.
Angewandte
Communications
Table 1: Optimization of the reaction conditions and Wei-Phos com-
[a]
pounds for 3-aroyl acrylates and methyl vinyl ketone.
[b]
[c]
Entry Cat.
X
Solvent T [8C] t [h] Yield [%]
ee [%]
1
2
3
4
5
6
7
8
9
10
(S,R )-W1 10
THF
25
25
25
25
25
25
25
0
3
3
1
3
1
4
6
1
1
94
90
95
93
96
92
90
96
96
81
83
65
81
87
71
87
90
91
93
93
93
94
94
93
94
94
94
S
(S,R )-W1 10
Et O
S
2
(S,R )-W1 10
DCE
S
(S,R )-W1 10
CH Cl
Scheme 2. Concise synthetic approach to Wei-Phos compounds.
S
2
2
(S,R )-W1 10
CHCl3
S
(S,R )-W1 10
CH CN
S
3
(S,R )-W1 10
toluene
CHCl3
CHCl3
CHCl
CHCl3
S
their application in the highly enantioselective intermolecular
cross-R-C reaction of two active olefins (Scheme 1b).
(S,R )-W1 10
S
(S,R )-W1 10
À10
À20
À25
S
Our initial study was concentrated on the exploration for
the concise synthetic route to Wei-Phos. Fortunately, we were
pleased to find that this new type of bisphosphine catalyst
could be easily prepared on a gram scale from commercially
available starting materials through a two-step strategy. The
(S,R )-W1 10
S
3
1.5 95
4
1
1
1
1
1
1
2
3
4
5
(S,R )-W1 10
90
84
S
(S,R )-W1 10
CHCl3
À30 24
S
(S,R )-W2 10
CHCl3
CHCl3
CHCl3
CHCl3
À20
À20
À20
À20
À20
1.5 96
1.5 93
1.5 95
2
8
S
(S,R )-W3 10
S
(S,R )-W4 10
S
[13]
chiral (R )-sulfinimines could be obtained in good yields
16
17
(S,R )-W2
5
96
96
89
S
S
[14]
from the corresponding 2-diarylphosphino benzaldehyde
and tert-butylsulfinamide via Ti(OiPr) mediated condensa-
(S,R )-W2
S
2.5 CHCl
3
1
8
(S,R )-W2
2
CHCl3
À20 24
S
4
[15]
tion. The nucleophilc addition of Ph PCH Li, generated in
2
2
[a] Unless otherwise specified, all reactions were carried out with 1a
situ from Ph PCH and nBuLi in the presence of TMEDA, to
(0.2 mmol), 2a (0.6 mmol) in solvent (2 mL); the absolute configuration
of 3aa were assigned by comparison with optical rotation in Huang’s
report. [b] Yield of isolated products. [c] Determined by HPLC analysis
using a chiral stationary phase.
2
3
the sulfinimines furnished Wei-Phos compounds W1–W4 in
moderate yields with good diastereoselectivity (Scheme 2).
With Wei-Phos compounds W1–W4 in hand, we then
focused on the performance of Wei-Phos compounds in the
reaction of 3-aroyl acrylate 1a and methyl vinyl ketone 2a
[12]
(
Table 1). To our delight, the desired R-C product 3aa was
naphthyl- and heteroaryl-containing substrates 1j–1m, fur-
nishing the corresponding products 3ja–3ma in 91–97% yield
with 91–95% ee (Table 2, entries 10–13). To our delight,
achieved in 96% yield with 87% ee (Table 1, entry 5) by
utilizing (S,R )-W1 as catalyst. Further intensive screening of
S
various solvents demonstrated that CHCl3 was the best
reaction medium in terms of reactivity and enantioselectivity
(S,R )-W2 was also effective for the challenging aliphalic
S
substrates 1n and 1o to give the desired products in good
yiled with high ee, albeit with a higher catalyst loading and
longer reaction time (Table 2, entries 14,15). Further results
demonstrated that the reaction of 3-aroyl acrylates bearing
bulky ester group result in the enantioselectivity dropping
slightly to 90% ee (Table 2, entries 16–18). The scope of vinyl
ketone component was then examined. We were pleased to
find that ethyl vinyl ketone and propyl vinyl ketone are
applicable to the present transformation, delivering the
corresponding 3ab and 3ac in high yield with good to
excellent ee (Table 2, entries 19,20). Finally, with regard to
(
Table 1, entries 1–7). Gratifyingly, the ee value of 3aa was
improved to 93% without loss of efficiency when lowering the
reaction temperature from 258C to À208C (Table 1,
entries 8–10). However, much lower reaction temperature
was not beneficial for the enantioselectivity and reactivity any
more (Table 1, entries 11,12). (S,R )-W2 displayed better
S
performance in enantioselectivity than (S,R )-W1 and the
S
corresponding 3aa could be delivered in 96% yield with 94%
ee (Table 1, entry 13). (S,R )-W3 and (S,R )-W4 with more
S
S
bulkier aryl substituents on the side phosphine chain could
not improve the efficiency and enantioselctivity (Table 1,
entries 14,15). It is noteworthy that lowering catalyst loading
to 2.5 mol% did not bring negative effect on the yield and ee
aryl vinyl ketone, (S,R )-W2 also performed effectively under
S
slightly modified reaction conditions (Table 2, entry 21).
Encouraged by these results, we decided to pursue the
application of Wei-Phos to the cross-R-C reaction of 2-ene-
(
Table 1, entries 16–18).
[16]
Having identified the optimized reaction conditions, we
1,4-dione and vinyl ketone, which has not been reported to
date (Table 3). Gratifyingly, the reactions of (E)-1,4-diary-
lbut-2-ene-1,4-diones and methyl vinyl ketone works well
then investigated the generality of this enantioselective cross-
R-C reaction with a variety of 3-acyl acrylates and vinyl
ketones. Various electron-withdrawing groups, such as F, Cl,
under 2.5 mol% of (S,R )-W2, delivering the desired cross-R-
S
and Br, and electron-donating groups, such as CH , MeO, and
Ph, on the phenyl rings of 3-aroyl acrylates 1b–1i were well
tolerated, and the desired R-C products were achieved in high
C products 5aa–5ea in good yield with 93–96% ee (Table 3,
entries 1–5). Unfortunately, the change from (E)-1,4-diary-
lbut-2-ene-1,4-dione to (E)-hex-3-ene-2,5-dione leads to
enantioselectivity decreasing to 73% ee (Table 3, entry 6).
Gratifyingly, the ee value of 5 fa was improved to 82% when
3
yield with 90–96% ee (Table 2, entries 2–9). Of note, (S,R )-
S
W2 also displayed good performance in the reactions of
1
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 14853 –14857