Exploring stereogenic phosphorus: Synthetic strategies for diphosphines containing bulky, highly symmetric substituents

Article abstract of DOI:10.1021/jo020130l

Diphosphine ligands bearing highly symmetric, bulky substituents at a stereogenic P atom were prepared, exploiting established protocols, which include the use of chiral synthons such as 3,4- dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane (3a) and phenylmethylchlorophosphine borane (10) and the enantioselective deprotonation of dimethylarylphosphine boranes. However, only (Bu^t)(Me)PCH₂CH₂P(Bu^t)Me (8a) could be prepared from 3a. The diphosphines (S,S)-1,2-bis-(mesitylmethylphosphino)ethane, ((S,S)-8b) and (S,S)-1,2- bis(9-anthrylmethylphosphino)ethane ((S,S)-8c), which contain 2,6-disubstituted aryl P-substituents, were prepared by Evans' sparteine-assisted enantioselective deprotonation of P(Ar)(Me)₂(BH₃) (Ar = mesityl or 9-anthryl), but the enantioselectivity did not exceed 37% ee. The asymmetrically substituted, methylene-bridged diphosphine (2R,4R)-(Ph)(CH₃)PCH₂P(Mes)(CH₃) ((2R,4R)-12) (Mes = mesityl) was prepared by the newly developed stereospecific reaction of the enantiomerically pure chlorophosphine borane PCl(Ph)(Me)(BH₃) (10) with the racemic, monolithiated dimethylmesitylphosphine borane P(Mes)(Me)(CH₂Li)(BH₃). Diastereomerically pure (2R,4R)-12 was obtained with 86% ee. The rhodium(I) derivatives [Rh(COD)(P-P)]BF₄ containing the diphosphine ligands 8a, 8b, and 12, as well as the previously reported (S,S)-1,2-bis(1-naphthylphenylphosphino)ethane ((S,S)-8d), were prepared and tested in the enantioselective catalytic hydrogenation of acetamidocinnamates. The best catalytic result (98.6% ee) was obtained with [Rh(COD)(8d)]⁺ as catalyst and methyl Z-α-acetamidocinnamate as substrate. Some of the catalytic results are discussed in terms of the preferred conformations of the substituents at phosphorus, as calculated by molecular modeling.

Full text of DOI:10.1021/jo020130l

Exp lor in g Ster eogen ic P h osp h or u s: Syn th etic Str a tegies for
Dip h osp h in es Con ta in in g Bu lk y, High ly Sym m etr ic Su bstitu en ts
Francesca Maienza,† Felix Spindler,‡ Marc Thommen,‡ Benoˆıt Pugin,‡ Christophe Malan,‡ and
Antonio Mezzetti*,†
Department of Chemistry, Swiss Federal Institute of Technology, ETH Ho¨nggerberg,
CH-8093 Zu¨rich, Switzerland, and Solvias AG, Klybeckstrasse 191, CH-4002 Basel, Switzerland
mezzetti@inorg.chem.ethz.ch
Received February 25, 2002
Diphosphine ligands bearing highly symmetric, bulky substituents at a stereogenic P atom were
prepared, exploiting established protocols, which include the use of chiral synthons such as 3,4-
dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane (3a ) and phenylmethylchlorophosphine
borane (10) and the enantioselective deprotonation of dimethylarylphosphine boranes. However,
only (But)(Me)PCH2CH2P(But)Me (8a ) could be prepared from 3a . The diphosphines (S,S)-1,2-bis-
(mesitylmethylphosphino)ethane, ((S,S)-8b) and (S,S)-1,2-bis(9-anthrylmethylphosphino)ethane
((S,S)-8c), which contain 2,6-disubstituted aryl P-substituents, were prepared by Evans’ sparteine-
assisted enantioselective deprotonation of P(Ar)(Me)2(BH3) (Ar ) mesityl or 9-anthryl), but the
enantioselectivity did not exceed 37% ee. The asymmetrically substituted, methylene-bridged
diphosphine (2R,4R)-(Ph)(CH3)PCH2P(Mes)(CH3) ((2R,4R)-12) (Mes ) mesityl) was prepared by
the newly developed stereospecific reaction of the enantiomerically pure chlorophosphine borane
PCl(Ph)(Me)(BH3) (10) with the racemic, monolithiated dimethylmesitylphosphine borane P(Mes)-
(Me)(CH2Li)(BH3). Diastereomerically pure (2R,4R)-12 was obtained with 86% ee. The rhodium(I)
derivatives [Rh(COD)(P-P)]BF4 containing the diphosphine ligands 8a , 8b, and 12, as well as the
previously reported (S,S)-1,2-bis(1-naphthylphenylphosphino)ethane ((S,S)-8d ), were prepared and
tested in the enantioselective catalytic hydrogenation of acetamidocinnamates. The best catalytic
result (98.6% ee) was obtained with [Rh(COD)(8d )]+ as catalyst and methyl Z-R-acetamidocinnamate
as substrate. Some of the catalytic results are discussed in terms of the preferred conformations of
the substituents at phosphorus, as calculated by molecular modeling.
In tr od u ction
came first with Imamoto’s work on borane-protected
phosphines,4 which stimulated the recent development
of powerful stereoselective synthetic methods. These are
mainly based on diastereomerically pure oxazaphospho-
lidine boranes5 and on the enantioselective deprotonation
of dimethylphosphine boranes6a or of racemic secondary
phosphine boranes.6b An extremely promising catalytic
approach to the synthesis of P-stereogenic phosphines is
the asymmetric hydrophosphination of olefins.7
J uge´’s method is excellently suitable for the introduc-
tion of ortho-substituted aryl groups onto a stereogenic
phosphorus atom.5 The diphosphines 1a ,8a 2a ,8b,c and
2b,8b,c which have been developed in our and van Leeu-
Chiral diphosphines have become an important class
of ligands for asymmetric catalysis. It is the success itself
of enantioselective catalysis that has enhanced the
demand for new chiral ligands for essentially two rea-
sons. The first one is that no class of ligands can be
considered as “universal” anymore, as it is linked to a
finite, however broad, scope of substrates and reactions.1
The second reason is the proprietary protection of estab-
lished ligands.
If one considers that asymmetric hydrogenation with
phosphine-containing catalysts begins with dipamp,2
whose chirality derives from a phosphorus-based stereo-
center, it seems paradoxical that the development of
P-stereogenic ligands has been so slow.3 A breakthrough
(3) For excellent reviews on the synthesis and applications of
P-stereogenic ligands, see: (a) Pietrusiewicz, K. M.; Zablocka, M. Chem.
Rev. 1994, 94, 1375. (b) Ohff, M.; Holz, J .; Quirmbach, M.; Bo¨rner, A.
Synthesis 1998, 1391.
(4) For a seminal paper, see: Imamoto, T.; Oshiki, T.; Onozawa, T.;
Kusumoto, T.; Kazuhiko, S. J . Am. Chem. Soc. 1990, 112, 5244.
(5) J uge´, S.; Ste´phan, M.; Laffitte, J . A.; Genet, J . P. Tetrahedron
Lett. 1990, 31, 6357.
(6) (a) Muci, A. R.; Campos, K. R.; Evans, D. A. J . Am. Chem. Soc.
1995, 117, 9075. (b) Wolfe, B.; Livinghouse, T. J . Am. Chem. Soc. 1998,
120, 5116.
(7) (a) Kovacik, I.; Wicht, D. K.; Grewal, N. S.; Glueck, D. S.;
Incarvito, C. D.; Guzei, I. A.; Rheingold, A. L. Organometallics 2000,
19, 950. (b) For the catalytic arylation of enantiomerically pure P(BH3)-
(CH3)(Ph)H, see: Al-Masum, M.; Kumaraswamy, G.; Livinghouse, T.
J . Org. Chem. 2000, 65, 4776.
† Swiss Federal Institute of Technology.
‡ Solvias AG.
(1) Some classes of ligands. For binap, see: Akutagawa, S. Appl.
Catal., A: 1995, 128, 171. Kumobayashi, H. Recl. Trav. Chim. Pays-
Bas 1996, 115, 201. For J osiphos, see: Togni, A. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1475. For Duphos, see: Burk, M. J .; Gross, M. F.;
Harper, T. G. P.; Kalberg, C. S.; Lee, J . R.; Martinez, J . P. Pure Appl.
Chem. 1996, 68, 37.
(2) Seminal papers: (a) Knowles, W. S.; Sabacky, M. J .; Vineyard,
B. D.; Weinkauff, D. J . J . Am. Chem. Soc. 1975, 97, 2567. (b) Vineyard,
B. D.; Knowles, W. S.; Sabacky, M. J .; Bachmann, G. L.; Weinkauff,
D. J . J . Am. Chem. Soc. 1977, 99, 5946.
10.1021/jo020130l CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/22/2002
J . Org. Chem. 2002, 67, 5239-5249
5239

Maienza et al.
CHART 1
SCHEME 1
wen’s laboratories with this method, are excellent ligands
for the asymmetric hydrogenation of acetamido cinna-
mates (Chart 1). Unfortunately, the screening of different
substrates suggests that these P-stereogenic ligands are
specific for dehydroamino acids, whereas nonfunctional-
ized olefins and carbonyl compounds are hydrogenated
with low enantioselectivity.8a,b
As the ortho-substituted aryls in ligands 1a , 2a , and
2b assume different conformations both in solution and
in the solid state,8a,b we speculated that the restricted
scope of these ligands could be caused by the formation
of rotamers. With this working hypothesis, we set out to
develop strategies for the introduction of C2-symmetric
aryl substituents (or other highly symmetric, bulky
groups) onto a stereogenic P atom. Some efforts in this
direction have been undertaken independently by Brown
and J uge´ with the introduction of a ferrocenyl group at
phosphorus.9 Although this synthetic goal of preparing
diphosphines containing very bulky P-substituents is not
yet fully achieved, the results of the present investigation
throw some light onto the relationship between the steric
properties of the diphosphine and those of the P-substit-
uents, as indicated by molecular modeling.
hands, the corresponding phosphinoamino alcohol 4 was
produced in low yield (<15%) and was not isolated
(Scheme 1b).10 A modified approach was the introduction
of the bulky substituent R in the third reaction step, that
is, in the nucleophilic substitution at the P atom of
phenylmethyl(methyl phosphinite) borane (S)-5a (Scheme
1b). Also in this case, only tert-butyllithium (3 equiv)11
reacted with (S)-5a to give phenyl-tert-butylmethylphos-
phinoborane (S)-6a (66% yield). These attempts suggest
that 2,6-disubstituted aryl groups are too bulky to react
with either 3a or 5a , which restricts the application of
the oxazaphospholidine methodology.
The reaction of (S)-5a with t-BuLi occurs with inver-
sion of configuration at the P atom and gives (S)-6. This
is confirmed by the (S,S) absolute configuration of the
corresponding diphosphine (see below). The product was
purified by chromatography and isolated with 92% ee. A
further crystallization step gave the enantiomerically
pure phosphine borane (S)-6. The enantiomeric excess
of (S)-6a was determined by HPLC on a chiral column
by comparison between the chromatograms of (R)-6a and
(S)-6a .12
Resu lts a n d Discu ssion
Syn th esis of th e Liga n d s. The first approach devised
is the extension of J uge´’s procedure to 2,6-disubstituted
aryls (Scheme 1). In fact, in contrast to the ortho-
substituted aryl groups (such as o-anisyl, 1-naphthyl,
etc.), the oxazaphospholidine borane 3a did not react with
mesityllithium, 9-anthryllithium, or 2,4,6-trimethoxy-
phenyllithium. Only tert-butyllithium reacted, but in our
With (S)-6 in our hands, we developed an alternative
synthesis of 1,2-bis(tert-butylmethylphosphino)ethane,
(8) (a) Stoop, R. M.; Mezzetti, A.; Spindler, F. Organometallics 1998,
17, 668. (b) Maienza, F.; Wo¨rle, M.; Steffanut, P.; Mezzetti, A.; Spindler,
F. Organometallics 1999, 18, 1041. (c) Nettekoven, U.; Kamer, P. C.
J .; van Leeuwen, P. W. N. M.; Widhalm, M.; Spek, A. L.; Lutz, M. J .
Org. Chem. 1999, 64, 3996. (d) Nettekoven, U.; Widhalm, M.; Kalch-
hauser, H.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Lutz, M.; Spek,
A. L. J . Org. Chem. 2001, 66, 759.
(9) (a) Brown, J . M.; Laing, J . C. P. J . Organomet. Chem. 1997, 529,
435. (b) Kaloun, E. B.; Merde`s, R.; Geneˆt, J . P.; Uziel, J .; J uge´, S. J .
Organomet. Chem. 1997, 529, 455.
(10) In contrast, other groups have managed to obtain good yields
in the same reaction: (a) Moulin, D.; Darcel, C.; J uge´, S. Tetrahedron:
Asymmetry 1999, 10, 4729. (b) Rippert, A. J .; Linden, A.; Hansen, H.
J . Helv. Chim. Acta 2001, 83, 311.
(11) One equivalent of RLi is consumed in the deprotonation of the
methyl group.
(12) The enantiomeric phosphine borane (R)-6a was prepared with
the same method starting from the oxazaphospholidine borane enan-
tiomer (2S,4R,5S)-3a .
5240 J . Org. Chem., Vol. 67, No. 15, 2002

Synthetic Strategies for Diphosphines
SCHEME 2
SCHEME 4
SCHEME 3
The next approach devised was based on Evans’
sparteine-assisted enantioselective deprotonation of di-
methylphosphine boranes P(R)(Me)2(BH3).6a This method
has been successfully applied for the synthesis of Ar(Me)-
PCH2CH2P(Me)Ar (Ar ) Ph, o-anisyl, o-tolyl, 1-naphthyl).6a
By using the same method, Imamoto prepared (Me)(R)-
PCH2CH2P(Me)(R) (R ) But, CEt3, c-C5H9).14,15 We adapted
this approach to our idea of using aryl substituents
possessing C2 symmetry (or higher). The mesityl group
was introduced at the P atom by the reaction between
PCl(NEt2)2 and mesityl magnesium bromide.16 Pure
P(Mes)(NEt2)2 (Mes ) mesityl) was reacted, in sequence,
with HCl, MeMgBr, and BH3‚SMe2 to give the phosphine
borane P(Mes)(CH3)2(BH3) (6b) in 80% overall yield. The
9-anthryl group was introduced at the P atom by reaction
between PCl(NEt2)2 and 9-anthryllithium. Pure 9-an-
thryldichlorophosphine17 was isolated and reacted se-
quentially with methyl magnesium bromide and BH3‚
SMe2 to give 9-anthryldimethylphosphine borane (6c) in
good overall yield (70%).
The monophosphine borane 6b was deprotonated with
s-BuLi and oxidatively coupled with Cu(II) both in the
presence of and without (-)-sparteine. The latter reac-
tion, which gave access to the racemic diphosphines,
yielded a mixture of the (l)- and (u)-diastereoisomers of
1,2-bis(mesitylmethylphosphino)ethane diborane, (l)-7b
and (u)-7b, with 4:1 diastereoselectivity and 75% overall
yield. In the case of the enantioselective deprotonation,
6b was dissolved in THF and added to a mixture of (-)-
sparteine and s-BuLi cooled at -78 °C (Scheme 4). The
reaction mixture was warmed to -10 °C during 3 h to
which Imamoto has prepared by fractional crystallization
of diastereomeric menthyl esters.4 The monodentate
phosphine borane (S)-6a was deprotonated with tert-
butyllithium at -78 °C in THF. The resulting P(BH3)-
(Ph)(But)(CH2Li) was oxidatively coupled with Cu(II) to
give the diphosphine borane (S,S)-7a (44% yield) (Scheme
2). The absolute configuration is attributed by assuming
retention of configuration at the P atom. The free
diphosphine (S,S)-8a was obtained from the phosphine
borane (S,S)-7a by deprotection with morpholine at 50
°C and was purified by filtration on a short column of
alumina under argon. The absolute configuration and
enantiomeric purity (>98% ee) of (S,S)-8a were deter-
mined by comparison with the values reported by Ima-
moto for (R,R)-8a .4
The second approach was the introduction of a 2,6-
disubstituted aryl group at the oxazaphospholidine stage.
Diastereomerically pure (2R,4S,5R)-(-)-3,4-dimethyl-2-
mesityl-5-phenyl-1,3,2-oxazaphospholidine-2-borane, (RP)-
3b, was obtained in 50% yield by refluxing bis(diethyl-
amino)mesitylphosphine in toluene in the presence of
(1R,2S)-(-)-ephedrine for 12 h, followed by protection
with BH3‚SMe2 (Scheme 3). The configuration at the P
atom was assigned by analogy with the corresponding
2-phenyl-1,3,2-oxazaphospholidine borane (RP)-3a (Scheme
1).13 The ring-opening reaction with alkyllithium reagents
gave low yields of 4b, if at all, and was not synthetically
useful. Indeed, mesityl oxazaphospholidine borane 3b did
not react with MeLi and reacted with PhLi, giving the
corresponding amino alcohol (RP)-4b in only 9% yield. The
methanolysis of (RP)-4b gave the phosphinite borane (S)-
5b with 55% yield. Because of the low overall yields, the
strategy was abandoned.
(14) Imamoto, T.; Watanabe, J .; Wada, Y.; Masuda, H.; Yamada,
H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J . Am. Chem. Soc.
1998, 120, 1635.
(15) Imamoto, T. Pure Appl. Chem. 2001, 73, 373.
(16) van der Knaap, T. A.; Klebach, T. C.; Visser, F.; Bickelhaupt,
F.; Ros, P.; Baerends, E. J .; Stam, C. H.; Konijn, M. Tetrahedron 1984,
40, 765.
(13) J uge´, S.; Stephan, M.; Merde`s, R.; Geneˆt, J . P.; Halut-desportes,
S. J . Chem. Soc., Chem. Commun. 1993, 531.
(17) Wesemann, J .; J ones, P. G.; Schomburg, L.; Heuer, L.; Schmut-
zler, R. Chem. Ber./ Recl. 1992, 125, 2187.
J . Org. Chem, Vol. 67, No. 15, 2002 5241

Maienza et al.
SCHEME 5
allow the deprotonation of 6b and then cooled to -78 °C
before adding CuCl2 for the oxidative coupling step
(Scheme 4). In this case, the reaction occurred with
complete diastereoselectivity. Only (l)-7b was observed
but with lower yield (62%). The enantiomeric excess was
37% (see below). Experiments directed at increasing the
enantioselectivity were carried out at lower temperatures
(-50 °C, -30 °C) and in different solvents (Et2O, DME)
but gave poor yields or no product at all.
When the coupling reaction of the 9-anthryl derivative
6c was carried out without (-)-sparteine, a mixture of
the diastereoisomers (l)-7c and (u)-7c was formed with
6:1 diastereoselectivity in 72% overall yield. In the case
of the enantioselective deprotonation, the phosphine
borane 6c was added to a mixture of (-)-sparteine and
sec-butyllithium cooled at -78 °C, and the mixture was
stirred for 3 h at -78 °C before coupling with CuCl2
(Scheme 4). Workup gave (S,S)-7c and (R,S)-7c in a 6:1
ratio and 70% total yield. Diastereomerically pure (S,S)-
7c was obtained by crystallization from CH2Cl2/Et2O with
39% yield and 18% ee.
The diphosphine boranes (S,S)-7b and (S,S)-7c were
deprotected by stirring in morpholine solution at room
temperature for 12 h. The diphosphines (S,S)-8b and
(S,S)-8c were isolated after purification through a short
column of alumina under argon. The enantiomeric ex-
cesses of (S,S)-8b and (S,S)-8c were determined on the
corresponding phosphine oxides (R,R)-1,2-bis(P-oxomesi-
tylmethylphosphino)ethane, (R,R)-9b, and (R,R)-1,2-bis-
(P-oxo-9-anthrylmethylphosphino)ethane, (R,R)-9c, which
were prepared by oxidation of 8b and 8c with an excess
of H2O2. In the presence of the chiral solvating agent (S)-
(+)-2,2,2-trifluoro-1-(9-anthryl)ethanol, (R,R)- and (S,S)-
9b and (R,R)- and (S,S)-9c formed diastereomeric ad-
ducts with resolved 31P NMR signals,18 whose attribution
was checked by comparison with the 31P NMR spectra of
racemic 9b and 9c recorded under the same conditions.
The integration of these signals showed 37% ee in the
case of the mesityl derivative (R,R)-9b and 18% ee in the
case of (R,R)-9c. As the oxidation of trivalent phosphorus
generally occurs with retention of configuration,19 these
values were taken as diagnostic of the enantiomeric
excess of the diphosphines. The configurations S,S at the
P atoms for the major enantiomer of the diphosphines
were assigned by analogy to the other ligands prepared
by enantioselective deprotonation with (-)-sparteine.6a,14
At this point, we tested the diastereoselective reaction
between the racemic monodeprotonated phosphine bo-
rane and a suitable chiral synthon P(BH3)RR′X. Prelimi-
nary experiments showed that the crucial point is the
choice of X. Indeed, the phosphinite borane P(OMe)(Ph)-
(Me)(BH3) (5a ) did not react with P(R)(CH3)(CH2Li)(BH3)
(R ) 9-anthryl or mesityl), even in the presence of an
excess of the latter. Looking for more reactive synthons,
we tried the chlorophosphine borane PCl(Ph)(Me)(BH3)
(10), which has been recently prepared by J uge´ by
acidolysis of 4a with anhydrous HCl.9b,10a,20 This proce-
dure yields enantiomerically pure 10, which we used as
synthon for the asymmetrically substituted, methylene-
bridged diphosphine (2R,4R)-2-mesityl-4-phenyl-2,4-
diphosphapentane, (2R,4R)-12 (Scheme 5). Ligand 12 is
similar to Imamoto’s MiniPHOS but has lower symmetry
(C1 instead of C2).21
We prepared the chlorophosphine (S)-PCl(Ph)(CH3)-
(BH3) (10) described by J uge´9b,10a,20 by reacting the
phosphinoamino alcohol (RP)-N-methyl[(1S,2R)-(2-hydroxy-
1-methyl-2-phenyl)ethyl]aminomethylphenylphosphine bo-
rane, (RP)-4a , with HCl (titrated Et2O solution, 2.1 equiv
vs 4a ) at room temperature. After 1 h, the ephedrine
chlorohydrate was filtered off, and the formation of the
chlorophosphine (S)-10 was found to be quantitative by
31P NMR spectroscopy. The 20 mM toluene/ether solution
containing the chlorophosphine 10 was directly utilized
for the reaction with the monodeprotonated, racemic
P(Mes)(Me)(CH2Li)(BH3) (2 equiv). The latter was pre-
pared by reaction of 6b with sec-butyllithium in THF (at
-78 °C),22 and the resulting solution was added slowly
to a solution of the chlorophosphine 10, which was
precooled at -78 °C (Scheme 5). The methylene-bridged
diphosphine diborane (BH3)(Me)(Mes)PCH2P(BH3)(Me)-
(Ph) (11) was isolated with a total yield of 66%. The
(2R,4R)-diastereoisomer of 11 was formed predominantly
and with >85% ee (see below). A minor diastereoisomer
indicated as (S,R) was also formed in the reaction, as
observed by 31P NMR spectroscopy, which gave a ratio
of 83:17 between the two diastereomers.23
The absolute stereochemistry at the P(4) atom of the
major diastereoisomer was assumed to be R, considering
that chlorophosphine boranes generally react with inver-
sion of configuration at the P atom.20 The relative
(21) (a) Yamanoi, Y.; Imamoto, T. J . Org. Chem. 1999, 64, 2988. (b)
Gridnev, I. D.; Yamanoi, Y.; Higashi, N.; Tsuruta, H.; Yasutake, M.;
Imamoto, T. Adv. Synth. Catal. 2001, 343, 118. (c) Gridnev, I. D.;
Yasutake, M.; Higashi, N.; Imamoto, T. J . Am. Chem. Soc. 2001, 123,
5268.
(22) At temperatures higher than -78 °C, sec-butyllithium depro-
tonates also the ortho-methyl of the mesityl group. The lithiated
mesityl methyl group reacts with the chlorophosphine 10 to give the
diborane adduct of (2-(methylphenylphosphino)methyl-4,6-dimeth-
ylphenyl)dimethylphosphine. The latter was the main product when
the deprotonation was carried out at 20 °C. Its formation was confirmed
by NMR spectroscopy (1H NMR, 13C NMR, and 31P,1H NMR 2D
correlation spectra).
(18) Togni, A.; Pastor, S. D. Tetrahedron Lett. 1989, 30, 1071.
(19) Brown, J . M.; Carey, J . V.; Russell, M. J . H. Tetrahedron 1990,
46, 4877.
(20) Moulin, D. Ph.D. Thesis, Universite´ de Cergy-Pontoise, 1999.
5242 J . Org. Chem., Vol. 67, No. 15, 2002

Synthetic Strategies for Diphosphines
CHART 2
stereochemistry of the P atoms in the major diastereomer
of 11 (and consequently in the free diphosphine (2R,4R)-
(Ph)(CH3)PCH2P(Mes)(CH3), (2R,4R)-12) was established
by 2D NOESY spectroscopy on [Rh(COD)((2R,4R)-12)]+,
which confirmed that the methyl groups lie on opposite
sides of the P-Rh-P plane (see below). Thus, the major
diastereoisomer is regarded as (2R,4R)-12. Although no
mechanistic study was carried out, a possible interpreta-
tion of the above results is that (S)-10 reacts preferen-
tially with (S)-P(BH3)(Mes)(Me)(CH2Li) to give (2R,4R)-
11 as the major product (83%).
To determine the enantiomeric excess of (R,R)-11, we
prepared the opposite enantiomer (2S,4S)-11 from the
enantiomeric phosphinoamino alcohol (SP)-4a . The chlo-
rophosphine (R)-10 was coupled with P(Mes)(CH2Li)-
(CH3)(BH3), as described above. The diastereomeric
diphosphine boranes (2S,4S)-11 and (2R,4S)-11 were
formed in a 5:1 ratio and were separated by flash
chromatography. All four stereoisomers of 11 were
separated by HPLC on a chiral column (Daicel Chiralcel
OD-H). The peaks of the different diastereomers were
attributed by comparison of the chromatograms of the
products obtained from the enantiomeric phosphino-
amino alcohols (RP)-4a and (SP)-4a . Thus, (S)-10 gave
(2R,4R)-11 with 85.6% ee. The minor, pseudo-meso
diastereomer (S,R)-11 was formed with 81.8% ee. The
enantiomeric chlorophosphine borane (R)-10 gave (2S,4S)-
11 with 82.3% ee and (2R,4S)-11 with 79.1% ee. As the
ee values measured by J uge´ for the phosphine boranes
prepared from chiral chlorophosphines are in the range
80-90% ee,20 (2R,4R)-11 is formed with the same enan-
tiomeric excess of the starting material (S)-10. Chro-
matographic purification gave diastereomerically pure
(2R,4R)-11.
The deprotection of (2R,4R)-11 with morpholine yielded
the free diphosphine (2R,4R)-12. The enantiomer (2S,4S)-
12 was obtained from (2S,4S)-11 by the same procedure.
Diphosphines (2R,4R)-12 and (2S,4S)-12 were isolated
as colorless oils after purification on a short column of
alumina under argon to avoid oxidation. The 31P NMR
spectra of both enantiomers showed two doublets cen-
tered at δ -38 and δ -50 with J P,P ) 144 Hz. The
enantiomeric excess of 12 was determined by reprotection
with Me2S‚BH3 and HPLC analysis on a chiral column.
The enantiomeric excess of the resulting diphosphine
borane (2R,4R)-11 was the same as before de- and
reprotection (86% ee). The same was observed for the
enantiomeric product (2S,4S)-11 (82% ee). This indicates
that no epimerization occurs upon deprotection and that
the P-configuration of the free diphosphines is stable in
solution, as for Imamoto’s ligands.4,14,15 In contrast, the
corresponding 1,2-ethanediyl-bridged ligands of the type
(Ar)(Me)PCH2CH2P(Ar)(Me) (Ar ) phenyl, o-anisyl, o-
tolyl, 1-naphthyl) are configurationally unstable in
solution.6a
Rh od iu m Com p lexes. In previous work with P-
stereogenic ligands, we have found that the isolated
rhodium complexes give better enantioselectivity than
the corresponding systems formed in situ.8b Also, the
isolation of the complexes introduces a further purifica-
tion step, which is particularly appropriate in the present
case in view of the low (for 8b) or moderate (for 12)
enantiopurity of some of the ligands. Thus, rhodium
complexes of the type [Rh(COD)(P-P)]+ (COD ) 1,5-
cyclooctadiene; P-P ) diphosphine) were prepared with
the P-P ligands (S,S)-8a, (S,S)-8b, (S,S)-8d, and (2R,4R)-
12.
The reaction of [Rh(COD)2]BF4 with (S,S)-8a (1 equiv)
in THF gave analytically pure [Rh(COD)((S,S)-8a )]BF4
(13a ) (Chart 2). For the sake of comparison, we similarly
prepared the rhodium derivative [Rh(COD)(8d)]BF4 (13d),
which contains the previously reported ligand (S,S)-1,2-
bis(1-naphthylphenylphosphino)ethane24 ((S,S)-8d ). The
31P NMR spectrum (CDCl3, room temperature) of both
complexes showed a regular doublet due to coupling to
rhodium and, contrary to the cases of the analogues
[Rh(COD)(P-P)]+ (P-P ) 1a or 2a ,b),8a-c does not show
any evidence of slow conformer interconversion.
The rhodium derivative [Rh(COD)((S,S)-8b)] (13b)
containing the enantiomerically enriched ligand (S,S)-
8b (37% ee) was prepared similarly as catalyst precursor
for asymmetric hydrogenation. This was directed at
assessing the performance of 8b in catalysis and at
deciding whether the preparation of the enantiomerically
pure ligand should be investigated further. Complex 13b
was recrystallized from CH2Cl2/Et2O to increase the
enantiomeric excess, which, however, was not deter-
20
mined. After recrystallization, the specific rotation [R]D
of 13b was -9.5 (CHCl3, c ) 0.15). The 31P NMR
spectrum consists of a doublet with J Rh,P ) 145 Hz, which
confirms that this highly symmetric 1,2-ethanediyl-
bridged diphosphine does not form slowly interconverting
conformers (at least in solution at room temperature).
The ligand (2R,4R)-12 (86% ee) did not react with
[Rh(COD)2]BF4 or with [Rh(NBD)2]BF4. In the case of
Imamoto’s MiniPHOS ligand Ph(Me)PCH2P(Me)Ph (14),
the reaction between [Rh(NBD)2]BF4 and 14 afforded the
bischelate complexes [Rh(14)2]BF4, even with the use of
[Rh(NBD)2]BF4 and the diphosphine in a 1:1 molar
(23) When a stoichiometric amount of (rac)-P(BH3)(Me)(Mes)(CH2-
Li) (1 equiv vs 10) was used, 11 was formed in less than 50% yield (on
the basis of chlorophosphine 10). With 2 equiv of (rac)-P(BH3)(Me)-
(Mes)(CH2Li), the yield of 11 was 65%. The latter value did not improve
when 3 equiv of (rac)-P(BH3)(Me)(Mes)(CH2Li) was used. The diaster-
eomeric ratio (2R,4R)-11/(S,R)-11 was roughly 5:1 in all experiments.
The absolute configuration of the minor diastereoisomer of 11 is either
(2R,4S) or (2S,4R). However, this is scarcely relevant from a practical
viewpoint, as this isomer has pseudo-meso character, which makes it
uninteresting, at least in principle, for asymmetric catalysis.
(24) (a) Stoop, R. M.; Bauer, C.; Setz, P.; Worle, M.; Wong, T. Y. H.;
Mezzetti, A. Organometallics 1999, 18, 5691. (b) For a nonstereose-
lective synthesis, see: Yoshikuni, T.; Bailar, J . C., J r. Inorg. Chem.
1982, 21, 2129.
J . Org. Chem, Vol. 67, No. 15, 2002 5243

Maienza et al.
TABLE 1. Asym m etr ic Rh -Ca ta lyzed Hyd r ogen a tion of Meth yl Z-r-Aceta m id ocin n a m a tesa
ligand
product
ee (%)
run
type
ee (%)
conf
substr
R1
R2
p(H2) (bar)
yield (%)
conf
1
2
3
4
5
6
7
8b
9
8a
8a
8a
8d
8d
8d
8b
8b
12
>98
>98
>98
>99
>99
>99
37
(S,S)
(S,S)
(S,S)
(S,S)
(S,S)
(S,S)
(S,S)
(S,S)
(2R,4R)
16a
16b
16c
16a
16b
16c
16a
16b
16a
H
Me
Me
Ph
Me
Me
Ph
Me
Me
Me
1.1
1.1
5.0
1.1
1.1
6
1.1
5.0
1.0
>70
>99
90
>99
37
33
37
>99
>99
6.3
5.2
2.4
98.6
18.3
26.9
racemic
racemic
racemic
(R)
(R)
(R)
(S)
(S)
(S)
Me
Me
H
Me
Me
H
37
86
Me
H
a
b
Other reaction conditions: 18 h reaction time, unless otherwise stated. The reaction time was 65 h.
TABLE 2. Asym m etr ic Rh -Ca ta lyzed Hyd r ogen a tion of
ratio.21a In the case of C1-MiniPHOS (2R,4R)-12, no
reaction occurred even when 2 equiv of diphosphine
versus Rh[(NBD)2]BF4 was used. Thus, we prepared
[Rh(COD)((2R,4R)-12)]PF6 (15) by reaction of the di-
nuclear rhodium complex [RhCl(COD)]2 with (2R,4R)-12
in THF in the presence of NH4PF6. The 31P NMR
spectrum consists of two doublets of doublets centered
at δ -10.6 and δ -22.0, with J P,P ) 80 Hz and J P,Rh ) 95
Hz, respectively. A 2D NOESY spectrum (see Supporting
Information, Figure S1) did not show any cross peak for
the methyl groups bonded to the P atoms (δ 1.81 and δ
2.03), confirming that they are positioned on opposite
sides with respect to the P-Rh-P plane. Molecular
modeling (Cerius 2) shows that, in the (S,R)-diastereo-
isomer, the two methyl groups are as close as 2.73 Å
(Figure S2) and should therefore give rise to significant
transfer of magnetization in the 2D NOESY spectrum.
Additionally, only one conformer was observed in solution
at room temperature, confirming that the combination
of C2-symmetric substituents at the P atoms with a rigid
backbone reduces the conformational freedom of the
ligand in the rhodium complexes [Rh(diolefin)(P-P)]+.
Rh -Ca ta lyzed Asym m etr ic Hyd r ogen a tion . Com-
plexes 13a , 13b, 13d , and 15 were tested in the rhodium-
(I)-catalyzed hydrogenation of functionalized olefins. The
results of the asymmetric hydrogenation of R-acetami-
docinnamic acid derivatives are summarized in Table 1.
Complex 13a hydrogenated methyl (Z)-R-acetamidocin-
namate (16a ) to (R)-N-acetylphenylalanine methyl ester
(16a H2) with 6.3% ee at 20 °C and 1 bar H2 (run 1). Also,
the N-methylated analogues methyl (Z)-N-methyl-R-
acetamidocinnamate (16b) and methyl (Z)-N-methyl-R-
benzamidocinnamate (16c) were hydrogenated with low
enantioselectivity (runs 2, 3), whereas the analogous
complexes containing 1a and 2a ,b have been found to
be excellent catalysts for this reaction.8a,b Complex 13d ,
which contains the dipamp-analogue 8d , hydrogenated
16a with excellent enantioselectivity (98.6%, run 4),
which exceeds the 97.5% ee obtained with the dipamp
rhodium catalyst.2 Bailar and Yoshikuni have reported
that [Rh(COD)(8d )]+ hydrogenates R-acetamido acrylic
acid with 76% ee.24b Complex 13d is much less efficient
in the hydrogenation of the N-methylated substrates 16b
and 16c (runs 5 and 6).
E-2-Meth ylcin n a m ic Acid a
ligand
run type ee (%) p(H2) (bar) time (h) yield (%)
ee (%)
1b
2
8a
8d
12
>98
>99
>99
5
6
5
65
65
17
>95
>95
53
3
34
racemic
3b
a
Other reaction conditions: NEt3 (2 mL) was added to the
reaction solution. The absolute configuration of the product was
b
not determined. A black precipitate, presumably rhodium metal,
was observed at the end of the reaction.
We also tested complex 13b, which contains enantio-
merically enriched (S,S)-8b (37% ee). Two experiments
were carried out in the asymmetric hydrogenation of
methyl (Z)-R-acetamidocinnamate (16a ) (run 7) and
methyl (Z)-R-N-methyl acetamidocinnamate (16b) (run
8). Both these substrates gave the racemic products (0%
ee). This suggests that, independently from the low
enantiomeric purity of the ligand (37% ee), the chirality
transfer from ligand (S,S)-8b is inefficient. Therefore, no
further experiments were carried out with complex 13b,
and no attempts to increase its enantiomeric purity were
undertaken. Finally, also ligand 12 gave disappointing
results. Methyl (Z)-R-acetamidocinnamate (16a ) was
converted quantitatively (>99% yield) to the racemic
N-acetylphenylalanine methyl ester (run 9).
To better define the scope of the ligands, we also tested
(E)-2-methylcinnamic acid (17) as substrate. Complex
13d hydrogenated 17 with low enantioselectivity (34%
ee, Table 2, run 2), and 13a and 15 gave racemic (E)-2-
methyldihydrocinnamic acid (runs 1 and 3). With the
latter complexes, a black precipitate, presumably rho-
dium metal, was observed at the end of the catalytic
reaction. This fact suggests that ligands 8a and 12
coordinate weakly to rhodium in at least one of the
rhodium complexes involved in the catalytic cycle, as will
be discussed below.
Chart 3 summarizes the effect of changing the sub-
stituents at stereogenic phosphorus in the ligands R(R′)-
5244 J . Org. Chem., Vol. 67, No. 15, 2002

Synthetic Strategies for Diphosphines
CHART 3
F IGURE 1. Energy-minimized (Cerius2) conformations of
[Rh(COD)(8a )]+ (13a ) with relative energies.
and extended by Imamoto.27 The quadrant rule predicts
the (S) configuration for 16a H2 when bulky substituents
are present in the lower left and upper right quadrants
(as seen from the side of the olefin).26
It is of interest to note that Knowles’ formulation,
which was based on structural data of the dipamp (8f)
complex [Rh(COD)(8f)]+,26 implies that the role of the
“small” substituent is played by the larger aryl group,
which occupies an equatorial position with a face-on
conformation. The “bulky” substituents are the smaller
phenyl groups, which are forced in an axial, edge-on
conformation. The steric hindrance of the phenyl groups
is caused by their edge-on conformation with respect to
the incoming olefin. Accordingly, ligand (R,R)-8f gives
(S)-16a H2 (Chart 3).2 This holds when two aryl substit-
uents are present at the stereogenic P atom. In the case
of diphosphines bearing two (highly symmetrical) alkyl
groups, Imamoto has shown that the “absolute bulkiness”
of the alkyl group determines the absolute configuration
of 16H2 in agreement with the quadrant rule.27 Thus,
ligand (S,S)-8e gives (R)-16H2 (Chart 3).27
In this context, the intermediate case, in which an aryl
group is combined with a bulky alkyl group, is particu-
larly interesting. The MM calculations on 13d indicate
that two conformations of the phenyl rings are possible
(Figure 1). In the more stable conformation A, the phenyl
groups are face-on with respect to the sp2 plane of the
coordinated CdC bond, and the equatorial and axial
positions are not clearly defined. The conformation B is
5 kcal/mol higher in energy and features clearly distin-
guishable axial and equatorial positions, with edge-on
phenyl groups in the latter. van der Waals contacts in B
(∆E ) 6.3 kcal mol-1) account for the large energy
difference between A and B. In the latter, the phenyl
groups play the role of the bulky substituent, as they are
edge-on. The conformational change from B to A involves
the rotation of the phenyl groups from the edge-on to the
face-on conformation. This change reduces the “relative
steric bulk” of Ph, as compared to But. Consequently, the
equatorial phenyl groups move away from the equatorial
positions in B to give rise to the flattened conformation
of A, in which the equatorial and axial positions are not
clearly defined.
PCH2CH2P(R′)R on the enantioselectivity of the hydro-
genation of 16a . The catalytic results show that the ideal
combinations for the two terminal substituents at phos-
phorus are either two aryl groups, such as in 8f,2 8d , 1a ,8a
and 2a ,8b or two alkyl groups, such as in 8e.14,21b In
contrast, the combination of an aryl with an alkyl group
in (Ar)(R)P-groups is inefficient, as indicated by the low
enantioselectivity obtained with 8a . Similar consider-
ations hold for the methylene-bridged diphosphines 12
and 14. In fact, Me(Ph)PCH2P(Me)Ph, the only ligand of
the MiniPHOS series featuring an aryl and an alkyl
group, hydrogenated (E)-2-acetamidoacrylic acid with
only 26% ee.21a In the following sections, we suggest two
possible explanations for this observation.
Qu a d r a n t Ru le a n d Molecu la r Mod elin g. We car-
ried out molecular modeling (MM) calculations (Cerius2)25
to find out the preferred conformation of the P-substit-
uents of (S,S)-8a in the rhodium complex 13a . The aim
was to correlate the absolute configuration of the phen-
ylalanine derivative 16a H2 with the ligand conformation
by means of the “quadrant rule”, as proposed by Knowles26
(25) Cerius2 uses the Universal Force Field (UFF): Rappe´, A. K.;
Casewit, C. J .; Colwell, K. S.; Goddard, W. A., III; Skiff, W. M. J . Am.
Chem. Soc. 1992, 114, 10024. Rappe´, A. K.; Colwell, K. S.; Casewit, C.
J . Inorg. Chem. 1993, 32, 3438.
(27) Gridnev, I. D.; Higashi, N.; Asakura, K.; Imamoto, T. J . Am.
Chem. Soc. 2000, 122, 7183.
(26) Knowles, W. S. Acc. Chem. Res. 1983, 16, 106.
J . Org. Chem, Vol. 67, No. 15, 2002 5245

Maienza et al.
The conformational difference between A and B is
small but distinct (note the relative positions of the ipso-C
atoms of the Ph and But groups). The (unfortunate)
overall effect is that, in the most stable conformer A, the
Ph and But groups have nearly the same (apparent) steric
bulk, as indicated by the flattening of the half-chair
conformation28 and as reflected by the very low enantio-
selectivity (6.3% ee) observed in the hydrogenation of 16a
by complex 13a . Application of the quadrant rule sug-
gests that tert-butyl is slightly more bulky than phenyl,
as (R)-16a H2 is formed with ligand (S,S)-8a . We conclude
that the combination of one alkyl and one aryl group
destroys the interplay of the two aryl groups and allows
for the detrimental conformational flexibility, as dis-
cussed for ligand 8a . Clearly, such effects are difficult to
predict on paper, and MM calculations can be very
helpful. Interestingly, van Koten29 has recently reported
that a P-stereogenic PCP pincer ligand containing the
P(But)Ph group gives lower enantioselectivity in the
palladium-catalyzed aldol condensation of 2-isocyanoac-
etate and benzaldehyde than the related C-stereogenic
analogue developed by Venanzi and Zhang.30
The quadrant rule is an extraordinarily successful rule-
of-thumb to predict the absolute configuration of the
hydrogenation product 16a H2 with a number of different
ligands including, besides dipamp, the already mentioned
1, 2a , and 2b. Therefore, we were surprised to find that
ligand 8d is an exception. In fact, (S)-16a H2 is formed
with [Rh(COD)((S,S)-8d )]+, instead of the expected (R)
enantiomer (Table 1, run 4). Also, the N-methylated
substrates 16b and 16c give the (S) products (runs 5 and
6). This behavior is exceptional, as the related ligands
with a similar stereogenic environment, such as 1a 8a and
2a 8b,c (besides dipamp 8f itself),2 give (R)-16a H2.31 We
conclude that, albeit extremely useful, the quadrant rule
should be applied with caution, as the steric interplay
in the [Rh(diolefin)(P-P)]+ complexes is complicated, and
it is even more so in the intermediates of the catalytic
cycle.
aryl ligands Ar(R)P-P(R)Ar are basic enough to switch
on the “dihydride mechanism” but are not basic enough
to afford a substantial stabilization of the resulting
dihydride complex, which decomposes during the cata-
lytic reaction. We speculate that steric effects (including
chelate ring size) enhance this effect. In fact, ligand 8a
bears two bulky substituents at phosphorus, one of which
is an alkyl group (tert-butyl). In 8b, the mesityl group is
also extremely bulky. In ligand 12, the strained four-
membered ring labilizes the Rh-P bond, introducing a
further element of instability.
Con clu sion
The stereoselective introduction of 2,6-disubstituted
aryl groups at stereogenic phosphorus is still a challenge.
Amenable synthetic protocols led to some new methyl-
aryl-substituted diphosphines, which, however, turned
out to be ineffective in the rhodium-catalyzed hydrogena-
tion of olefins. The present study suggests that this is a
more general problem, which is possibly related to the
combination of an alkyl and an aryl substituent rather
than to the nature of the aryl substituent alone. Indeed,
whereas (both new and well-established) bis(aryl)- and
bis(alkyl)-substituted ligands are highly effective in the
rhodium-catalyzed hydrogenation of acetamidocinnamic
esters, all the mixed arylalkyl derivatives R(Ar)PCH2-
CH2P(Ar)R tested are not. Both steric (R ) But) and
electronic reasons (R ) Me, But) account for the low
performance of R(Ar)PCH2CH2P(Ar)R. Still, such ligands
should be tested in catalytic reactions other than the
rhodium-catalyzed hydrogenation of olefins. A posteriori,
some of the results can be rationalized by simple molec-
ular modeling calculations, suggesting that the sensible
application of molecular modeling should be used as a
tool guiding synthetic work.
Exp er im en ta l Section
Gen er a l Com m en ts. Reactions with air- or moisture-
sensitive materials were carried out under an argon atmo-
sphere using Schlenk techniques. Solvents were purified by
standard procedures. P(Mes)(NEt2)2,16 9-anthryldichlorophos-
phine,17 (2R,4S,5R)-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphos-
pholidine-2-borane ((2R,4S,5R)-3a ) (and its enantiomer (2S,-
4R,5S)-3a ),5,9b (RP)-N-methyl[(1S,2R)-(2-hydroxy-1-methyl-2-
phenyl)ethyl]aminomethylphenylphosphine borane ((RP)-4a )
(and its enantiomeric form (SP)-4a ),5,9b (S)-phenylmethyl-
(methyl phosphinite) borane ((S)-5a ),5 and (S,S)-1,2-bis(1-
naphthylphenylphosphino)ethane (8d )24a were prepared ac-
cording to literature procedures. The 1H, 31P, and 11B NMR,
mass spectra, HPLC, GC, melting points, specific rotations,
and elemental analyses were measured as described before.8b
(S)-(-)-ter t-Bu tylp h en ylm eth ylp h osp h in obor a n e, (S)-
6a . A 1.7 M hexane solution of t-BuLi (48.2 mL, 0.082 mol, 3
equiv vs 5a ) was added slowly to a solution of (S)-5a (4.59 g,
0.027 mol) in THF (60 mL) cooled at -78 °C, and the resulting
solution was then allowed to reach room temperature over-
night. The reaction was quenched with H2O (60 mL), THF was
evaporated, and the product was extracted with CH2Cl2 and
dried with MgSO4. Evaporation of the solvent and flash
chromatography (silica gel, hexane/ethyl acetate 95:5, Rf 0.32)
gave (S)-6a as a white solid (46 g, 66%, 0.018 mol). HPLC (OD,
hexane/2-propanol 99:1): Rt (S)-6a ) 10.5 min, Rt (R)-6a )
11.3 min (92% ee). The enantiomerically pure product (only
(S)-6a was detected) was obtained by recrystallization from
Sta bility of th e Ca ta lytic System . With ligands 8a
and 12, a black precipitate of rhodium metal is observed
after the reaction time. The occurrence of a parallel
heterogeneous reaction is an alternative explanation of
the low enantioselectivity observed with ligands 8a , 8b,
and 12. As the instability of the rhodium complexes
containing these ligands is not self-evident, we suggest
a possible explanation thereof. This is based on Imamo-
to’s observation that increasing the basicity of the
diphosphine ligands substantially favors the oxidative
addition of dihydrogen, as compared to bis(aryl)diphos-
phines.27 With ligands of the type RR′P-PRR′ (R ) alkyl
group), this causes the change from the unsaturated to
the dihydride mechanism. It is possible that the dialkyl-
(28) The negative effects of the flattening of the chelate ring on
enantioselectivity have been thoroughly discussed by Seebach for a
number of chiral diphosphines: Seebach, D.; Devaquet, E.; Ernst, A.;
Hayakawa, M.; Ku¨hnle, F. N. M.; Schweizer, W. B.; Weber, B. Helv.
Chim. Acta 1995, 78, 1636.
(29) Williams, B. S.; Dani, P.; Lutz, M.; Spek, A. L.; van Koten, G.
Helv. Chim. Acta 2001, 84, 3519.
(30) (a) Gorla, F.; Togni, A.; Venanzi, L. M.; Albinati, A.; Lianza, F.
Organometallics 1994, 13, 1607. (b) Longmire, J . M.; Zhang, X.; Shang,
M. Organometallics 1998, 17, 4374.
(31) Consistently with our observation, (-)-[Rh(COD)(8d )]Cl (in
which ligand 8d has the S,S configuration, according to our attribution)
hydrogenates R-acetamidoacrylic acid to N-acetyl-(S)-alanine.24b
hot hexane. [R]D ) -4.6 (c 1, CHCl3).31P NMR (CDCl3): δ
20
9.7 (br q, 1P). 1H NMR (CDCl3): δ 7.75-7.46 (m, 5H, 1Ph),
5246 J . Org. Chem., Vol. 67, No. 15, 2002

Synthetic Strategies for Diphosphines
1
1.55 (d, 3H, J P,H ) 8.9 Hz, 1CH3), 0.86 (s, 9H, 3CH3), 1.3-0.8
(CDCl3): δ 65.8 (br q, 1P). H NMR (CDCl3): δ 7.47-7.16 (m,
(br, 3H, BH3). MS m/z (FAB+): 180 (M+ - BH3, 9), 151 (M+
-
12H, ArH), 4.68 (d, 1H, 3J H,H′ ) 7.0, CH(Ph)OH), 4.06 (m, 1H,
3
BH3 - 2CH3, 80), 124 (M+ - BH3 - 4CH3 + 3H, 63). Anal.
Calcd for C11H20BP‚0.25C6H14: C, 69.64; H, 10.98. Found: C,
70.05; H, 10.02.
NCHMe), 3.46 (d, 3H, J P,H ) 6.2, NCH3), 2.25 (s, 6H, 2CH3),
2.15 (s, 3H, CH3), 2.01 (br s, 1H, OH), 1.82 (d, 3H, 3J H,H ) 9.1,
3
NC(CH3)H), 1.69 (d, 3H, J P,H ) 6.0, PCH3), 1.8-0.5 (m, 3H,
BH3). MS m/z (FAB+): 404 (M+ - H, 100), 392 (M+ - BH3,
31), 284 (M+ - H - Mes, 42), 227 (M+ - BH3 - ephedrine,
39).
(R)-(+)-ter t-Bu tylp h en ylm eth ylp h osp h in obor a n e, (R)-
6a . (R)-6a was prepared and purified as described for (S)-6a
starting from (R)-P(OMe)(Ph)(Me)(BH3). Same spectroscopic
properties as (S)-6a , 91% ee (by HPLC, see above).
(S)-(-)-Mesit ylp h en yl(m et h yl p h osp h in it e) Bor a n e,
(S)-5b. Concentrated H2SO4 (0.12 mL, 97%) was added to a
solution of the aminophosphine borane (RP)-4b (0.855 g, 2.1
mmol) in MeOH (20 mL) at room temperature. The reaction
solution was stirred for 15 h. After evaporation of the solvent,
flash chromatography (silica gel, hexane/ethyl acetate 95:5, Rf
0.18) gave pure (S)-5b (0.286 g, 55%). [R]D20 ) -23 (c 1, CHCl3).
31P NMR (CDCl3): δ 112.8 (br, 1P). 1H NMR (CDCl3): δ 7.86-
7.31 (m, 7H, ArH), 3.63 (d, 3H, J P,H ) 12.2 Hz, POCH3), 2.21
(S,S)-(-)-1,2-Bis(ter t-bu tylph en ylph osph in o)eth an e Di-
bor a n e, (S,S)-7a . A 1.2 M hexane solution of s-BuLi (5.5 mL,
6.63 mmol) was added slowly to a solution of (S)-P(Ph)(But)-
(Me)(BH3), (S)-6a , (1.175 g, 6.03 mmol) in THF (50 mL) cooled
at -78 °C. The reaction solution was stirred for 3 h at -78
°C. A suspension of CuCl2 (2.43 g, 18.1 mmol) in THF (43 mL)
was added slowly by cannula, and the resulting solution was
allowed to reach room temperature overnight. The reaction
was quenched with 1 M HCl (50 mL) and diluted with ethyl
acetate. The organic layer was washed with 37% NH3 (15 mL),
brine (15 mL), and water (2 × 15 mL) and dried with MgSO4,
3
(s, 6H, 2CH3), 2.12 (s, 3H, CH3), 1.82 (d, 3H, J P,H ) 9.1 Hz,
PCH3), 1.3-0.6 (m, 3H, BH3). MS m/z (FAB+): 258 (M+ - BH3,
84), 243 (M+ - BH3 - CH3, 41), 196 (M+ - Ph, 100).
Mesityld im eth ylp h osp h in e Bor a n e, 6b. A HCl solution
(1 M in Et2O, 206 mL, 0.206 mol) was added to P(Mes)(NEt2)2
in THF (200 mL). The resulting solution was stirred for 1 h,
and the white precipitate was filtered off. After cooling to -78
°C, a 3 M Et2O solution of MeMgCl (70 mL, 0.21 mol) was
added slowly. The solution was stirred for 3 h, during which
it reached room temperature. The magnesium chloride was
filtered off, and BH3‚SMe2 (29.3 mL, 23.47 g, 0.309 mol) was
slowly added. The solution was stirred for 3 h, and then the
solvent was evaporated. Chromatography (silica gel, toluene)
gave 6b as a colorless oil (15 g, 77%, 0.77 mol).31P NMR
(CDCl3): δ 0.1 (br q, 1P). 1H NMR (CDCl3): δ 6.89 (m, 2H,
ArH), 2.59 (s, 6H, 2 CH3), 2.37 (s, 3H, CH3), 1.74 (d, 6H, 2CH3,
J P,H ) 9.8 Hz), 1.64-1.04 (br, 3H, BH3). MS m/z (FAB+): 180
(M+ - BH3, 100), 165 (M+ - BH3 - CH3, 33), 45 (M+ - BH3 -
CH3 - Mes, 72).
(S,S)-(+)-1,2-Bis(m esitylm eth ylp h osp h in o)eth a n e Di-
bor a n e, (S,S)-7b. A 1.3 M hexane solution of s-BuLi (3.5 mL,
4.52 mmol) was added slowly to a solution of (-)-sparteine
(1.04 mL, 1.06 g, 4.52 mmol) in THF (15 mL) cooled at -78
°C. After stirring for 15 min, a solution of P(Mes)(Me)2(BH3)
(0.797 g, 4.106 mmol) in THF (20 mL) cooled at -78 °C was
added slowly thereto. The resulting solution was warmed to
-10 °C during 3 h and then cooled to -78 °C. A suspension of
CuCl2 (1.657 g, 12.319 mmol) in THF (20 mL) was added slowly
by cannula, and the resulting solution was allowed to reach
room temperature overnight. The reaction was quenched with
1 M HCl (20 mL). The organic layer was diluted with ethyl
acetate and washed with 37% NH3 (10 mL), brine (20 mL),
and water (2 × 20 mL). After drying over MgSO4, the solvent
was evaporated. Chromatography (silica gel, toluene, Rf 0.3)
and the solvent was evaporated. Crystallization from hot
20
hexane gave (S,S)-7a as a white solid (510 mg, 44%). [R]D
)
-37 (c 1, CHCl3).4 31P NMR (CDCl3): δ 19.4 (br q, 2P). 1H NMR
(CDCl3): δ 7.70-7.42 (m, 10 H, 2Ph), 1.88-1.56 (m, 4H, 2CH2),
0.83 (s, 18H, 6CH3), 1.28-0.67 (br, 6 H, 2BH3). MS m/z
(FAB+): 358 (M+ - 2BH3, 33), 329 (M+ - C(CH3)3, 100). Anal.
Calcd for C22H38B2P2: C, 68.44; H, 9.92. Found: C, 68.62; H,
9.53.
(S,S)-(-)-1,2-Bis(ter t-b u t ylp h en ylp h osp h in o)et h a n e,
(S,S)-8a . (S,S)-1,2-Bis(tert-butylphenylphosphino)ethane dibo-
rane, (S,S)-7a , (300 mg, 0.78 mmol) was dissolved in morpho-
line (5 mL). The solution was stirred for 2 h at 50 °C and then
evaporated to dryness at room temperature. Chromatography
(alumina, toluene) under argon gave pure (S,S)-8a (260 mg,
93%). The absolute configuration and enantiomeric purity of
(S,S)-8a ([R]D20) -78, C6H6, c 0.9, >98% ee) were determined
by comparison with the values reported by Imamoto for (R,R)-
8a ([R]D ) +78.7, c 0.9, C6D6).4 31P NMR (CDCl3): δ -18.6
20
1
(s, 2P). H NMR (CDCl3): δ 7.50-7.32 (m, 10H, 2Ph), 2.8 (m,
4H, 2CH2), 0.82 (s, 18H, 6CH3). MS m/z (FAB+): 358 (M+, 47),
329 (M+ - C(CH3)3, 100). Anal. Calcd for C22H38B2P2: C, 73.73;
H, 9.00. Found: C, 73.62; H, 9.17.
(2R,4S,5R)-(+)-3,4-Dim et h yl-2-m esit yl-5-p h en yl-1,3,2-
oxa za p h osp h olid in e-2-bor a n e, (RP )-3b. (1R,2S)-(-)-Ephe-
drine (6.41 g, 0.039 mol) was added to a solution of P(Mes)-
(NEt2)2 (11.445 g, 0.039 mol) in toluene (220 mL). The solution
was refluxed for 15 h and then cooled to room temperature.
BH3‚SMe2 (11.1 mL, 8.88 g, 0.117 mol) was added under
stirring. After 3 h, the solvent was evaporated, and the
resulting thick oil was purified by flash chromatography (silica
gel, hexane/ethyl acetate, Rf 0.4). Pure (RP)-3b (one single
diastereoisomer) was isolated as a white crystalline solid (5.359
20
gave (S,S)-7b as a white solid (490 mg, 62%). [R]D ) +13 (c
1, CHCl3). 31P NMR (CDCl3): δ 8.1 (br q, 2P). 1H NMR
(CDCl3): δ 6.89 (m, 4H, ArH), 2.49 (s, 12H, 4CH3), 2.29 (s,
6H, 2CH3), 1.75-1.49 (m, 4H, 2CH2), 1.66 (d, 6H, 2CH3,
J P,H ) 6.2 Hz), 1.25-0.47 (br, 6H, 2BH3). MS m/z (FAB+): 385
(M+, 79) 371 (M+ - BH3, 100), 359 (M+ - 2BH3, 43), 240
(M+ - 2BH3 - Mes, 29). Anal. Calcd for C22H38B2P2: C, 68.44;
H, 9.92. Found: C, 68.20; H, 9.77.
g, 42%, 0.016 mol). [R]D ) +5.7 (c 1, CHCl3). Mp 102 °C. 31P
20
NMR (CDCl3): δ 138.3 (s, 1P). 1H NMR (CDCl3): δ 7.42-7.27
(m, 5H, PhH), 6.85-6.84 (m, 2H, MesH), 5.16 (dd, 1H,
3J H,H′ ) 5.8 Hz, 3J P,H ) 3.8 Hz, OCHPh), 3.64 (m, 1H, NCHMe),
3
2.87 (d, 3H, J P,H ) 10.5 Hz, NCH3), 2.54 (s, 6H, 2CH3), 2.24
3
(s, 3H, CH3), 0.85 (d, 3H, J H,H′ ) 6.7 Hz, CH3), 1.7-0.2 (m,
3H, BH3). MS m/z (FAB+): 326 (M+, 66), 313 (M+- BH3, 100).
(S,S)-1,2-Bis(m esitylm eth ylp h osp h in o)eth a n e, (S,S)-
8b. (S,S)-1,2-Bis(mesitylmethylphosphino)ethane diborane,
(S,S)-7b, (490 mg, 1.27 mmol) was dissolved in morpholine (6
mL). The solution was stirred for 24 h at room temperature
and then evaporated to dryness at room temperature. Chro-
matography (alumina, toluene) under argon gave pure (S,S)-
8b (392 mg, 86%). The enantiomeric excess (37% ee) was
determined, as described below. 31P NMR (CDCl3): δ -39.1
(RP )-(+)-N-Meth yl[(1S,2R)-(2-h ydr oxy-1-m eth yl-2-ph en -
yl)et h yl]a m in om esit ylp h en ylp h osp h in e Bor a n e, (RP )-
4b. A hexane solution of PhLi (16.9 mL, 0.02 mol, 1.18 M, 1.6
equiv vs 3b) was added slowly to a THF solution (18 mL) of
(RP)-3b (5.083 g, 0.0156 mol) cooled at -78 °C. After stirring
for 30 min at -78 °C, the solution was allowed to reach room
temperature overnight. The reaction was quenched with H2O
(20 mL), and the THF was removed under vacuum. The crude
product was extracted with CH2Cl2 and dried over MgSO4.
Evaporation of the solvent and flash chromatography (silica
gel, toluene, Rf 0.19) gave (RP)-4b as a single diastereoisomer
(0.57 g, 91%). [R]D20 ) +17.2 (c 1, CH2Cl2). Mp 105 °C. 31P NMR
1
(s, 2P). H NMR (CDCl3): δ 6.84 (m, 4H, ArH), 2.50 (s, 12H,
4CH3), 2.25 (s, 6H, 2CH3), 1.89-1.79 (m, 4H, 2CH2), 1.42 (d,
6H, 2CH3, J P,H ) 6.4 Hz). MS m/z (FAB+): 359 (M+, 100), 343
(M+ - CH3, 39), 239 (M+ - Mes, 40). Anal. Calcd for
C
22H32P2: C, 73.73; H, 9.00. Found: C, 73.42; H, 8.91.
J . Org. Chem, Vol. 67, No. 15, 2002 5247

Maienza et al.
(R ,R )-Bis(1,2-(P -oxo-m e sit ylm e t h ylp h osp h in o)e t h -
a n e, (R,R)-9b. An excess of H2O2 (30%, 2 mL) was added to a
THF solution (2 mL) of (S,S)-8b (20 mg, 0.056 mmol). After
stirring for 15 min, H2O (5 mL) was added, the THF was
evaporated, and the product was extracted with CH2Cl2.
Evaporation of the solvent gave (R,R)- 9b as a white oil (21.6
mg, 99%). 31P NMR (CDCl3): δ 43.55 (s, 2P). The addition of
(S)-(+)-2,2,2-trifluoro-1-(9-anthryl)ethanol (4 equiv vs 9b) gave
separate signals for (R,R)-9b and (S,S)-9b. (R,R)-9b 31P NMR
(CDCl3): δ 47.09 (s, 2P, 68.4%). (S,S)-9b 31P NMR (CDCl3): δ
47.21 (s, 2P, 31.6%). 37% ee.
(R,R)- + (S,S)-1,2-Bis(m esitylm eth ylp h osp h in o)eth a n e
Dibor a n e, (l)-7b. A 1.3 M hexane solution of s-BuLi (2.5 mL,
3.19 mmol) was added slowly to a solution of P(Me)2(Mes)-
(BH3) (0.562 g, 2.896 mmol) in THF (10 mL) cooled at -78 °C.
The reaction solution was warmed to -10 °C during 3 h and
then cooled to -78 °C. A suspension of CuCl2 (1.164 g, 8.69
mmol) in THF (10 mL) was added slowly by cannula, and the
resulting solution was allowed to reach room temperature
overnight. Workup (as for (S,S)-7b) gave (l)-7b (335 mg, 60%)
and (u)-9b (84 mg, 15%). Diastereomerically pure (l)-9b was
obtained by crystallization from hexane/ethyl acetate 5:1. (l)-
9b has the same analytic properties as (S,S)-9b.
(M+ - 2BH3, 38), 251 (M+ - 2BH3 - P(Ant)(CH3), 93). Anal.
Calcd for C32H34P2B2: C, 76.54; H, 6.82. Found: C, 76.48; H,
6.61.
(S,S)-1,2-Bis(9-a n th r ylm eth ylp h osp h in o)eth a n e, (S,S)-
8c. (S,S)-7c (200 mg, 0.4 mmol) was dissolved in morpholine
(8 mL), and the solution was stirred for 24 h at room
temperature and then evaporated to dryness at room temper-
ature. A short column of alumina in toluene under argon gave
pure (S,S)-8c as a yellow solid (166 mg, 88%). The enantio-
meric excess (18% ee) was determined as described below. 31
P
1
NMR (CDCl3): δ -27.3 (s, 2P). H NMR (CDCl3): δ 8.52 (m,
2H, AntH), 8.21 (s, 1H, AntH), 8.02 (m, 2H, AntH), 7.67 (m,
2H, AntH), 7.53 (m, 2H, AntH), 2.23 (m, 4H, 2CH2), 1.61 (d,
6H, 2CH3, J P,H ) 8.3 Hz). MS m/z (FAB+): 472 (M+, 68), 295
(M+ - Ant, 23). Anal. Calcd for C32H28P2: C, 81.00; H, 5.95.
Found: C, 81.26; H, 5.66.
(R,R)-1,2-Bis(P -oxo-9-a n t h r ylm et h ylp h osp h in o)et h -
a n e, (R,R)-9c. An excess of H2O2 (30%, 2 mL) was added to
(S,S)-8c (20 mg, 0.04 mmol) in THF (2 mL). After stirring for
15 min, H2O (5 mL) was added, the THF was evaporated, and
the product was extracted with CH2Cl2. Evaporation of the
solvent gave (R,R)-9c as a yellow powder (19.7 mg, 99%). 31P
NMR (CDCl3): δ 42.2 (s, 2P). The addition of (S)-(+)-2,2,2-
trifluoro-1-(9-anthryl)ethanol (2 equiv vs 9c) gave (R,R)- 9c
and (S,S)- 9c. (R,R)- 9c 31P NMR (CDCl3): δ 45.28 (s, 2P,
59.1%). (S,S)- 9c 31P NMR (CDCl3): δ 45.19 (s, 2P, 40.9%).
18% ee.
(R,R)- + (S,S)-1,2-Bis(9-a n th r ylm eth ylp h osp h in o)eth -
a n e Dibor a n e, (l)-7c. A hexane solution of s-BuLi (0.65 mL,
0.8 mmol, 1.3 M) was added slowly to a solution of 6c (0.194
g, 0.8 mmol) in THF (3 mL) cooled at -78 °C. The mixture
was then stirred for 3 h at -78 °C. A suspension of CuCl2
(0.311 g, 2.3 mmol) in THF (5 mL) was added slowly by
cannula, and the resulting solution was allowed to reach room
temperature overnight. Workup was as for (S,S)-7c. Chroma-
tography (silica gel, hexane/ethyl acetate 7:1, Rf 0.35) yielded
(l)-7c (114 mg, 57%, 0.3 mmol) and some (u)-7c (30 mg, 15%).
31P NMR (CDCl3): δ 14.8 (br q, 2P). 11B NMR (CDCl3): δ 35.6
(d, 2B, J P,B ) 60 Hz). 1H NMR (CDCl3): δ 8.44 (m, 2H, AntH),
8.26 (s, 1H, AntH), 7.99 (m, 2H, AntH), 7.47 (m, 2H, AntH),
7.25 (m, 2H, AntH), 2.14 (m, 4H, 2CH2), 1.68 (d, 6H, 2CH3,
J P,H ) 8.3 Hz), 1.72-0.94 (br, 3H, BH3).
(R,R)- + (S,S)-1,2-Bis(m esitylm eth ylp h osp h in o)eth a n e,
(l)-8b. Same preparation and analytic properties as those
given for (S,S)-8b.
(R,R)- + (S,S)-1,2-Bis(P -oxo-m esitylm eth ylp h osp h in o)-
eth a n e, (l)-9b. The racemic phosphine oxide (l)-9b was
prepared from (l)-8b with the same procedure used for (R,R)-
9b. 31P NMR (CDCl3): δ 43.55 (s, 2P). The addition of (S)-(+)-
2,2,2-trifluoro-1-(9-anthryl)ethanol (4 equiv vs (l)-9b) gave
separate signals for (R,R)-9b and (S,S)-9b. (R,R)-9b 31P NMR
(CDCl3): δ 47.67 (s, 2P, 50%). (S,S)-9b 31P NMR: δ 47.81 (s,
2P, 50%).
9-An th r yld im eth ylp h osp h in e Bor a n e, 6c. A 3 M Et2O
solution of methylmagnesium chloride (48 mL, 0.143 mol) was
added slowly to 9-anthryldichlorophosphine (20 g, 0.072 mol)
in THF (500 mL) at -50 °C, and the solution was stirred
overnight to reach room temperature. BH3‚SMe2 (20.5 mL,
0.216 mol) was slowly added. After stirring for 3 h, the solvent
was evaporated, and the crude product was extracted with
toluene. Recrystallization from hexane/ethyl acetate 4:1 gave
6c as a yellow solid (18.04 g, 99%, 0.071 mol). 31P NMR
(R,R)- + (S,S)-1,2-Bis(9-a n th r ylm eth ylp h osp h in o)eth -
a n e, (l)-8c. Same preparation and analytic properties as those
given for (S,S)-8c.
1
(CDCl3): δ -5.9 (br q, 1P). H NMR (CDCl3): δ 8.94 (m, 2H,
AntH), 8.61 (s, 1H, AntH), 8.05 (m, 2H, AntH), 7.62 (m, 2H,
AntH), 7.52 (m, 2H, AntH), 2.05 (d, 6H, 2CH3, J P,H ) 9.6 Hz),
1.95-1.24 (br, 3H, BH3). MS m/z (FAB+): 237 (M+ - BH3, 100),
221 (M+ - BH3 - CH3, 39), 207 (M+ - BH3 - 2CH3, 17).
(R,R)- + (S,S)-1,2-Bis(P -oxo-9-a n th r ylm eth ylp h osp h i-
n o)eth a n e, (l)-9c. The racemic phosphine oxide was prepared
from (l)-8c with the same procedure used for (R,R)-9c. 31P
NMR (CDCl3): δ 43.55 (s, 2P). The addition of (S)-(+)-2,2,2-
trifluoro-1-(9-anthryl)ethanol (4 equiv vs (l)-9c) gave separate
signals for (R,R)-9c and (S,S)-9c. (R,R)-9c 31P NMR (CDCl3):
δ 45.28 (s, 2P, 50%); (S,S)-9c 31P NMR (CDCl3): δ 45.19 (s,
2P, 50%).
(2R,4R)-2-Mesityl-4-p h en yl-2,4-d ip h osp h a p en ta n e Di-
bor a n e, (2R,4R)-11. A 1.3 M hexane solution of s-BuLi (9.8
mL, 12.8 mmol) was added slowly to a solution of 6b (2.26 g,
11.6 mmol) in THF (80 mL) cooled at -78 °C. The orange
solution was allowed to reach -10 °C in 5 h. (S)-PCl(Ph)(Me)-
(BH3), (S)-10, was prepared in situ by slowly adding a 1 M
solution of HCl in Et2O (12 mL, 12 mmol) to a solution of (RP)-
(-)-N-methyl[(1S,2R)-(2-hydroxy-1-methyl-2-phenyl)ethyl]ami-
nomethylphenylphosphine borane, (RP)-4a , (1.75 g, 5.8 mmol)
in toluene (60 mL) under stirring. After 1 h, the white salt
was filtered off. The yield of the chlorophosphine borane (S)-
10 was found to be 99% by NMR spectroscopy (31P NMR: δ
96 (br q, 1P)). The orange solution of (R)- and (S)-P(Mes)(CH2-
Li)(Me)(BH3) (cooled at -78 °C) was slowly added to the
colorless solution of (S)-10 (cooled at -78 °C). The resulting
solution was allowed to reach room temperature overnight and
was then quenched with water (20 mL). The product was
extracted with ethyl acetate and dried with MgSO4. The 1H
and 31P NMR spectra of the crude product indicate the
(S,S)-(+)-1,2-Bis(9-an th r ylm eth ylph osph in o)eth an e Di-
bor a n e, (S,S)-7c. A hexane solution of s-BuLi (1.7 mL, 2.2
mmol, 1.3 M) was added slowly to a solution of (-)-sparteine
(0.5 mL, 0.511 g, 2.2 mmol) in THF (6 mL) cooled at -78 °C.
After stirring for 15 min, a solution of 6c (0.500 g, 1.9 mmol)
in THF (7 mL) cooled at -78 °C was added slowly to the first
solution. The mixture was then stirred for 3 h at -78 °C. A
suspension of CuCl2 (0.800 g, 5.95 mmol) in THF (10 mL) was
added slowly by cannula, and the resulting solution was
allowed to reach room temperature overnight. The reaction
was quenched with 1 M HCl (10 mL) and diluted with ethyl
acetate. The organic layer was washed with NH3 37% (6 mL),
brine (10 mL), and water (2 × 10 mL). After drying with
MgSO4, the solvent was evaporated. The crude product was
purified by chromatography (silica gel, hexane/ethyl acetate
5:1, Rf 0.5) and isolated as a 6:1 mixture of the diastereoiso-
mers (l)-7c and (u)-7c (690 mg, 70%). Pure (S,S)-7c was
crystallized as a yellow solid from CH2Cl2/Et2O 1:1 (385 mg,
39%). [R]D20 ) +11.3 (c 0.25, CHCl3). 31P NMR (CDCl3): δ 14.8
1
(br q, 2P). 11B NMR (CDCl3): δ 35.6 (d, 2B, J P,B ) 60 Hz). H
NMR (CDCl3): δ 8.44 (m, 2H, AntH), 8.26 (s, 1H, AntH), 7.99
(m, 2H, AntH), 7.47 (m, 2H, AntH), 7.25 (m, 2H, AntH), 2.14
(m, 4H, 2CH2), 1.68 (d, 6H, 2CH3, J P,H ) 8.3 Hz), 1.72-0.94
(br, 3H, BH3). MS m/z (FAB+): 486 (M+ - BH3, 15), 472
5248 J . Org. Chem., Vol. 67, No. 15, 2002

Synthetic Strategies for Diphosphines
presence of two diasteromers in a 5:1 ratio. Evaporation of the
solvent and chromatography (silica gel, toluene, Rf 0.35) gave
(2R,2R)-11 as a white solid (1.266 g, 66%). HPLC (OD, hexane/
2-propanol 98:2): (2R,4R)/(2S,4S) ) 92.7:7.3 ((2R,4R)-11 )
11.96 min, (2S,4S)-11 ) 13.73 min). 85.6% ee. 31P NMR
the solution was concentrated under vacuum (1 mL), and Et2O
was added. The resulting orange precipitate was filtered off,
washed with Et2O, and dried in a vacuum. The product was
isolated as its water adduct 13a ‚3H2O (42 mg, 76%), as
20
indicated by integration of the 1H NMR spectrum. [R]D
)
1
(CDCl3): δ 6.4 (br q, 1P), 9.5 (br q, 1P). H NMR (CDCl3): δ
-9.5 (c 0.15, CHCl3). 31P NMR (CDCl3, 162 MHz): δ 39.2 (d,
1J Rh,P ) 145.1 Hz, 2P). 1H NMR (CDCl3): δ 6.9 (m, 4H, MesH),
5.25 (s, 2H, CH2Cl2), 4.24, 3.65 (2 s br, 4H, 4 dCH), 2.79-
2.49 (m, 4H, 2CH2), 2.54-2.29, 1.85-1.57 (2 m, 8H, 4CH2),
2.46 (s, 6H, 2CH3), 2.29 (s, 12H, 4CH3), 2.14 (d, 6H, 2CH3,
7.43 (m, 5H, PhH), 6.81 (m, 4H, H3Mes, H5Mes), 2.45 (s, 6H,
2CH3), 2.28 (s, 3H, CH3), 2.21 (m, 2H, CH2), 1.94 (d, 3H, CH3,
J P,H ) 9.5 Hz), 1.88 (d, 3H, CH3, J P,H ) 10.1 Hz), 1.29-0.82
(br, 6H, 2BH3). 11B NMR (CDCl3): δ -29 (br d, 1B, J P,B ) 59
Hz), -38 (br d, 1B, J P,B ) 61 Hz). MS m/z (FAB+): 329 (M+,
J P,H) 7.4 Hz), 1.60 (s, 6H, 3H2O). MS m/z (FAB+): 569 (M+
-
25), 315 (M+ - BH3, 100), 303 (M+ - 2BH3, 97), 196 (M+
2BH3 - 2BH3 - Ph, 96), 179 (MesPCH3+, 95), 137 (PhPCH3
-
BF4, 83), 461 (M+ - BF4 - COD, 100). Anal. Calcd for C30H44
-
+
,
BF4P2Rh‚CH2Cl2‚3H2O: C, 46.82; H, 6.59. Found: C, 47.41;
H, 6.23.
83). Anal. Calcd for C18H30B2P2: C, 65.52; H, 9.16. Found: C,
65.38; H, 9.10.
[Rh (COD)((S,S)-8d )]BF 4, 13d . [Rh(COD)2]BF4 (82 mg,
0.201 mmol) and (S,S)-8d (100 mg, 0.201 mmol) were dissolved
in THF (5 mL). After stirring for 15 h at room temperature,
the solution was concentrated to 1 mL, and Et2O was added.
The resulting yellow precipitate was filtered off, washed with
(2R,4R)-2-Mesityl-4-ph en yl-2,4-diph osph apen tan e, (2R,-
4R)-12. (2R,4R)-11 (590 mg, 1.8 mmol) was dissolved in
morpholine (8 mL), and the solution was stirred for 24 h at
room temperature. After evaporating the solution to dryness
at room temperature, chromatography under argon (alumina,
toluene) gave (2R,4S)-12 as a thick oil (443 mg, 82%). 31P NMR
20
Et2O, and dried in a vacuum (159 mg, 99%). [R]D ) -274 (c
1
0.41, CHCl3). 31P NMR (CDCl3, 162 MHz): δ 51.6 (d, J Rh,P
)
1
(CDCl3): δ -38.2 (d, 1P, J P,P′ ) 144 Hz), -50.2 (d, 1P, J P,P′
)
149.6 Hz, 2P). H NMR (CDCl3): δ 8.12 (m, 2H, NpH), 7.99-
7.31 (m, 22H, ArH), 4.90, 3.75 (2 s br, 4H, 4 dCH), 2.54-2.29,
1.85-1.57 (2 m, 8H, 4 CH2). MS m/z (FAB+): 709.2 (M+ - BF4,
1
144 Hz). H NMR (CDCl3): δ 7.47 (m, 5H, PhH), 6.83 (m, 4H,
H3Mes, H5Mes), 2.42 (s, 6H, 2CH3), 2.27 (s, 3H, CH3), 2.13 (m,
2H, CH2), 1.92 (d, 3H, CH3, J P,H ) 9.5 Hz), 1.85 (d, 3H, CH3,
J P,H ) 10.1 Hz). MS m/z (FAB+): 303 (M+, 93), 287 (M+ - CH3,
100), 179 (MesPCH3+, 84). Anal. Calcd for C18H24P2‚0.25C7-
H8: C, 72.91; H, 8.05. Found: C, 72.93; H, 7.98.
100), 599.1 (M+ - BF4 - COD, 57). Anal. Calcd for C42H40
-
BF4P2Rh: C, 63.34; H, 5.06. Found: C, 62.84; H, 5.84.
[Rh (COD)((2R,4R)-12)]P F 6, 15. [RhCl(COD)]2 (61 mg,
0.124 mmol) and NH4PF6 (40 mg, 0.248 mmol) were dissolved
in THF (5 mL). A solution of (2R,4R)-12 (75 mg, 0.248 mmol)
in THF (6 mL) was added under argon. After stirring for 15 h
at room temperature, the white precipitate was filtered off,
and Et2O was added. The resulting orange solution was filtered
and dried in a vacuum to give 15 as an orange powder (110
(2S,4S)-2-Mesityl-4-p h en yl-2,4-d ip h osp h a p en ta n e Di-
bor a n e, (2S,4S)-11. A 1.3 M hexane solution of s-BuLi (1.98
mL, 2.58 mmol) was added slowly to a solution of 6b (500 mg,
2.58 mmol) in THF (20 mL) cooled at -78 °C. The orange
solution was allowed to reach -10 °C in 5 h. (R)-PCl(Ph)(Me)-
(BH3) was prepared in situ by slowly adding a 1 M solution of
HCl in Et2O (12 mL, 12 mmol) to a solution of (SP)-N-methyl-
[(1R,2S)-(2-hydroxy-1-methyl-2-phenyl)ethyl]aminomethyl-
phenylphosphine borane, (SP)-4a , (775 mg, 1.3 mmol) in
toluene (60 mL) under stirring. Reaction conditions and
workup as those described for (2R,4R)-11 gave (2S,4S)-11
(0.258 g, 66%). HPLC (OD, hexane/2-propanol 98:2): (2S,4S)/
(2R,4R) ) 91.2:8.8 ((2R,4R)-11 ) 11.96 min, (2S,4S)-11 ) 13.73
min). 82.3% ee. Same analytical properties as those given for
(2R,4R)-11.
(2S,4S)-2-Mesityl-4-p h en yl-2,4-d iph osp h a p en ta n e, (2S,-
4S)-12. (2S,4S)-11 (0.200 mg, 0.61 mmol) was dissolved in
morpholine (8 mL), and the solution was stirred for 24 h at
room temperature. After evaporating the solution to dryness
at room temperature, chromatography under argon (alumina,
toluene) gave (2S,4S)-12 as a thick oil (151 mg, 82%). Same
analytical properties as those given for (2R,4R)-12.
mg, 68%). [R]D ) -49.3 (c 0.125, CHCl3). 31P NMR (CDCl3):
20
δ -10.6 (dd, 1P, J P,Rh ) 95 Hz, J P,P′ ) 80 Hz), -22.0 (dd, 1P,
J P,Rh ) 95 Hz, J P,P′ ) 80 Hz), -150 (septet, 1P, PF6, J P,F ) 713
Hz). 1H NMR (CDCl3): δ 7.39 (m, 5H, PhH), 6.85 (m, 4H,
H3Mes, H5Mes), 4.22, 3.62 (2 s br, 4H, 4 dCH), 2.53 (m, 2H,
CH2), 2.41 (s, 6H, 2CH3), 2.25 (s, 3H, CH3), 2.38, 1.65 (2 m,
8H, 4CH2), 2.03 (d, 3H, CH3, J P,H ) 11.3 Hz), 1.81 (d, 3H, CH3,
J P,H ) 9.1 Hz). MS m/z (FAB+): 527 (M+ - PF6 + CH3, 100),
512 (M+ - PF6, 43), 405 (M+ - PF6 - COD, 14). Anal. Calcd
for C26H36F6P3Rh: C, 47.43; H, 5.51. Found: C, 47.41; H, 5.66.
Ca ta lytic Hyd r ogen a tion . The standard procedure was
as follows: the substrate and the catalyst were dissolved in
10 mL of the solvent under argon. The solution was stirred
for 15 min and then transferred via a steel capillary into a
180-mL thermostated glass reactor or a 50-mL stainless steel
autoclave. The inert gas was then replaced by hydrogen (three
cycles), and the pressure was set. After completion of the
reaction (total reaction times 15-65 h), the conversion was
determined by gas chromatography, and the product was
recovered quantitatively after filtration of the reaction solution
on a plug of silica to remove the catalyst. See the Supporting
Information for analytical details concerning the determination
of the enantiomeric excess of the products.
[Rh (COD)((S,S)-8a )]BF 4, 13a . [Rh(COD)2]BF4 (57 mg,
0.139 mmol) and (S,S)-8a (50 mg, 0.139 mmol) were dissolved
in THF (5 mL). After stirring for 12 h at room temperature,
the solution was concentrated under vacuum (1 mL), and Et2O
was added. The resulting orange precipitate was filtered off,
washed with Et2O, and dried in a vacuum. The product was
20
isolated as its water adduct 13a ‚H2O (53 mg, 81%). [R]D
)
-92 (c 0.25, CHCl3). 31P NMR (CDCl3, 162 MHz): δ 55.3 (d,
1J Rh,P ) 148.9 Hz, 2P). 1H NMR (CDCl3): δ 7.3 (m, 10H, PhH),
5.58, 4.22 (2 s br, 4H, 4 dCH), 2.69-2.46 (m, 4H, 2CH2), 2.35,
1.69 (2 m, 8H, 4CH2), 1.61 (s, 4H, H2O), 1.25 (s, 18H, 6CH3).
MS m/z (FAB+): 569 (M+ - BF4, 72), 461 (M+ - BF4 - COD,
100), 211 (M+ - BF4 - P-P, 23). Anal. Calcd for C30H44BF4P2-
Rh‚H2O: C, 53.43; H, 6.87. Found: C, 53.21; H, 6.69.
Ack n ow led gm en t. We thank the Novartis For-
schungsstiftung for financial support to F.M.
Su p p or tin g In for m a tion Ava ila ble: Analytical details
of the determination of the enantiomeric purity (Figure S1)
and energy-minimized conformations of 15 (Figure S2). This
material is available free of charge via the Internet at
http://pubs.acs.org.
[Rh (COD)((S,S)-8b)]BF 4, 13b. [Rh(COD)2]BF4 (34 mg,
0.084 mmol) and (S,S)-8b (30 mg, 0.084 mmol) were dissolved
in THF (5 mL). After stirring for 12 h at room temperature,
J O020130L
J . Org. Chem, Vol. 67, No. 15, 2002 5249