.
Asym m etr ic Hyd r ogen a tion Rea ction s (Typ ica l P r o-
ced u r e). A solution of [Rh(nbd)2]ClO4 (0.01 mmol) and ligand
(0.011 mmol) in 10 mL of absolute methanol was degassed by
three freeze-thaw cycles and stirred for 30 min at room
temperature. It was then transferred via cannula in a 70 mL
glass autoclave, followed by a degassed solution of substrate
(1 mmol) in 4 mL of methanol. The argon atmosphere was
replaced by hydrogen, initial pressure was set to 2.0 bar, and
the reaction mixture was stirred for 6 h at 25 °C. Conversion
was checked by NMR measurement of the crude product.
Compound 9c was filtered over a plug of silica to remove the
catalyst, while products 9a and 9b were subjected to extractive
workup and subsequently transformed into their methylest-
ers.32 Enantiomeric purities were determined by chiral GC
(Chiralsil-L-Val, isothermal, T ) 150 °C for N-acetylphenyla-
lanine methylester, tR (R) ) 13.0 min, tR (S) ) 14.8 min; T )
180 °C for N-benzoylphenylalanine methylester, tR (R) ) 28.2
min, tR (S) ) 30.3 min).
(R,R)-(-)-1,1′-Bis[(2-m eth oxyph en yl)ph en ylph osph in o]-
fer r ocen e, 1c. Yield: 73%. Mp: 153 °C. 1H NMR (400.13
MHz): δ 3.57 (m, 2H); 3.65 (s, 6H); 4.21 (m, 2H); 4.26 (m, 2H);
4.37 (m, 2H); 6.77 (dd, 2H, J ) 4.8, 8.3 Hz); 6.80-6.83 (m,
4H); 7.20-7.28 (m, 8H); 7.31-7.36 (m, 4H) ppm. 13C NMR
(100.61 MHz): δ 55.58 (CH3); 72.48 (br, CH); 72.68 (d, CH,
J CP ) 3.1 Hz); 72.84 (br, d, CH, J CP ) 6.9 Hz); 75.00 (d, CH,
J CP ) 26.0 Hz); 76.39 (d, C, J CP ) 6.1 Hz); 110.23 (CH); 120.67
(CH); 127.81 (d, CH, J CP ) 7.6 Hz); 127.97 (d, C, J CP ) 12.2
Hz); 128.46 (CH); 129.93 (CH); 133.50 (CH); 133.54 (d, CH,
J CP ) 19.9 Hz); 137.67 (d, C, J CP ) 8.4 Hz); 160.67 (d, C, J CP
) 15.3 Hz) ppm. 31P NMR (121.50 MHz): δ -29.19 (s) ppm.
[R]20 ) -198.9 (c ) 0.272; CHCl3). HRMS (EI+): m/z calcd
D
for C36H32FeO2P2 614.1227, obsd 614.1239. Anal. Calcd for
C
36H32FeO2P2: C, 70.37; H, 5.25. Found: C, 70.63; H, 5.60.
(R,R)-(-)-1,1′-Bis(2-b ip h en ylylp h en ylp h osp h in o)fer -
r ocen e, 1d . Separation of meso-(R,S)-diphosphine diborane
was achieved by column chromatography (SiO2; hexane/CH2-
Cl2 ) 3:2), followed by recrystallization of the (R,R)-diphos-
phine diborane complex from CH2Cl2/hexane. The thus-
obtained product was subjected to decomplexation as described
above. Yield: 81%. Mp: 160 °C. 1H NMR (400.13 MHz): δ 3.43
(m, 2H); 4.01 (m, 2H); 4.28 (m, 4H); 7.03-7.10 (m, 6H); 7.15-
7.38 (m, 22H) ppm. 13C NMR (100.61 MHz): δ 72.27 (d, CH,
J CP ) 1.4 Hz); 72.50 (d, CH, J CP ) 1.8 Hz); 72.89 (dd, CH, J CP
) 1.8, 7.2 Hz); 75.84 (d, CH, J CP ) 32.2 Hz); 76.95 (d, C, J CP
) 8.5 Hz); 126.80 (d, CH, J CP ) 1.5 Hz); 127.49 (2CH); 127.71
(d, CH, J CP ) 8.3 Hz); 127.97 (CH); 128.45 (br, CH); 129.54
(d, CH, J CP ) 3.8 Hz); 129.75 (d, CH, J CP ) 3.8 Hz); 132.51
(br, CH); 134.16 (d, CH, J CP ) 20.7 Hz); 137.71 (d, C, J CP
)
7.8 Hz); 138.77 (d, C, J CP ) 14.7 Hz); 141.66 (d, C, J CP ) 5.1
Hz); 146.60 (d, C, J CP ) 24.3 Hz) ppm. 31P NMR (121.50
MHz): δ -22.52 (s) ppm. [R]20 ) -208.9 (c ) 0.257; CHCl3).
D
HRMS (EI+): m/z calcd for C46H36FeP2 706.1642, obsd 706.1639.
Anal. Calcd for C46H36FeP2: C, 78.19; H, 5.14. Found: C, 77.95;
H, 5.15.
(R,R)-(-)-1,1′-Bis(9-p h en a n th r ylp h en ylp h osp h in o)fer -
r ocen e, 1e. Yield: 72%. Mp: 252-253 °C dec. 1H NMR
(400.13 MHz): δ 3.67 (m, 2H); 4.32 (m, 2H); 4.46 (m, 4H);
7.17-7.30 (m, 6H); 7.37 (d, 2H, J ) 5.0 Hz); 7.40-7.69 (m,
14H); 8.33 (ddd, 2H, J ) 1.0, 4.5, 8.0 Hz); 8.59-8.66 (m, 4H)
ppm.13C NMR (100.62 MHz, CD2Cl2): δ 72.99 (CH); 73.15
(CH); 73.39 (d, CH, J CP ) 8.0 Hz); 76.36 (d, C, J CP ) 5.6 Hz);
76.45 (d, CH, J CP ) 30.8 Hz); 122.73 (CH); 123.26 (CH); 126.67
(d, CH, J CP ) 3.0 Hz); 126.71 (CH); 126.99 (d, CH, J CP ) 26.2
Hz); 127.00 (CH); 127.35 (CH); 128.54 (d, CH, J CP ) 7.9 Hz);
129.05 (CH); 129.47 (CH); 130.40 (d, C, J CP ) 4.1 Hz); 130.83
(C); 131.60 (d, CH, J CP ) 2.1 Hz); 132.92 (CH); 133.15 (C);
134.44 (d, CH, J CP ) 20.7 Hz); 136.18 (d, C, J CP ) 15.4 Hz);
136.69 (d, C, J CP ) 7.5 Hz) ppm. 31P NMR (121.50 MHz,
Ack n ow led gm en t. We are indebted to Mrs. Lilian
Blijlevens and Dr. J . G. de Vries (DSM Research N.V.,
Geleen, The Netherlands) for cooperation concerning
chiral GC analysis of hydrogenation products. Financial
support from the IOP-Katalyse program (project IKA
94081) is gratefully acknowledged. Part of this work
(A.L.S. and M.L.) was financially supported by the
(29) Beurskens, P. T.; Admiraal, G.; Bosman, W. P.; Garcia-Granda,
S.; Gould, R. O.; Smits, J . M. M.; Smykalla, C. The DIRDIF Program
System, Technical Report of the Crystallography Laboratory; Univer-
sity of Nijmegen, Nijmegen, The Netherlands, 1997.
(30) Sheldrick, G. M. SHELXL-97. Program for Crystal Structure
Refinement; University of Go¨ttingen: Go¨ttingen, Germany, 1997.
(31) Spek, A. L. PLATON. Program for Crystal Structure Calcula-
tions; Utrecht University: The Netherlands, 1998.
CDCl3: δ -24.24 (s) ppm. [R]20 ) -349.3 (c ) 0.152, CHCl3).
D
HRMS (EI+): m/z calcd for C50H36FeP2 754.1642, obsd 754.1628.
Anal. Calcd for C50H36FeP2: C, 79.58; H, 4.81. Found: C, 79.18;
H, 4.86.
Exp er im en ta l Deta ils for Cr ysta l Str u ctu r e Deter m i-
n a tion . Intensity data were collected at T ) 150 K on a Enraf-
Nonius CAD4T diffractometer with rotating anode and Mo KR
(32) Miyashita, A.; Takaya, H.; Souchi, T.; Noyori, R. Tetrahedron
1984, 40, 1245. Characterization data for hydrogenation products were
found to be identical to those of authentic samples.
radiation (λ ) 0.710 73 Å) up to a resolution of (sin θ/λ)max
)

4004 J . Org. Chem., Vol. 64, No. 11, 1999
Nettekoven et al.
atomic coordinates, isotropic and anisotropic displacement
parameters, and a complete listing of bond angles and bond
lengths. This material is available free of charge via the
Internet at http://pubs.acs.org.
Council for Chemical Sciences of The Netherlands
Organization for Scientific Research (CW-NWO).
Su p p or tin g In for m a tion Ava ila ble: Crystal structure
refinement data for compounds 1a , 1b , and 1d including
J O982481Z