Chiral 1,2-bis(phosphetano)benzenes: Preparation and use in the Ru- catalyzed hydrogenations of carbonyl derivatives

Article abstract of DOI:10.1002/(SICI)1521-3765(19990401)5:4<1160::AID-CHEM1160>3.0.CO;2-3

Chiral 1,2-bis(phosphetano)benzenes are readily prepared from accessible, optically pure 1,3-diol cyclic sulfates. Their ruthenium complexes catalyze the enantioselective hydrogenations of functionalized carbonyls with moderate-to-high enantiomeric excesses. High levels of diastereo- and enantioselectivity are achieved, especially in the hydrogenation of β-diketones to the corresponding anti-1,3-diols.

Full text of DOI:10.1002/(SICI)1521-3765(19990401)5:4<1160::AID-CHEM1160>3.0.CO;2-3

FULL PAPER
Chiral 1,2-Bis(phosphetano)benzenes: Preparation and Use in the
Ru-Catalyzed Hydrogenations of Carbonyl Derivatives
Angela Marinetti,* Jean-Pierre GeneÃt,* SeÂbastien Jus, Delphine Blanc,
and Virginie Ratovelomanana-Vidal[a]
Abstract: Chiral 1,2-bis(phosphetano)benzenes are readily prepared from accessi-
ble, optically pure 1,3-diol cyclic sulfates. Their ruthenium complexes catalyze the
enantioselective hydrogenations of functionalized carbonyls with moderate-to-high
enantiomeric excesses. High levels of diastereo- and enantioselectivity are achieved,
especially in the hydrogenation of b-diketones to the corresponding anti-1,3-diols.
Keywords: catalysts ´ chiral phos-
phetanes ´ hydrogenations ´ phos-
phorus ´ ruthenium
also reduce their suitability as auxiliaries in transition-metal-
promoted reactions.[5] In order to address these points, we
explored the potential of the bis(phosphetano)benzenes 1 as
chiral auxiliaries in various catalytic reactions. We began with
their use in ruthenium-catalyzed reactions as part of our
ongoing research into both new and known chiral ligands for
ruthenium chemistry.[6]
Here we report the synthetic procedure for preparation of
the new chiral bis(phosphetano)benzenes 1b ± d, (abbreviated
to R-CnrPHOS), as well as details of the synthesis of 1a.
Preliminary evaluations of these diphosphines as chiral
auxiliaries in the ruthenium-catalyzed hydrogenations of
carbonyl derivatives are also presented.
Introduction
Electron-rich, C2-symmetric diphosphines, in which the phos-
phorus atom is located in a cyclic moiety, have emerged
recently as a valuable class of chiral ligands in transition
metal-promoted asymmetric catalysis. The pioneering work of
M. J. Burk et al. led to the phospholane-based DuPHOS and
BPE ligands,[1] while the subsequent use of bicyclic phospho-
rus derivatives by X. Zhang and co-workers, established the
PennPHOS ligand series.[2]
With the same general approach, use of the 2,4-disubsti-
tuted phosphetane moiety as a chiral motif for ligand design
can be envisaged. Thus, we reported recently the synthesis of
the 1,2-bis[(S,S)-2,4-dimethylphosphetano]benzene 1a (R ˆ
Me),[3] which represents a new
class of bidentate phosphines
(related structurally to the Du-
Results and Discussion
PHOS ligands) with potential
applications in enantioselec-
tive catalysis.
From the high catalytic effi-
ciency and enantiomeric ex-
cesses achieved with DuPHOS,
The synthesis of 1,2-bis(phosphetano)benzenes with various
R substituents on the phosphetane ring has been studied. The
chiral induction from ligands 1 is related to the steric
requirements of the R substituents, such that structural
modifications are expected to affect significantly and optimize
enantioselectivities in the catalytic reactions.
As mentioned in a preliminary communication,[3] the
synthesis of 1a was performed from the optically pure
(R,R)-2,4-pentanediol via the corresponding cyclic sulfate.
The same approach has been extended to the preparation of
the new chiral bis(phosphetano)benzenes 1b ± d, as shown in
Scheme 1.
one can reasonably anticipate interesting catalytic properties
for phosphetanes like 1. However, although the low con-
formational flexibility of the four-membered ring is expected
to have a positive effect on asymmetric reactions, the
stability[4] of such strained four-membered heterocycles might
A solution of dilithio-1,2-diphosphinobenzene in THF was
added at low temperature to a solution in THF of the
appropriate cyclic sulfate 2. (The sulfate was prepared in
quantitative yields from the corresponding 1,3-diols, accord-
ing to the Sharpless procedure.[7]) Subsequent addition of
sBuLi induced deprotonation of each remaining P H group
Ã
[a] Dr. A. Marinetti, Prof. J.-P. Genet, S. Jus, D. Blanc,
Dr. V. Ratovelomanana-Vidal
Á
Â
Laboratoire de Synthese Selective Organique et Produits Naturels
UMR C.N.R.S. 7573, 11, rue Pierre et Marie Curie
F-75231 Paris, Cedex 05 (France)
Fax : (‡ 33)144071062
E-mail: marinet@ext.jussieu.fr
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Chem. Eur. J. 1999, 5, No. 4

1160±1165
Scheme 2. Catalytic hydrogenation of the b-diketones 4. i) (L*)RuBr2
0.2 ± 0.5%, H2, 40 ± 100 bar, MeOH, 30 ± 508C, 70 h (L* ˆ (S)-BINAP or
(S)-MeO-BIPHEP).
diethyl ether/pentane mixture gave the optically pure diol
(R,R)-5b. This procedure provides a practical and efficient
route to relatively large quantities of 5b and compares
favourably with the previously described approaches, which
produce the optically pure diol in a maximum total yield of
60%.[9]
The highly diastereo- and enantioselective hydrogenation
of 4c (R ˆ Et) in the presence of ruthenium ± BINAP com-
plexes has already been reported by M. Saburi et al.[8b] With
slightly modified reaction conditions (hydrogenation at room
temperature; H2, 40 bar), the optically pure diol 5c was
obtained after crystallization of the crude reaction mixture.
The optimal procedure for synthesis of 5d involved hydro-
genation of 4d at room temperature with a pressure of
100 bar, followed by crystallization.
The availability of the optically pure 1,3-diols on a large
scale makes the phosphetanes 1 a new and easily accessible
class of chiral ligands with potential practical use. A con-
current patent application by Chiroscience Ltd describes the
synthesis of 1,3-diols by analogous hydrogenation reactions
and their involvement in the preparation of monodentate
phosphetanes.[10]
For a preliminary evaluation of the catalytic efficiency and
enantioselectivity of complexes containing the bis(phosphe-
tano)benzenes 1, we examined the ruthenium-promoted
hydrogenations of carbonyl derivatives on a few model
substrates. The screening tests were carried out on a one
millimolar scale with preparation of the (phosphine)RuBr2
complexes in situ (Scheme 3); this has already been applied to
a wide range of chiral ligands to form active hydrogenation
catalysts.[6] The ruthenium dibromide complex 6 is thought to
be the catalyst precursor.
Scheme 1. Preparation of the bis(phosphetano)benzenes 1. i) dilithio-1,2-
diphosphinobenzene, THF, 788C/258C; ii) sBuLi, 788C/258C;
iii) BH3 ´ SMe2; iv) DABCO, 408C, 2 h, benzene.
with ring closure to the desired bis(phosphetano)benzenes
1a ± d. Inversion of stereochemistry is expected at the carbon
centers of the cyclic sulfates. Complexation of the phosphorus
atoms by BH3 was envisaged in order to prevent accidental
oxidation during the purification steps. Thus, addition of
BH3 ´ SMe2 to the reaction mixture afforded the monoborane
adducts 3, which were isolated in 40 ± 50% yields after
chromatography. The bis-borane complex (3a') was obtained
in very small amounts only when a large excess of borane was
added to the crude phosphetane 1a. Quantitative displace-
ments of 1 from their borane complexes were achieved by
reaction of 3 with 1,4-diazabicyclo[2.2.2]octane (DABCO,
1.0 equiv) at 408C in benzene. Phosphetanes 1a and 1c are
colorless, air-sensitive oils, while 1b and 1d are colorless
solids, which are relatively air stable both in the solid state and
in solution (about 40% conversion of 1b to the phosphine
oxide was observed on standing for 2 weeks in solution in
C6D6). The sterically hindered environment of the phosphorus
atoms probably accounts for such air stability.
The phosphetane synthesis depends on the availability of
the enantiomerically pure 1,3-diols, whose cyclic sulfates are
involved in the above reaction. (R,R)-2,4-Pentanediol is
commercially available, but the other diols were prepared
conveniently by the (S)-BINAP or (S)-MeO-BIPHEP/ruthe-
nium-catalyzed hydrogenations[8] of 2,6-dimethyl-3,5-hep-
tanedione, 3,5-heptanedione, and 1,3-dicyclohexyl-1,3-pro-
panedione (Scheme 2), respectively. The ruthenium catalyst
was prepared in situ from (S)-BINAP or (S)-MeO-BIPHEP
and [(COD)Ru(2-methylallyl)2] by addition of methanolic
HBr as in the previously published method.[6]
Hydrogenation of 4b (6 g, R ˆ iPr) afforded the (R,R)-anti
diol as the only detectable product, with an enantiomeric
1
excess higher than 95% (determined by H and 19F NMR
spectroscopy of the corresponding (R)-methoxy(trifluorome-
thyl)phenylacetyl (MTPA) diester). Crystallization from a
Scheme 3. Preparation of the ruthenium-1 catalysts for hydrogenation
reactions.
Representative substrates such as a- and b-ketoesters, b-
thioketones, and b-dicarbonyls have been considered. The
results for nonoptimized reaction conditions are given in
Tables 1 and 2.
Most of the catalytic tests have been performed with
phosphetane 1b as the chiral auxiliary. Comparative tests
have been run with 1a, 1b, and 1d. In all cases, the steric
hindrance of the isopropyl or cyclohexyl groups in 1b or 1d
improves significantly the chiral induction with respect to the
Abstract in French: Les 1,2-bis(phosphØtano)benz›nes chi-
raux sont facilement accessibles à partir des sulfates cycliques
de diols-1,3 optiquement purs. En association avec le ruthØ-
nium, ces nouveaux ligands catalysent lꢀhydrogØnation Ønan-
tiosØlective de dØrivØs carbonylØs fonctionnalisØs avec des exc›s
ØnantiomØriques significatifs. De bonnes diastØrØo- et Ønantio-
sØlectivitØs sont obtenues tout particuli›rement dans lꢀhydro-
gØnation de b-dicØtones en diols-1,3 anti.
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Ã
A. Marinetti, J.-P. Genet et al.
FULL PAPER
Table 1. Ruthenium-catalyzed hydrogenations of functionalized carbonyl de-
rivatives.
formed mostly with the atropoisomeric BINAP and BI-
PHEMP ligands,[8] which showed high catalytic efficiency and
selectivity. Somewhat lower activity and selectivity were
observed for the reduction of 2,4-pentanedione with Skew-
PHOS.[11]
With the ruthenium ± phosphetane complexes, high temper-
atures (808C) and hydrogen pressures (70 ± 80 bar) are
required to achieve complete conversion of the 1,3-diketones
into the corresponding diols. Milder conditions (508C, 20 bar)
gave a conversion rate of only 75% after 64 hours for
hydrogenation of even the most reactive substrate 2,4-
pentanedione. With ligand 1b, the anti diols were formed as
the sole reaction products (within the limits of detection of
1H NMR analysis) in high enantiomeric excesses, despite the
harsh, nonoptimized reaction conditions. The sense of chiral
induction is fully consistent with the stereochemical issues of
the BINAP-catalyzed reactions. For instance, (R)-BINAP and
(S,S)-1b, which give the same differentiation of the space
sectors, afford the same enantiomers of the final diols.
Substrate
Ligand Conditions
Conversion ee [%][b]
[%][a]
1
2
3
4
5
6
7
8
9
MeCOCH2CO2Me 1a
50 bar, 508C, 64h 100
20(S)
76(R)
84(R)
42(R)
87(S)
84(S)
94(S)
50(R)
45(R)
97(S)
1b
1d
100
95
50
100
100
75
80 bar, 808C, 22h
50 bar, 508C, 64h
PhCOCH2CO2Et
PhCOCO2Et
1a
1b
1d
1b
1b
1d
20 bar, 508C, 64h
20 bar, 508C, 90h
80 bar, 808C, 22h
76
94
10
MeCOCH2CH2SPh 1b
80 bar, 808C, 22h 100
[a] Conversion rates were determined by 1H NMR on the crude reaction
mixture. [b] The enantiomeric excesses were determined by chiral GC on a
Lipodex A column, for a- and b-hydroxyesters, and on a Megadex 5 column, for
the g-hydroxysulfide. The absolute configurations were established from the
GC retention times by comparison with known samples.
Table 2. Ruthenium-catalyzed hydrogenations of b-diketones.
R
Ligand
Diol
Conversion [%][a]
ee [%][b]
1
2
3
4
5
Me
Me
Me
Et
1a
1b
1d
1b
1b
5a
5a
5a
5c
5b
100 (de ˆ 85%)
82 (S,S)
98 (R,R)
97 (R,R)
95 (R,R)
98 (S,S)
Scheme 4. Stereochemical correlation between the chiral ligand and the
final diol.
100
100 (de ˆ 94%)
100
100
iPr
The isopropyl groups of (S,S)-1b block the upper-left and
bottom-right quadrants at the metal atom (Scheme 4a). The
b-dicarbonyl substrate should enter the coordination sphere
of the metal so as to minimize steric interactions with these
hindered groups (Scheme 4b). Hydrogen addition to this
intermediate affords the predominant product observed
experimentally. The graphical sketch above is based on the
generally accepted coordination mode of chelating substrates
in analogous hydrogenation reactions. The actual structure of
the catalytic intermediate cannot be defined at present.
From a practical standpoint, the most significant test in
Table 2 is the reduction of 2,6-dimethyl-3,5-heptanedione by
the ruthenium-1b complex, which affords the (S,S)-diol 5b in
high enantiomeric excess (entry 5). The enantiomer of this
diol was used as the starting material for the synthesis of (S,S)-
1b. Thus, we have presented a new example of a crossed self-
breeding process, in which the chiral ligand catalyzes the
formation of an intermediate, which can be converted into the
other enantiomer of the same ligand. Previous examples of
asymmetric self-breeding systems applied to the synthesis of
chiral phosphines are the preparations of ProPHOS,[12]
SkewPHOS,[11] and BPE.[13]
1
[a] Conversion rates were determined by H NMR on the crude reaction
mixture. Unless otherwise noted, diastereomeric excesses higher than 95%
were obtained, according to the 1H NMR spectra. [b] Enantiomeric
excesses and absolute configurations of the diols were determined by
1H NMR and/or GC on the corresponding (R)-methoxy(trifluoromethyl)-
phenylacetyl diesters, by comparison with known samples.
a-methyl-substituted phosphetane 1a (entries 1 vs 2 or 3, and
4 vs 5 or 6 in Table 1; entry 1 vs 2 or 3 in Table 2). Ligands 1b
and 1d behave much the same way.
Catalytic activity in the hydrogenations of b-ketoesters is
moderate. Nevertheless, significant enantiomeric excesses can
be obtained with 1b (or 1d), especially in the case of ethyl
benzoylacetate. This substrate can be reduced with an
enantiomeric excess of up to 94%, albeit in conditions in
which incomplete conversion is obtained (Table 1, entry 7).
For the reduction of ethyl benzoylformate promoted by
ruthenium-1b (or 1d) complexes, both the activity and
enantiomeric excesses are moderate (entries 8, 9). On the
other hand, high enantiomeric excesses and complete con-
version were observed for the reduction of 1-phenylthio-3-
butanone in forcing conditions (80 bar, 808C, entry 10).
Ligand 1b also promoted highly diastereo- and enantioselec-
tive hydrogenations of the three b-diketones considered so
far: 2,4-pentanedione, 3,5-heptanedione, and 2,6-dimethyl-
3,5-heptanedione (Table 2). To date, analogous ruthenium-
catalyzed hydrogenations of 1,3-diketones have been per-
This first series of catalytic tests shows that the bidentate
phosphetanes 1 are suitable chiral auxiliaries for ruthenium-
promoted hydrogenations. Significant levels of enantioselec-
tivity are obtained with selected substrates when the phos-
phetane rings bear hindered substituents.
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Chiral Phosphetanes
1160±1165
(R,R)-1,3-Dicyclohexyl-1,3-propanediol (5d): The hydrogenation of 4d
was performed at room temperature over 70 h (H2, 100 bar) with (S)-
BINAP as the chiral auxiliary. (The amount of catalyst was 0.5%.) Diol 5d
was obtained as a colorless solid (75%) after crystallization from diethyl
ether. 1H NMR (CDCl3): d ˆ 0.9 ± 2.0 (m), 2.19 (br, OH), 3.68 (m, CHOH);
13C NMR (CDCl3): d ˆ 26.1, 26.2, 26.5, 28.6, 29.0 (CH2-cyclohexyl), 36.3
(CH2), 43.5 (CH), 73.6 (CHOH); [a]2D5 ˆ ‡ 22 (c ˆ 1, CHCl3). The absolute
configuration was assumed to be R,R by analogy with the hydrogenation of
4b.
Conclusion
In summary, three new ligands of the CnrPHOS series have
been prepared by a convenient synthetic procedure, which
involves the catalytic hydrogenation of b-diketones into 1,3-
diols as the enantioselective step. We have shown that C2-
symmetric bis(phosphetano)benzenes represent a new class of
easily accessible chiral diphosphines. Preliminary experiments
demonstrate the significant potential of these ligands in
asymmetric catalysis. Further studies directed towards opti-
mization of the catalytic efficiency of the phosphetane ± ru-
thenium complexes are under way. Application of these chiral
phosphetanes to other fields of organometallic catalysis
are envisaged, and such investigations are already in pro-
gress.
Preparation of the cyclic sulfates 2b ± d: The synthesis of 2b is given as a
representative example.
(R,R)-2,6-Dimethyl-3,5-heptanediol cyclic sulfate (2b): Thionyl chloride
(0.50 mL, 6.9 mmol) was added to a solution of (R,R)-2,6-dimethyl-3,5-
heptanediol (1.0 g, 6.3 mmol) in CCl4 (10 mL). The resulting solution was
refluxed for 1 h. The solvent was removed by rotary evaporation, and the
residue was dissolved in a mixture of CCl4 (4 mL), MeCN (4 mL), and
water (6 mL) and then cooled to 08C. RuCl3 (10 mg, 5 Â 10 2 mmol) and
NaIO4 (2.0 g, 9.4 mmol) were also added. The mixture was warmed to room
temperature and stirred for about 1 h. Diethyl ether (50 mL) was added,
and the organic phase was separated, washed with water, and dried over
MgSO4. The ethereal solution was subsequently filtered through a pad of
silica gel. Evaporation of the solvent afforded pure 2b (1.2 g, 86%), which
was recrystallized from a hexane/diethyl ether mixture. 1H NMR (CDCl3):
d ˆ 0.98 (d, 3J(H,H) ˆ 6.8 Hz, 6H; CHMe2), 1.08 (d, 3J(H,H) ˆ 6.7 Hz, 6H;
CHMe2), 2.08 (t, 3J(H,H) ˆ 6.5 Hz; CH2), 2.14 (m, CHMe2), 4.45 (q,
Experimental Section
All reactions were carried out under argon in solution in dry solvents. NMR
spectra were recorded on a Bruker AM 200 spectrometer (200.13 MHz for
1H; 50.32 MHz for 13C; 81.01 MHz for 31P). (S)-MeO-BIPHEP was kindly
supplied by Dr Schmid (Hoffman ± La Roche).
3J(H,H) ˆ 6.5 Hz; CH O); [a]2D5
ˆ
14 (c ˆ 1, CHCl3).
(S,S)-3,5-Heptanediol cyclic sulfate (2c): The cyclic sulfate 2c was obtained
as a greenish oil (96%) after filtration of the crude reaction mixture
through silica gel. 1H NMR (CDCl3): d ˆ 1.06 (t, 3J(H,H) ˆ 7.4 Hz; Me),
1.64 ± 1.85 (m, 2H; CH2Me), 1.96 ± 2.16 (m, 2H; CH2Me), 2.05 (t,
3J(H,H) ˆ 5.9 Hz; CH2), 4.79 (dq, 3J(H,H) ˆ 8.5, 5.7 Hz, 2H; CH O);
Ruthenium-catalyzed hydrogenations of the b-diketones 4b ± d
(Scheme 2): The samples of b-diketones 4b and 4d used in this study were
made by Claisen condensation of the phenyl ester with the corresponding
methyl ketone in the presence of LDA, and then purified by the copper
chelate complex.[14] The catalytic hydrogenation of 4b to 5b is given below
as a representative example.
[a]2D5
ˆ
62 (c ˆ 1, CHCl3).
(R,R)-1,3-Dicyclohexyl-1,3-propanediol cyclic sulfate (2d): The cyclic
sulfate 2d was obtained as a colorless solid (97%) after filtration of the
crude reaction mixture through silica gel. 1H NMR (CDCl3): d ˆ 1.0 ± 1.8
(m), 2.09 (t, 3J(H,H) ˆ 6.5 Hz; CH2), 4.49 (q, 3J(H,H) ˆ 6.5 Hz; CH O);
13C NMR (CDCl3): d ˆ 25.3, 25.5, 26.0, 28.3, 28.5 (CH2-cyclohexyl), 28.7
(R,R)-2,6-Dimethyl-3,5-heptanediol (5b): Both (S)-BINAP and (S)-MeO-
BIPHEP were used as chiral auxiliaries in the ruthenium-catalyzed
hydrogenation of 2,6-dimethyl-3,5-heptanedione. Comparable yields and
enantiomeric excesses were obtained. The BINAP-catalyzed hydrogena-
tion reaction is described as a representative procedure. (S)-BINAP
(72 mg, 0.11 mmol) and [(COD)Ru(2-methylallyl)2] (32 mg, 0.10 mmol)
were placed in a flask (50 mL), and anhydrous acetone (9 mL, distilled over
K2CO3) was added. A methanolic HBr solution (1.3 mL, 0.18m) was added
to the resulting suspension, and the reaction mixture was stirred at room
temperature for 40 min. The solvent was then removed under vacuum, and
the yellow solid residue obtained was used as the catalyst for the
hydrogenation reaction. Methanol (20 mL) and 2,6-dimethyl-3,5-heptane-
dione (6.0 g, 38 mmol) were added to the reaction vessel, which was then
placed in a stainless steel autoclave (250 mL) under argon. The argon
atmosphere was replaced by hydrogen and the autoclave was subjected to
an initial pressure of 50 bar. The reaction was allowed to proceed at 508C
for 70 h. Complete conversion to the anti diol 5b was confirmed by NMR
spectroscopy. 1H NMR (CDCl3): d ˆ 0.90 (d, 3J(H,H) ˆ 6.8 Hz, 6H;
CHMe2), 0.96 (d, 3J(H,H) ˆ 6.7 Hz, 6H; CHMe2), 1.60 (dd, 3J(H,H) ˆ
6.4 Hz, 5.1 Hz; CH2), 1.70 (m, CHMe2), 2.16 (OH), 3.65 (m, 2H; CHOH).
The enantiomeric purity of 5b was greater than 95%, as determined by 1H
and 19F NMR spectroscopy of its Mosher ester,[15] prepared from (S)-
MTPA-Cl in pyridine at 608C over 4 h. 1H NMR of the (R,R)-5b-(R)-
MPTA diester: d ˆ 0.76 (d, 3J(H,H) ˆ 6.9 Hz, 6H; Me), 0.85 (d, 3J(H,H) ˆ
(CH2), 40.7 (CH), 87.7 (CH O); [a]D25
ˆ
23 (c ˆ 1, CHCl3).
Synthesis of the bis(phosphetano)benzene borane complexes 3: A repre-
sentative procedure is given below for the synthesis of 3b.
1,2-Bis[(S,S)-2,4-diisopropylphosphetano]benzene borane complex (3b):
A
solution of 1,2-bis(phosphino)benzene (0.32 g, 2.2 mmol) in THF
(15 mL) was cooled to 788C and nBuLi (1.6m solution in hexane,
3.1 mL, 2.2 equiv) was added. Once warmed to room temperature, the
resulting orange-red solution of dilithium bis(phosphino)benzene was then
added to a solution of the cyclic sulfate 2b (1.0 g, 4.5 mmol) in THF
(150 mL). The reaction mixture was warmed to room temperature and then
stirred for 30 min. The solution was cooled once more to 788C, and sBuLi
(3.7 mL, 4.8 mmol, 2.2 equiv) was added. The reaction proceeded for about
30 min at 788C. The mixture was then warmed up to room temperature
and stirred for 1 h. A few drops of water were added to quench any excess
BuLi. The BH3 ´ SMe2 complex (0.33 mL, 1.5 equiv) was then added at 08C.
The crude mixture was concentrated under vacuum. Addition of degassed
hexane gave a gelatinous precipitate, which was filtered under an inert
atmosphere. The colorless solution was evaporated and the residue purified
by chromatography through alumina. The borane complex 3b (0.36 g,
40%) was eluted with a hexane/diethyl ether (95:5) mixture, and recrystal-
3
3
lized from pentane. 31P NMR (C6D6): d ˆ 3.4 (d, J(P,P) ˆ 34.6 Hz), 45.9
6.9 Hz, 6H; Me), 1.65 (dd, J(H,H) ˆ 7.3, 4.9 Hz, 2H; CH2), 1.90 (m, 2H;
(br); 1H NMR (C6D6; selected data): d ˆ 0.44 (d, 3J(H,H) ˆ 6.8 Hz, 3H;
CHMe2), 0.63 (d, 3J(H,H) ˆ 6.4 Hz, 3H; CHMe2), 0.75 ± 0.81 (3Me), 0.87
(d, 3J(H,H) ˆ 6.6 Hz, 3H; CHMe2), 0.89 (d, 3J(H,H) ˆ 6.6 Hz, 3H;
CHMe2), 1.07 (d, 3J(H,H) ˆ 6.0 Hz, 3H; CHMe2); 13C NMR (C6D6): d ˆ
17.6 (Me), 20.1 (d, 3J(C,P) ˆ 14.2 Hz; Me), 20.6, 20.7, 20.9, 21.1 (3Me), 22.3
CHMe2), 3.63 (6H, OMe), 4.83 (m, 2H; CH O). The crude reaction
mixture was recrystallized from diethyl ether/pentane to afford enantio-
merically pure (R,R)-2,6-dimethyl-3,5-heptanediol (5.2 g, 85%). The
absolute configuration was assigned from the optical rotation value, by
comparison with literature data ([a]2D5 ˆ ‡ 64 (c ˆ 1, MeOH)).[9]
3
3
(S,S)-3,5-heptanediol (5c): The hydrogenation of 4c (3 g, 40 bar H2) was
performed at room temperature over 70 h with (S)-MeO-BIPHEP as the
chiral auxiliary. Ruthenium catalyst (0.2%) was also used. Diol 5c was
obtained as a colorless solid after crystallization (86%). 1H NMR (CDCl3):
(d, J(C,P) ˆ 12.2 Hz; Me), 22.6 (Me), 23.2 (d, J(C,P) ˆ 2.3 Hz; Me), 25.4
(d, 2J(C,P) ˆ 11.4 Hz; CH2), 28.4 (dd, J(C,P) ˆ 10.5 Hz, J(C,P) ˆ 8.1 Hz;
CH), 29.3 (d, J(C,P) ˆ 4.6 Hz; CH), 29.8 (CH2), 30.3 (CH), 33.3 (d,
J(C,P) ˆ 18.2 Hz; CH), 39.3 (d, J(C,P) ˆ 5.3 Hz; CH), 40.26 (s, CH), 41.8
(dd, 1J(C,P) ˆ 39.7 Hz, 4J(C,P) ˆ 7.7 Hz; PCH), 44.8 (dd, 1J(C,P) ˆ 36.6 Hz,
4J(C,P) ˆ 3.0 Hz; PCH), 140.2 (dd, 1J(C,P) ˆ 36.7 Hz, 2J(C,P) ˆ 27.5 Hz; C),
3
d ˆ 0.96 (t, J(H,H) ˆ 7.4 Hz, 6H; Me), 1.48 ± 1.66 (m, 6H; CH2), 2.26 (br,
2H; OH), 3.88 (m, 2H; CHOH); [a]2D5 ˆ‡ 25 (c ˆ 1, CHCl3). The absolute
configuration was assumed to be S,S by analogy with refs. [8b] and [16].
‡
141.3 (dd, 1J(C,P) ˆ 41.3 Hz, 2J(C,P) ˆ 11.2 Hz; C); MS: m/z (%): 404 [M]
Chem. Eur. J. 1999, 5, No. 4
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Ã
A. Marinetti, J.-P. Genet et al.
FULL PAPER
(5), 321 (70), 293 (100); [a]D25
71.29, H 10.72; found C 71.22, H 10.79.
ˆ
202 (c ˆ 0.5, CH2Cl2); C23H43BP2: calcd C
(m, 4H), 7.1 (m, 2H), 7.5 (m, 2H); 13C NMR (C6D6): d ˆ 12.3 (Me), 13.1 (t,
3J(C,P) ˆ 6.0 Hz; Me), 25.5 (CH2), 28.5 (t, J(C,P) ˆ 10.0 Hz; CH2), 32.1 (t,
J(C,P) ˆ 5.0 Hz; CH), 32.7 (CH2), 33.9 (t, J(C,P) ˆ 7.6 Hz; CH), 130.0
(CH), 143.6 (C).
1,2-Bis[(S,S)-2,4-dimethylphosphetano]benzene borane complexes (3a,
3a'): The cyclic sulfate (R,R)-2a (0.74 g, 4.5 mmol) was used in the same
experimental procedure as above to afford the borane complex 3a (0.30 g,
46%), which was eluted with hexane/diethyl ether (85:15) and recrystal-
lized from hexane. Spectroscopic data for 3a have been published.[3] When
a large excess of the BH3 ´ SMe2 complex was added to the reaction mixture,
3a was obtained as the major product, but a small amount of the
bis(borane) complex 3a' was also isolated after column chromatography
(hexane/diethyl ether, 1:1). 3a': colorless solid; 31P NMR (CDCl3): d ˆ 52.7;
1,2-Bis[(S,S)-2,4-dicyclohexylphosphetano]benzene (1d): Colorless solid;
31P NMR (C6D6): d ˆ 7.8; 1H NMR (C6D6): d ˆ 0.7 ± 2.6 (m), 7.2 (m, 2H), 7.6
(m, 2H); 13C NMR (C6D6): d ˆ 26.4 ± 27.2 (CH2), 29.7 (CH2), 30.3 (CH2),
31.9 (t, J(C,P) ˆ 4.3 Hz; CH2), 33.3 (t, J(C,P) ˆ 4.0 Hz; CH2), 37.4 (t,
J(C,P) ˆ 1.6 Hz; CH), 37.7 (t, J(C,P) ˆ 6.8 Hz; CH), 39.5 (CH), 43.1 (t,
‡
J(C,P) ˆ 7.2 Hz; CH), 131.3 (CH), 144.4 (C); MS: m/z (%): 550 [M] (25),
357 (45), 345 (100).
1H NMR (CDCl3): d ˆ 1.09 (dd, J(H,H) ˆ 7.4 Hz, J(H,P) ˆ 15.9 Hz; Me),
1.37 (dd, 3J(H,H) ˆ 7.0 Hz, 3J(H,P) ˆ 18.1 Hz; Me), 2.10 (dtd, 3J(H,P) ˆ
44.7 Hz, J(H,H) ˆ 11.0, 2.5 Hz, 1H; CH2), 2.5 (m, 1H), 3.0 (m, 1H), 3.4
3
3
Ruthenium-catalyzed hydrogenations of carbonyl derivatives: The ruthe-
nium catalyst was prepared as in ref. [6] by reaction of [(COD)Ru(2-
methylallyl)2] (3.2 mg, 1 Â 10 2 mmol) with ligand 1 (1.2 Â 10 2 mmol) in
acetone. Methanolic HBr (2.2 equiv) was added to the solution, which was
subsequently stirred for 30 min. The solvent was then evaporated in vacuo.
A solution of the appropriate substrate (1 mmol or 0.5 mmol) in degassed
methanol or ethanol (1 mL) was added to the catalyst. The glass vessel was
(m, 1H), 7.6 (m, Ph); 13C NMR (CDCl3): d ˆ 13.8 (Me), 16.3 (d, J(C,P) ˆ
2
7.7 Hz; Me), 28.8 (d, 1J(C,P) ˆ 39.6 Hz; CH), 34.0 (d, 2J(C,P) ˆ 9.5 Hz;
CH2), 34.3 (d, 1J(C,P) ˆ 40.1 Hz; CH), 130.4 (d, J(C,P) ˆ 5.3 Hz; CH), 133.6
(t, J(C,P) ˆ 7.5 Hz; CH), 133.8 (dd, 1J(C,P) ˆ 25 Hz, 2J(C,P) ˆ 10.5 Hz; C);
C16H30P2B2: calcd C 62.81, H 9.88; found C 62.07, H 9.88.
placed under argon in
a stainless steel autoclave, which was then
pressurized with H2. The reaction proceeded at the temperatures given in
Tables 1 and 2. Conversion rates were determined by 1H NMR spectro-
scopy. The absolute configurations of the final alcohols were assigned from
the GC retention times (Lipodex A column or Megadex 5 column) by
comparison with known compounds. The enantiomeric excesses of the 1,3-
diols were determined by 1H NMR spectroscopy and/or GC analysis of the
Mosher diesters prepared from the crude diols and (S)-MPTA-Cl.
(S,S)-5b-(R)-MPTA diester: 1H NMR (CDCl3): d ˆ 0.76 (d, 3J(H,H) ˆ
6.7 Hz, 6H; Me), 0.79 (d, 3J(H,H) ˆ 6.8 Hz, 6H; Me), 1.69 (dd,
3J(H,H) ˆ 7.3, 5.2 Hz, 2H; CH2), 1.90 (m, 2H; CHMe2), 3.53 (6H, OMe),
4.87 (m, 2H).
(R,R)-5a-(R)-MTPA diester: 1H NMR (CDCl3): d ˆ 1.26 (d, 3J(H,H) ˆ
6.1 Hz, 6H; Me), 1.87 (dd, 3J(H,H) ˆ 7.6, 5.8 Hz, 2H; CH2), 3.53 (6H,
OMe), 5.15 (m, 2H; CH O).
(R,R)-5c-(R)-MPTA diester: 1H NMR (CDCl3): d ˆ 0.79 (t, 3J(H,H) ˆ
7.4 Hz, 6H; Me), 1.6 (4H, CH2), 1.85 (dd, 3J(H,H) ˆ 7.1, 5.7 Hz, 2H;
CH2), 3.55 (6H, OMe), 4.99 (m, 2H; CH O). Absolute configurations were
assigned from either the GC retention times (DB 1701 column) or 1H NMR
spectra, by comparison with known compounds.
1,2-Bis[(R,R)-2,4-diethylphosphetano]benzene borane complex (3c): The
cyclic sulfate (S,S)-2c was used in the same experimental procedure to
afford the borane complex 3c as an air-sensitive colorless oil (40%). 31P
NMR (C6D6): d ˆ 49.7 (br), 9.4 (3J(P,P) ˆ 36 Hz); 1H NMR (C6D6): d ˆ 0.67
3
3
(t, J(H,H) ˆ 7.3 Hz, 3H; Me), 0.68 (t, J(H,H) ˆ 7.2 Hz, 3H; Me), 0.84 (t,
3J(H,H) ˆ 7.2 Hz, 3H; Me), 0.92 (t, 3J(H,H) ˆ 7.3 Hz, 3H; Me), 1.0 ± 2.7
(m), 7.0 ± 7.3 (m, 3H), 7.5 (m, 1H); 13C NMR (250 MHz, C6D6): d ˆ 12.0 (d,
3J(C,P) ˆ 11.9 Hz; Me), 12.2 (d, 3J(C,P) ˆ 4.9 Hz; Me), 12.9 (d, 3J(C,P) ˆ
11.0 Hz; Me), 13.3 (d, 3J(C,P) ˆ 8.2 Hz; Me), 23.6 (CH2), 24.3 (t, 2J(C,P) ˆ
8.0 Hz; CH2), 25.4 (d, 2J(C,P) ˆ 5.1 Hz; CH2), 28.5 (d, 2J(C,P) ˆ 21.6 Hz;
CH2), 29.4 (d, 2J(C,P) ˆ 11.4 Hz; CH2), 32.5 (dd, J(C,P) ˆ 8.4, 0.7 Hz; CH),
1
33.2 (d, J(C,P) ˆ 6.2 Hz; CH), 33.6 (CH2), 36.7 (dd, J(C,P) ˆ 37.4, 3.2 Hz;
PCH), 37.5 (dd, J(C,P) ˆ 40.3, 9.7 Hz; PCH), 129.0 (d, J(C,P) ˆ 8.2 Hz;
CH), 129.8 (d, J(C,P) ˆ 2.4 Hz; CH), 130.7 (dd, J(C,P) ˆ 9.3, 8.4 Hz; CH),
133.1 (dd, J(C,P) ˆ 7.9, 2.3 Hz; CH), 139.6 (dd, J(C,P) ˆ 34.7, 30.4 Hz; C),
‡
141.0 (dd, J(C,P) ˆ 38.7, 11.0 Hz; C); MS: m/z (%): 334 [M BH3] (30),
‡
305 [M BH3 C2H5] (30), 249 (100).
1,2-Bis[(S,S)-2,4-dicyclohexylphosphetano]benzene borane complex (3d):
The cyclic sulfate (R,R)-2d was used in the same procedure to give 3d as a
colorless solid (40%). 31P NMR (C6D6): d ˆ 46.5 (br), 2.3 (3J(P,P) ˆ
35 Hz); 1H NMR (C6D6): d ˆ 0.8 ± 2.9 (m), 7.2 (m, 2H), 7.5 (m, 1H), 7.7
(m, 1H); 13C NMR (250 MHz, C6D6): d ˆ 25.8 ± 26.8 (CH2), 28.2 (d, CH2),
28.4 (d, J(C,P) ˆ 2.0 Hz; CH2), 30.8 (d, 3J(C,P) ˆ 3.9 Hz; CH2), 31.0 (d,
3J(C,P) ˆ 13.4 Hz; CH2), 31.6 (d, 3J(C,P) ˆ 10.4 Hz; CH2), 32.2 (d,
3J(C,P) ˆ 3.7 Hz; CH2), 32.3 (d, 3J(C,P) ˆ 8.3 Hz; CH2), 33.1 (CH2), 34.1
(d, 3J(C,P) ˆ 3.0 Hz; CH2), 38.1 ± 38.6 (CH), 39.3 (CH), 39.5 (CH), 42.5 (dd,
J(C,P) ˆ 39.5, 8.1 Hz; PCH), 43.2, 43.4 (CH), 43.8 (dd, J(C,P) ˆ 35.5,
3.4 Hz; PCH), 130.5 (t, J(C,P) ˆ 9.2 Hz; CH), 133.3 (dd, J(C,P) ˆ 7.9,
2.2 Hz; CH), 140.5 (dd, J(C,P) ˆ 36.6, 27.0 Hz; C), 141.6 (dd, J(C,P) ˆ 42.0,
Acknowledgements
The authors thank Mrs Isabelle Brezulier for technical assistance.
[1] M. J. Burk, J. E. Feaster, R. L. Harlow, Organometallics 1990, 9, 2653;
M. J. Burk, J. E. Feaster, W. A. Nugent, R. L. Harlow, J. Am. Chem.
Soc. 1993, 115, 10125; for a recent review see: M. J. Burk, M. F. Gross,
T. G. P. Harper, C. S. Kalberg, J. R. Lee, J. P. Martinez, Pure Appl.
Chem. 1996, 68, 37.
‡
‡
11.5 Hz; C); MS: m/z (%): 563 [M H] (25), 550 [M BH3] (20), 357
(50), 345 (100); C36H59BP2: calcd C 76.58, H 10.53; found C 76.52, H 10.50.
Displacement of phosphetanes 1 from their borane complexes: Decom-
plexation of the phosphetane 1b from its borane complex 3b is described
below as a representative example.
[2] Q. Jiang, Y. Jiang, D. Xiao, P. Cao, X. Zhang, Angew. Chem. 1998, 110,
1203; Angew. Chem. Int. Ed. 1998, 37, 1100.
1,2-Bis[(S,S)-2,4-diisopropylphosphetano]benzene (1b): The phosphine ±
borane complex 3b (100 mg, 0.25 mmol) was treated with DABCO (28 mg,
0.25 mmol) in benzene (3 mL) at 408C for 2 h. The reaction mixture was
purified directly by chromatography under argon through a short alumina
column with hexane/diethyl ether (97:3) as eluent. The final product 1b was
obtained as a colorless solid in quantitative yield. 31P NMR (C6D6): d ˆ 6.2;
1H NMR (C6D6; selected data): d ˆ 0.69 (d, 3J(H,H) ˆ 6.5 Hz, 6H;
CHMe2), 0.80 (d, 3J(H,H) ˆ 6.5 Hz, 6H; CHMe2), 0.95 (d, 3J(H,H) ˆ
6.5 Hz, 6H; CHMe2), 1.02 (d, 3J(H,H) ˆ 6.6 Hz, 6H; CHMe2), 7.2 (m,
2H), 7.6 (m, 2H); 13C NMR (C6D6): d ˆ 20.0 (Me), 20.9 (t, J(C,P) ˆ 4.7 Hz;
Me), 21.4 (t, J(C,P) ˆ 4.6 Hz; Me), 22.5 (t, J(C,P) ˆ 4.7 Hz; Me), 30.0 (CH),
30.8 (CH2), 33.6 (t, J(C,P) ˆ 9.7 Hz; CH), 38.5 (CH), 38.9 (t, J(C,P) ˆ
[3] A. Marinetti, V. Kruger, F.-X. Buzin, Tetrahedron Lett. 1997, 38, 2947.
[4] 1-Phenylphosphetane rapidly polymerizes: D. C. R. Hockless, Y. B.
Kang, M. A. McDonald, M. Pabel, A. Willis, S. B. Wild, Organo-
metallics 1996, 15, 1301; while C-substituted species display high
thermal stability, as shown by a number of literature reports: T.
Kawashima, R. Okazaki in Comprehensive Heterocyclic Chemistry II,
Vol. 1 (Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriven), Pergamon,
1996, p. 833, and references therein.
[5] Little is known about the catalytic behaviour of chiral phosphetanes.
Only highly substituted, hindered species have been used in palla-
dium-promoted reactions: A. Marinetti, L. Ricard, Organometallics
1994, 13, 3956; A. Marinetti, V. Kruger, L. Ricard, J. Organomet.
Chem. 1997, 529, 465.
7.9 Hz; CH), 128.3, 131.4, 144.2 (Ar); [a]D25
ˆ
288 (c ˆ 0.5, CH2Cl2); MS:
‡
‡
m/z (%): 390 [M] (5), 320 [M iPrCHCH2] (40), 292 (100).
Ã
[6] J.-P. Genet, C. Pinel, V. Ratovelomanana-Vidal, S. Mallart, X. Pfister,
1,2-Bis[(R,R)-2,4-diethylphosphetano]benzene (1c): Colorless oil; 31P
NMR (C6D6): d ˆ 12.3; 1H NMR (C6D6): d ˆ 0.73 (t, 3J(H,H) ˆ 7.3 Hz,
6H; Me), 0.93 (t, 3J(H,H) ˆ 7.3 Hz, 6H; Me), 1.0 ± 1.8 (m), 2.2 (m, 4H), 2.4
L. Bischoff, M. C. Cano De Andrade, S. Darses, C. Galopin, J. A.
Ä
Laffitte, Tetrahedron: Asymmetry 1994, 5, 675; D. Blanc, J. C. Henry,
V. Ratovelomanana-Vidal, J.-P. Genet, Tetrahedron Lett. 1997, 38,
Ã
1164
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0947-6539/99/0504-1164 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Chiral Phosphetanes
1160±1165
Ã
6603; for recent reviews see: J.-P. Genet in Reductions in Organic
tartrate-catalyzed Sharpless epoxidation of 2,6-dimethyl-4-hepten-3-
ol: C. Jacoby, J. C. Braekman, D. Daloze, Tetrahedron: Asymmetry
1995, 6, 753; or by hydrogenation over Raney Nickel modified with
tartaric acid: T. Sugimura, M. Yoshikawa, T. Yoneda, A. Tai, Bull.
Chem. Soc. Jpn. 1990, 63, 1080; A. Tai, T. Kikukawa, T. Sugimura, Y.
Inoue, T. Osawa, S. Fujii, J. Chem. Soc. Chem. Commun. 1991, 795.
[10] U. Berens (Chiroscience Ltd.), WO 98/02445, 1998.
[11] H. Brunner, A. Terfort, Tetrahedron: Asymmetry 1995, 6, 919.
[12] M. D. Fryzuk, B. Bosnich, J. Am. Chem. Soc. 1978, 100, 5491.
[13] M. J. Burk, T. G. P. Harper, C. S. Kalberg, J. Am. Chem. Soc. 1995, 117,
4423.
[14] H. D. Murdoch, D. C. Nonhebel, J. Chem. Soc. 1962, 2153; J. T.
Adams, C. R. Hauser, J. Am. Chem. Soc. 1944, 66, 1220.
[15] J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34, 2543.
[16] S. D. Rychnovsky, G. Griesgraber, S. Zeller, D. J. Skalitzky, J. Org.
Chem. 1991, 56, 5161.
Synthesis (Ed.: A. F. Abdel Magid), A. C. S. Symposium Series 641,
1996, pp. 31 ± 51; J.-P. Genet, in Advances in Asymmetric Synthesis
(Ed.: G. R. Stephenson), Chapman and Hall, London, 1996, pp. 60 ±
92.
Ã
[7] Y. Gao, K. B. Sharpless, J. Am. Chem. Soc. 1988, 110, 7538.
[8] Ruthenium-catalyzed hydrogenations of b-diketones with atropoiso-
meric ligands as chiral auxiliaries: a) M. Kitamura, T. Ohkuma, S.
Inoue, N. Sayo, H. Kumobayashi, S. Akutagawa, T. Ohta, H. Takaya,
R. Noyori, J. Am. Chem. Soc. 1988, 110, 629; b) H. Kawano, Y. Ishii,
M. Saburi, Y. Uchida, J. Chem. Soc. Chem. Commun. 1988, 87; c) A.
Mezzetti, G. Consiglio, J. Chem. Soc. Chem. Commun. 1991, 1675;
d) A. Mezzetti, A. Tschumper, G. Consiglio, J. Chem. Soc. Dalton
Trans. 1995, 49; e) D. Pini, A. Mandoli, A. Iuliano, P. Salvadori,
Tetrahedron: Asymmetry 1995, 6, 1031; f) Q. Fan, C. Yeung, A. S. C.
Chan, Tetrahedron: Asymmetry 1997, 8, 4041.
[9] Diol 5b can be obtained from 2,6-dimethyl-3,5-heptanedione either
by a multistep synthesis including the Ti(OiPr)4/L-(‡)-diisopropyl
Received: July 8, 1998 [F1248]
Chem. Eur. J. 1999, 5, No. 4
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0947-6539/99/0504-1165 $ 17.50+.50/0
1165