Rh(I) complexes with new C2-symmetric chiral diphosphoramidite ligands: Catalytic activity for asymmetric hydrogenation of olefins

Article abstract of DOI:10.1002/aoc.3837

The design and synthesis of three new C₂-symmetric chiral diphosphoramidite ligands starting from simple and cheap building blocks have been developed. Rhodium(I) cationic complexes bearing these chelate ligands have been prepared and applied in asymmetric hydrogenation of model olefins. A rhodium complex with a diphosphoramidite containing a chiral diamine configurationally stable and two fluxional chiral biphenyl units gave higher enantioselectivity with increasing hydrogen pressure (87% ee) in the hydrogenation of dimethyl itaconate.

Full text of DOI:10.1002/aoc.3837

Received: 8 February 2017
DOI: 10.1002/aoc.3837
Revised: 6 March 2017
Accepted: 17 March 2017
F U L L PA P E R
Rh(I) complexes with new C ‐symmetric chiral diphosphoramidite
2
ligands: Catalytic activity for asymmetric hydrogenation of olefins
Dario Drommi
| Carmela Grazia Arena
Dipartimento di Scienze Chimiche,
Biologiche, Farmaceutiche ed Ambientali,
Viale F. Stagno d'Alcontres 31, 98166
Messina, Italy
The design and synthesis of three new C ‐symmetric chiral diphosphoramidite
2
ligands starting from simple and cheap building blocks have been developed.
Rhodium(I) cationic complexes bearing these chelate ligands have been prepared
and applied in asymmetric hydrogenation of model olefins. A rhodium complex
with a diphosphoramidite containing a chiral diamine configurationally stable and
two fluxional chiral biphenyl units gave higher enantioselectivity with increasing
hydrogen pressure (87% ee) in the hydrogenation of dimethyl itaconate.
Correspondence
Carmela Grazia Arena, Dipartimento di
Scienze Chimiche, Biologiche,
Farmaceutiche ed Ambientali, Viale F.
Stagno d'Alcontres 31, 98166 Messina, Italy.
Email: arenac@unime.it
KEYWORDS
2
asymmetric hydrogenation, C ‐symmetric ligand, chiral rhodium complexes, diphosphoramidite
1
| INTRODUCTION
applied in the rhodium catalyzed asymmetric hydrogenation
of functionalized olefins with outstanding results. Although,
diphosphoramidites are readily obtainable from inexpensive
achiral/chiral diamines, only a few of them have been evalu-
The development of a really worthwhile catalytic system for
asymmetric synthesis is still a challenge for the chemical
community. Presently, most efficient enantioselective cata-
lysts are chiral ligand modified transition metal complexes.
Therefore, the chiral environment generated by the
enantiopure ligand coordinated to the metal is a crucial ele-
ment in determining the outcome of the process.
Although significant enantiomeric excesses were
achieved with chiral metal complexes, the cost and avail-
ability of the ligands remain critical factors for larger scale
applications. Industrial demand for economical and mod-
ular chiral ligands have given rise to the development of
rationally designed syntheses of chiral ligands derived from
a simple and inexpensive enantiopure source. In this con-
text, over the last years phosphoramidites have arisen as
cheap and easily available chiral ligands for asymmetric
[
10,2]
ated in the asymmetric hydrogenation.
Some years ago, we reported a family of C ‐symmetric
2
bidentate diphosphoramidite ligands containing the inexpen-
sive chiral source (1R,2R)‐diaminocyclohexane as the back-
bone and two biaryl units (Figure 1). We tested these P,P
ligands in transition metal catalyzed asymmetric reactions
[
11]
[12]
such as conjugate addition,
hydrosilylation,
Diels‐
[
13]
[14]
Alder
and hydrogenation.
[
1]
Interestingly, we observed an uncommon positive H2
pressure effect on the stereoselectivity in the Rh‐catalyzed
asymmetric hydrogenation of dimethyl itaconate using
the diphosphoramidite (R,R,S S )‐L2 which contains two
a a
(S)‐BINOL (1,1′‐binaphthalene‐2,2′‐diol) moieties.
We also note that rhodium catalyst bearing the
diphosphoramidite ligand L3 in which each BINOL‐unit
was replaced by a fluxional axially chiral 2,2′‐biphenol con-
taining sterically demanding ortho tert‐butyl groups, showed
very low activity as well as poor asymmetric induction in the
same reaction.
[
2]
catalysis.
Among catalytic asymmetric reactions, the hydrogenation
of C¼C bond catalyzed by chiral ligand modified transition
metal complexes is an important and efficient tool for the
[
3,4]
[5]
organic synthesis
and fine chemical production.
Several monodentate phosphoramidites as MonoPhos,
The results achieved with diphosphoramidites L1‐L3
prompt us to develop a series of new readily accessible dia-
[6,7]
SiPhos, DpenPhos, PipPhos, Morphos, PegPhos
as well
have been
[8,9]
as bidentate phosphine‐phosphoramidites
stereomeric C ‐symmetric diphosphoramidite ligands.
2
Appl Organometal Chem. 2017;e3837.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 8
https://doi.org/10.1002/aoc.3837

2
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DROMMI AND ARENA
all materials were commercially available and were used
without further purification. (1R,2R)‐diaminocyclohexane
was treated with NaOH pellets for 3 days prior to use.
The nuclear magnetic resonance spectra were recorded
with a Bruker AMX R‐300 and with a Varian 500 MHz
spectrometer equipped with a pulsed field gradient probe.
1
The values of chemical shifts (δ) for H spectra and
13
1
C{ H} NMR are measured relative to the solvent peak
and are reported in ppm in reference to the value for
the tetramethylsilane (TMS δ = 0 ppm). The chemical
31
1
shifts for the P{ H} NMR spectra were measured using
aqueous H PO4 (85% D O) as an external reference
3
2
FIGURE 1
2
C ‐symmetric chiral diphosphoramidite ligands L1‐L3
(
δ = 0 ppm). For phase‐sensitive methods (TPPI)
1
13
1
H‐2D‐NOESY and C– H‐correlation (adiabatic HSBC)
The new chiral ligands L4‐L6 (Figure 2) were designed
either by changing the biaryl group in the two P/O heterocy-
cles of (1R,2R)‐diaminocyclohexane unit or by replacing the
chiral backbone with an achiral one. Moreover, the
diphosphoramidite L4 was planned with the aim to assess
the steric hindrance influence of the ortho substituents in
have been employed to standard pulse sequences. In addi-
tion, experiments they were performed two‐dimensional
1
1
1
1
1
13
1
13
H‐ H gCOSY, H‐ H gTOCSY, H‐ C gHSQC, H‐ C
gHMBC using a broad‐band with Z‐Gradient Probe BBI
1H–BBZ‐GRD Z8421 300 MHz 5mm. The evolution of
1
13
mating long‐range H‐ C HMBC experiment has been
2
,2′‐biphenol moieties on catalyst performance.
set at 80 ms and a mixing time for the experiment
H‐ H NOESY of 80 ms.
1
1
In this work, we report on C ‐diphosphoramidite
2
ligands L4‐L6 and their corresponding 1,5‐cyclooctadiene
rhodium(I) cationic complexes. We also describe the cata-
lytic activity of these new chiral diphosphoramidite rho-
dium complexes in the asymmetric hydrogenation of
model olefins.
Hydrogenation experiments were performed in a 100 ml
stainless steel autoclave equipped with glass reaction vessel.
1
Conversion was determined by H NMR and GC coupled
to a mass spectrometer GCMS‐QP 5000 Shimadzu.
Enantioselectivity was measured by Fisons GC 8000
ThermoQuest (using helium as a carrier gas and a flame ion-
ization detector FID): for determination of hydrogenated
products of dimethyl itaconate, Lipodex E was applied as
chromatographic column; Chirasil‐Val was used for determi-
nation of hydrogenated products methyl 2‐(acetylamino)
propanoate and methyl 2‐(acetylamino)‐3‐phenylpropanoate.
Enantiomeric excess values were confirmed by a Shimadzu
HPLC LC8A with a 5u Lux Cellulose‐1 250 x 4.6 mm
Phenomenex column (Substrate 11, UV λ 250 nm, Hexane/
Isopropanol 95/5, 25 °C; Substrate 9 and 12, UV λ 215 nm,
Hexane/Isopropanol 98/2, 25 °C). The absolute configura-
tions of the materials were determined by comparison with
2
2
| EXPERIMENTAL
.1 | Materials and methods
All reactions were performed under a dry argon atmosphere
using standard Schlenk techniques. Solvents were purchased
in crown cap anhydrous bottles. Unless otherwise indicated,
[
15,16]
reported data.
Optical rotations were measured on a
Jasco P‐1010 polarimeter at 25 °C. Elemental analyses were
performed by Redox Srl, Monza, Milan.
2
.2 | Preparation of 2‐Chloro‐(4S,5S)‐
dicarboethoxy‐1,3,2‐dioxaphospholane 3
1‐methyl‐2‐pyrrolidone (43 mg, 0.44 mmol) was added to a
stirred mixture of diethyl (2S,3S)‐tartrate (907 mg, 4.4 mmol)
and PCl (9.06 g, 66 mmol) at room temperature. Upon addi-
3
tion, a rapid evolution of HCl bubbles was observed which
were removed by a slow flow of argon. After 5 min., the bulk
of excess PCl was removed under reduced pressure and then
3
FIGURE 2
C
2
‐symmetric chiral diphosphoramidite ligands L4‐L6
the final traces were removed by azeotropic distillation with

DROMMI AND ARENA
3 of 8
toluene (10 ml). The product was obtained as a colourless oil,
which was used without further purification. For spectral data
see ref.
4.83 (m, CH, 4H), 3.87 (m, CH , 8H), 2.72 (m, NH, 2H),
2
2.46 (m, *CHcyclohex, 2H), 1.94 (m, CHcyclohex, 4H), 1.34 (m,
[
17]
13
1
CHcyclohex, 4H), 0.95 (m, CH , 12H). C{ H} NMR
3
(
75 MHz, Benzene‐d ) δ 171.23 (s, CC=O(q), 4C), 74.63 (s,
6
CAr(q), 4C), 62.14 (s, *Ccyclohex, 2C), 58.76 (s, CH , 4C),
2
2
.3 | General procedure for the preparation of
3
2
4
5.22 (s, Ccyclohex, 2C), 24.51 (s, CH , 4C), 14.34 (s, Ccyclohex,
3
diphosphoramidites L4‐L5
C). Anal. Calcd. for C H N O P : C, 45.37; H, 6.23; N,
22 36 2 12 2
.81. Found: C, 45.53; H, 6.30; N, 4.67.
A solution of (1R,2R)‐diaminocyclohexane (2.2 mmol) and
Et N (8.8 mmol) in 10 ml of toluene was added dropwise
3
to a stirred solution of the appropriate phosphorochloridite
1
2
(4.4 mmol) at 0 °C. The mixture was stirred overnight at
2
.6 | N ,N ‐Bis((11bR)‐dinaphtho[2,1‐d:1′,2′‐
room temperature and Et N·HCl precipitate was removed
3
f][1,3,2]‐dioxaphosphepin‐4‐yl)benzene‐1,2‐
by filtration. The solvent was evaporated under reduced pres-
sure to give the crude product which was washed with hexane
diamine L6
[
18]
A
(
solution of (R,R)‐BINOL‐phosphorochloridite
1,82 g, 5.20 mmol) in toluene (10 ml) was added dropwise
to a stirred solution of o‐phenylenediamine 4 (0.281 g,
5
(3x5 ml). The resulting pale yellow solid was purified by
extraction in toluene and recrystallization from toluene/
hexane.
2
.60 mmol), Et N (1.32 g, 13 mmol) and DMAP (0.012 g,
3
0
.1 mmol) in toluene (25 ml) at 0 °C. The reaction mixture
1
2
2
.4 | (1R,2R)‐N ,N ‐bis(dibenzo[d,f][1,3,2]
was stirred for 12 h at room temperature and then Et N·HCl
3
dioxaphosphepin‐6‐yl)cyclohexane‐1,2‐diamine
precipitate was removed by filtration. The filtrate was subse-
quently concentrated to a volume of 5 mL and upon addition
of 25 ml di hexane a white solid was deposited. This solid
was filtered off, washed with pentane and dried under
reduced pressure. White powder. (1.63 g, yield 85%). Mp
L4
White powder (0.894 g, yield 75%). Mp 120–127 °C.
2
1
31
1
½
αꢀ = + 12.2 (c 1.0 THF). P{ H} NMR (122 MHz,
D
1
Benzene‐d ) δ 152.40. H NMR (300 MHz, Benzene‐d ) δ
21
D
31
1
6
6
1
34–137 °C. ½αꢀ = + 104 (c 0.75 CHCl ). P{ H} NMR
3
3
3
7
.46 (d, J = 7.9 Hz, HAr‐ortho, 4H), 7.30 (dd, J = 7.5,
HH HH
1
(122 MHz, Benzene‐d ) δ 145.23. H NMR (300 MHz, Ben-
4
3
4
6
3
JHH = 1.8 Hz, H , 4H), 7.08 (dt, J = 7.8, J = 1.8 Hz,
Ar
HH
HH
zene‐d ) δ 7.62 (d, J
= 8.0 Hz, H , 2H), 7.58 (d,
Ar
3
4
6
HH
H , 4H), 6.99 (dd, J = 7.3, J = 1.4 Hz, H , 4H), 3.06
Ar
HH
HH
Ar
3
JHH = 8.8 Hz, H , 2H), 7.52 (m, H , 2H), 7.44 (d,
Ar
Ar
(
(
s, NH, 1H), 3.03 (s, NH, 1H), 2.53 (m, *CHcyclohex, 1H), 2.48
m, *CHcyclohex, 1H), 1.88 (m, Hcyclohex, 1H), 1.76 (m,
Hcyclohex, 1H), 1.33 (m, Hcyclohex, 1H), 1.28 (m, Hcyclohex
H), 0.85 (m, Hcyclohex, 1H), 0.79 (m, H
m, Hcyclohex, 1H), 0.70 (m, Hcyclohex, 1H). C{ H} NMR
3
3
JHH = 8.4 Hz, H , 2H), 7.38 (d, J = 9.2 Hz, H , 2H),
Ar
HH
Ar
3
3
7
.34 (d, J = 9.0 Hz, H , 2H), 7.29 (d, J = 8.9 Hz,
HH Ar HH
,
3
HAr‐ortho, 2H), 7.22 (d, J
= 8.3 Hz, HAr‐Ph, 4H), 7.09
HH
3
1
(
(
, 1H), 0.76
cyclohex
(
(
m, H
d, J = 8.7 Hz, H
, 4H), 7.00 (d, J = 6.9 Hz, H , 2H), 6.90
1
3
1
Ar‐ortho
HH
Ar
3
, 2H), 6.84 (m, H , 2H), 2.11 (s,
Ar
2
HH
Ar‐Ph
75 MHz, Benzene‐d ) δ 151.40 (d, J = 31.2 Hz, CAr(q)
,
6
CP
13
1
NH, 2H). C{ H} NMR (75 MHz, Benzene‐d ) δ 153.49
2
6
2
C), 150.98 (d, J = 31.2 Hz, CAr(q), 2C), 132,50 (d,
CP
s, CAr(q), 4C), 148.41(s, CAr‐Ph(q), 2C), 134.27 (s, CAr(q)
( ,
3
3
JCP = 10.0, Hz, CAr(q), 2C), 132,36 (d, J = 10.0, Hz,
CAr(q), 2C), 130.02 (s, C , 2C), 129.28 (s, C , 2C),
CP
4
C), 133.34 (s, CAr(q), 4C), 131.38 (s, C , 2C), 130.51 (s,
Ar
Ar
Ar
C , 2C), 130.02 (s, C
, 2C), 128.66 (s, C , 4C),
Ar
Ar‐Ph
Ar
1
24.90 (s, C , 2C), 124.83 (s, C , 2C), 122.80 (s, CAr‐ortho,
Ar Ar
1
27.63 (s, C , 2C), 127.45 (s, C
Ar(q)
, 4C), 126.73 (s, CAr,
3
Ar
4
C), 56.89 (d, J = 3.9 Hz, *Ccyclohex, 1C), 56.61 (d,
JCP = 3.8 Hz, *Ccyclohex,1C), 36.21 (s, Ccyclohex, 1C),
6.16 (s, Ccyclohex, 1C), 25.25 (s, Ccyclohex, 2C). Anal. Calcd.
for C 0H N O P : C, 66.42; H, 5.20; N, 5.16. Found: C,
CP
2
C), 126.49 (s, C , 2C), 125.39 (s, C , 2C), 125.15 (s,
3
Ar
Ar
CAr(q), 2C), 124.81 (s, C , 2C), 124.06 (s, CAr‐ortho, 2C),
Ar
3
1
22.55 (s, CAr‐Ph, 2C), 118.26 (s, CAr‐ortho, 2C). Anal. Calc.
3
28 2 4 2
for C H N O P : C, 75.00; H, 4.10; N, 3.80. Found: C,
7
46 30 2 4 2
6
6.71; H, 5.15; N, 5.29.
5.38; H, 4.18; N, 3.72.
2
.5 | Tetraethyl 2,2′‐(((1R,2R)‐cyclohexane‐
,2‐diyl)bis‐(azanediyl))(4S,4′S,5S,5′S)‐
1
2
.7 | Synthesis of [Rh(COD)(P,P)]BF4
bis(1,3,2‐dioxaphospholane‐4,5‐dicarboxylate)
complexes 6–8
L5
Diphosphoramidite ligand (0.11 mmol) was added to a solu-
tion of [Rh(COD) ]BF (0.099 mmol, 40 mg) in CH Cl
2
(4 ml). The reaction mixture was then stirred for 15 min. at
room temperature. The solution was subsequently reduced
Colorless solid. (0.833 g, yield 65%). Mp 69–73 °C.
2
4
2
2
1
31
1
½
αꢀ = + 10.3 (c 1.2 THF). P{ H} NMR (122 MHz,
D
1
Benzene‐d ) δ 149.95. H NMR (300 MHz, Benzene‐d ) δ
6
6

4
of 8
DROMMI AND ARENA
to ~2 ml and by addition of hexane, a powder was obtained. It
was collected, washed with hexane and dried.
2H), 2.22 (m, Hcod, 4H), 2.04 (m, Hcod, 2H), 1.72 (m, Hcod,
2H). C{ H} NMR (126 MHz, Chloroform‐d) δ 147.40 (s,
13
1
CAr(q), 2C), 146.99 (s, CAr(q), 2C), 145.55 (s, CAr‐Ph(q), 2C),
1
2
34.13 (s, CAr(q), 4C), 132.33 (s, CAr(q), 2C), 132.30 (s, CAr(q)
,
2
.8 | [Rh(cod)(L4)]BF 6
4
C), 132.05 (s, C , 2C), 131.93 (s, CAr(q), 2C), 131.60 (s,
Ar
3
1
1
Yellow powder. (0.0784 g, yield 91%) P{ H} NMR
CAr(q), 2C), 131.52 (s, C , 2C), 131.27 (s, CAr‐Ph, 2C),
128.77 (s, C , 2C), 128.55 (s, C , 2C), 127.39 (s, C ,
Ar
1
(122 MHz, Chloroform‐d) δ 136.60 (d, JRhP = 233.5 Hz). H
Ar
Ar
Ar
NMR (300 MHz, Chloroform‐d) δ 7.53 (m, H , 4H), 7.48
2C), 127.14 (s, C , 2C), 127.07 (s, C , 2C), 126.84 (s,
C , 2C), 126.10 (s, C , 2C), 126.05 (s, C , 2C), 120.72
Ar Ar Ar
Ar
Ar
Ar
(
m, H , 4H), 7.37 (m, H , 4H), 7.35 (m, HAr‐ortho, 4H),
Ar
Ar
5
3
2
.76 (s, Hcod, 2H), 5.34 (s, Hcod, 2H), 4.06 (s, NH, 2H),
.71 (m, *CHcyclohex,2H), 2.49 (m, Hcod, 2H), 2.36 (m, Hcod
H), 2.27 (m, Hcod, 2H), 2.20 (m, Hcyclohex, 2H), 2.10 (m,
(s, CAr‐ortho, 2C), 120.27 (s, CAr‐Ph + CAr‐ortho, 4C), 111.49
(m, Ccod, 2C), 106.66 (m, Ccod, 2C), 30.06 (s, Ccod, 2C),
29.72 (s, Ccod, 2C). Anal. Calcd. for C H BF N O P Rh:
,
56
48
4 2 4 2
Hcod, 2H), 1.84 (m, Hcyclohex, 2H), 1.53 (m, Hcyclohex, 2H),
C, 63.18; H, 4.54; N, 2.63. Found: C, 63.54; H, 4.62; N, 2.75.
1
3
1
1
.39 (m, Hcyclohex, 2H).
Chloroform‐d) δ 152.67 (s, CAr(q), 4C), 148.28 (s, CAr(q)
C), 129.66 (s, C , 4C), 129.31 (s, C , 4C), 126.01 (s,
C{ H} NMR (75 MHz,
,
4
Ar
Ar
2
.11 | General procedure for the Rh(I)‐
C , 4C), 121.82 (s, CAr‐ortho, 4C), 106.09 (s, Ccod, 4C),
Ar
catalyzed asymmetric hydrogenation
58.34 (s, *Ccyclohex, 2C), 35.01 (s, Ccyclohex, 2C), 30.44 (s,
−
3
[
Rh(cod)(P,P)]BF 6–8, (2 × 10 mmol) and 2 mmol of sub-
Ccod, 2C), 29.27 (s, Ccod, 2C), 24.51 (s, Ccyclohex, 2C). Anal.
Calcd. for C H BF N O P Rh: C, 55.19; H, 5.33; N, 3.22.
4
strate was dissolved in CH Cl (2.5–7.5 ml) under argon. The
2
2
40
46
4 2 4 2
yellow solution was introduced with a syringe into a 100 ml
glass‐lined, stainless steel autoclave containing a magnetic
stirring bar. Hydrogen was introduced to the desired pressure
and the reaction mixture was stirred at 25 °C for 20 h. Then,
the hydrogen pressure was released and the solution was
passed through a short pad of silica and analyzed by
Found: C, 55.48; H, 5.27; N, 3.16.
2
.9 | [Rh(cod)(L5)]BF 7
4
3
1
1
Yellow powder. (0.0767 g, yield 89%). P{ H} NMR
122 MHz, Methylene Chloride‐d2) 144.64 (d,
(
δ
1
1
H NMR, GC and HPLC.
JRhP = 226.8 Hz). H NMR (300 MHz, Methylene
Chloride‐d ) δ 6.05 (m, Hcod, 2H), 5.58 (m, Hcod, 2H), 4.97
2
(
m, CH, 4H), 4.54 (s, NH, 2H), 4.32 (m, CH + *CHcyclohex,
2
1
2
0H), 2.67 (m, Hcod, 2H), 2.64 (m, Hcod, 2H), 2.47 (m, Hcod
,
3 | RESULTS AND DISCUSSION
H), 2.38 (m, Hcod, 2H), 1.83 (m, CHcyclohex, 4H), 1.35 (m,
1
3
1
CH + CH
, 16H). C{ H} NMR (75 MHz, Methylene
cyclohex
The chiral diphosphoramidite ligands L4‐L5 were synthesized
by reaction of (1R,2R)‐diaminocyclohexane 1 with two equiv-
alents of phosphorochloridites 2 and 3 respectively, using
triethylamine as base (Scheme 1). The compounds 2 and 3
were prepared, in a short time and in high yields, by treatment
of 1,1′‐biphenyl‐2,2′‐diol and diethyl (2S,3S)‐tartrate with
PCl3 without solvent and in the presence of a catalytic
amount of 1‐methyl‐2‐pyrrolidone. This protocol was
3
Chloride‐d ) δ 172.18 (s, CC=O(q), 4C), 107.00 (s, Ccod, 2C),
2
1
*
3
4
06.87 (s, Ccod, 2C), 77.29 (s, CAr(q), 4C), 63.64 (s,
Ccyclohex, 2C), 62.96 (s, CH , 4C), 31.11 (s, Ccod, 2C),
2
0.61 (s, Ccod, 2C), 24.62 (s, Ccyclohex, 2C), 14.44 (s, CH3,
C), 9.19 (s, Ccyclohex
,
2C). Anal. Calcd. for
C H BF N O P Rh: C, 42.87; H, 6.11; N, 3.03. Found:
C, 43.54; H, 6.22; N, 2.92.
3
3
56
4 2 12 2
[
18]
[19]
previously applied by us
and others
for preparing
diarylphosphorochloridites but, to our knowledge, never
applied to the synthesis of alkylphosphorochloridites.
2
.10 | [Rh(cod)(L6)]BF 8
4
[17,20]
3
1
1
Red‐brown powder. (0.0980 g, yield 93%). P{ H} NMR
Ligands L4‐L5 are quite stable in a dry and inert atmo-
sphere as solids but in common organic solvents they decom-
pose slowly giving an insoluble white powder. The
multinuclear NMR spectra are in agreement with the pro-
posed structures. In particular, the two equivalent phosphorus
(
122 MHz, Chloroform‐d) δ 128.04 (d, JRhP = 260.4 Hz).
H NMR (500 MHz, Chloroform‐d) δ 8.18 (d, J = 9.0 Hz,
1
3
HH
3
H , 2H), 8.11 (d, JHH = 8.9 Hz, H , 2H), 7.98 (d,
Ar
Ar
3
3
JHH = 8.9 Hz, H
, 2H), 7.96 (d, J = 8.4 Hz, H ,
HH Ar
Ar‐Ph
3
3
31
1
2H), 7.93 (d, J = 8.4 Hz, H , 2H), 7.85 (d, J = 8.9 Hz,
atoms appear as a singlet in the P{ H} NMR spectra of L4
HH
Ar
HH
3
1
HAr‐ortho, 2H), 7.64 (d, J = 9.0 Hz, HAr‐ortho, 2H), 7.44
(δ 152.42) and L5 (δ 149.95) ligands. The H NMR spectrum
HH
(
(
m, H , 2H), 7.34 (m, H , 2H), 7.23 (m, H , 2H), 7.15
exhibits all estimated signals relative to the two ligands, such
as two NH protons, two 1,2‐(R,R) methynic chiral protons
relative to the cyclohexane ring and all remaining expected
aliphatic and aromatic protons.
Ar
Ar
Ar
3
d, J
= 8.5 Hz, H , 2H), 7.03 (m, H , 2H), 6.90 (d,
Ar Ar
HH
3
3
JHH = 8.6 Hz, H , 2H), 6.72 (d, J = 8.9 Hz, HAr‐Ph
,
Ar
HH
2
H), 5.84 (m, Hcod, 2H), 4.46 (m, Hcod, 2H), 3.05 (m, NH,

DROMMI AND ARENA
5 of 8
The chiral rhodium(I) complexes [Rh(cod)(P,P)]BF4
(
cod = 1,5‐cyclooctadiene) 6–8 containing the bidentate
ligands L4‐L6 chelated to the metal center were synthe-
sized by reaction of [Rh(cod) ]BF with a slight excess
2
4
of the corresponding P,P ligand in dichloromethane solu-
tion. Compounds [Rh(cod)(L4)]BF 6 and [Rh(cod)(L5)]
4
BF 7 were isolated as fairly stable yellow solids under
4
a dry argon atmosphere. Instead, the complex [Rh(cod)
(
(
L6)]BF 8 is a red‐brown solid stable in inert atmosphere
Scheme 3).
4
All proton and carbon resonances belonging to 6 and 7
complexes were assigned through mono‐ and bi‐dimensional
SCHEME 1 Synthesis of ligands L4‐L5
1
31
1
13
NMR spectroscopy (2D–gCOSY, H‐ P gHMBC, H‐ C
1
13
31
1
The chiral diphosphoramidite L6 having the 1,2
diaminobenzene fragment as the achiral backbone, was pre-
pared by reaction of o‐phenylenediamine 4 with (R)‐
BINOL‐phosphorochloridite 5 in the presence of an excess
gHSQC and H‐ C gHMBC experiments). In the P{ H}
NMR spectra, compound [Rh(cod)(L4)]BF 6 shows a dou-
4
1
blet at 136.60 ppm with a coupling constant J
value of
RhP
233 Hz while the [Rh(cod)(L5)]BF 7 exhibits a doublet at
4
1
of NEt and a catalytic amount of 4‐(dimethylamino)pyridine
144.64 ppm ( J
value of 227 Hz), in agreement with
3
RhP
(
DMAP) (Scheme 2). The white solid obtained is stable for a
already reported values for similar mononuclear complexes
of rhodium with a cis arrangement of the two phosphorus
atoms.
3
1
1
long time under argon. The P{ H} NMR spectrum of L6,
show a sharp singlet at 145.23 ppm for the two phosphorus
atoms. In the aromatic region of the H NMR spectrum, there
are many buried peaks, that have needed COSY and C,H
bidimensional correlation spectra for their completely assign-
ment (See Experimental part).
[
12]
1
1
The H NMR spectra for the two complexes 6 and 7
exhibit all expected signals relative to the L4‐L5 and
cyclooctadiene ligands chelated to the rhodium center.
31 1
In particular, for the complex 6, the P, H–HMBC corre-
lation map allowed us to assign the broad signal at 4.06 ppm
relative to the two NH protons and at 3.71 ppm to the two
(1R,2R) chiral methinic protons of the cyclohexane ring.
The coordination of cod ligand was confirmed by the pres-
ence of two broad signal at 5.76 and 5.34 ppm relative to
alkene double bond hydrogens.
In the same way, we have assigned the hydrogen ligands
1
of complex 7. The H NMR spectrum shows widened signals
so it was indispensable study the compound by 2D NMR
spectroscopy; we assigned the shift of the methinic protons
of fragment (1R,2R)‐diaminocyclohexane at 4.32 ppm while
the hydrogen atoms of the NH group are moved (broad
SCHEME 2 Synthesis of ligand L6
SCHEME 3 Synthesis of cationic diphosphoramidite rhodium(I) complexes 6–8 (Rh/L 1:1.1)

6
of 8
DROMMI AND ARENA
singlet at 4.54 ppm) in lower field compared to the free
ligand. The aliphatic protons of tartrate fragment are very
broad; indeed, methinic protons CH resonate at 4.97 ppm
TABLE 1 Asymmetric hydrogenation of dimethyl itaconate 9 cata-
4 4
lyzed by [Rh(cod)(L4)]BF 6, [Rh(cod)(L5)]BF 7 and [Rh(cod)(L6)]
a
4
BF 8
(two broad multiplets), methylenic protons CH2 at
Entry
Catalyst
P (bar)
t (h)
Conv. (%)
ee. (%)
4
1
.32 ppm (broad multiplet) and the methylic protons CH at
3
1
2
3
4
5
6
7
6
7
8
6
6
7
8
1
1
20
20
20
6
100
0
27 (S)
‐
.35 ppm (broad multiplet).
31
1
The P{ H} NMR spectrum of complex 8 in CDCl ,
3
presents a broad doublet at 128.04 ppm with a constant
1
60
45 (R)
27 (S)
87 (S)
37 (R)
27 (R)
1
JRhP = 260.4 Hz whose value proves the ligand chelation
1
100
100
100
100
to the rhodium metal center.
20
10
5
6
1
The most important information is given by the H NMR
20
20
spectrum wherein the signals of the aromatic BINOL hydro-
gens appear to be split and separated in chemical shift with
respect to the ligand because the steric hindrance between
L6 and cyclooctadiene ligands coordinated to the rhodium
metal center. The hydrogen atoms of the NH group (broad
singlet at 3.06 ppm) are shifted at lower fields than the free
ligand and it was noted that the olefinic hydrogens of
a
1
Substrate/Rh = 1000, 25 °C. Conversion was determined by H NMR and
GCMS‐QP 5000 Shimadzu while ee values were measured by GC 8000
ThermoQuest and Shimadzu HPLC LC8A (for details see Experimental Section).
[
14]
Previously, we observed a significant positive effect of
1,5‐cyclooctadiene give rise to two distinct signals at 5.84
H pressure on the enantioselectivity of the hydrogenation of
2
and 4.45 ppm.
dimethyl itaconate catalyzed by the cationic rhodium
complex bearing diastereomeric diphosphoramidite ligand
(
R ,R ,S ,S )–L2. In that case, an ee value of 88% (S) was
c
c
a
a
3
.1 | Asymmetric hydrogenation of
reached at 60 bar.
functionalized olefins
With complex 6 a very good 87% ee (S) was obtained at
2
0 bar (Entry 5). Unfortunately, a further enhancement of the
To evaluate the potential of the new chiral ligands L4‐L6 in
the asymmetric hydrogenation of functionalized olefins, we
initially used dimethyl itaconate 9 as model substrate
hydrogenpressure produced metallicrhodiumintheautoclave.
In the complex 6, the chelate diphosphoramidite L4
contains a chiral diamine configurationally stable and two
fluxional chiral biphenyl moieties.
(Scheme 4).
The pre‐catalysts [Rh(cod)(P,P)]BF 6–8 were first tested
4
Thus, a mixture of three rapidly interconverting
at 1 bar of H pressure in CH Cl and at 25 °C for 20 h, with
2
2
2
(
R ,R ,R ,R ), (R ,R ,S ,S ), (R ,R ,R ,S ) diastereomeric cat-
c c a a c c a a c c a a
a substrate:[Rh] ratio of 1000:1.
[
21]
alysts should be present in solution.
It is likely that at 20 bar, one of three possible diastereo-
meric catalysts results most selective.
Rhodium complex 7 with diphosphoramidite L5 which
contains two (S,S) diethyltartrate groups completed the
reduction of substrate 9 under 10 bar of H with only 37%
ee (R) (Entry 6).
Complex 8 bearing the BINOL‐diphosphoramidite ligand
L6 with an achiral backbone, gave complete conversion at
The results, reported in Table 1, show that only complex
quantitatively hydrogenated the dimethyl itaconate with
6
low enantioselectivity (27% ee (S)) (Entry 1–3).
Interestingly, the complex [Rh(cod)(L4)]BF 6 proved to
4
be a very active catalyst. Indeed, complete reduction of sub-
strate 9 was achieved in 6 h under the same catalytic condi-
tions (Entry 4). Moreover, the rhodium catalyst derived
from diphosphoramidite L4 containing unsubstituted
biphenol fragments turned out more active than that derived
from diphosphoramidite L3 containing bulky ortho tert‐butyl
2
5
bar with an ee value 27% (R) (Entry 7).
In both cases, no change in the enantioselectivity was
[
14]
groups.
observed when increasing the H pressure to 30 atm.
2
In view of significant catalytic activity displayed by the
cationic complex 6 in the hydrogenation of dimethyl
The cationic complexes of rhodium(I) 6–8 were then
assessed in the hydrogenation of (Z)‐methyl‐2‐acetamido‐3‐
phenylacrylate 11 and methyl 2‐acetamido acrylate 12
itaconate 9, we decided studying the effect of H pressure
2
on stereoselectivity of the reaction.
(Scheme 5). The results summarized in Table 2 indicate that
all pre‐catalysts 6–8 are not very effective for hydrogenation
of substrates 11 and 12.
Complex 6 reduced quantitatively substrate 11 at 10 bar
of H (S/Rh = 500) giving very poor enantioselectivity
2
SCHEME 4 Hydrogenation of dimethyl itaconate catalyzed by
rhodium (I) complexes 6–8
(11% ee) (Entry 1). At higher hydrogen pressure, no effect
was observed on the enantiomeric excess.

DROMMI AND ARENA
7 of 8
rhodium(I) complexes useful as pre‐catalysts for asymmetric
hydrogenation of dimethyl itaconate.
In particular,
a
rhodium complex with
a
diphosphoramidite ligand which bears unsubstituted
biphenol groups was more active than that with bulky ortho
substituted tert‐butyl biphenols.
SCHEME
5
Hydrogenation of 2‐methyl acetamidoacrylate
derivatives catalyzed rhodium (I) complexes 6–8
Moreover, the same rhodium complex containing a chiral
diamine configurationally stable and two fluxional chiral
biphenyl units gives higher enantioselectivity with increasing
hydrogen pressure (87% ee).
In contrast, these rhodium/diphosphoramidite catalysts
showed poor performance in the hydrogenation of
α‐dehydroamino acid esters.
TABLE 2 Asymmetric hydrogenation of 2‐methyl acetamidoacrylate
4 4
derivatives 11–12 catalyzed by [Rh(cod)(L4)]BF 6, [Rh(cod)(L5)]BF
a
7
4
and [Rh(cod)(L6)]BF 8
Entry
Substr.
Catalyst
P (bar)
Conv. (%)
ee. (%)
Comparing the results obtained with new ligands L4‐L5
and those previously reported L1‐L3 we noted that the
BINOL group is determining for improving the catalytic out-
come. Moreover, substitution of the chiral backbone in the
BINOL‐derived ligands L1‐L2 with achiral one produced a
poorer catalyst.
We are currently studying the coordination chemistry of
these new diphosphoramidites with other transition metals.
Furthermore, other catalytic applications in asymmetric syn-
thesis are currently in progress.
1
2
3
4
5
6
7
11
11
11
11
12
12
12
6
7
7
8
6
7
8
10
10
20
10
10
10
10
100
75
100
0
11 (R)
68 (S)
65 (S)
‐
‐
‐
‐
0
0
0
a
1
Substrate/Rh = 500, 25 °C, 20 h. Conversion was determined by H NMR and
GCMS‐QP 5000 Shimadzu while ee values were measured by GC 8000
ThermoQuest and Shimadzu HPLC LC8A (for details see Experimental Section).
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| CONCLUSIONS
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SUPPORTING INFORMATION
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How to cite this article: Drommi D, Arena CG.
Rh(I) complexes with new C ‐symmetric chiral
2
diphosphoramidite ligands: Catalytic activity for
asymmetric hydrogenation of olefins. Appl
Organometal Chem. 2017;e3837. https://doi.org/
1
0.1002/aoc.3837