.
Angewandte
Communications
nations of monomers. Owing to the diversity of the supra-
molecular structures of chiral magnesium(II) binaphtholates
as cooperative Brønsted/Lewis acid–base catalysts, conven-
tional substituents at the 3,3’-positions in the binol skeleton
would not be necessary. We describe herein the first catalytic
enantioselective 1,4-hydrophosphinylation of a,b-unsatu-
rated esters with diaryl phosphine oxides and the still
problematic catalytic enantioselective 1,2-hydrophosphony-
Table 2: 1,4-Hydrophosphinylation of a,b-unsaturated esters with diaryl
phosphine oxides.
[
a]
1
2
Entry
1
R
R
2
3
T
t
[h]
Yield
[%]
ee
[%]
lation of a,b-unsaturated ketones with dialkyl phosphites by
[8C]
II
the use of 3:2 catalysts of (R)-(H )binolate/Mg in situ.
8
Ph
Ph
4-ClC H
4-MeOC H
4-MeC
2-furyl
3-pyridyl
PhCH=CH
c-C H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
3a
3a
3b
3c
3d
3e
3 f
3g
3h
3i
À40
À40
À40
À20
À20
À20
À40
À20
À20
À40
À20
À20
16
40
5
91
92
93
80
86
89
89
70
86
78
91
84
95
96
92
95
95
90
85
85
95
91
92
96
We initially investigated the enantioselective hydrophos-
phinylation of methyl cinnamate (1a) with diphenylphos-
phine oxide (2a) in the presence of (R)-binol (10–20 mol%),
Bu Mg (10 mol%), and H O (10 mol%) in THF at 08C for
[b]
2
3
4
5
6
7
8
9
6
4
4
4
3
5
6
4
H
4
2
2
6
2
2 h (Table 1, entries 1–3; see also Tables S1–S5). Interest-
ingly, the use of 15 mol% of (R)-binol (Table 1, entry 2) gave
20
18
10
4
6
11
[
a]
1
1
1
0
1
2
Ph
Ph
Ph
Table 1: Optimization of the catalyst in the 1,4-hydrophosphinylation.
Me
Me
3j
3k
[
c]
10
[
a] Reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), (R)-H -binol
8
(
15 mol%), Bu Mg (10 mol%), H O (10 mol%), THF, À408C. [b] The
2
2
reaction was carried out with (R)-H -binol (7.5 mol%), Bu Mg (5 mol%),
8
2
Entry
Ligand (mol%)
T [8C]
t [h]
Yield [%]
ee [%]
and H O (5 mol%). [c] The reaction was carried out with 3.5 mmol each
2
1
2
3
4
5
(R)-binol (10)
(R)-binol (15)
(R)-binol (20)
0
0
0
22
22
22
2
16
22
81
76
52
88
91
38
80
85
82
86
95
60
of 1a and 2c.
(R)-H -binol (15)
0
8
sterically demanding diaryl phosphine oxides 2b and 2c could
be used, and the corresponding 1,4-adducts 3j and 3k were
obtained with 92 and 96% ee, respectively, even on a gram
scale (yield of 3k: 1.24 g; entries 11 and 12). To test the
synthetic potential of our approach, we carried out a large-
scale synthesis with 33 mmol of each of the two substrates
(R)-H -binol (15)
À40
8
[
b]
6
(R)-binol (15)
0
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), (R)-H -binol
8
(
10–20 mol%), Bu Mg (10 mol%), H O (10 mol%), THF. [b] The
2 2
reaction was carried out without water.
(Scheme 3). From the 1:1 mixture of 1a and 2a, the crude
3
a in good yield with better enantioselectivity than the use of
1
0 or 20 mol% of (R)-binol (Table 1, entries 1 and 3). This
II
result suggests that a 3:2 molar ratio of (R)-binol and Mg
might be more effective than a 1:1 or 2:1 molar ratio [i.e.,
II
II
(
(R)-binolate)Mg or ((R)-binolate) Mg ]. The catalytic
2
activity was increased and the reaction time was decreased
to 2 h when we used (R)-H -binol in place of (R)-binol
8
(
Table 1, entry 4). Ultimately, the reaction proceeded
smoothly at À408C, and 3a was obtained with high enantio-
selectivity (95% ee; Table 1, entry 5). Water was essential to
induce the catalytic activity: a low yield and low enantio-
selectivity were observed under dry conditions without water
Scheme 3. Catalytic 1,4-addition reaction on a 10 g scale.
product was obtained almost quantitatively. The product 3a
was highly crystalline, and when the crude mixture was
washed with ether, we obtained 10.7 g of pure 3a as a powder
in 88% yield with 93% ee without silica-gel column chroma-
tography. Furthermore, the recrystallization of 3a from
chloroform gave a single crystal (> 99% ee), and we deter-
mined the absolute configuration of 3a by X-ray crystal-
structure analysis.
[
14]
(
Table 1, entry 6).
On the basis of this preliminary investigation, we exam-
ined the unprecedented 1,4-hydrophosphinylation of various
methyl cinnamates with diaryl phosphine oxides (Table 2).
For a variety of a,b-unsaturated methyl esters with an aryl
moiety (compounds 3a–d), a heteroaryl moiety (compounds
3
e,f), a conjugated olefin (compound 3g), or an alicyclic
moiety (compound 3h), the corresponding 1,4-adducts were
obtained exclusively with 85–95% ee (Table 2, entries 1–9).
When the catalyst loading was decreased to 5 mol%, the
reaction between 1a and 2a proceeded smoothly, and 3a was
obtained with 96% ee (Table 2, entry 2). Ethyl cinnamate was
also a suitable substrate (Table 2, entry 10). Moreover, the
We took advantage of the synthetic utility of esters to
synthesize a chiral palladium(II) complex with a phosphine–
oxazoline ligand derived from the 1,4-adduct 3k, since their
use as chiral P,N ligands is one of the most important
[
2,4g,15]
applications of organophosphorus compounds.
The
optically active 1,4-adduct 3k (96% ee) was hydrolyzed,
4
550
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 4549 –4553