Synthesis of chiraphos via asymmetric hydrogenation of 2,3- bis(diphenylphosphinoyl)-buta-1,3-diene

Article abstract of DOI:10.1039/a908447i

(S,S)-2,3-Bis(diphenylphosphinoyl)butane, an immediate precursor of (S,S)-CHIRAPHOS, can be obtained with 70% de and 71% op via double asymmetric hydrogenation of 2,3-bis(diphenylphosphinoyl)buta-1,3-diene in the presence of Ru-(S)-BINAP catalysts.

Full text of DOI:10.1039/a908447i

Synthesis of Chiraphos via asymmetric hydrogenation of
2,3-bis(diphenylphosphinoyl)-buta-1,3-diene
Valentina Beghetto, Ugo Matteoli* and Alberto Scrivanti
Dipartimento di Chimica, Università di Venezia, Calle Larga S. Marta, 2137, 30123 Venezia, Italy.
E-mail: matteol@unive.it
Received (in Liverpool, UK) 20th October 1999, Accepted 1st December 1999
(S,S)-2,3-Bis(diphenylphosphinoyl)butane, an immediate
precursor of (S,S)-CHIRAPHOS, can be obtained with 70%
de and 71% op via double asymmetric hydrogenation of
2,3-bis(diphenylphosphinoyl)buta-1,3-diene in the presence
of Ru–(S)-BINAP catalysts.
benzene/n–hexane to remove the catalyst.6 In the case of runs 1
and 4, owing to the presence of the chiral intermediate 3, a
catalyst-free sample of the crude reaction mixture was treated
with (1S)-(+)-camphorsulfonic acid to form inter alia the
corresponding (S,S)-2–(1S)-(+)-camphorsulfonic and (R,R)-
2–(1S)-(+)-camphorsulfonic adducts. The enantioselectivity of
the reaction was then calculated by integration of their relevant
resonances in the 31P NMR spectrum.7
Both catalysts require rather severe reaction conditions to
carry out the hydrogenation. With [RuCl(p-cymene){(S)-
BINAP}]Cl the hydrogenation of 1 proceeds with complete
Recently, we have described a new strategy for the synthesis of
Chiraphos,1† a well-known bidentate chiral ligand for asym-
metric catalysis. The key step of the synthesis is the diastereo-
selective hydrogenation of 2,3-bis(diphenylphosphinoyl)-
buta-1,3-diene 1 which affords a pair of enantiomers (R,R)- and
(S,S)-2 and the meso species (R,S)-2. This latter isomer is
useless, therefore its formation must be avoided in order to
remove the need for a difficult purification step. In the
previously reported synthesis,1 a racemic mixture of (R,R)- and
(S,S)-2 was obtained in ca. 70% yield by reacting 1 with
NaBH4. Using this reducing agent, ca. 30% of meso-2 was also
produced, but was promptly separated and discarded since it
forms an insoluble adduct with one molecule of NaOH and one
molecule of NaBH4.1
The recent improvements achieved in asymmetric hydro-
genation2 by means of homogeneous chiral transition metal
catalysts prompted us to investigate the direct synthesis of
enantiopure (R,R)-2 or (S,S)-2 by hydrogenation of 1 in the
presence of an asymmetric catalyst (Scheme 1).
Interest in this subject goes beyond the synthetic application
envisaged here since, although a large number of reports
concerned with asymmetric reduction of monoenes have been
published, only a few examples of asymmetric reduction of
dienes have appeared so far.3 Further interest is added by the
peculiar nature of 1.
Two different Ru-BINAP complexes, i.e. [RuCl(p-cym-
ene){(S)-BINAP}]Cl4 and [Ru(OAc)2{(S)-BINAP}],5 were
tested as catalysts. The relevant data, together with the reaction
conditions, are reported in Table 1.
The reactions were carried out in a magnetically stirred
stainless steel autoclave. The product’s composition was
determined by NMR spectroscopy, since in previous studies we
found that all the species which may form during the reaction
(see Scheme 1) give well-separate signals in the 31P NMR
spectrum.1
When only the stereoisomers of 2 were present into the crude
reaction mixture, the enantioselectivity of the reaction was
determined by polarimetry on samples recrystallized from
Scheme 1 Reagents and conditions: i, H2, catalyst; ii, HSiCl3, NEt3.
Table 1 Hydrogenation of 2,3-bis(diphenylphosphinoyl)buta-1,3-diene 1 with Ru–BINAP catalystsa
Yield (%)
Run
Catalyst
T/°C
t/h
3
(R,S)-2
(S,S)-2 + (R,R)-2
Op 2 (%)b
1
2
3
4
5
[RuCl(p-cymene){(S)-BINAP}]Clc
[RuCl(p-cymene){(S)-BINAP}]Clc
[Ru(OAc)2{(S)-BINAP}]d
50
100
100
100
100
216
120
67
163
310
53
0
45
18
—
0
0
10
13
15
47
100
45
69
85
0
8
NDe
68
71
[Ru(OAc)2{(S)-BINAP}]d
[Ru(OAc)2{(S)-BINAP}]d
a MeOH (15 ml), substrate (2.0 mmol), P(H2) = 100 atm. b In all cases the prevailing configuration is (S,S)-2. c Substrate/Ru = 120. d Substrate/Ru = 10.
e Not determined.
Chem. Commun., 2000, 155–156
This journal is © The Royal Society of Chemistry 2000
155

5 M. Kitamura, M. Tokunaga and R. Noyori, J. Org. Chem., 1992, 57,
4053.
6 Polarimetry measurements on different recrystallised samples of 2 have
shown that there is no variation in the op due to recrystallisation from
benzene–n-hexane.
7 The adducts between 2 and (1S)-(+)-camphorsulfonic acid were
prepared as follows: an 80+20 mixture of 2+3 ( ~ 500 mg recovered by
recrystallisation of a sample of run 4) was dissolved in 10 ml of CHCl3
and the mixture was heated to reflux temperature (mixture A).
Separately, 220 mg (0.88 mmol) of (1S)-(+)-camphorsulfonic acid were
dissolved in 15 ml of EtOAc (mixture B). The hot mixture B was added
to mixture A and the system was further heated for 2 min. The crude
solid recovered after evaporation of the solvents was characterised by
31P NMR (CDCl3): d 40.7 (s), 40.4 (s). Signals due to the adducts
between 3 and (1S)-(+)-camphorsulfonic acid were also present: d 38.23
diastereoselectivity since no meso-2 is formed. Surprisingly,
operating at 50 °C in the presence of this catalyst, a racemic
mixture of 2 is obtained, while working at 100 °C a modest
induction is observed (run 2). This rather unusual enhancement
of the enantioselectivity on increasing the reaction temperature
suggests that different catalytic species are actually at work; an
example of such behaviour has been previously reported in the
literature.8
With [Ru(OCOCH3)2{(S)-BINAP}] lower reaction rates are
obtained. Thus, even at 100 °C and using a substrate/catalyst
ratio of 10, long reaction times are necessary to achieve
complete hydrogenation of diene 1 (run 5). Most significant is
that the reaction proceeds with good diastereo- (de = 70%) and
enantio-selectivity [the op of the prevailing (S,S)-2 isomer is
71%]. Presumably the PNO bond is acting as a co-ordinating
group in the reaction, rather as an amide does in the
hydrogenation of acylamino acrylates.9,10
Concerning the reaction mechanism, there are two possible
pathways for the hydrogenation of the diene 1 (Scheme 1): (i)
two consecutive 1,2-hydrogen additions; (ii) an initial 1,4-hy-
drogen addition to give (cis or trans) 4 followed by hydro-
genation of the remaining double bond.
At shorter reaction times (runs 3 and 4) only 2 and 3 are
detected in the reaction mixture, suggesting that the reaction
proceeds via two consecutive 1,2-hydrogen additions; moreover
it appears that the first double bond hydrogenation is faster than
the second one. On the other hand, an independent experiment
showed that a pure sample of 411 is not hydrogenated in the
presence of [Ru(OCOCH3)2{(S)-BINAP}] under the conditions
in Table 1.
(d, JP,P 20.0), 38.21 (d, JP,P 21.0 ), 35.06 (d, JP,P 21.0 ), 35.00 (d, JP,P
=
20.0). Pure samples of (S,S)-(2)-2–(1S)-(+)-camphorsulfonict and
(R,R)-(+)-2–(1S)-(+)-camphorsulfonic adducts were synthesised as
described above starting from pure samples of (S,S)-(2)-2 or (R,R)-
(+)-2 and (1S)-(+)-camphorsulfonic acid to identify the two species
present in the 31P NMR spectrum. Selected data for (S,S)-(2)-2–(1S)-
(+)-camphorsulfonic adduct: dP(CDCl3, 85% H3PO4) 40.7 (s);
dH(CDCl3) 0.83 (3H, s, CH3C), 1.07 (3H, s, CH3C), 1.25 (6H, m, CH3)
1.50–2.70 (7H, m, CH2CH2CHCH2), 3.00 (2H, m, CH3CH), 3.00 (1H,
d, CH2SO3H, JH,H 15.0), 3.50 (1H, d, CH2SO3H, JH,H 15.0), 7.30–-7.80
(20H, m, arom), 8.20 (1H, s, CH2SO3H); nmax(KBr)/cm21 3400 (OH,
br), 3000–2900 (aliphatic and aromatic C–H, w), 1700 (CNO, s); [a]D23
214.0 (c 2.0 in CH2Cl2). For (R,R)-(+)-2–(1S)-(+)-camphorsulfonic
adduct: dP (CDCl3, 85% H3PO4) 40.4 (s); dH(CDCl3) 0.91 (3H, s,
CH3C), 1.08 (3H, s, CH3C), 1.30 (6H, m, CH3) 1.54–2.60 (7H, m,
CH2CH2CHCH2), 2.95 (2H, m, CH3CH), 3.05 (1H, d, CH2SO3H, JH,H
15.2), 3.54 (1H, d, CH2SO3H, JH,H 15.2), 7.30–7.80 (20H, m, arom),
8.20 (1H, s, CH2SO3H); nmax(KBr)/cm21 3400 (OH, br), 3000–2900
(aliphatic and aromatic C–H, w), 1700 (CNO, s); [a]2D3+25.0 (c 2.0 in
CH2Cl2). Slight differences in the 31P NMR (CDCl3) chemical shifts of
the mixture containing the two diastereoisomers may be observed due to
variations in sample concentration.
In conclusion, even if the process is not yet ready for practical
application owing to the incomplete stereoselectivity this work
demonstrates the possibility of employing the asymmetric
catalysis in the synthesis of a chiral diphosphine. According to
this strategy a chiral ligand could be synthesised using another
chiral phosphine ligand, thus giving a new example of chiral
amplification.
8 M. Kitamura, M. Tokunaga, T. Ohkuma and R. Noyori, Tetrahedron
Lett., 1991, 32, 4163.
9 A. S. Chan, J. J. Pluth and J. Halpern, J. Am. Chem. Soc., 1980, 102,
5952; H. Kawano, T. Ikariya, Y. Ishii, S. Yoshikawa, Y. Uchida and H.
Kumobayashi, J. Chem. Soc., Perkin Trans. 1, 1989, 1571.
10 We are indebted to a referee for this suggestion.
11 A sample of pure monoene 4 was obtained by hydrogenation of 1 in the
presence of Pd on carbon (10% Pd) at 80 °C and P(H2) = 100 bar
followed by recrystallisation from benzene. dP (CDCl3, 85% H3PO4)
31.88 (s); dH(CDCl3) 1.99 (6 H, m, CH3), 7.4–7.8 (20H, m, arom);
dC(CDCl3) 22.2 [CH3, appt t, X part of an AAAX (A and AA are the P
atoms) spin system], 128.6 (C, arom, appt t), 131.4 (C, arom, appt t),
131.9 (C, s, arom.), 133.3 (C, s, arom.), 145.3 (CN, quin, AAAX spin
system). Owing to the high symmetry of the molecule, the NMR data
do not allow determination of the stereochemistry of the molecule.
Notes and references
† Chiraphos: 2,3-bis(diphenylphosphino)butane.
1 U. Matteoli, V. Beghetto, C. Schiavon, A. Scrivanti and G. Menchi,
Tetrahedron: Asymmetry, 1997, 8, 1403.
2 Catalytic Asymmetric Synthesis, ed. I. Ojima, VCH, New York, 1993.
3 H. Muramatstu, H. Kawano, Y. Ishii, M. Saburi and Y. Uchida, J. Chem.
Soc., Chem. Commun., 1989, 769.
4 K. Mashima, K. Kusano, T. Ohta, R. Noyori and H. Takaya, J. Chem.
Soc., Chem. Commun., 1989, 1208.
Communication a908447i
156
Chem. Commun., 2000, 155–156