Novel bis(1,3,2-diazaphospholidine) ligands for asymmetric catalysis

Article abstract of DOI:10.1021/om400185q

A family of modularly designed chiral bis(1,3,2-diazaphospholidines) with N-aryl substituents (NP-PN) is reported. These compounds have been prepared in two steps from readily available (R,R)-1,2-diaminocyclohexane and tetrachlorodiphosphines. Examples in the set differ in the backbone and the aryl substituents, aiming at their application in asymmetric catalysis. Thus, [Rh(NBD)(NP-PN)]BF₄ complexes lead to active catalysts in the hydrogenation of methyl α-acetamidoacrylate, which provide enantioselectivities up to 96% ee. In addition, NP-PN ligands also generate active catalysts in the hydroformylation of vinyl acetate, leading to high regioselectivities (iso:n ratio higher than 99:1) and enantioselectivities up to 65% ee.

Full text of DOI:10.1021/om400185q

Communication
pubs.acs.org/Organometallics
Novel Bis(1,3,2-diazaphospholidine) Ligands for Asymmetric
Catalysis
́
Inmaculada Arribas, Eleuterio Alvarez, and Antonio Pizzano*
́
Instituto de Investigaciones Quımicas (IIQ), Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Avda
Americo Vespucio No. 49, Isla de la Cartuja, 41092 Sevilla, Spain
́
S
* Supporting Information
ABSTRACT: A family of modularly designed chiral bis(1,3,2-
diazaphospholidines) with N-aryl substituents (NP-PN) is
reported. These compounds have been prepared in two steps
from readily available (R,R)-1,2-diaminocyclohexane and
tetrachlorodiphosphines. Examples in the set differ in the
backbone and the aryl substituents, aiming at their application
in asymmetric catalysis. Thus, [Rh(NBD)(NP-PN)]BF4 complexes lead to active catalysts in the hydrogenation of methyl α-
acetamidoacrylate, which provide enantioselectivities up to 96% ee. In addition, NP-PN ligands also generate active catalysts in
the hydroformylation of vinyl acetate, leading to high regioselectivities (iso:n ratio higher than 99:1) and enantioselectivities up to
65% ee.
C2 -symmetric bis(phospholanes) (Figure 1, A) constitute a
in B could rely on an steric interaction between the appropriate
R and R′ groups. Some precedents suggest the feasibility of this
approach. For instance, the group of Tsuji has described an
efficient Pd catalyst based on secondary aryl diamines with
chiral backbones.9 On the other hand, Pfaltz and co-workers
have described highly enantioselective Ir phosphine−oxazoline
catalysts containing N-aryl diazaphospholidine fragments.10 In
this contribution we describe the synthesis of the first bis(1,3,2-
diazaphospholidine) ligands bearing N-aryl substituents, along
with preliminary catalytic results which include a highly
enantioselective hydrogenation reaction.
prominent class of ligands in asymmetric catalysis.1,2 The
Figure 1. Generic structures of R-substituted phospholanes (A) and
1,3,2-diazaphospholidines (B) and the ESPHOS ligand (C).
trans-1,2-Cyclohexanediamine was chosen as the starting
diamine scaffold because it is readily available as both
enantiomers and can easily be arylated to provide a wide
variety of chiral secondary amines.9−11 Among the latter,
phenyl (1a) and p-tolyl (1b) diamines were selected as
representative examples and reacted with commercially
available tetrachlorodiphosphines, in the presence of an excess
of NEt3 (Scheme 1). These reactions provide a family of
bis(1,3,2-diazaphospholidines) 2−4, which differ in the nature
of the backbone. In contrast with the reaction between
secondary aliphatic amines and 1,2-bis(dichlorophosphino)-
ethane,6 b the generation of the present bis-
(diazaphospholidines) is slow at room temperature and
prolonged heating is needed to reach a good conversion. For
instance, the reaction between 1a and 1,2-bis-
(dichlorophosphino)benzene shows at room temperature the
formation of an intermediate mono(diazaphospholidine)
compound (P−P′, Figure 2), characterized by two doublets
centered at 104 and 154 ppm with a JPP coupling constant of
151 Hz, along with some starting material at 150 ppm. These
outstanding performance of these compounds is due to the
proximity of the stereogenic centers to the metal and, as well, to
the ability to finely tune the R group. However, the range of
these substituents is largely limited to alkyl groups, while
examples bearing aryl substituents are restricted to the 2,5-
diphenylphospholane moiety,3 due to the highly difficult
synthesis of these derivatives.4 It is worth noting that the
presence of aryl substituents in positions 2 and 5 may have a
profound influence on the catalytic process, as has been
observed in asymmetric hydroformylation reactions.5
A seemingly related structure to bis(phospholanes) A is
provided by bis(1,3,2-diazaphospholidines) (B). The latter
compounds are attractive ligands for synthetic reasons, due to
the easy formation of P−N bonds from the appropriate amines
and phosphorus chlorides. Some alkyl examples (R = Me, CH2-
t-Bu, CH2Ph) have already been described in the literature,
although the efficiency of compounds B as ligands for
asymmetric catalysis has not yet been substantiated.6 In this
respect, a problem arises from the poorly defined position of R
substituents in B, due to the expectedly easy nitrogen inversion.
This aspect has successfully been circumvented by the use of
bridgehead N atoms in ESPHOS (C)7 and related
diaminophosphite ligands.8 In contrast, an arrested N inversion
Received: March 7, 2013
© XXXX American Chemical Society
A
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Organometallics
Communication
ability intermediate between phosphines and phosphites.12
However, the N-aryl fragments in 3a reduce the σ-donor ability
of 2a, in comparison with N-alkyl 1,3,2-diazaphospholidines,13
making it comparable with that provided by structurally related
diaminophosphites.14
Scheme 1. Preparation of Bis(diazaphospholidines) 2−4
To provide information about the structural features of the
diazaphospholidine fragment in compounds 2−4, a representa-
tive example (4b) has been characterized by X-ray crystallog-
raphy (Figure 3). The structure of this compound clearly shows
Figure 3. ORTEP view of complex 4b at the 50% probability level. H
atoms have been omitted for clarity. Selected bond lengths (Å) and
angles (deg): P(1)−C(21) = 1.8191(13); P(1)−N(1) = 1.7474(10);
P(1)−N(2) = 1.7225(11); N(1)−C(7) = 1.4250(16); N(2)−P(1)−
N(1) = 91.40(5); C(7)−N(1)−P(1) = 114.96(8); C(14)−N(2)−
P(1) = 120.88(9); C(14)−N(2)−C(2)-C(3) = 76.63(15); C(7)−
N(1)−C(1)−-C(6) = 64.09(15).
the presence of the two phosphorus heterocycles, each fused
with a cyclohexane ring in a chair conformation. The most
interesting aspect is with regard to the anti position of the N-
aryl substituents, defined by C(7) and C(14), relative to the
cyclohexane carbons C(6) and C(3), respectively. On the other
hand, the sum of the bond angles involving the nitrogen atoms
amount to 342.1° (∑N(1)) and 350.9° (∑N(2)), indicative of
a geometry intermediate between tetrahedral and trigonal
planar for these atoms. The important influence of the chiral
cyclohexane fragment on the nitrogen geometry in 4b is
evident upon comparison with the structure of 2-phenyl-1,3-di-
p-tolyl-1,3,2-diazaphospholidine,15 which shows two planar
nitrogens with a ∑N value of 359.1°. It should finally be
mentioned that the N−C(aryl) distances in 4b (1.416 and
1.425 Å) are significantly shorter than the exocyclic N−C bond
lengths observed in related N-alkyl derivatives (1.72−1.75 Å).6b
We next examined the coordination of ligands 2 and 3 to
cationic rhodium complexes. Thus, these bis-
(diazaphospholidines) cleanly react with [Rh(NBD)2]BF4 to
give the corresponding complexes [Rh(NBD)(NP-PN)]BF4 (6
and 7; Scheme 2). These compounds appear in the 31P{1H}
NMR spectra as a doublet centered between 120 and 140 ppm,
Figure 2. 31P{1H} NMR (162 MHz, toluene) monitoring of the
formation of 3a.
signals disappeared upon heating, and the singlet of the desired
compound 3a started to grow as the very predominant product.
Interestingly, this reaction is rather clean and shows a high
conversion. However, in order to guarantee the elimination of
reactive phosphorus chloride impurities, the resulting mixture
was purified through neutral alumina with some decrease in the
yield of isolated 3a.
Compounds 2−4 have been characterized by NMR, and the
data collected are in accord with the structures proposed for
them. Thus, they show relatively simple 1H and 13C{1H} NMR
spectra due to the C2 symmetry of these compounds. In
addition, the two 31P nuclei are equivalent and appear as a
singlet in the 31P{1H} NMR spectra. The latter signals appear
at ca. 110 ppm for ligands 2 and 4 and at ca. 130 ppm for
compounds 3.
1
with JRhP coupling constants between 208 and 215 Hz. In
addition, the 1H and 13C{1H} NMR spectra show the
In order to estimate the donor properties of this family of
ligands, the reaction between 3a and Se has been performed.
This reaction produces the corresponding diselenophosphine
5a, which appears as a singlet at 73.1 ppm in the 31P{1H} NMR
Scheme 2. Preparation of Rh Complexes 6 and 7
1
spectrum. Measurement of the JSeP coupling constant in the
satellites corresponding to the 77Se isotopomer indicates a
coupling of 868 Hz. This value shows, as expected, a donor
B
dx.doi.org/10.1021/om400185q | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
a
equivalence between groups, in accord with the presence of a
C2 symmetry axis.
It is important to note that, upon coordination of ligands 2−
4, different structures for complexes 6 and 7 are possible due to
nitrogen inversion (Figure 4a−c). Interestingly, these structures
Table 1. Hydrogenation of MAA Using Complexes 6 and 7
entry
cat. precursor
conversn, %
ee, % (confign)
1
2
3
4
6a
6b
7a
7b
100
100
100
100
75 (R)
39 (R)
96 (R)
88 (R)
a
Reactions were carried out under an initial hydrogen pressure of 4 bar
at S/C = 100 in CH2Cl2 at room temperature. The reaction time was
24 h. Conversion was determined by 1H NMR and enantiomeric
excess (ee) by chiral GC. Absolute configurations are shown in
parentheses.
On the other hand, a preliminar study of the utility of ligands
2 and 3 in the asymmetric hydroformylation of vinyl acetate as
a representative reaction has also been performed (eq 2, Table
Figure 4. (a−c) Conformers resulting from N epimerization. For
clarity, only structures corresponding to one N inversion from the anti-
anti structure have been drawn. (d) Schematic drawing rationalizing
the shielding effect on the NBD olefin protons.
Table 2. Vinyl Acetate Hydroformylation Using Ligands 2
and 3
a
rntry
ligand
Rh/L
i:n
conversn, %
ee, % (confign)
differ in the steric interactions between the Ar substituents and
the cyclohexane fragment and in the proximity of the aryl rings
to the NBD olefinic protons. In this respect, an inspection of
the 1H NMR spectra of complexes 6 and 7 indicates that one of
the olefin signals appears between 5.62 and 5.97 ppm, in the
range found for other NBD complexes with diphosphine
ligands.16 In contrast, the second olefinic signal for 6 and 7
appears significantly shifted upfield, between 4.36 and 5.10
ppm. The shift of the latter signal can be attributed to the
shielding caused by a close aryl ring (d). As a confirmation, an
analysis of complex 7b by a 2D NOESY experiment has allowed
us to assign signals corresponding to tolyl groups pointing to
the NBD ligand. Notably, the ortho hydrogens of the latter aryl
rings exhibit a NOE signal with the high-field olefin protons.
Moreover, an examination of the NOE signals observed
between these aromatic protons and the protons of the closer
CHN and CH2 fragments of the cyclohexane ring do not show
evidence of inversion of the N configuration in solution (see
the Supporting Information), in accord with a preferred C2-
symmetric anti-anti structure in solution for this complex.
To investigate the ability of the present bis-
(diazaphospholidine) ligands to induce enantioselectivity in a
catalytic process, their performance in representative asym-
metric hydrogenation and hydroformylation reactions has been
examined. First, compounds 6 and 7 have been tested in the
hydrogenation of methyl acetamidoacrylate (eq 1, Table 1).
1
2
3
4
2a
2b
3a
3b
1
1
1
1
99:1
99:1
98:2
99:1
99
99
73
99
65 (R)
63 (R)
47 (R)
60 (R)
a
Reactions were carried under an initial H2/CO (1:1) pressure of 10
bar at a S/C = 500 in toluene at 50 °C. Reaction time 24 h.
Conversion was determined by 1H NMR and enantiomeric excess (ee)
by chiral GC. Absolute configuration drawn in parentheses.
2). Reactions were performed at Rh/L = 1 at 50 °C and 10 atm
of a H2/CO (1/1) mixture. These reactions showed high
conversions, with the exception of the catalyst based on 3a,
which provided a moderate conversion (73% conversion, entry
3). Catalysts showed a high regioselectivity, with a branched to
linear ratio higher than 98:2. In contrast, enantioselectivities
were only moderate and, among the catalysts tested, that based
on ligand 2a provided the best value (65% ee, entry 1).
In summary, a convenient synthesis of modularly designed
C2-symmetric bis(1,3-diaryl-1,3,2-diazaphospholidines), based
on trans-1,2-diaminocyclohexane, has been reported. The
preliminary results indicate promising results in hydrogenation
and hydroformylation reactions. Research on the extension of
this class of ligands, as well as their application in asymmetric
catalysis, is currently in progress.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, tables, and a CIF file giving representative
experimental procedures, characterization data, and crystallo-
graphic information for 4b. This material is available free of
charge via the Internet at http://pubs.acs.org.
Under mild conditions, 4 bar of hydrogen and room
temperature, these compounds lead to active catalysts able to
complete reactions at S/C = 100 in 24 h. A comparison
between catalysts indicates that those bearing a benzene
backbone afforded better enantioselectivities. Of them, the Ph-
substituted complex 7a gave a good value of 96% ee (entry 3).
AUTHOR INFORMATION
■
Corresponding Author
*E-mail for A.P.: pizzano@iiq.csic.es.
C
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Communication
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
MICINN (CTQ2009-11867 and CONSOLIDER-INGENIO,
CSD2007-00006, FEDER support) and the Junta de Andalucıa
(2008/FQM-3830 and 2009/FQM-4832) are acknowledged
■
́
for financial support.
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