New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and alkylation

Article abstract of DOI:10.1016/j.tet.2020.131142

The synthesis of a broad library of new P-chirogenic Xantphos ligands is reported. A special feature is 2,7-di-tert.-butyl substituents in the backbone which requires the modification of the original synthetic approach. In comparison to related ligands reported formerly the substitution has a considerable influence on the results (yield and % e.e.) of metal catalyzed reactions, e.g. asymmetric rhodium catalyzed hydrogenation of isophorone and the palladium catalyzed alkylation, respectively.

Full text of DOI:10.1016/j.tet.2020.131142

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New P-chirogenic tert.-butyl-xantphos ligands and their application in
asymmetric hydrogenation and alkylation
,
Jens Holz a *, Gudrun Wenzel a, Anke Spannenberg a, Mark Gandelman b,
a, c, **
€
Armin Borner
a Leibniz-Institut für Katalyse e.V., A.-Einstein-Straße 29a, 18059 Rostock, Germany
b Schulich Faculty of Chemistry, Technion-Israel, Institute of Technology, Technion City, Haifa 32000, Israel
c
€
Institut für Chemie, Universitat Rostock, A.-Einstein-Straße 3a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of a broad library of new P-chirogenic Xantphos ligands is reported. A special feature is 2,7-
di-tert.-butyl substituents in the backbone which requires the modification of the original synthetic
approach. In comparison to related ligands reported formerly the substitution has a considerable in-
fluence on the results (yield and % e.e.) of metal catalyzed reactions, e.g. asymmetric rhodium catalyzed
hydrogenation of isophorone and the palladium catalyzed alkylation, respectively.
© 2020 Elsevier Ltd. All rights reserved.
Received 16 January 2020
Received in revised form
12 March 2020
Accepted 14 March 2020
Available online xxx
Keywords:
P-Chirogenic phosphines
Rhodium
Palladium
Asymmetric hydrogenation
Asymmetric allylic alkylation
Xantphos
1. Introduction
chirogenic ligands became visible. Thus, meanwhile well-known
diphosphines like BisP*[5], QuinoxP* [6], MiniPhos [7], and Tang-
Efforts in the application of chiral phosphines employed as li-
gands in asymmetric reactions were particularly inspired by the
conclusion of W. S. Knowles in his Nobel-Prize lecture in 2001: “We
felt strongly if one wanted to get high ee values, the asymmetry
would have to be directly on the phosphorus. That is where the
action is.” [1] An early highlight in this regard represents the
preparation of P-chirogenic compounds by Horner et al. [2] which
pathed the way for the synthesis and application of DiPAMP as
ligand in the homogeneous rhodium catalyzed asymmetric hy-
drogenation of prochiral enamides[3]. However, in the following
decades the focus in this area was mainly directed on the use of
chelating phosphines with chirality in the backbone (e.g. with C-
stereogenic centers, axes and planes) [4].
Phos [8] were developed showing excellent results in several
asymmetric transformations (Fig. 1). Stimulated by this success the
number of P-chirogenic ligands and its successful application in
asymmetric reactions has grown enormously in the last years [9].
Recently, we have published a large family of diphosphines with
two P-chirogenic triarylphosphines interlinked via an ether-bridge
with xanthene, diphenyl ether, or dibenzofuran backbone, respec-
tively [10].
Some of these meanwhile commercially available ligands
showed excellent results in the rhodium catalyzed asymmetric
hydrogenation of isophorone [10] and in the stereoselective copper
catalyzed hydroallylation of disubstituted cyclopropenes [11].
Xantphos itself developed by van Leeuwen and co-workers and
used in numerous transition metal catalyzed reaction, e.g. hydro-
formylation[12], is characterized by two tert.-butyl groups in 2,7-
position of the xanthene backbone. Taking the effect of remote
substituents in phosphorus ligands on the course of the catalytic
reactions into account[13], now we tried to introduce two P-chi-
rogenic groups in this particular backbone. This target required a
modified synthesis. Moreover, in subsequent asymmetric catalytic
Around the turn of the millennium a renewed interest in P-
* Corresponding author. Leibniz-Institut für Katalyse e.V., A.-Einstein-Straße 29a,
18059, Rostock, Germany
** Corresponding author. Leibniz-Institut für Katalyse e.V., A.-Einstein-Straße 29a,
18059 Rostock, Germany.
E-mail address: jens.holz@catalysis.de (J. Holz).
https://doi.org/10.1016/j.tet.2020.131142
0040-4020/© 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

2
J. Holz et al. / Tetrahedron xxx (xxxx) xxx
2.2. Rhodium catalyzed asymmetric hydrogenation
Our first intention was to apply the new diphosphines 2 as li-
gands in the rhodium catalyzed asymmetric hydrogenation of neral
and geranial (parts of citral) for the stereoselective synthesis of
citronellal as precursor for the technical menthol manufacture [17].
But the enantioselectivities noted were only poor (less than 30%
e.e.). Therefore, some of these new diphosphines were tested in the
asymmetric hydrogenation of isophorone 3 like already described
for other similar P- chirogenic ligands (Scheme 2) [10].
For the catalytic reaction we employed two metal sources
Rh(acac)(cod) (I) and Rh(acac)(CO)2 (II). These metal complexes
allowed the asymmetric hydrogenation of both components of
citral at ambient and enhanced pressure [17]. Like citral compo-
nents (neral and geranial) also isophorone 3 represents structurally
an a,b-unsaturated carbonyl compound but without the possibility
of E/Z-isomerization. After prolongation of the reaction time the
formation of the undesired alcohol 5 by reduction of carbonyl
group was observed. For comparison the results of “nondecorated”
P*-chirogenic Xantphos 6 derivatives have been added to Table 1.
Our preliminary tests clearly showed that the application of
Rh(cod)(acac) (I) led to significantly lower enantioselectivities in
comparison to the use of Rh(acac)(CO)2 (II) (Table 1, entries 1 and
2). Obviously, the catalytically active species in both reactions are
different. We already noted this effect in the (non-asymmetric)
hydrogenation of neral and geranial, respectively [17]. The relevant
kinetic curves of the hydrogenation consumption were different.
Up to now, the reason for this behavior is not clear.
Fig. 1. Some prominent examples of P-chirogenic ligands.
reactions significant effects caused by the additional tert.-butyl
substituents in comparison to the parent structures became
obvious.
Therefore, we have used in subsequent trials only Rh(acac)(CO)2
(II) as metal source. Beside the ortho-aryloxyphenyl group (xan-
thene backbone) all chiral diphosphines of types 2 and 6 bear
phenylphosphino moieties with a methyl, or an o-, m-p-substituted
aryl as second substituent. In the asymmetric hydrogenation of
isophorone under identic conditions the effect of the additional
tert.-butyl groups in the xanthene backbone is significant in some
2. Results and discussion
2.1. Synthesis
In the first part of the synthesis of P-chirogenic 2,7-tert.-butyl-
Xantphos derivatives 2a-t we followed the established method of
ꢀ
Juge et al. for the preparation of borane-protected P-chirogenic
methyl aryl(phenyl)phosphinites 1a-t and their free derivatives 1′
a-t [9g,14]. Based on the experiences in the synthesis of other P-
chirogenic Xantphos ligands (see reference 10) the borane-group in
1a-t was removed first in situ and then the unprotected chiral
methyl phosphinite 1′a-t was added to dilithiated 2,7-di-tert.-
butyl-xanthene (Scheme 1). In first trials, we started with the
simple and commercially available 2,7-di-tert.-butyl-xanthene and
followed the approach recently published for non-substituted
Xantphos derivatives [10,15]. But the yields of 2 were unsatisfac-
torily. Therefore, we switched to the relevant 4,5-di-bromo com-
pounds. With them in hand we noted significant better results [16].
By variation of the corresponding aryl groups in 1 twenty 2,7-di-
tert.-butyl derivatives 2a-t were obtained as enantiopure com-
pounds after crystallization or purification by column chromatog-
raphy, respectively, from the raw products.
Scheme 2. Rhodium catalyzed asymmetric hydrogenation of isophorone 3.
Scheme 1. Synthetic approach to P-chirogenic 2,7-di-tert.-butyl-xantphos derivatives 2.
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

J. Holz et al. / Tetrahedron xxx (xxxx) xxx
3
Table 1
Comparison of results in the asymmetric hydrogenation of isophorone with P-chirogenic diphosphines of type 2 and 6a
ligand
2a-t
6a-t
entry
1
ligand (Ar)
precatalystb
solvent
time [h]
conversionc [%]
% e.e. (abs. conf.)d
time [h]
conversionc [%]
% e.e. (abs. conf.)d
a (2-MeO-Ph)
I
I
II
II
I
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
thf
toluene
4
8
4
20
2
100 (19)
100 (14)
100 (2)
100 (5)
100 (10)
99 (5)
20.6 (S)
5.4 (S)
79.9 (S)
77.4 (S)
0.1 (R)
0.1 (S)
4
8
4
20
15
15
4
4
4
8
8
8
4
8
4
4
20
20
4
4
4
4
4
4
4
100 (25)
100 (30)
100 (3)
100 (19)
85 (3)
70 (2)
100 (1)
100 (1)
87 (1)
74 (1)
94 (2)
45 (4)
20 (1)
19 (1)
84 (2)
87 (2)
57 (3)
50 (1)
89 (1)
89 (1)
50 (3)
20 (0)
80 (6)
15 (0)
22 (0)
15 (0)
8.8 (R)
8.8 (R)
84.0 (S)
84.0 (S)
36.5 (R)
50.1 (R)
96.5 (S)
96.4 (S)
10.1 (S)
12.5 (S)
0.5 (S)
2
b (2-Me-Ph)
I
15
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
15
4
8
8
8
4
8
15
15
8
33 (0)
46 (1)
41 (1)
88 (2)
92 (2)
21 (1)
19 (1)
54 (1)
12 (1)
56 (1)
15 (1)
89.3 (S)
6.7 (S)
9.0 (S)
3
c (3-MeO-Ph)
e (4-MeO-Ph)
f (4-Me-Ph)
4
0.7 (R)
2.5 (R)
1.3 (R)
1.3 (R)
66.7 (S)
82.6 (S)
17.4 (S)
17.1 (S)
1.5 (S)
0.3 (R)
1.7 (S)
5
6
g (1-naphthyl)
h (2-naphthyl)
i (4-phenantryl)
j (3,5-MeO-Ph)
k (2-EtO-Ph)
l (2-Et-Ph)
91.2 (S)
91.9 (S)
19.7 (S)
17.0 (S)
91.9 (S)
91.9 (S)
24.6 (S)
25.8 (S)
29.1 (S)
36.2 (S)
16.0 (S)
19.0 (S)
7
8
8
15
4
4
4
8
4
4
4
8
17 (0)
50 (7)
87 (2)
98 (7)
100 (1)
22 (0)
10 (0)
69 (1)
46 (5)
81.0 (S)
16.0 (S)
38.9 (S)
83.5 (S)
85.1 (S)
87.9 (S)
85.1 (S)
13.2 (S)
10.3 (S)
9
10
11
12
13
4
n (3-Et-Ph)
t (4-DBF)
4
8
81 (1)
47 (0)
18.1 (S)
14.3 (S)
a
Rh/2/isophorone ¼ 1/1.2/200, 5 MPa H2, 40 ꢀC.
Rh(acac)(cod) ¼ I, Rh(acac)(CO)2 ¼ II.
b
c
Estimated by 1H NMR, in parenthesis the part of alcohol 5.
Enantioselectivity of 4 estimated by GC on chiral column.
d
cases. Differences in the yield of the saturated ketone by more than
60% have been noted (e.g. entry 2). It seems that the new ligands of
type 2 suppress more the formation of the undesired alcohols 5
than ligands of type 6 especially when Rh(cod)(acac) (I) was used as
rhodium source.
In general, structurally related ligands induced similar ee-
values. Enantioselectivities ranges from almost zero, e.g. ligands
of type 2f/6f until 80 to >90% e.e. with ligands of type 2a/6a or 2g/
6g. The latter are characterized either by ortho-methoxy groups or
1-naphthyl groups.
Aryl substituents away from the ortho-position in the third aryl
group have only marginal (meta-position) or nearly no influence
(para-substitution) on the stereoselective induction of the asym-
metric hydrogenation (e.g. entries 2, 3 and 5 or entries 6, 7, 8). In the
latter example the change from the 1-naphthyl group (phenyl ring
owing benzannulated ring in 2,3-position) to the 2-naphthyl group
(now 3,4-position) the enantioselectivity of product dropped. But
with derivative 2i having a phenantryl group as a combination of
both benzannulated rings the stereoselectivity increased again.
Also, some surprising results has been noted. While for the 2-
methoxy/2-methyl substituted derivatives 2a and 2b and also for
the “undecorated” xanthene bridge ones 6a and 6b good enantio-
selectivities were concluded the enantioselectivity dropped down
dramatically in case of the 2-ethoxy/2-ethyl derivatives (2k and 2l
vs. 6k and 6l). Interestingly, from point of view enantioselectivity
the introduction of the additional tert.-butyl groups in the
backbone of xanthene had an unfavorable effect.
2.3. Pd-mediated asymmetric alkylation
To test the asymmetric induction of P-chirogenic Xantphos li-
gands in stereoselective transformation, we employed them in
allylation of dimethylmalonate by 1,3-diphenylallyl acetate using
chiral palladium complexes (Scheme 3). This benchmark reaction
was chosen because the only hitherto known P-chirogenic Xant-
phos ligand 2u (owing a chiral PPhMe-moiety, Fig. 2) was applied in
this reaction by the Hamada group in 1997 (up to 85% e.e.) [18].
For comparison we synthesized also the analogous Xantphos
analogue 6u without tert.-butyl substituents in 2,7-position by the
same procedure applying (S)-methoxy(methyl)(phenyl)phosphine
borane complex. In contrast to the ligand of type 2a-t or 6a-t
diphosphines 2u and 6u possess two aryl groups and one methyl
group (Fig. 2). Due to this substitution pattern the phosphine
Scheme 3. Pd-catalyzed asymmetric alkylation of 1,3-diphenylallyl acetate with
dimethyl malonate.
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

4
J. Holz et al. / Tetrahedron xxx (xxxx) xxx
3. Conclusion
The new P-chirogenic P*-Xantphos ligands 2a-t can serve as
ligands in the asymmetric reaction of the rhodium catalyzed hy-
drogenation of isophorone and the palladium mediated alkylation
of allyl acetate. In general, only ligands bearing ortho-aryl sub-
stituents induced satisfying enantioselectivities in both asym-
metric transformations. The molecular structure of diphosphine 2j
corresponds well to that of the already published “nondecorated”
P-chiral Xantphos ligands of type 6 [10]. Obviously the additional
tert.-butyl groups in the backbone do not influence the geometric
structure (P1eP2 distance 4.34 Å, (C1eO1eC13 angle 119.22(13)ꢀ,
angle between planes (C1eC6) vs. (C8eC13) 3.86(9)ꢀ) of the ligand
(Fig. 3). Differences in the catalytic performance must therefore be
Fig. 2. Examples for P-chirogenic Xantphos derivatives with P-methyl groups.
groups become more electron donating.
As Table 2 illustrates superior enantioselectivities can also be
find by application of ligands bearing additional ortho-substituents
in the second aryl group (beside the ortho-substituted aryl group of
xanthene).
Thus, ligands with 2-methoxy or 2-methyl groups (2a, and 6a,b)
yielded results in stereoselectivity superior than those noted by
Hamada et al. applying diphosphine 2u (entries 1 and 2 vs. entry
11). The similar compound 6u (without 2,7-tert.-butyl groups, see
Fig. 2) gives under our reaction conditions only 59% e.e. (entry 11).
Also, ligands with 1-naphthyl and 4-phenantryl group owing
annulated aryl rings in 2,3-position allow the formation of 7 with
enantioselectivities up to 90% (entries 6 and 8). As already found for
the hydrogenation reaction the shift to the 3- and 4-substituted
derivatives leads to a significant lowering of enantioselectivity
(entries 3, 4, 5, 7 and 9). Comparing the results of 3-MeO-phenyl
derivatives with the double substituted 3,5-di-MeO-phenyl com-
pound the downward trend can held back slightly (entries 3 and 9).
Also, in this stereoselective reaction it seems that with increasing
bulkiness of the ortho-substituent the stereoselectivity of reaction
is negatively affected (entries 1 and 2 vs. 10). Reduction of the
amount of the additive (LiOAc) did not significantly influence the
results. Only in a few cases the conversion was diminished (entries
8 and 9).
Fig. 3. Molecular structure of the P-chirogenic 3,5-dimethoxy-phenyl derivative 2j in
the crystal. Displacement ellipsoids correspond to 30% probability. Hydrogen atoms are
omitted for clarity [19].
Table 2
Results in asymmetric Pd-catalyzed alkylation of 1,3-diphenylallyl acetate with P-chirogenic Xantphos derivatives 2 and 6a
ligand
entry
ligand (R)
LiOAc [eq.]b
yieldc [%]
% e.e. (abs. conf.)d
yieldc [%]
% e.e. (abs. conf.)d
1
2
3
4
5
6
a (2-MeO-Ph)
b (2-Me-Ph)
c (3-MeO-Ph)
e (4-MeO-Ph)
f (4-Me-Ph)
1
1
1
1
1
1
0.5
0.2
0.1
1
1
0.2
1
0.5
0.2
1
92
90
81
86
90
88
96
91
90
83
89
88.6 (R)
80.0 (R)
12.8 (R)
9.4 (S)
92
82
88
91
90
89
93.3 (R)
90.4 (R)
15.1 (R)
7.0 (S)
4.7 (S)
87.4 (R)
8.2 (S)
g (1-naphthyl)
90.2 (R)
88.7 (R)
88.8 (R)
88.8 (R)
1.8 (S)
7
8
h (2-naphthyl)
i (4-phenantryl)
92
88
91
92
90
31
13.4 (R)
87.9 (R)
88.5 (R)
36.4 (R)
36.4 (R)
39.9 (R)
89.9 (R)
9
j (3,5-MeO-Ph)
86
46.1 (R)
10
11
q (2-iPr-Ph))
u (Me)
79
45.2 (R)
85 (R)e,f
1
96e,f
48
58.5 (S)
a
Pd(dba)2/ligand/allyl acetate/DMM/BSA ¼ 1/1/100/100/100, ꢁ20 ꢀC to r.t.
In relation to the amount of substrate.
Isolated yield after chromatographic separation.
Enantioselectivity of compound 7 estimated by HPLC on chiral column.
Amount of LiOAc was not indicated in the literature.
Published in reference 18.
b
c
d
e
f
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

J. Holz et al. / Tetrahedron xxx (xxxx) xxx
5
attributed to different polarities.
133.8 (m, 4xCH), 133.5 (2xCH), 129.5 (4xCH), 129.0 (2xC-C), 127.8
(2xCH), 127.6 (m, 4xCH), 126.6 (m, 2xC-P), 124.3 (m, 2xC-P), 122.2
(2xCH), 120.6 (2xCH), 110.0 (2xCH), 55.4 (2xOCH3), 34.9 (m, C), 34.4
(2xC), 31.6 (2xCH3), 31.3 (6xCH3); dP (121.5 MHz, CDCl3) ꢁ25.5; m/z
(EI, 70 eV) 750 (100, [M]þ), 735 (5, [M ꢁ CH3]þ), 673 (15, [M-Ph]þ),
521 (15, [M-CH3-PPh(2-anisyl)þH]þ); HRMS (EI, [M]þ) m/z calcu-
lated for C49H52O3P2 750.33862, found: 750.33755.
4. Experimental section
All solvents were dried and freshly distilled under argon before
use. All reactions were performed under an argon atmosphere by
using standard Schlenk techniques. Thin-layer chromatography
was performed on precoated TLC plates (silica gel). Flash chroma-
tography was carried out with silica gel 60 (particle size
0.040e0.063 mm) with a CombiFlash RF system (Teledyne ISCO).
NMR spectra were recorded generally at Bruker AV 400 spec-
trometer at the following frequencies: 400.13 MHz (1H),
4.1.2. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-methylphenyl)(phenyl)phosphine) (2b)
Yield: 805 mg (75%) as white solid from column chromatog-
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 91e93 ꢀC; [
a
]
23 þ7.9 (c 1.0,
D
100.61 MHz
(
13C), 161.98 MHz
(
31P) or at Bruker AV 300
CHCl3); dH (300.1 MHz, CDC13) 7.37 (2H, d, J 2.3 Hz, arom. H),
7.25e7.07 (14H, m, arom. H), 6.97 (2H, dt, J 7.4, 1.4 Hz, arom. H), 6.70
(2H, m, arom. H), 6.47 (2H, m, arom. H), 2.29 (6H, s, 2xCH3), 1.66
(6H, s, 2xCH3), 1.08 (18H, s, 6xCH3); dC (100.6 MHz, CDCl3) 150.7 (m,
2xC-O), 145.3 (2xC-C), 142.2 (m, 2xC-Me), 136.6 (m, 2xC-P), 136.3
(m, 2xC-P), 134.1 (m, 4xCH), 132.6 (2xCH), 129.7 (m, 2xCH), 129.5
(2xCH), 128.9 (2xC-C), 128.2 (2xCH), 128.1 (2xCH), 128.0 (m, 4xCH),
125.6 (2xCH), 123.6 (m, 2xC-P), 122.8 (2xCH), 34.9 (C), 34.4 (2xC),
32.0 (2xCH3), 31.2 (6xCH3), 21.3 (m, 2xCH3); dP (121.5 MHz,
CDCl3) ꢁ22.7; m/z (EI, 70 eV) 718 (100, [M]þ), 703 (10, [M ꢁ CH3]þ),
641 (5, [M-Ph]þ), 505 (13, [M-CH3-PPh(2-tolyl)þH]þ); HRMS (ESI,
[MþH]þ) m/z calculated for C49H53OP2 719.35662, found:
719.35675.
(300.13 MHz (1H), 75.47 MHz (13C), 121.49 MHz (31P)). Chemical
shifts of 1H and 13C NMR spectra are reported in ppm downfield
from used solvent CDCl3 as internal standard (7.25 ppm/
77.00 ppm). Chemical shifts of 31P NMR spectra are referred to
H3PO4 as external standard. Signals are quoted as s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet) and br (broad).
Mass spectra were recorded on a Thermo Electron MAT 95-XP or an
Agilent 1200/6210 Time-of-flight LC-MS. For chiral HPLC-analysis a
device Agilent 1100 Series was used. For GC-analysis a device Agi-
lent 7890 was applied. The X-ray diffraction data were collected on
a Bruker Kappa APEX II Duo diffractometer with Cu-Ka radiation.
The structure was solved using SIR2004 [20] and refined by full-
matrix least-squares techniques on F2 (SHELXL-2014) [21]. Mer-
cury was applied for graphical representation [22].
The various (R)-(aryl)(methoxy)(phenyl)phosphine P-borane
complexes 1a-t were prepared by the already described procedure
[10].
The enantiomeric purity of diphosphines 2a-t and 6a-u were
verified by NMR-measurement (resulting meso-compounds by
epimerization show different nmr-shifts) and comparison of the
optical rotation after the synthesis and storage for a longer time.
4.1.3. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3-methoxyphenyl)(phenyl)phosphine) (2c)
Yield: 905 mg (47%) as a white solid from column chromatog-
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 84e85 ꢀC; [
a
]
23 ꢁ 7.3 (c 1.0,
D
CHCl3); dH (300.1 MHz, CDC13) 7.36 (2H, d, J 2.3 Hz, arom. H),
7.24e7.08 (12H, m, arom. H), 6.79e6.71 (6H, m, arom. H), 6.53 (2H,
m, arom. H), 3.64 (6H, s, 2xOCH3), 1.65 (6H, s, 2xCH3), 1.08 (18H, s,
6xCH3); dC (75.5 MHz, CDCl3) 159.1 (m, 2xC-OMe),150.5 (m, 2xC-O),
145.3 (2xC-C), 139.2 (m, 2xC-P), 137.4 (m, 2xC-P), 133.9 (m, 4xCH),
129.3 (2xCH), 128.9 (2xC-C), 128.9 (m, 2xCH), 128.1 (2xCH), 128.0
(m, 4xCH), 126.3 (m, 2xCH), 124.4 (m, 2xC-P), 123.0 (2xCH), 118.8
(m, 2xCH), 114.3 (2xCH), 55.0 (2xOCH3), 34.8 (m, C), 34.5 (2xC), 32.1
(2xCH3), 31.3 (6xCH3); dP (121.5 MHz, CDCl3) ꢁ15.2; m/z (EI, 70 eV)
750 (44, [M]þ), 735 (9, [M ꢁ CH3]þ), 673 (1, [M-Ph]þ), 643 (1, [M-(3-
anisyl)]þ); HRMS (EI, [M]þ) m/z calculated for C49H52O3P2
750.33862, found: 750.33735.
4.1. General procedure for the synthesis (1S,10S)-(2,7-di-tert-butyl-
9,9-dimethyl-9H-xanthene-4,5-diyl)bis((aryl)(phenyl)phosphine)
(2a-t)
Methyl phosphinite P-borane complex 1a-t (3.3 mmol) was
dissolved in hexane (10 mL) and DABCO (6.6 mmol, 739 mg) was
added. After stirring at 40 ꢀC for 20 h the precipitate (DABCO*BH3)
was filtered off quantitatively. In a second Schlenk-tube 3.3 mmol of
n-butyllithium (2.06 mL of 1.6 M solution in hexane) was added
slowly to a solution of 4,5-dibromo-2,7-di-tert-butyl-9,9-dimethyl-
9H-xanthene (1.5 mmol, 720 mg) in thf (10 mL) at a temperature
of ꢁ78 ꢀC for the dilithiation. The stirring was continued for 3e4 h
and during this period the temperature was allowed to rise up
to ꢁ20 ꢀC. The above yielded filtrate was added slowly to the cooled
solution (ꢁ45 ꢀC) of the dilithiated xanthene. After further stirring
for 20 h at ambient temperature the volume was reduced to 1/3
under vacuum and water (10 mL) was added. After extraction with
DCM (2 ꢂ 25 mL) the combined organic phases were washed again
and dried (Na2SO4). The solvent was evaporated, and the residue
was purified by column chromatography or crystallization.
4.1.4. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3-methylphenyl)(phenyl)phosphine) (2d)
Yield: 585 mg (54%) as white solid from column chromatog-
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 71e73 ꢀC; [
a
]
24 þ7.5 (c 1.0,
D
CHCl3); dH (300.1 MHz, CDC13) 7.37 (2H, d, J 2.3 Hz, arom. H),
7.25e7.16 (10H, m, arom. H), 7.14e7.01 (6H, m, arom. H), 6.94 (2H,
m, arom. H), 6.55 (2H, m, arom. H), 2.23 (6H, s, 2xCH3), 1.67 (6H, s,
2xCH3), 1.10 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 150.6 (m, 2xC-O),
145.2 (2xC-C),137.8 (m, 2xC-P),137.4 (m, 2xC-Me),137.2 (m, 2xC-P),
134.7 (m, 2xCH), 133.9 (m, 4xCH), 130.8 (m, 2xCH), 129.4 (2xCH),
128.9 (2xCH), 128.9 (2xC-C), 127.9 (2xCH), 127.9 (m, 4xCH), 127.9
(2xCH), 124.7 (m, 2xC-P), 122.8 (2xCH), 34.8 (C), 34.5 (2xC), 31.9
(2xCH3), 31.3 (6xCH3), 21.4 (m, 2xCH3); dP (121.5 MHz,
CDCl3) ꢁ16.2; m/z (EI, 70 eV) 718 (100, [M]þ), 703 (21, [M ꢁ CH3]þ),
641 (2, [M-Ph]þ), 505 (4, [M-CH3-PPh(3-tolyl)þH]þ); HRMS (ESI,
[MþH]þ) m/z calculated for C49H53OP2 719.35662, found:
719.35724.
4.1.1. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-methoxyphenyl)(phenyl)phosphine) (2a)
Yield: 905 mg (80%) as white solid crystallized from EtOH;
mp. ¼104e106 ꢀC; [
a
]
20 þ28.5 (c 1.0, CHCl3); dH (300.1 MHz, CDC13)
D
7.36 (2H, d, J 2.4 Hz, arom. H), 7.22 (2H, m, arom. H), 7.19e7.09 (10H,
m, arom. H), 6.80 (2H, m, arom. H), 6.69 (2H, dt, J 7.5, 0.9 Hz, arom.
H), 6.54e6.48 (4H, m, arom. H), 3.68 (6H, s, 2xOCH3), 1.65 (6H, s,
2xCH3), 1.08 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 161.2 (t, J 7.6 Hz,
2xC-OMe), 151.0 (t, J 9.9 Hz, 2xC-O), 144.9 (2xC-C), 137.5 (m, 2xC-P),
4.1.5. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((4-methoxyphenyl)(phenyl)phosphine) (2e)
Yield: 585 mg (52%) as white solid from column chromatog-
raphy (heptane/AcOEt 98/2); mp. ¼ 160e164 ꢀC; [
a
]
D
21 ꢁ 38.7 (c 1.0,
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

6
J. Holz et al. / Tetrahedron xxx (xxxx) xxx
CHCl3); dH (400.1 MHz, CDC13) 7.42 (2H, d, J 2.3 Hz, arom. H),
7.23e7.11 (14H, m, arom. H), 6.76 (4H, m, arom. H), 6.54 (2H, m,
arom. H), 3.78 (6H, s, 2xOCH3), 1.68 (6H, s, 2xCH3), 1.18 (18H, s,
6xCH3); dC (100.6 MHz, CDCl3) 159.8 (2xC-OMe), 150.4 (t, J 9.3 Hz,
2xC-O), 145.1 (2xC-C), 138.5 (m, 2xC-P), 135.6 (m, 4xCH), 133.5 (m,
4xCH), 129.2 (2xCH), 128.8 (2xC-C), 128.2 (m, 2xC-P), 127.9 (m,
4xCH), 127.7 (2xCH), 125.1 (m, 2xC-P), 122.7 (2xCH), 113.7 (m,
4xCH), 55.1 (2xOCH3), 34.8 (m, C), 34.4 (2xC), 32.1 (2xCH3), 31.3
(6xCH3); dP (162.0 MHz, CDCl3) ꢁ17.5; m/z (EI, 70 eV) 750 (100,
[M]þ), 735 (5, [M ꢁ CH3]þ), 536 (30, [M-PPh(4-anisyl)þH]þ), 521
(30, [M-CH3-PPh(4-anisyl)þH]þ); HRMS (EI, [M]þ) m/z calculated
for C49H52O3P2 750.33862, found: 750.34064.
790 (100, [M]þ), 775 (15, [M ꢁ CH3]þ), 664 (3, [M-C10H7þH]þ);
HRMS (ESI, [MþH]þ) m/z calculated for C55H53OP2 791.35662,
found: 791.35657, (ESI, [MþNa]þ) m/z calculated for C55H52NaOP2
813.33856, found: 813.33800.
4.1.9. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((9-phenantryl)(phenyl)phosphine) (2i)
Yield: 700 mg (52%) as white solid from CH2Cl2/hexane after
chromatographical
purification
(cyclohexane/AcOEt
98/2);
22
mp. ¼ 170e173 ꢀC; [
a]
ꢁ 22.3 (c 1.0, CHCl3); dH (300.1 MHz,
D
CDC13) 8.71e8.61 (4H, m, arom. H), 8.24 (2H, m, arom. H), 7.64e7.56
(4H, m, arom. H), 7.47e7.38 (8H, m, arom. H), 7.08 (2H, m, arom. H),
6.98e8.78 (10H, m, arom. H),6.46 (2H, m, arom. H), 1.75 (6H, s,
2xCH3), 0.99 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 151.1 (m, 2xC-O),
145.5 (2xC-C), 135.9 (m, 2xC-P), 134.0 (m, 4xCH), 131.6 (m, 2xC-C),
131.6 (m, 2xC-C), 132.9 (2xCH), 131.6 (m, 2xC-C), 130.8 (m, 2xC-C),
130.1 (m, 2xCH), 130.0 (m, 2xC-P), 129.5 (2xC-C), 128.7 (2xCH),
128.0 (2xCH),128.0 (2xCH),127.8 (m, 4xCH),126.6 (2xCH),126.3 (m,
2xCH), 126.1 (m, 2xCH), 126.0 (2xCH), 123.5 (m, 2xC-P), 122.6
(2xCH), 122.6 (2xCH), 122.4 (2xCH), 35.1 (m, C), 34.4 (2xC), 31.2
(2xCH3), 31.2 (6xCH3); dP (121.5 MHz, CDCl3) ꢁ21.0; m/z (EI, 70 eV)
890 (100, [M]þ), 875 (22, [M ꢁ CH3]þ), 591 (21, [M-CH3-PPh(9-
Phen)þH]þ), 178 (31, [C14H10]þ); HRMS (ESI, [MþH]þ) m/z calcu-
lated for C63H57OP2 890.38009, found: 891.388840, (ESI, [MþNa]þ)
m/z calculated for C63H56NaOP2 913.36986, found: 913.36767.
4.1.6. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((4-methylphenyl)(phenyl)phosphine) (2f)
Yield: 875 mg (81%) as white solid from column chromatog-
24
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 80e82 ꢀC; [
a]
ꢁ 29.3 (c
D
1.0, CHCl3); dH (300.1 MHz, CDC13) 7.36 (2H, d, J 2.3 Hz, arom. H),
7.25e7.15 (10H, m, arom. H), 7.13e7.06 (4H, m, arom. H), 7.03e6.98
(4H, m, arom. H), 6.58 (2H, m, arom. H), 2.31 (6H, s, 2xCH3), 1.65
(6H, s, 2xCH3), 1.10 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 150.5 (m,
2xC-O), 145.1 (2xC-C), 138.0 (m, 2xC-Me), 137.6 (m, 2xC-P), 133.9
(m, 4xCH), 133.9 (4xCH), 133.4 (m, 2xC-P), 129.5 (m, 2xCH), 128.9
(m, 4xCH), 128.9 (2xC-C), 127.9 (m, 4xCH), 127.9 (2xCH), 124.4 (m,
2xC-P), 123.0 (2xCH), 34.8 (C), 34.5 (2xC), 32.1 (2xCH3), 31.3
(6xCH3), 21.3 (m, 2xCH3); dP (121.5 MHz, CDCl3) ꢁ16.8; m/z (EI,
70 eV) 718 (100, [M]þ), 703 (26, [M ꢁ CH3]þ), 520 (21, [M-PPh(4-
tolyl)þH]þ); 505 (46, [M-CH3-PPh(4-tolyl)þH]þ); HRMS (ESI,
[MþH]þ) m/z calc.: for C49H53OP2 719.35662, found: 719.35675;
(ESI, [MþNa]þ) m/z calculated for C49H52NaOP2 741.33856, found:
741.33748.
4.1.10. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3,5-dimethoxyphenyl)(phenyl)phosphine) (2j)
Yield: 775 mg (64%) as white solid from column chromatog-
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 78e80 ꢀC; [
a]
21 ꢁ 5.7 (c 1.0,
D
4.1.7. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((1-naphthyl)(phenyl)phosphine) (2g)
CHCl3); dH (300.1 MHz, CDC13) 7.37 (2H, d, J 2.3 Hz, arom. H),
7.24e7.16 (10H, m, arom. H), 6.56 (2H, m, arom. H), 6.39e6.33 (4H,
m, arom. H), 6.31 (2H, m, arom. H), 3.64 (12H, s, 4xOCH3), 1.66 (6H,
s, 2xCH3), 1.11 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 160.2 (m, 4xC-
OMe), 150.6 (m, 2xC-O), 145.3 (2xC-C), 140.1 (m, 2xC-P), 137.2 (m,
2xC-P), 133.9 (m, 4xCH), 129.3 (2xCH), 129.0 (2xC-C), 128.2 (2xCH),
127.9 (m, 4xCH), 124.2 (m, 2xC-P), 122.9 (2xCH), 111.3 (4xCH), 100.9
(2xCH), 55.1 (4xOCH3), 34.8 (m, C), 34.4 (2xC), 31.9 (2xCH3), 31.3
(6xCH3); dP (121.5 MHz, CDCl3) ꢁ13.7; m/z (EI, 70 eV) 810 (100,
[M]þ), 795 (43, [M ꢁ CH3]þ), 779 (11, [M-OCH3]þ), 551 (16, [M-CH3-
PPh(3,5-MeO-Ph)þH]þ); HRMS (EI, [M]þ) m/z calculated for
Yield: 885 mg (74%) as white solid crystallized from column
chromatography (cyclohexane/AcOEt 98/2); mp. ¼ 110e112 ꢀC;
[
a]
21 ꢁ 24.2 (c 1.0, CHCl3); dH (300.1 MHz, CDC13) 8.20 (2H, m, arom.
D
H), 7.82 (2H, m, arom. H), 7.74 (2H, m, arom. H), 7.44 (2H, ddd, J 8.1,
7.0, 1.3 Hz, arom. H), 7.38 (2H, m, arom. H), 7.32 (2H, ddd, J 8.3, 6.8,
1.4 Hz, arom. H), 7.22 (2H, m, arom. H), 7.16e6.99 (10H, m, arom. H),
6.86 (2H, m, arom. H), 6.39 (2H, m, arom. H), 1.69 (6H, s, 2xCH3),
0.99 (18H, s, 6xCH3); dC (100.6 MHz, CDCl3) 150.8 (m, 2xC-O), 145.3
(2xC-C), 136.4 (m, 2xC-P), 135.6 (m, 2xC-P), 135.0 (m, 2xC-C), 134.2
(m, 4xCH), 133.3 (m, 2xC-C), 131.5 (2xCH), 130.0 (2xCH), 129.2 (2xC-
C), 128.9 (2xCH), 128.2 (2xCH), 128.2 (2xCH), 127.9 (m, 4xCH), 127.0
(m, 2xCH), 125.7 (2xCH), 125.5 (2xCH), 125.3 (2xCH), 123.6 (m, 2xC-
P), 122.8 (2xCH), 35.0 (C), 34.4 (2xC), 31.7 (2xCH3), 31.2 (6xCH3); dP
(121.5 MHz, CDCl3) ꢁ23.6; m/z (EI, 70 eV) 790 (100, [M]þ), 775 (13,
[M ꢁ CH3]þ), 664 (21, [M-C10H7þH]þ); HRMS (ESI, [MþH]þ) m/z
calculated for C55H53OP2 791.35662, found: 791.35706.
C51H56O5P2 810.35975, found: 810.35888.
4.1.11. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-ethoxyphenyl)(phenyl)phosphine) (2k)
Yield: 740 mg (63%) as white solid from column chromatog-
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 78e80 ꢀC; [
a
]
21 ꢁ 2.2 (c 1.0,
D
CHCl3);
d (300.1 MHz, CDC13) 7.36 (2H, d, J 2.4 Hz, arom. H),
4.1.8. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-naphthyl)(phenyl)phosphine) (2h)
7.26e7.09 (12H, m, arom. H), 6.76 (2H, m, arom. H), 6.69 (2H, dt, J
7.4, 1.0 Hz, arom. H), 6.64e6.55 (4H, m, arom. H), 3.88 (4H, m,
2xOCH2), 1.66 (6H, s, 2xCH3), 1.09 (18H, s, 6xCH3), 0.98 (6H, t, J
7.0 Hz, 2xCH3); dC (75.5 MHz, CDCl3) 160.4 (m, 2xC-OEt), 150.8 (m,
2xC-O), 144.9 (2xC-C), 136.8 (m, 2xC-P), 134.0 (m, 4xCH), 133.4 (m,
2xCH), 129.6 (2xCH), 129.5 (2xCH), 128.8 (2xC-C), 128.0 (2xCH),
127.7 (m, 4xCH), 126.3 (m, 2xC-P), 123.7 (m, 2xC-P), 122.7 (2xCH),
120.6 (2xCH), 111.0 (2xCH), 63.8 (2xOCH2), 34.9 (m, C), 34.4 (2xC),
32.0 (2xCH3), 31.3 (6xCH3), 14.4 (2xCH3); dP (121.5 MHz,
CDCl3) ꢁ23.8; m/z (EI, 70 eV) 778 (100, [M]þ), 763 (6, [M ꢁ CH3]þ),
701 (35, [M-Ph]þ), 673 (20, [M-Ph-C2H4]þ), 535 (17, [M-CH3-PPh(2-
EtO-Ph)þH]þ); HRMS (ESI, [MþH]þ) m/z calculated for C51H57O3P2
779.37775, found: 779.37897, ([MþNa]þ) m/z calculated for
Yield: 710 mg (60%) as white solid from CH2Cl2/hexane;
21
mp. ¼ 152e154 ꢀC; [
a
]
ꢁ 101.8 (c 1.0, CHCl3); dH (400.1 MHz,
D
CDC13) 7.77 (2H, m, arom. H), 7.70e7.60 (6H, m, arom. H), 7.48e7.39
(6H, m, arom. H), 7.26 (2H, m, arom. H), 7.13e7.06 (4H, m, arom. H),
7.04e6.98 (6H, m, arom. H), 6.58 (2H, m, arom. H), 1.72 (6H, s,
2xCH3), 1.07 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 150.8 (m, 2xC-O),
145.4 (2xC-C), 137.3 (m, 2xC-P), 135.2 (m, 2xC-P), 133.9 (2xCH),
133.8 (m, 4xCH), 133.2 (m, 2xC-C), 133.2 (m, 2xC-C), 130.4 (m,
2xCH), 129.3 (2xCH), 129.2 (2xC-C), 128.1 (2xCH), 128.0 (2xCH),
127.8 (m, 4xCH), 127.6 (2xCH), 127.2 (m, 2xCH), 126.0 (2xCH), 125.7
(2xCH), 124.3 (m, 2xC-P), 122.8 (2xCH), 34.9 (m, C), 34.5 (2xC), 31.8
(2xCH3), 31.3 (6xCH3); dP (162.0 MHz, CDCl3) ꢁ15.0; m/z (EI, 70 eV)
C51H56NaO3P2 801.35969, found: 801.35636.
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

J. Holz et al. / Tetrahedron xxx (xxxx) xxx
7
4.1.12. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-ethylphenyl)(phenyl)phosphine) (2l)
C),138.5 (m, 2xC-P),135.7 (m, 4xCH),133.5 (m, 4xCH),129.2 (2xCH),
128.8 (2xC-C),128.2 (m, 2xC-P),127.9 (m, 4xCH),127.7 (2xCH),125.1
(m, 2xC-P), 122.7 (2xCH), 114.3 (m, 4xCH), 63.1 (2xOCH2), 34.8 (m,
C), 34.4 (2xC), 32.1 (2xCH3), 31.3 (6xCH3), 14.8 (2xCH3); dP
(121.5 MHz, CDCl3) ꢁ17.5; m/z (EI, 70 eV) 778 (100, [M]þ), 701 (17,
[M-Ph]þ), 577 (20), 535 (9, [M-CH3-PPh(4-EtO-Ph)þH]þ); HRMS
(ESI, [MþH]þ) m/z calculated for C51H57O3P2 779.37775, found:
779.37787.
Yield: 615 mg (55%) as white solid crystallized from ethanol
after chromatographical purification (cyclohexane/AcOEt 98/2);
mp. ¼ 139e140 ꢀC; [
a]
24 þ46.8 (c 1.0, CHCl3);
d (400.1 MHz, CDC13)
D
7.34 (2H, d, J 2.4 Hz, arom. H), 7.25e7.13 (14H, m, arom. H), 6.97 (2H,
m, arom. H), 6.72 (2H, m, arom. H), 6.45 (2H, m, arom. H), 2.78 (4H,
m, 2xCH2), 1.66 (6H, s, 2xCH3), 1.07 (18H, s, 6xCH3), 1.06 (6H, t, J
7.5 Hz, 2xCH3); dC (100.6 MHz, CDCl3) 150.4 (m, 2xC-O), 148.5 (m,
2xC-Et), 145.0 (2xC-C), 137.6 (m, 2xC-P), 136.1 (m, 2xC-P), 134.0 (m,
4xCH), 133.5 (2xCH), 129.6 (2xCH), 128.7 (2xC-C), 128.4 (2xCH),
127.9 (m, 4xCH), 127.8 (2xCH), 127.7 (2xCH), 125.6 (2xCH), 124.5 (m,
2xC-P), 122.6 (2xCH), 34.8 (m, C), 34.4 (2xC), 32.1 (2xCH3), 31.3
(6xCH3), 27.1 (m, 2xCH2), 15.1 (2xCH3); dP (121.5 MHz,
CDCl3) ꢁ25.5; m/z (EI, 70 eV) 746 (100, [M]þ), 731 (5, [M ꢁ CH3]þ),
669 (16, [M-Ph]þ), 641 (14, [M-Ph-C2H4]þ), 534 (10, [M-PPh(2-Et-
Ph)þH]þ), 519 (14, [M-PPh(2-Et-Ph)þH]þ); HRMS (ESI, [MþH]þ) m/
z calculated for C51H57OP2 747.38792, found: 747.38815.
4.1.16. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-isopropoxyphenyl)(phenyl)phosphine) (2p)
Yield: 835 mg (69%) as white solid from column chromatog-
23
raphy (cyclohexane/AcOEt 99/1); mp. ¼ 78e80 ꢀC; [
a]
þ17.5 (c
D
1.0, CHCl3);
d (300.1 MHz, CDC13) 7.34 (2H, d, J 2.3 Hz, arom. H),
7.29e7.21 (4H, m, arom. H), 7.18e7.10 (8H, m, arom. H), 6.72 (2H, m,
arom. H), 6.67e6.54 (6H, m, arom. H), 4.38 (2H, sept, J 6.1 Hz,
2xOCH), 1.65 (6H, s, 2xCH3), 1.09 (18H, s, 6xCH3), 1.01 (6H, t, J 6.1 Hz,
2xCH3), 0.96 (6H, t, J 6.1 Hz, 2xCH3); dC (75.5 MHz, CDCl3) 159.2 (m,
2xC-OiPr), 150.9 (m, 2xC-O), 144.6 (2xC-C), 137.7 (m, 2xC-P), 134.2
(m, 4xCH), 133.7 (m, 2xCH), 129.7 (2xCH), 129.1 (2xCH), 128.7 (2xC-
C),127.9 (m, 2xC-P),127.7 (2xCH),127.6 (m, 4xCH), 124.5 (m, 2xC-P),
122.5 (2xCH), 120.1 (2xCH), 111.6 (2xCH), 69.9 (2xOCH), 34.8 (m, C),
34.4 (2xC), 32.1 (2xCH3), 31.3 (6xCH3), 22.0 (2xCH3), 21.6 (2xCH3);
dP (121.5 MHz, CDCl3) ꢁ24.6; m/z (EI, 70 eV) 806 (100, [M]þ), 729
(12, [M-Ph]þ), 687 (20, [M-Ph-C3H6]þ); HRMS (ESI, [MþH]þ) m/z
calculated for C53H61O3P2 807.40905, found: 807.40956, ([MþNa]þ)
m/z calculated for C53H60NaO3P2 829.39099, found: 829.39036.
4.1.13. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3-ethoxyphenyl)(phenyl)phosphine) (2m)
Yield: 400 mg (34%) as a white solid from column chromatog-
raphy (cyclohexane/AcOEt 99/1); mp. ¼ 63e65 ꢀC; [
a
]
22 ꢁ 8.3 (c 1.0,
D
CHCl3); dH (300.1 MHz, CDC13) 7.36 (2H, d, J 2.3 Hz, arom. H),
7.24e7.15 (10H, m, arom. H), 7.10 (2H, m, arom. H), 6.79e6.71 (6H,
m, arom. H), 6.57 (2H, m, arom. H), 3.85 (4H, m, 2xOCH2), 1.64 (6H,
s, 2xCH3), 1.29 (6H, t, J 7.0 Hz, 2xCH3), 1.09 (18H, s, 6xCH3); dC
(75.5 MHz, CDCl3) 158.5 (m, 2xC-OEt),150.5 (m, 2xC-O), 145.3 (2xC-
C), 138.9 (m, 2xC-P), 137.3 (m, 2xC-P), 133.9 (m, 4xCH), 129.4
(2xCH), 128.9 (2xC-C), 128.9 (m, 2xCH), 128.2 (2xCH), 127.9 (m,
4xCH), 126.2 (m, 2xCH), 124.4 (m, 2xC-P), 123.0 (2xCH), 119.2 (m,
2xCH), 115.1 (2xCH), 63.1 (2xOCH2), 34.9 (m, C), 34.5 (2xC), 32.0
(2xCH3), 31.3 (6xCH3), 14.7 (2xCH3); dP (121.5 MHz, CDCl3) ꢁ15.0;
m/z (EI, 70 eV) 778 (4, [M]þ), 576 (12), 561 (27); HRMS (ESI,
[MþH]þ) m/z calculated for C51H57O3P2 779.37775, found:
779.37755, (ESI, [MþNa]þ) m/z calculated for C51H56NaO3P2
801.35969, found: 801.35945.
4.1.17. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((2-isopropylphenyl)(phenyl)phosphine) (2q)
Yield: 550 mg (47%) as white solid crystallized from ethanol
after chromatographical purification (cyclohexane/AcOEt 98/2);
mp. ¼ 157e159 ꢀC; [
a
]
22 þ40.2 (c 1.0, CHCl3);
d (400.1 MHz, CDC13)
D
7.35 (2H, d, J 2.3 Hz, arom. H), 7.32e7.16 (14H, m, arom. H), 6.95 (2H,
dt, J 7.5, 1.4 Hz, arom. H), 6.73 (2H, m, arom. H), 6.45 (2H, m, arom.
H), 3.66 (2H, m, 2xCH), 1.67 (6H, s, 2xCH3), 1.12 (6H, 6, J 6.8 Hz,
2xCH3), 1.09 (18H, s, 6xCH3), 1.08 (6H, 6, J 6.8 Hz, 2xCH3); dC
(100.6 MHz, CDCl3) 153.4 (m, 2xC-O),150.1 (m, 2xC-iPr),145.0 (2xC-
C), 138.0 (m, 2xC-P), 135.4 (m, 2xC-P), 134.2 (m, 4xCH), 133.5
(2xCH), 129.6 (2xCH), 128.7 (2xCH), 128.5 (2xC-C), 127.8 (m, 4xCH),
127.8 (2xCH), 125.6 (2xCH), 125.0 (2xCH), 124.9 (m, 2xC-P), 122.7
(2xCH), 34.8 (m, C), 34.4 (2xC), 32.3 (2xCH3), 31.3 (6xCH3), 30.8 (m,
2xCH), 24.4 (m, 2xCH3), 23.7 (2xCH3); dP (121.5 MHz, CDCl3) ꢁ26.4;
m/z (EI, 70 eV) 774 (26, [M]þ), 697 (9, [M-Ph]þ), 655 (11, [M-2-iPr-
Ph]þ), 548 (69, [M-PPh(2-iPr-Ph)þH]þ), 548 (100, [M-CH3-PPh(2-
iPr-Ph)þH]þ); HRMS (ESI, [MþH]þ) m/z calculated for C53H61OP2
775.41922, found: 775.41890, ([MþNa]þ) m/z calculated for
4.1.14. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3-ethylphenyl)(phenyl)phosphine) (2n)
Yield: 550 mg (49%) as white solid from column chromatog-
24
raphy (cyclohexane/AcOEt 98/2); mp. ¼ 66e68 ꢀC; [
a
]
þ16.5 (c
D
1.0, CHCl3); dH (400.1 MHz, CDC13) 7.37 (2H, d, J 2.2 Hz, arom. H),
7.25e7.17 (10H, m, arom. H), 7.15e7.04 (6H, m, arom. H), 6.94 (2H,
m, arom. H), 6.53 (2H, m, arom. H), 2.53 (4H, q, J 7.6 Hz, 2xCH2), 1.66
(6H, s, 2xCH3), 1.12 (6H, t, J 7.6 Hz, 2xCH3), 1.10 (18H, s, 6xCH3); dC
(100.6 MHz, CDCl3) 150.6 (m, 2xC-O), 145.1 (2xC-C), 143.6 (m, 2xC-
Et) 137.8 (m, 2xC-P), 137.5 (m, 2xC-P), 133.9 (m, 4xCH), 133.6 (m,
2xCH), 131.1 (m, 2xCH), 129.3 (2xCH), 128.9 (2xC-C), 128.0 (2xCH),
127.9 (2xCH), 127.8 (m, 4xCH), 127.7 (2xCH), 124.9 (m, 2xC-P), 122.7
(2xCH), 34.8 (C), 34.4 (2xC), 31.9 (2xCH3), 31.3 (6xCH3), 28.8
(2xCH2), 15.6 (m, 2xCH3); dP (121.5 MHz, CDCl3) ꢁ16.1; m/z (EI,
70 eV) 746 (100, [M]þ), 731 (22, [M ꢁ CH3]þ), 519 (4, [M-CH3-PPh(3-
Et-Ph)þH]þ); HRMS (ESI, [MþH]þ) m/z calculated for C51H57OP2
747.38792, found: 747.38778.
C53H60NaOP2 797.40116, found: 797.40179.
4.1.18. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3-isopropoxyphenyl)(phenyl)phosphine) (2r)
Yield: 715 mg (59%) as a white solid from column chromatog-
raphy (cyclohexane/AcOEt 99/1); mp. ¼ 74e75 ꢀC; [
a
]
D
23 ꢁ 8.5 (c 1.0,
CHCl3); dH (300.1 MHz, CDC13) 7.35 (2H, d, J 2.3 Hz, arom. H),
7.24e7.16 (10H, m, arom. H), 7.11 (2H, m, arom. H), 6.80e6.69 (6H,
m, arom. H), 6.54 (2H, m, arom. H), 4.32 (2H, sept, J 6.1 Hz, 2xOCH),
1.64 (6H, s, 2xCH3), 1.19 (6H,d, J 6.0 Hz, 2xCH3), 1.18 (6H,d, J 6.0 Hz,
2xCH3), 1.09 (18H, s, 6xCH3); dC (75.5 MHz, CDCl3) 157.5 (m, 2xC-
OiPr), 150.5 (m, 2xC-O), 145.2 (2xC-C), 138.8 (m, 2xC-P), 137.4 (m,
2xC-P), 133.9 (m, 4xCH), 129.3 (2xCH), 129.0 (m, 2xCH), 128.9 (2xC-
C),128.2 (2xCH),127.9 (m, 4xCH),126.2 (m, 2xCH),124.5 (m, 2xC-P),
122.9 (2xCH), 120.4 (m, 2xCH), 116.7 (2xCH), 69.7 (2xOCH), 34.8 (m,
C), 34.5 (2xC), 32.0 (2xCH3), 31.3 (6xCH3), 22.0 (2xCH3), 22.0
(2xCH3); dP (121.5 MHz, CDCl3) ꢁ15.3; m/z (EI, 70 eV) 806 (90,
[M]þ), 791 (10, [M ꢁ CH3]þ), 564 (89, [M-PPh(3-iPrO-Ph)þH]þ), 549
4.1.15. (1S,10S)-(ꢁ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((4-ethoxyphenyl)(phenyl)phosphine) (2o)
Yield: 640 mg (55%) as white solid crystallized from ethanol
after chromatographical purification (cyclohexane/AcOEt 98/2);
mp. ¼ 84e86 ꢀC; [
a
]
22 ꢁ 39.0 (c 1.0, CHCl3); dH (300.1 MHz, CDC13)
D
7.37 (2H, d, J 2.4 Hz, arom. H), 7.24e7.10 (14H, m, arom. H), 6.76 (4H,
m, arom. H), 6.57 (2H, m, arom. H), 4.01 (4H, q, J 7.0 Hz, 2xOCH2),
1.67 (6H, s, 2xCH3), 1.42 (6H, t, J 7.0 Hz, 2xCH3), 1.12 (18H, s, 6xCH3);
dC (75.5 MHz, CDCl3) 159.2 (2xC-OEt), 150.4 (m, 2xC-O), 145.1 (2xC-
Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

8
J. Holz et al. / Tetrahedron xxx (xxxx) xxx
(100, [M-PPh(3-iPrO-Ph)-CH3þH]þ); HRMS (ESI, [MþH]þ) m/z
Yield: 200 mg (22%) as white solid after crystallization
26
calculated for
C53H61O3P2 807.40956, found: 807.40894, (ESI,
(dichloromethane/hexane); mp. ¼ 173e175 ꢀC; [
a]
þ8.4 (c 1.0,
D
[MþNa]þ) m/z calculated for C53H60NaO3P2 829.39099, found:
CHCl3); dH (300.1 MHz, CDC13) 7.57e7.49 (4H, m, arom. H),
7.42e7.33 (8H, m, arom. H), 6.98 (2H, t, J 7.6 Hz, arom H), 6.76 (2H,
m, arom. H), 1.64 (6H, s, 2xCH3), 1.57 (6H, t, J 1.9 Hz, 2xCH3); dC
(75.5 MHz, CDCl3) 151.9 (m, 2xC-O), 138.6 (m, 2xC-P), 132.9 (m,
4xCH), 129.8 (2xCH), 129.6 (2xC-C), 128.5 (m, 2xC-P), 128.4 (d, J
5.8 Hz, 2xCH), 128.4 (d, J 6.5 Hz, 2xCH), 126.1 (2xCH), 123.3 (2xCH),
34.3 (C), 32.2 (2xCH3), 11.6 (m, 2xCH3); dP (121.5 MHz,
CDCl3) ꢁ36.6; m/z (EI, 70 eV) 454 (100, [M]þ), 439 (28, [M ꢁ CH3]þ),
332 (28, [M-PMePh þ H]þ), 317 (90, [M-PMePh-Me þ H]þ); HRMS
(EI, [M]þ) m/z calculated for C29H28OP2 454.16099, found:
454.16077.
829.39147.
4.1.19. (1S,10S)-(þ)-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-
4,5-diyl)bis((3-isopropylphenyl)(phenyl)phosphine) (2s)
Yield: 675 mg (58%) as white solid from column chromatog-
21
raphy (cyclohexane/AcOEt 99/1); mp. ¼ 74e75 ꢀC; [
a]
þ26.7 (c
D
1.0, CHCl3); dH (400.1 MHz, CDC13) 7.35 (2H, d, J 2.4 Hz, arom. H),
7.24e7.18 (10H, m, arom. H), 7.15e7.08 (6H, m, arom H), 6.91 (2H, m,
arom. H), 6.50 (2H, m, arom. H), 2.78 (2H, sept, J 6.9 Hz, 2xCH), 1.64
(6H, s, 2xCH3), 1.14 (6H, d, J 7.0 Hz, 2xCH3), 1.13 (6H, t, J 6.9 Hz,
2xCH3), 1.08 (18H, s, 6xCH3); dC (100.6 MHz, CDCl3) 150.5 (m, 2xC-
O), 148.2 (m, 2xC-iPr), 145.1 (2xC-C), 137.6 (m, 2xC-P), 137.3 (m,
2xC-P), 133.9 (m, 4xCH), 132.2 (m, 2xCH), 131.3 (m, 2xCH), 129.3
(2xCH), 128.9 (2xC-C), 128.0 (2xCH), 128.0 (2xCH), 127.9 (m, 4xCH),
126.3 (2xCH), 125.0 (m, 2xC-P), 122.7 (2xCH), 34.8 (m, C), 34.4
(2xC), 34.0 (2xCH), 31.9 (2xCH3), 31.3 (6xCH3), 24.0 (2xCH3), 23.9
(m, 2xCH3); dP (121.5 MHz, CDCl3) ꢁ16.0; m/z (EI, 70 eV) 774 (100,
[M]þ), 759 (14, [M ꢁ CH3]þ), 698 (3, [M-Ph þ H]þ), 656 (3, [M-(3-
iPr-Ph)þH]þ), 548 (69, [M-PPh(3-iPr-Ph)þH]þ), 533 (1, [M-CH3-
PPh(3-iPr-Ph)þH]þ); HRMS (ESI, [MþH]þ) m/z calculated for
The absolute stereochemistry of 6u was confirmed by X-ray
analyses. CCDC 1985240 contains the supplementary crystallo-
graphic data.
4.2. General procedure for the asymmetric hydrogenation
All reactions were carried out using an automatic device
[HPChemScan, Fa. HEL Ltd.] which allows the parallel hydrogena-
tion in up to eight mini-autoclaves (16 mL). Every autoclave was
equipped with a proper glass vial and loaded with 0.5
mmmol Rh-
C
53H61OP2 775.41922, found: 775.41913.
precursor and 0.6 mol of ligand 2 or 6. After assembling of auto-
m
claves into the device isophorone (1 mmol, 3 mL of a 0.333 M stock
solution) was added under argon atmosphere. The autoclaves were
purged three times with argon (0.6 MPa) and then three times with
hydrogen (1 MPa). The autoclaves were heated to 40 ꢀC under
ambient pressure. Then hydrogen pressure was adjusted to 5 MPa.
When the reaction was finished the system was cooled down and
after release of pressure the autoclaves were purged again with
argon (5 cycles). The conversion and parts of product and undesired
alcohol were estimated by NMR. The enantioselectivities were
determined by gas chromatography.
4.1.20. (1S,10S)-(ꢁ)-(2,7-di-tert.-butyl-9,9-dimethyl-9H-xanthen-
4,5-diyl)bis((dibenzo[b,d]-furan-4-yl)(phenyl)phosphine) (2t)
Yield: 630 mg (48%) as white solid from column chromatog-
raphy (cyclohexane/AcOEt 99/1); mp. ¼ 115e118 ꢀC; [
a
]
D
22 ꢁ 55.5 (c
1.0, CHCl3); dH (300.1 MHz, CDC13) 7.92 (2H, m, arom. H), 7.80 (2H,
dd, J 7.7, 1.3 Hz, arom. H), 7.45e7.27 (8H, m, arom. H), 7.13e6.98 (8H,
m, arom. H), 6.93e6.85 (4H, m, arom. H), 6.76 (2H, m, arom. H), 6.53
(2H, m, arom. H), 1.70 (6H, s, 2xCH3), 1.01 (18H, s, 6xCH3); dC
(100.6 MHz, CDCl3) 158.1 (m, 2xC-O), 156.0 (2xC-O), 151.0 (m, 2xC-
O), 145.4 (2xC-C) 135.7 (m, 2xC-P), 133.6 (m, 4xCH), 131.5 (2xCH),
129.4 (2xCH), 129.2 (2xC-C), 128.1 (2xCH), 127.6 (m, 4xCH), 126.8
(2xCH), 124.3 (2xC-C), 123.3 (2xC-C), 122.8 (2xCH), 122.7 (m, 2xC-
P), 122.6 (2xCH), 122.3 (2xCH), 121.3 (m, 2xC-P), 120.7 (2xCH), 120.4
(2xCH), 112.1 (2xCH), 35.0 (m, C), 34.4 (2xC) 31.6 (2xCH3), 31.2
(6xCH3); dP (121.5 MHz, CDCl3) ꢁ27.3; m/z (EI, 70 eV) 870 (100,
[M]þ), 855 (34, [M ꢁ CH3]þ), 581 (23, [M-PPh(4-DBF)-CH3þH]þ),
168 (15, [DBF]þ; HRMS (ESI, [MþH]þ) m/z calculated for C59H53O3P2
871.34644, found: 871.34658, (ESI, [MþNa]þ) m/z calculated for
4.3. General procedure for the asymmetric alkylation
A solution of dimethyl malonate (1 mmol, 132 mg), ( )-trans-
1,3-diphenylallyl acetate (1 mmol, 252 mg) and lithium acetate
(1 mmol, 66 mg) in 1,2-dichloroethane (5 mL) was cooled down
to ꢁ20 ꢀC in a Schlenk-tube. Then (N,O)-bis(trimethylsilyl) acet-
amide (BSA, 1 mmol, 203 mg) and Pd(dba)2-complex (0.01 mmol,
5.75 mg) were added. The solution was stirred for 24 h and the
temperature increased to room temperature. To work-up the so-
lution was diluted with dichloromethane (20 mL) and washed once
with water (10 mL). After phase separation the organic phase was
dried (Na2SO4) and filtrated. The solvents were removed under
vacuum on a rotavapor and the residue was purified by column
chromatography (cyclohexane/AcOEt ¼ 19:1) to yield the pure
alkylation product 7. The enantiomeric purity was estimated by
chiral HPLC (Chiralpak IA (150 ꢂ 4.6 mm), hexane/iso-PrOH ¼ 95/5,
1 mL/min, tR ¼ 6.1 min (R)-enantiomer and tR ¼ 7.3 min (S)-
enantiomer).
C
59H62NaO3P2 893.32839, found: 893.32840.
4.1.21. (1R,10R)-(þ)-(9,9-dimethyl-9H-xanthene-4,5-diyl)
bis(methyl-(phenyl)phosphine) (6u)
(S)-Methoxy(methyl)(phenyl)phosphine borane complex [23]
(4.4 mmol, 740 mg) was dissolved in hexane (15 mL) and DABCO
(8.8 mmol, 987 mg) was added. After stirring at 40 ꢀC for 20 h the
precipitate (DABCO*BH3) was filtered off quantitatively. In a second
Schlenk-tube 4.4 mmol of n-butyllithium (2.75 mL of 1.6 M solution
in hexane) was added slowly to a solution of 9,9-dimethyl-9H-
xanthene (2.0 mmol, 421 mg) and TMEDA (4.4 mmol, 511 mg) in
diethyl ether (15 mL) at ꢁ45 ꢀC for the dilithiation. The stirring was
continued for 18 h and during this period the temperature rises to
ambient temperature. The above yielded filtrate was added slowly
to the cooled solution (ꢁ45 ꢀC) of the dilithiated xanthene. After
further stirring for 20 h at ambient temperature the volume was
reduced to 1/3 under vacuum and water (10 mL) was added. After
extraction with DCM (2 ꢂ 25 mL) the combined organic phases
were washed again and dried (Na2SO4). The solvent was evapo-
rated, and the residue was purified by column chromatography
(cyclohexane/AcOEt ¼ 95/5). For further purification the yielded
residue was recrystallized (dichloromethane/hexane).
Acknowledgments
Dr. Ch. Fischer, Mrs. S. Buchholz, and Mrs. S. Schareina are
acknowledged for careful analysis of reaction products. We thank
for financial support by the German-Israeli Foundation for Scien-
tific Research and Development (GIF, Research Agreement project I-
1369-302.5/2016).
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Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142

J. Holz et al. / Tetrahedron xxx (xxxx) xxx
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Please cite this article as: J. Holz et al., New P-chirogenic tert.-butyl-xantphos ligands and their application in asymmetric hydrogenation and
alkylation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131142