Communication
phosphine ligand 1i, which performed best in the literature,[5a]
only gave 12.2% ee (entry 23).
Table 1. Asymmetric hydrogenation catalyzed by Rh/1.[a]
Although the chiral P(O)H group is assumed to play an es-
sential role in this asymmetric induction, the contribution of
the chiral menthoxy auxiliary cannot be ruled out. Dimenthoxy
phosphite 1h gave 29.2% ee of the product under the opti-
mized reaction conditions (entry 22). In addition, the hydroge-
nation of 2a by using 1a (1b) with RP/SP =50:50 was conduct-
ed (entries 5 and 10). The enantioselectivity was low, leading
to the product in 4.3% ee (0.3% ee), showing that the asym-
metric induction is predominantly influenced by the chiral
phosphorus center and that the contribution of the chiral
menthoxy auxiliary is small.
Entry Ligand Rh
Conditions
Yield [%][b] ee [%]
(config.)[c]
1
2
1a
–
–
CH2Cl2, 3h
CH2Cl2, 3h
CH2Cl2, 3h[e]
CH2Cl2, 3h[f]
CH2Cl2, 3h
CH2Cl2, 3h
CH2Cl2, 48h
100
83
100
100
99
100
<1
5
86.4 (S)
[d]
[Rh(cod)2]OTf
86.0 (S)
81.6 (S)
84.7 (S)
4.3 (R)
50.1 (S)
–
3
4
5
–
–
–
–
–
–
[g]
6
7
–
–
[Rh(cod)2]BF4
[Rh(cod)Cl]2
8
–
[Rh(C2H4)2Cl] 2 CH2Cl2, 72h
–
With these preliminary results in hand, we decided to inves-
tigate the reaction. Since the formation of metallic rhodium
was observed in these reactions, we felt that there might be
a problem with the current system in generating the catalyst.
Thus, probably owing to the relatively low ligating ability of
[(À)MenO]RP(O)H compared to a phosphine R3P, the combina-
tion of the rhodium complex [Rh(cod)2]OTf with (MenO)RP(O)H
might not readily produce the expected active Rh/L system,
which catalyzes the asymmetric hydrogenation. Consequently,
the remaining nonligated rhodium may also catalyze the hy-
drogenation, resulting in a decrease in enantioselectivity of the
product.
9
1b
–
1c
1d
1e
–
–
–
–
–
[Rh(cod)2]OTf
CH2Cl2, 3h
CH2Cl2, 3h
CH2Cl2, 3h
THF, 40h
CH2Cl2, 3 h
CH2Cl2, 12h[h]
toluene, 40h
THF, 3h
94
71
100
80
100
37
14.1 (S)
0.3 (R)
27.2 (S)
13.6 (S)
86.1 (S)
46.1 (S)
69.4 (S)
52.7 (S)
60.2 (S)
38.3 (S)
31.5 (S)
77.6 (S)
19.3 (S)
29.2 (S)
12.2 (S)
[g]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
–
–
–
–
–
–
–
–
–
–
–
–
–
–
29
100
100
97
59
100
86
Et2O, 3h
acetone, 18h
MeOH, 40h
CH2Cl2, 3h
CH2Cl2, 12h
CH2Cl2, 3h
CH2Cl2, 3h
–
1 f
1g
1h
1i
84
80
This indeed was true. As confirmed by 31P NMR spectrosco-
py,
a
mixture of 1b (0.062 mmol) and [Rh(cod)2]OTf
[a] Unless otherwise noted, reactions were conducted by using a 0.048m
solution of 2a. [b] 1H NMR yield. [c] Enantiomeric excesses were deter-
mined by chiral HPLC. The absolute configuration was determined by
comparison with reported data.[7] [d] 5 mol% ligand. [e] 358C. [f] 20atm
of H2. [g] 1 with RP/SP =50:50 was used. [h] 0.1 equiv H2O was added.
(0.031 mmol) in CD2Cl2 (0.5 mL) at room temperature only
slowly reacted to produce a new complex, which was observed
in the 31P NMR spectrum at d=122.3 ppm (d, JPÀRh =206.2 Hz)
and was assigned to complex 4b, as described later (Figure 2).
As followed by 31P NMR spectroscopy, the completion of this
reaction required more than two days (time, yield of 4b:
40 min, 11%; 14 h, 75%; 48 h, 97%). Ligand 1a reacted similar-
ly. Interestingly, in the above reaction of 1a (1b) with [Rh-
(cod)2]OTf, only one cod was replaced by two phosphinate li-
gands 1a (1b) to give 4a (4b) exclusively (Scheme 1). Thus,
further replacement of cod in 4a by 1a was not observed at
room temperature, even when a large amount of 1a (5 equiv
to Rh) was used.
product strongly depends on the structure of the R group,
that is, a tiny change on R can dramatically change the ee. In-
terestingly, benzylphosphinate 1a (entry 1) and isopropylphos-
phinate 1e (entry 13) gave the highest selectivity (ca.
86.4% ee), followed by n-propylphosphinate 1 f (77.6% ee),
whereas an aryl group (entry 9, Ph, 1b and entry 11, 1-naph-
thyl, 1c) gave a low ee of the product. Both the bulky tert-bu-
tylphosphinate 1d (entry 12) and the small methylphosphinate
1g (entry 21) only gave a low selectivity. Surprisingly, using
5 mol% of 1a (Rh/P=1:1) also led to a similar selectivity of
86.0% ee (entry 2). The selectivity slightly decreased when the
reaction was conducted at 358C (entry 3), whereas a higher
pressure of hydrogen (entry 4) did not improve the ee. The
choice of the rhodium complex also strongly affected the reac-
tion. Thus, the ee decreased when [Rh(cod)2]BF4 was used
(entry 6), and the reduction hardly progressed with [Rh(cod)Cl]2
(entry 7) or [Rh(C2H4)2Cl]2 (entry 8). Solvents also greatly affect-
ed the results. Among the solvents investigated (entries 13–
19), CH2Cl2 gave the best results, whereas the commonly used
solvent methanol only gave a low ee of the product. Water
lowered both the reactivity and enantioselectivity of the reac-
tion; thus, in the presence of 0.1 equivalents of H2O (entry 14),
the reduction product was obtained in only 37% yield with
46.1% ee, even after 12 hours. Finally, the chiral secondary
The resulting complexes 4a and 4b were only slightly solu-
ble in toluene. Taking advantage of this low solubility in tolu-
ene, good crystals of 4b that are suitable for X-ray analysis
were isolated in 95% yield.
Scheme 1. Formation of rhodium complexes 4a and b.
Chem. Eur. J. 2014, 20, 3631 – 3635
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