Modular chiral diphosphite derived from l-tartaric acid. Applications in metal-catalyzed asymmetric reactions

Article abstract of DOI:10.1016/j.molcata.2010.06.001

A new family of C₂-symmetric chiral diphosphites was synthesized using two different chiral backbones derived from tartaric acid, combined with chiral binaphthyls or non-chiral substituted biphenyl moieties. Diphosphites were applied to Rh-catalyzed hydroformylation of styrene producing good conversions in mild conditions, fair regioselectivities but low enantioselectivities in all cases. Ligands were also essayed in Pd-catalyzed allylic substitution reactions of linear and cyclic substrates using dimethyl malonate as nucleophile. Conversion rates up to 7200 h^-1 were reached, while moderated ee's were attained. In this reaction, a kinetic resolution of rac-1,3-diphenyl-3-acetoxyprop-1-ene was observed, leading to 99% ee of for the unreacted S-substrate and 60% ee of S-alkylated product. Coordination properties of diphosphites in rhodium and palladium complexes related to catalytic species involved in the two previous reactions were investigated. Some ligands form equatorial-equatorial chelates in pentacoordinated complexes [RhH(CO)(PPh₃)(diphosphite)], while other act as bridge between two metal atoms. In the catalytic active species [Pd(η³-PhCHCHCHPh)(diphosphite)]PF₆ one or two diastereoisomers are formed, depending on the diphosphite structure.

Full text of DOI:10.1016/j.molcata.2010.06.001

Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Modular chiral diphosphite derived from l-tartaric acid. Applications in
metal-catalyzed asymmetric reactions
a
a
a,∗
b
b
Alonso Rosas-Hernández , Edgar Vargas-Malvaez , Erika Martin , Laura Crespi , J. Carles Bayón
a
Departamento de Química Inorgánica, Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico
Departament de Química, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A new family of C -symmetric chiral diphosphites was synthesized using two different chiral backbones
derived from tartaric acid, combined with chiral binaphthyls or non-chiral substituted biphenyl moieties.
2
Received 16 December 2009
Received in revised form 19 May 2010
Accepted 1 June 2010
Diphosphites were applied to Rh-catalyzed hydroformylation of styrene producing good conversions in
mild conditions, fair regioselectivities but low enantioselectivities in all cases. Ligands were also essayed
in Pd-catalyzed allylic substitution reactions of linear and cyclic substrates using dimethyl malonate as
Available online 8 June 2010
−1
nucleophile. Conversion rates up to 7200 h were reached, while moderated ee’s were attained. In this
reaction, a kinetic resolution of rac-1,3-diphenyl-3-acetoxyprop-1-ene was observed, leading to 99% ee of
for the unreacted S-substrate and 60% ee of S-alkylated product. Coordination properties of diphosphites
in rhodium and palladium complexes related to catalytic species involved in the two previous reactions
were investigated. Some ligands form equatorial-equatorial chelates in pentacoordinated complexes
Keywords:
Asymmetric catalysis
Chiral diphosphite
Hydroformylation
Allylic alkylation
[
RhH(CO)(PPh3)(diphosphite)], while other act as bridge between two metal atoms. In the catalytic active
3
species [Pd(␩ -PhCHCHCHPh)(diphosphite)]PF6 one or two diastereoisomers are formed, depending on
the diphosphite structure.
©
2010 Elsevier B.V. All rights reserved.
1
. Introduction
catalytically active species. As (R,R)-Chiraphite, sugar-based
diphosphites producing good enantioselectivities form eight-
membered chelate rings when they coordinate to the metal center
[6,7]. In contrast, (S,S)-Kelliphite, one of the most efficient ligands
for asymmetric hydroformylation forms a nine-membered metal
chelate [2,8]. Moreover, it has been shown that a diphosphite form-
ing 16-membered chelate ring is able to produce fair asymmetric
induction in the hydroformylation of vinylarenes [9].
The development of asymmetric transition-metal catalysis
depends on the availability of enantiomerically pure ligands.
Among them, chiral diphosphites are especially attractive because
their structural properties can be easily modified allowing a fine-
tuning of the performance of the corresponding metal catalyst [1].
Since chiral diphosphites are readily prepared from a diol back-
bone and an appropriate phosphorochloridite, a great variety of
these ligands have been described generating libraries in which
both, electronic and steric properties are systematically modified.
These libraries have been very often screened in hydroformylation
and allylic substitution reactions [2,3].
Asymmetric rhodium-catalyzed hydroformylation using
diphosphites derived from chiral alkyl-diol backbones was initially
explored by Babin and Whiteker [4] and later by van Leeuwen
and coworkers [5]. High enantioselectivities were achieved in the
hydroformylation of vinylarenes with Chiraphite, a ligand derived
from (2R,4R)-pentanediol, but similar diphosphites based on
shorter or longer alkyl backbones, render poorly enantioselective
catalysts. This difference has been attributed to the ability of Chi-
Since the beginning of this decade, reports on the application of
chiral diphosphites to the allylic substitution reaction have greatly
increased [10–19]. Most of the new ligands synthesized have been
tested in alkylation of rac-1,3-diphenyl-3-acetoxy-1-ene, which
often gave better enantioselectivities than unsymmetrically sub-
stituted or less-sterically demanding allylic substrates. It should
be noted that (R,R)-Chiraphite and sugar-based diphosphites that
perform well in asymmetric hydroformylation are among the
best ligands for the alkylation of rac-1,3-diphenyl-3-acetoxy-1-
ene [13,14]. These type of ligands produced ee’s near to 95%,
−
1
with high turnover frequencies (>2000 h ). Even higher rates and
98% ee, were achieved in the same reaction using a C2 diphos-
phite, containing bulky silyl substituents on furanoside backbone
[15] however; this ligand produces poor stereoselectivity in the
rhodium-catalyzed styrene hydroformylation [20].
raphite to form bis-equatorial chelate in [RhH(CO) (diphosphite)]
2
With the aim to get further insight into the relation between
the structure of diphosphites and their catalytic performance, we
report here a new family of these ligands (Scheme 1) and their
∗ Corresponding author. Tel.: +52 55 56223720; fax: +52 55 56223720.
E-mail address: erikam@unam.mx (E. Martin).
1
381-1169/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2010.06.001

A. Rosas-Hernández et al. / Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
69
Scheme 1. Syntheses of chiral diphosphite ligands 1-2. (i) PCl3, NEt3, THF, −40 ◦C to 20 ◦C, 4 h; (ii) NEt3, THF, −40 ◦C to 20 C, 18 h.
◦
catalytic screening in hydroformylation and allylic alkylation reac-
tions. The backbone of these diphosphites was built from tartaric
acid, a natural and readily available chiral source. Ligands 2b
and 2c, bearing four carbon atoms at the backbone, with some
restricted flexibility imposed by the 1,3-dioxolane fragment, and
atropoisomeric phosphite moieties, could mimic the conforma-
tional constrains of Kelliphite. For comparative purposes, ligand 2a,
with a non-chiral fragment as terminal phosphorous substituents,
has also been synthesized. The homologous series of ligands 1a–c,
in which the stiffness of the four carbon atoms backbone has been
released, is also studied.
procedures [26]. The rest of reagents were from commercial origin
and were used as received.
NMR spectra were recorded in Bruker Avance-250, Varian Unity
Inova-300, -400 and Bruker ARX-400 instruments using CDCl3 as
solvent. Coupling constants are in hertz and chemical shifts are
1
13
given in ppm referenced to solvent ( H and
C) or external
reference of 85% aqueous solution of H PO4 (31P). FAB+ mass
3
spectra were acquired in a Jeol SX102A spectrometer using 3-
nitrobenzylalcohol matrix. High resolution TOF mass spectra were
obtained by LC/MSD TOF on an Agilent Technologies equipment.
Optical rotations were measured in a Perkin-Elmer 241 polarime-
D
−1
2
−1
ter, [␣] values are in units of 10 deg cm g . Catalytic reaction
mixtures were analyzed by GC-Varian 3800, GC-HP 5890 or HPLC
Alliance-Waters chromatographs. Absolute configurations of chi-
ral products were assigned by comparing their retention times with
those of optically pure compounds. For further experimental details
see supplementary data.
2
. Experimental
2.1. General methods
All reactions were carried out under nitrogen atmosphere
using standard Schlenk techniques. Solvents were dried by stan-
dard procedures. NEt3 over KOH and PCl3 and were distilled
prior to use. Diols (2S,3S)-2,3-dimethoxy-1,4-butanediol [21,22],
2.2. Syntheses of diphosphites: general method
ꢀ
ꢀ
(
3
4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol
,3 -di-tert-butyl-5,5 -dimethoxy-2,2 -biphenyldiol [24] were pre-
[23]
and
To a solution containing 4.18 mmol of the (1,1 -biaryl-2,2 -
dioxy)chlorodiphosphine and NEt3 (2.28 g, 22.6 mmol) in THF
(20 mL), 2.1 mmol of the corresponding diol in THF (5 ml) were
ꢀ
ꢀ
ꢀ
pared according to literature procedures. Phosphorochloridite
intermediates, 6-chloro-4,8-bis(1,1-dimethylethyl)-2,10-
dimethoxy-dibenzo[d,f][1,3,2]dioxaphosphepine [25], and (R)- and
◦
slowly added at −40 C. The mixture was allowed to reach room
temperature and it was stirred overnight. The ammonium salt
formed was filtrated over celite and the filtrate was evaporated
ꢀ
ꢀ
(
S)-(1,1 -binaphthalene-2,2 -dioxy)chlorophosphine [9] were pre-
pared as previously described. Styrene (S1) was filtered through
neutral activated alumina and substrates rac-1,3-diphenyl-3-
acetoxyprop-1-ene (S2), 1-phenyl-3-acetoxyprop-1-ene (S3) and
rac-3-acetoxycyclohexene (S4) were prepared following standard
to dryness. The solid residue was purified over silica using CH Cl2
2
as eluent. The analytically pure products were recovered by evap-
orating the solvent, yielding white to slightly yellow powders (see
Scheme 1 for the labeling used for NMR data).

7
0
A. Rosas-Hernández et al. / Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
ꢀ
ꢀ
ꢀ
(2S,3S)-2,3-O-isopropyliden-2,3-dihydroxy-1,4-bis[((R)-1,1 -
(
2S,3S)-2,3-dimethoxy-1,4-bis[(3,3 -di-tert-butyl-5,5 -
ꢀ
ꢀ
ꢀ
1
dimethoxy-1,1 -bisphenyl-2,2 -diyl)phosphite]-butane 1a. Yield 73%.
H NMR (300 MHz): 6.97 (d, 4H, H8, H11, JH5-H8 = J
binaphthyl-2,2 -diyl)phosphite]-butane 2c. Yield 68%.
H NMR
1
4
4
= 3.17),
(250 MHz): 8.01–7.72, 7.56–7.10 (m, 24 H, H2-H19), 4.07–3.80
H11-H14
= 3.17), 3.94–3.82 (m, 4H,
4
4
13
1
6
.70 (d, 4H, H5, H14, JH5-H8 = J
(m, 2H, H22), 3.80–3.65 (m, 4H, H21), 1.33 (s, 6H, H24). C{ H}
NMR (62.8 MHz): 147.3, 147.3 (4C, C1, C20); 133.0, 133.0 (4C, C9,
C12); 131.5, 131.1 (4C, C3, C18); 130.9; 130.7 (4C, C4, C17); 128.8,
128.7 (4C, C5, C16); 127.4, 127.2 (4C, C7, C14); 126.8, 126.6 (4C,
C6, C15); 125.6, 125.4 (4C, C8, C13); 123.1, 122.8 (4C, C10, C11);
122.3, 121.9 (4C, C2, C19); 110.6 (1C, C23); 78.7 (2C, C22); 64.1
H11-H14
H21), 3.81 (s, 12H, H7, H13), 3.52–3.33 (m, 2H, H22), 3.27 (s, 6H,
H23), 1.54, 1.37 (2 s, 36H, H4, H17). 13C{ H} NMR (75.4 MHz):
1
1
1
(
(
3
55.8, 155.3 (4C, C6, C12); 142.4–141.9 (8C, C1, C18, C9, C10);
33.6–133.3 (4C, C2, C15); 114.5-114.0 (4C, C8, C11); 112.9–112.5
4C, C5, C14); 79.2–78.9 (2C, C22); 62.3–62.0 (2C, C21); 59.1–58.9
2C, C23); 55.9–55.3 (4C, C7, C13); 35.5–35.2 (4C, C3, C16);
31
1
(4C, C21); 27.4 (6C, C24). P{ H} NMR (101.3 MHz): 139.5 (s).
31
1
25 + +
◦
2.5–29.3 (12C, C4, C17). P{ H} NMR (121.3 MHz): 132.9 (s).
[␣]D = −449.27 (c = 1.24, CH Cl ) FAB MS: m/z: 791 [M+1] . TOF
2
2
25
◦
+
+
+
[
␣]D = + 15.82 (c = 1.24, CH Cl ). FAB MS: m/z: 922 [M] . TOF
MS: m/z: 813.1787 (Calcd. 813.1777 for C H O NaP ), error
47 37 8 2
2
2
MS: m/z: 945.4076 (Calcd. 945.4078 for C50H68O12NaP2+), error
ppm) = −0.2393.
2S,3S)-2,3-dimethoxy-1,4-bis[((S)-1,1 -binaphthyl-2,2 -
(ppm) = 1.1479.
(
ꢀ
ꢀ
(
2.3. Rhodium complexes: in situ NMR experiments
1
diyl)phosphite]-butane 1b. Yield 78%. H NMR (300 MHz): 8.0–7.7,
7
2
.5–7.0 (m, 24H, H2-H19), 4.10–3.70 (m, 4H, H21), 3.45–3.30 (m,
ANMR tube was charged under nitrogen with a CDCl stock solu-
3
13
1
H, H22), 3.24 (s, 6H, H23). C{ H} NMR (75.4 MHz): 148.5, 147.4
tion of [RhH(CO)(PPh ) ] (0.8 mL, 0.4 mmol) and the corresponding
3
3
2
(
2d, 4C, C1, C20, JC-P = 3.9); 132.8, 132.6 (4C, C9, C12); 131.5, 131.0
ligand (molar ratio diphosphite/Rh = 0.5). The solution was ana-
lyzed by 1H and P NMR and then was shaken at 25 C during 1 h.
After this time, the solution was analyzed again. The spectra were
simulated by the gNMR software [27].
31
◦
(
4C, C3, C18); 130.4, 130.1 (4C, C4, C17); 128.4, 128.3 (4C, C5, C16);
1
27.0, 126.9 (4C, C7, C14); 126.3, 126.2 (4C, C6, C15); 125.1, 124.9
3
(
4C, C8, C13); 124.1, 122.6 (2d, 4C, C10, C11,
J
= 3.9); 121.8,
C-P
3
3
1
21.5 (2d, 4C, C2, C19, J = 2.01); 79.1 (d, 2C, C22, J = 4.2); 62.7
C-P
C-P
2
31
1
(
d, 2C, C21,
J
= 6.6); 59.2 (2C, C23). P{ H} NMR (121.3 MHz):
2.4. Palladium complexes
C-P
2
5
◦
41.9 (s). [␣]D = + 413.41 (c = 1.23, CH Cl ). FAB MS: m/z: 778
2 2
+
1
+
+
3
[M] . TOF MS: m/z: 801.1777 (Calcd. 801.1777 for C46H36O NaP2 ),
Complexes [Pd(␩ -allyl)(diphosphite)]PF were prepared from
8
6
3
error (ppm) = −0.0829.
[Pd(␮-Cl)(␩ -PhCHCHCHPh)] , NH PF , and the appropriate chiral
2
4
6
ꢀ
ꢀ
(
2S,3S)-2,3-dimethoxy-1,4-bis[((R)-1,1 -binaphthyl-2,2 -
diphosphite ligand according to a previously reported method [28].
1
3
diyl)phosphite]-butane 1c. Yield 79%. H NMR (250 MHz): 7.98–7.71,
[Pd(␩ -PhCHCHCHPh)(1a)]PF (9). Yellow crystals (0.132 g, 72%
6
7
(
1
.49–6.95 (m, 24H, H2-H19), 4.08–3.81 (m, 4H, H21), 3.58–3.39
yield). 1H NMR (300 MHz) 1.19 (s, 9H), 1.50 (s, 9H), 1.55 (s, 9H),
1.62 (s, 9H), 3.04 (s, 3H), 3.10 (s, 3H), 3.36-3.51 (br m, 2H), 3.72
(s, 6H), 3.79 (s, 3H), 3.87 (s, 3H), 4.25–4.55 (br m, 2H), 4.85–5.10
m, 2H, H22), 3.24 (s, 6H, H23). 13C{ H} NMR (62.8 MHz): 153.2,
1
52.2 (4C, C1, C20). 133.9, 133.6 (4C, C9, C12); 131.7, 131.4 (4C,
31
1
C3, C18); 130.1, 131.4 (4C, C4, C17); 129.0, 128.8 (4C, C5, C16);
27.8, 127.4 (4C, C7, C14); 126.9, 126.7 (4C, C6, C15); 125.5, 125.4
4C, C8, C13); 124.7, 124.4 (4C, C10, C11); 118.7, 118.2 (4C, C2,
(br m, 2H), 6.21 (m, 1H), 6.37–7.25 (m, 20 H).
P{ H} NMR
1
+
1
(
(121.4 MHz): 122.14 (s), −144.37 (sept, JP-F = 710.44 Hz). FAB MS:
+
+
m/z 1221 [M] . HR-FAB MS: m/z: 1221.4251 (Calcd. 1221.4233 for
31
1
+
C19); 79.7 (2C, C22); 62.1 (2C, C21); 60.1 (2C, C23). P{ H} NMR
C65H81
O
P Pd ), error (ppm) = 1.51.
12
2
25
◦
+
3
(
101.3 MHz): 142.9 (s). [␣]D = −445.4 (c = 1.23, CH Cl ) FAB
[Pd(␩ -PhCHCHCHPh)(2a)]PF (10). Yellow solid (0.126 g, 68%
2
2
6
+
yield) 1H NMR (300 MHz): 1.09–1.12 (m, 6H), 1.17 (m, 9H), 1.50
(m, 9H), 1.55 (m, 9H), 1.64 (m, 9H), 3.72 (s, 3H, major), 3.73 (s,
3H, minor), 3.80 (s, 3H, major), 3.88 (s, 3H, minor), 4.08 (br m,
MS: m/z: 779 [M+1] . TOF MS: m/z: 801.1777 (Calcd. 801.1777 for
+
C46H36O NaP ), error (ppm) = −0.0829.
8
2
ꢀ
(
2S,3S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis[(3,3 -di-tert-
ꢀ
ꢀ
ꢀ
31
1
butyl-5,5 -dimethoxy-1,1 -bisphenyl-2,2 -diyl)phosphite]-butane
2
4H), 5.07 (br m, 2H), 6.23 (br m, 1H), 6.48–7.22 (m, 20 H). P{ H}
1
a. Yield 90%. H NMR (300 MHz): 7.00–6.93 (m, 4H, H8, H11);
NMR (121 MHz): two isomers, major isomer: 122.40, 122.29; minor
1
6
.72–6.65 (4H, H5, H14); 4.17–3.63 (m, 6H, H21, H22); 3.81 (s, 12H,
isomer: 121.22, 121.14, ratio 1.5:1; −143.90 (sept, JP-F = 708.46).
13
1
+
+
+
H7, H13); 1.48, 1.34 (2 s, 36H, H4, H17); 1.32 (s, 6H, H23). C{ H}
NMR (75.4 MHz): 155.7–155.3 (4C, C6, C12); 142.5–141.8 (8C, C1,
C18, C9, C10); 133.7–133.2 (4C, C2, C15); 114.7–114.0 (4C, C8,
C11); 113.1–112.3 (4C, C5, C14); 109.7–109.8 (1C, C23); 76.9–76.7
FAB MS: m/z: 1233 [M] . HR-FAB MS: m/z: 1233.4246 (Calcd.
+
1233.4233 for C66H81O12P Pd ), error (ppm) = 1.09.
2
2.5. Catalytic experiments
(
(
2C, C22); 64.4–64.1 (2C, C21); 55.8–55.3 (4C, C7, C13); 35.5–35.1
4C, C3, C16); 31.4–30.0 (12C, C4, C17); 27.3–26.6 (2C, C24).
Hydroformylation experiments were carried out as previously
31
1
25
◦
P{ H} NMR (121.3 MHz): 129.5 (s). [␣]D = −32.93 (c = 1.26,
reported [9]: [Rh(acac)(CO) ] (6.4 mg, 0.025 mmol) and the appro-
2
+
+
CH Cl ) FAB MS: m/z: 935 [M+1] . TOF MS: m/z: 935.4255 (Calcd.
9
priate amount of diphosphite in toluene (8 mL) was incubated at
2
2
+
◦
35.4258 for C51H69O12P2 ), error (ppm) = −0.4080.
30 bar of syn-gas and 60 C for 2 h. A solution of styrene (1.2 mL,
ꢀ
(
2S,3S)-2,3-O-isopropyliden-2,3-dihydroxy-1,4-bis[((S)-1,1 -
10.0 mmol) in toluene (7 mL) was then added. The temperature was
set and the autoclave was charged with syn-gas at working pres-
sure. The conversion and regioselectivity were determined by GC
analysis. The enantiomeric excess (ee) of the reaction was obtained
by analyzing 2-phenylpropanal, as well as 2-phenylpropanoic acid,
by a GC apparatus equipped with chiral columns (Supelco ␤-Dex
225 and ␤-Dex 120 chiral columns). Aldehydes were converted
ꢀ
1
binaphthyl-2,2 -diyl)phosphite]-butane 2b. Yield 73%.
(
H
NMR
300 MHz): 8.00–7.70, 7.56–7.10 (m, 24 H, H2-H19), 4.07–3.80 (m,
13
1
2
(
(
H, H22), 3.80–3.65 (m, 4H, H21), 1.33 (s, 6H, H24). C{ H} NMR
75.4 MHz): 148.7, 147.3 (2d, 4C, C1, C20, 2JC-P = 4.2); 132.8, 132.6
4C, C9, C12); 131.6, 131.0 (4C, C3, C18); 130.5; 130.9 (4C, C4,
C17); 128.4, 128.3 (4C, C5, C16); 127.0, 127.0 (4C, C7, C14); 126.3,
1
4
26.3 (4C, C6, C15); 125.1, 124.9 (4C, C8, C13); 124.0, 122.6 (2d,
to the corresponding acids by a treatment with KMNO /MgSO4 in
acetone [4,29].
4
3
3
C, C10, C11, JC-P = 4.0); 121.8, 121.5 (2d, 4C, C2, C19, JC-P = 2.2);
3
1
10.1 (1C, C23); 76.4 (d, 2C, C22, JC-P = 3.8); 64.1 (d, 4C, C21,
Allylic alkylation experiments were performed follow-
2
31
1
3
JC-P = 3.6); 27.1 (6C, C24). P{ H} NMR (121.3 MHz): 134.3 (s).
ing previously reported methods [28]: [Pd(␮-Cl)(␩ -C H5)]
3
2
25
◦
+
+
[
␣]D = +429.03 (c = 1.24, CH Cl ) FAB MS: m/z: 791 [M+1] .
(3.7 mg, 0.01 mmol) and the diphosphite ligand (0.025 mmol)
in dichloromethane (1 mL) was stirred for 30 min. In some
2
2
TOF MS: m/z: 791.1959 (Calcd. 791.1959 for C47H37O8P2+), error
(
ppm) = 0.0988.
experiments, 200 or 400 ␮L of a CH Cl stock solution of
2 2

A. Rosas-Hernández et al. / Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
71
Table 1
Table 2
a
a
Hydroformylation of S1 with [Rh(acac)(CO)2]/diphosphite catalysts. .
Pd-catalyzed allylic alkylation using ligands 1-2. .
Entry
L
% C (h)b
TOFc
%4
% ee 4d
Entry
Substrate
L
% C (min)
7/6
% eeb
1
2
3
4
5
6
1a
1b
1c
2a
2b
2c
79 (3)
86 (24)
98 (19)
83 (4)
85 (24)
95 (22)
109
93
87
89
94
89
89
4 (S)
12 (S)
10 (R)
<2
9 (S)
10 (R)
1
2
3
4
5
6
7
8
9
S2
S2
S2
S2
S2
S3
S3
S3
S3
S3
S4
S4
S4
2a
1a
1a
1c
1b
1a
2a
2b
2c
1b
1a
2a
1b
91 (3)
90 (15)
15 (R)
60 (S)
68 (S)
14 (R)
10 (R)
5 (R)
15
21
86
15
18
c
45 (360)
100 (240)
55 (180)
100 (12)
100 (5)
54 (240)
100 (90)
53 (240)
100 (15)
100 (15)
10 (120)
46/54
49/51
27/73
9/91
8 (R)
a
0
.25 mol% Rh: [Rh(acac)(CO)2] = 1.66 mM, [L] = 2.08 mM mmol, toluene = 15 mL;
15 (R)
20 (R)
16 (R)
28 (R)
5 (R)
◦
P = 15 bar, PCO = PH , T = 40 C, chemoselectivity was >99% in all cases.
2
b
Conversion, time in parenthesis.
TOF: turnover frequency calculated as average in the indicated time (h ).
Absolute configuration of 4 is shown in parenthesis.
10
11
12
13
49/51
c
−1
d
25 (R)
a
NaBAr’F (10 mM) were added. CH Cl2 solutions (1 mL) of the
2 mol% Pd: [Pd(␲-C3H5)Cl]2 = 2.5 mM, [L] = 6.25 mM, [KOAc] = 12.7 mM,
2
[
Substrate]:[CH2(COOMe)2]:[BSA] = 1:3:3, CH2Cl2 = 4 mL.
substrate (1 mmol), dimethyl malonate (396 mg, 3 mmol) and N,O-
bis(trimethylsilyl)acetamide (610 mg, 3 mmol) and 5 mg of KOAc
were added. Aliquots were treated with diethyl ether, saturated
aqueous ammonium chloride solution and filtered over silica using
diethyl ether (S2 and S3) or dichloromethane (S4) as eluents. The
conversion and selectivity were determined by HPLC (Nucleocel
Delta S) for S2, by HPLC (Chiralcel OJ-H) and GC (DB-WAX column)
for S3 and by GC (␤-DEX 225 column) for S4.
b
Absolute configuration of products is shown in parenthesis.
c
◦
Carried out at −40 C.
The regioselectivities attained with 1a and 2a in the branched alde-
hyde 4 were higher (93–94%) than those obtained with ligands 1b-c
and 2b-c (84–90%).
3
.3. Palladium-catalyzed asymmetric allylic alkylation reactions
3
. Results and discussion
Ligands 1-2 were screened in the palladium-catalyzed asym-
metric allylic alkylation of rac-1,3-diphenyl-3-acetoxyprop-1-ene
S2), 1-phenyl-3-acetoxyprop-1-ene (S3), and rac-3-
3.1. Syntheses of ligands
(
acetoxycyclohexene (S4) with dimethyl malonate as nucleophile
and BSA as base (Scheme 2). Table 2 shows selected catalytic data
for alkylation reactions of these substrates.
Diphosphites 1a–c and 2a–c were prepared by condensing the
corresponding phosphorochloridites with the appropriate diol, in
the presence of an excess of NEt (Scheme 1). Ligands were purified
3
The Pd/2a system is the most active of all catalysts tested
from the small amounts of hydrolysis products formed during the
(
Table 2, entry 1). Given the high activity of this system at
reaction by passing a CH Cl2 solution of the crude over activated
−2
2
2 mol% Pd in the alkylation of S2, experiments at 0.1, 2 × 10
silica. All diphosphites were fully characterized by conventional
−2
and 1 × 10 mol% were carried out and TOF’s of 2220, 6000 and
spectroscopic techniques. Because the C symmetry of the ligands,
−1
2
7200 h were achieved, respectively. The ee’s in the (R)-5 prod-
their 1 C NMR show a single set of signals for one half of the diphos-
phite. However, it should be noticed that the local C2 symmetry of
the free biarylic groups is lost in the diphosphites. This produces
slight differences on the chemical shift of equivalent carbons of the
two moieties of each biarylic fragment (0.5–1 ppm).
3
uct were around 15% in all cases and they do not significantly
enhance by lowering the temperature. Activities achieved with
the Pd/2a are among the highest reported for asymmetric allylic
alkylation [15]. Although the catalytic system Pd/1a is also fairly
active, the rates achieved were lower than those of Pd/2a (Table 2,
entry 2). Besides, the best asymmetric induction (ca. 70% in (S)-
The backbone of ligands type 2 has been only previously used
in two reported diphosphites [13,30]. Other diphosphites derived
from tartaric acid have been also described, but their structures are
not related to those of ligands in Scheme 1 [31,32]. Diphosphites
with the backbone of ligands 1a–c have not been ever reported. Lig-
ands 1a–c and 2a–c were applied in the metal-catalyzed reactions
showed in Scheme 2.
5) was achieved with ligand 1a (Table 2, entry 3) in spite that
the backbone of this ligand is more flexible than that of 2a. It is
also noteworthy that in these cases, the configurations of major
enantiomer of 5 are opposite. Recently, it was reported a positive
−
ꢀ
effect of the B[3,5-(CF ) C H ] (BAr F) counterion on the enan-
3
2
6
3 4
tioselectivity of the allylic alkylation of S2 [33]. Nonetheless, in
our case, attempts to improve the steroselectivity of the system
ꢀ
3.2. Rhodium-catalyzed asymmetric hydroformylation
Pd/1a by adding Na(BAr F) to the catalytic reaction were unsuc-
cessful.
Screening catalytic experiments were carried out using styrene
Catalysts with ligands 1b-c and 2b-c, bearing binaphthyl
moieties, provided lower activities than 1a and 2a and poorer
enantiomeric excesses (ca. 15%) in the alkylation of S2. Thus,
the presence of the atropoisomeric fragment has a detrimen-
tal effect on both, the asymmetric induction and the activity
of the catalyst, although the later effect is more remarkable.
These results contrast with those reported in the same reac-
tion for diphosphoroamidite, phosphite-phosphoroamidite and
phosphite-oxazoline palladium catalysts, where the use of binaph-
thyl moieties instead of substituted biphenyls improves the
enantioselectivity [34–36].
as substrate (S1, Scheme 2). Selected results are collected in Table 1.
The enantioselective discrimination achieved in the branched
aldehyde 4 was low in all cases. Those containing binaphthyl frag-
ment, 1b-c and 2b-c, produced ee’s around 10% with the two
backbones used and the stereochemistry of the major aldehyde is
controlled by the configuration of the binaphthyl fragment. Lig-
ands 1b and 2b constructed with a (S)-binaphthol yield slight ee’s
on (S)-4 (Table 1, entries 2 and 5), whereas similar ee’s for (R)-4
was obtained with ligands bearing a (R)-binaphthyl moiety (Table 1,
entries 3 and 6). Therefore, there is not a cooperative effect between
the chiral backbone and the binaphthyl fragments. Furthermore,
ligands 1a and 2a with achiral biarylic fragment render meaning-
less ee’s (Table 1, entries 1 and 4), but they are nearly ten times more
active than the other four diphosphites with binaphthyl fragments.
The allylic alkylation of S3 leads to the formation of linear
and branched isomers (6 and 7), depending on the termi-
nal allylic carbon attacked by the nucleophile (Scheme 2). In
palladium-catalyzed asymmetric alkylation of mono-substituted

7
2
A. Rosas-Hernández et al. / Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
Scheme 2. Rhodium-catalyzed asymmetric hydroformylation and palladium-catalyzed asymmetric allylic alkylation reactions.
linear substrates like S3, low regioselectivies are often reported,
since in most cases the achiral linear isomer 6 is favored rather than
the desired chiral branched isomer 7 [37–39]. Ligand 1a showed
good activity, moderated regioselectivity and low enantioselec-
tivity with this substrate (Table 2, entry 6). When the flexible
backbone of 1a was replaced by the stiffer one of 2a, the rate of
the reaction increased and the selectivity remains nearly the same
(
(
Table 2, entry 7). Further improvement on the turnover frequency
TOF = 1440 h ) was achieved with a lower catalyst load (0.1 mol%
−1
Pd). This is the highest rate reported for the allylic alkylation of
S3 catalyzed by palladium/diphosphite system. Moreover, regios-
electivities in the branched product 7 (ca. 50%) achieved with 1a
and 2a are the highest reported using a diphosphite ligand. Both,
the activity and the regioselectivity of the catalyst significantly
decreased when the biphenyl fragment in ligand 2a was replaced
by a binaphthyl one, ligands 2b and 2c, although the ee’s slightly
increased (Table 2, entries 8 and 9 vs. 7). Low-temperature exper-
iments with S3 were carried out, but the ee’s remained almost
invariable.
◦
Fig. 1. Kinetic resolution of S2 using chiral diphosphite ligand 1a at 20 C. Reaction
conditions are indicated in Table 3.
Diphosphites were also tested in alkylation of rac-3-
acetoxycyclohexene (S4) (Scheme 2, Table 2). The asymmetric
allylic alkylation of cyclic substrates is a difficult process due
to the presence of less sterically demanding syn substituents,
which often results in a low asymmetric induction. General trends
observed in the allylic alkylation of S2 and S3 were reproduced
with S4. Ee’s in the product (R)-8 were below 30%. The highest
activities were achieved with 1a and 2a. For 2a, the reaction was
also accomplished at a low catalyst concentration (0.1 mol% Pd),
the temperature on the relative reaction rates of the two enan-
tiomers of the substrate. It should be noted that these values were
calculated considering a first-order kinetic dependence for the sub-
strate in the reaction rate. However, the kinetic dependence of
the substrate can vary during the reaction course, leading to inac-
curate estimations of the s values [40]. Indeed, it was observed
Table 3
a
Kinetic resolution of S2 using ligand 1a. .
−
1
affording a high rate for substrate S4 (TOF = 225 h ).
◦
% ee S2b
% ee 5b
sc
Entry
T ( C)
% C (min)
During the alkylation of S2 with the catalyst Pd/1a, a kinetic
resolution of this substrate was observed. The unreacted substrate
was steadily enriched in the (S)-isomer along the reaction (Fig. 1),
while the ee of the product 5 remained unchanged. After 15 min
1
2
3
4
5
20
20
20
0
−40
28 (2)
36 (3)
90 (15)
28 (10)
30 (180)
9 (S)
15 (S)
>99 (S)
30 (S)
32 (S)
60 (S)
60 (S)
60 (S)
63 (S)
68 (S)
1.7
2.0
n.d.
10.4
9.4
(
ca. 90% conversion), enantioselectivities of 99% for (S)-S2 and 60%
◦
for (S)-5 were attained at 20 C.
a
For reaction conditions see Table 2.
Table 3 shows selected data obtained for the kinetic resolution
of S2 at different temperatures, providing also the s parameter
b
c
Absolute configurations of S2 and 5 are shown in parentheses.
s = kR/kS = ln[(1 − C/100)(1 − ee/100)]/ln[(1 − C/100)(1 + ee/100)]
(
defined as the ratio kR/kS or krel) in order to asses the effect of
(C = conversion; ee = ee of S2), n.d. = not determined.

A. Rosas-Hernández et al. / Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
73
Scheme 3. Rhodium and palladium complexes. (a) Hydrido-carbonyl rhodium species. (b) Allyl-palladium active species.
that the calculated values changed with the conversion (Table 3,
3.4. Coordination properties
entries 1–3). The inspection of the s factors at similar conver-
sions indicates that the racemic resolution is enhanced when
Evidence about the coordinating properties of diphosphites 1–2
◦
◦
the temperature is lowered from 20 C to 0 C, but no further
was gathered by exploring the structure of complexes formed in the
◦
3
improvement was observed at −40 C. The substrate was recov-
reactions of these ligands with [RhH(CO)(PPh ) ] and [Pd(␮-Cl)(␩ -
3
3
ered in low yields (10–15%) with ee’s > 99% (S) and 90% (S), at
PhCHCHCHPh)] . Complexes generated are related to the catalytic
2
◦
◦
2
0 C and 0 C, respectively. Because the ee of the product 5 is
species in hydroformylation and allylic alkylation respectively.
The reaction of [RhH(CO)(PPh ) ] with bidentate P-donor lig-
the same throughout the reaction course, both enantiomers of S2
must lead to the same cationic catalytic intermediate or if sev-
eral species are formed, they have to be involved in fast equilibria
3
3
ands is a useful probe to test their chelating properties [9,42].
Ligands with low tendency to produce chelates form species type
brid-ee (other isomers are also possible), while ligands that are
[
41].
Table 4
NMR data for hydrido-carbonyl rhodium species with ligands 1a-c and 2a-c. .
a
Ligand
Species
brid-ee
ı (ppm) phosphine
ı (ppm) phosphite
ı (ppm) hydride
J (Hz)
1
JRh-P1 = 1JRh-P2 = 148.9; 1JRh-P3 = 265.4;
JP1-P2 = 93.7; JP1-P3 = JP2-P3 = 180.2
1
1
1
1
a
P1: 34.1
P2: 36.2
P3: 151.4
−9.91
2
2
2
Broad
bb
b
c
brid-ee
chel-ee
brid-ee
P1: 37.4
P2: 40.3
P3: 175.8
−10.03
1
2
JRh-P1 = 143.5; JRh-P2 = 147.7; 1JRh-P3 = 259.5;
JP1-P2 = 86.3, JP1-P3 = 194.9; JP2-P3 = 167.5;
1
2
2
Broad
1
2
JRh-P1 = 152.7; 1JRh-P2 = 244.4; 1JRh-P3 = 256.5;
JP1-P2 = 122.8; JP1-P3 = 153.1; 2JP2-P3 = 326.2
P1: 32.9
P2: 158.1
P3: 171.6
−10.30
2
Broad
1
2
2
JRh-P1 = 149.4; JRh-P2 = 146.6; 1JRh-P3 = 256.4;
JP1-P2 = 88.5; JP1-P3 = 183.2; JP2-P3 = 192.3;
JH-P1/2/3 = 8.0; JH-Rh = 9.5
1
P1: 44.3
P2: 47.2
P3: 181.0
−9.90
2
2
1
1
2
1
2
JRh-P1 = 136.6; 1JRh-P2 = 244.1; 1JRh-P3 = 270.4;
JP1-P2 = 101.3; JP1-P3 = 161.7; 2JP2-P3 = 199.9
2a
chel-ee
+
brid-ee
P1: 32.4
P2: 120.9
P3: 123.0
P3: 147.3
−10.28
Broad
−9.94
Broad
2
1
1
P1: 34.2
P2: 37.2
JRh-P1 = 146.5; JRh-P2 = 148.3; JRh-P3 = 265.9;
JP1-P2 = 85.8; JP1-P3 = 2JP2-P3 = 179.5
2
1
2
JRh-P1 = 143.8; JRh-P2 = 147.6; 1JRh-P3 = 259.4;
1
2
2
2
bb
b
brid-ee
chel-ee
chel-ee
P1: 37.4
P2: 40.1
P3: 175.3
−9.87
2
2
Broad
JP1-P2 = 86.3; JP1-P3 = 168.6; JP2-P3 = 190.6
1
2
JRh-P1 = 139.7; 1JRh-P2 = 240.0; 1JRh-P3 = 240.0;
JP1-P2 = 117.5; JP1-P3 = 140.4; 2JP2-P3 = 240.0
P1: 32.0
P2: 164.2
P3: 169.7
−10.53
2
Broad
1
2
2
JRh-P1 = 137.3; 1JRh-P2 = 238.1; 1JRh-P3 = 247.2;
JP1-P2 = 128.2; JP1-P3 = 143.5; 2JP2-P3 = 289.0;
JH-P1 = 7.7, JH-P2/3 = 9.0, 1JH-Rh = 8.7
c
P1: 35.8
P2: 173.9
P3: 177.4
−9.99
2
2
a
◦
After 1 h of reaction at 25 C, [L]/[Rh] = 0.5 in CDCl3.
After 15 min of reaction.
b

7
4
A. Rosas-Hernández et al. / Journal of Molecular Catalysis A: Chemical 328 (2010) 68–75
prone to form a chelate complex render species type chel-ee or
chel-ae, depending on the bite angle of the ligand (Scheme 3a) [43].
The three species are easily distinguished by NMR, providing a sim-
ple diagnostic for the chelating properties of new ligands. Table 4
collects the results of 3 P and the hydride region of the 1H NMR
spectra for the species formed in this reaction.
product 5 were achieved. To sum up, the excellent activities of the
Pd systems with ligands 1a and 2a can be highlighted. Both ligands
share the presence of substituted biphenyl moieties, although the
stiffness of their backbone is remarkable different. The difference in
the stereoselectivity of these two ligands in alkylation reactions can
arise from the fact that, in solution, only one isomer was detected
1
31
3
+
P NMR spectra display two set of signals corresponding to
for the cationic allylic species [Pd(␩ -PhCHCHCHPh)(1a)] , while
3
+
coordinated phosphine and phosphite around 40 and 180 ppm
respectively. In the case of ligands 1a and 1c, the phosphine signals
integrate twice respect to those assigned to phosphite, which is
consistent with a phosphite bridge between two [RhH(CO)(PPh ) ]
two isomers were observed for [Pd(␩ -PhCHCHCHPh)(2a)] .
Acknowledgements
3
2
fragments. The high JP-P values (>85 Hz) and small coupling val-
ues between P and H ligands (ca. 10 Hz) indicate that the three
P-donor ligands occupy equatorial positions and that they are cis
respect to the hydride. These observations are in agreement with
a structure type brid-ee for these species. Similar behavior was
found by ligand 2a, although it partially evolves to a chel-ee species
The authors thank Conacyt-Mexico CB-060430 and CB-
060894, Dgapa-UNAM IN210607 and Spanish DGI through project
(CTQ2005-09187-C02-01) for the financial support and CYTED
(Project V9) for a bursary to E. Vargas-Malvaez.
Appendix A. Supplementary data
(
ca. 2:1 brid-ee:chel-ee) producing a stable mixture of species.
In contrast, ligand 2c forms a chel-ee species for the complex
RhH(CO)(PPh )(2c)]. The integration of the phosphite region is
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molcata.2010.06.001.
[
3
twice that of the phosphine, the values of all JP-P are high (>100 Hz)
and P-H coupling constants are below 10 Hz. These facts are com-
patible with a chel-ee structure. Similar behavior was observed for
Rh/1b and Rh/2b species, but brid-ee species were formed at the
first stages of the reaction. After 1 h at room temperature, binuclear
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In allylic alkylation reactions, Pd/2a system showed very high
−
1
rates for the disubstituted linear substrate S2 (TOF = 7200 h ),
[
−
1
the mono-substituted linear substrate S3 (TOF = 1440 h ) and the
−1
cyclic substrate S4 (TOF = 225 mol h ). These activities are among
the highest in Pd-catalyzed allylic substitutions reactions for these
substrates. In spite of the low enantioselectivity, the selectivity
obtained in the branched isomer 7 arising from S3 was fairly good
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9
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