Q. Wang et al. / Tetrahedron Letters 57 (2016) 658–662
659
Previous work3-5
:
phosgene and its derivatives:
NH2
O
O
*
or Cl3CO
Cl
COCl2
HN
O
OH
*
R
R
O
hazardous reagents
drastic reaction conditions
CO and CO2:
R1
*
CO/O2 or CO2 HN
R2
O
R2
*
*
*
HO
R1
NH2
This work:
O
O
mild reaction condition
high reactivity
high efficiency
Rh/L*
H2
O
O
*
N
H
N
H
R
R
Scheme 1. Synthesis of chiral 4-substituted oxazolinones.
O
O
1. (Diacetoxyiodo)benzene,
KOH, MeOH, 0 °C - rt
KOCN, AcOH,
iPrOH or THF, 50 °C
OH
O
R
R
2. 2 N HCl, rt
1
O
H
O
O
Rh-TangPhos
2 (30 atm), CH2Cl2, rt
N
H
N
H
H
P
P
H
R
R
tBu
tBu
2
3
Scheme 2. Design and synthesis of chiral 4-substituted oxazolinones.
metal precursor [Rh(NBD)2]BF4 obtained similar results with [Rh
(COD)2]BF4 (Table 1, entry 10).
Table 1
Solvent screening for Rh-catalyzed asymmetric hydrogenation of 4-phenyloxazol-2
(3H)-one 2aa
In our next experiments, a wide range of diphosphine ligands
were also tested (Fig. 1). As shown in Table 2, TangPhos devel-
oped by our group gave the best enantioselectivity (Table 2,
entry 1). Electron-donating P-chiral diphosphine ligands
(R,R)-QuinoxP and (Rc,Sp)-DuanPhos afforded high activities but
moderate enantioselectivities (Table 2, entries 5 and 8). When
some chiral bisphosphorus ligands such as (S)-Binapine, (S)-Seg-
Phos, (R)-MeO-Biphep, and (S)-C3-TunePhos were employed, the
expected product was obtained with excellent yields but lower
enantioselectivities (97–>99% con., 5–20% ee) (Table 2, entries
2, 6, 10, and 11). While chiral biaryl bisphosphorus ligand
(S)-BINAP and electron-donating P-chiral diphosphine ligand
(S,S)-Me-DuPhos provided neither high yields nor good enantios-
electivities (Table 2, entries 3 and 7). Chiral ferrocenyl ligands
f-Binapohane and (R)-WalPhos were also investigated with low
to moderate enantioselectivities and high activities (Table 2,
entries 4 and 9).
O
O
Rh / (S, S, R, R)-TangPhos (2 mol%)
O
O
N
N
H2 (30 atm), rt, 16 h
H
H
2a
3a
Entry
Cat.
Solvent
Conversionb
eec (%)
(%)
1
2
3
4
5
6
7
8
9
10
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(COD)(S,S,R,R)-TangPhos]BF4
[Rh(NBD)(S,S,R,R)-TangPhos]BF4
MeOH
CH2Cl2
IPA
EtOH
TFE
82
9.6
78
9.9
5
31
6.5
25.5
—
>99
46.3
13.5
32
THF
36
Dioxane
DME
Toluene
CH2Cl2
12.3
Trace
94
51
77
>99
Encouraged by these results, the hydrogen pressure and reac-
tion temperature were also evaluated with [Rh(COD)(S,S,R,R)-
TangPhos]BF4 as the catalyst and CH2Cl2 as the solvent. When
the hydrogen pressure reduced, the similar ee values were
obtained but with a slightly lower conversion (Table 3, entries
2 and 3). Under a lower reaction temperature, the enantioselec-
tivity was maintained but resulted in decreasing reactivity, while
increasing the temperature to 50 °C led to the decrease of
enantioselectivity (Table 3, entries 4 and 5). At last, we obtained
the best reaction condition was that [Rh(COD)(S,S,R,R)-TangPhos]
BF4 as the best catalyst for asymmetric hydrogenation of
4-substituted cyclic enamido esters in CH2Cl2 under 30 atm of
H2 at 25 °C.
a
Unless otherwise mentioned, all reactions were carried out with a [Rh]/(S,S,R,R)-
TangPhos/substrate ratio of 1:1.1:50 in 1 mL solvent, at room temperature under
hydrogen (30 atm) for 16 h.
b
Determined by 1H NMR spectroscopy.
Determined by HPLC analysis using a chiral stationary phase. NBD = 2,5-nor-
c
bornadiene, COD = 1,5-cyclooctadiene, IPA = isopropanol, TFE = trifluoroethanol,
THF = tetrahydrofuran, DCE = 1,2-dichloroethane.
in MeOH under 30 atm of H2 for 16 h. Under this condition, 2a was
hydrogenated to 3a with 82% conversion and low ee (10% ee,
Table 1, entry 1). Then, solvent screening showed that CH2Cl2
was the best choice with 78% ee (Table 1, entry 2). And we found