Chemistry Reference
In-Depth Information
Me
Me
Me
H
Me
Me
Me
Me
Me
OtBu
O
N
O
O
O
N
N
N
NHBu
NHBu
N
NHBu
N
N
H
NHBu
O
PPh
2
O
O
O
PPh
2
Ph
PPh
2
24
PPh
2
23
Me
Me
22
OtBu
25
Ligand for conjugate addition to
cyclic trisubstituted enones
Ligand for conjugate addition to
acyclic disubstituted enones
Ligand for conjugate addition to
unsaturated
N
-acyloxazolidinones
Ligand for conjugate addition to
cyclic disubstituted enones
Scheme 8A.15.
1-5 mol %
Chiral Cu complex
24
R
2
Zn
O
O
R
H
R
1
R
1
Alkyl
Alkyl
R
1
= Ph,
p
-OMePh,
p
-NO
2
Ph,
p
-CF
3
Ph,
Me,
n
-pent,
i
-Pr, (CH
2
)
3
OAC
alkyl = Me,
n
-hex,
i
-Pr,
t
-Bu
R = Me, Et
Up to 95%
ee
Scheme 8A.16.
Alkyl
O
O
O
O
2.4-6 mol %
25
0.5-2.5 mol % (CuOTf)
2
C
6
H
6
, [Zn(alkyl)
2
]
R
N
O
R
N
O
•
R = Me,
n
Pr, (CH
2
)
3
OTBS,
i
Pr
Alkyl = Et, Me,
i
Pr,
i
Pr(CH
2
)
3
76->98%
ee
Scheme 8A.17.
Subsequently, in 2005, Hoveyda et al. reported a general, effective method for the
conjugate addition of dialkylzinc reagents to various unsaturated heterocyclic enones
with different steric and electronic properties such as furanones, pyranones, and their
derivatives [28]. This method signifi cantly enhanced the general utility of Cu-catalyzed
asymmetric conjugate addition of alkylmetal reagents to unsaturated carbonyls (Scheme
8A.18 ).
Besides the above α , β - unsaturated ketones, nitro - olefi ns were also studied as sub-
strates for the catalytic asymmetric conjugate additions by Luchaco-Cullis and Hoveyda
[29]. In 2002, by using amino acid-based chiral phosphine ligand
29
, they demonstrated
the fi rst effi cient method for the catalytic asymmetric addition of alkylzincs to small-,
medium - , and large - ring nitro - olefi ns (Scheme 8A.19 ).
Feringa et al. reported the use of phosphoramidite ligand
30
for the conjugate addi-
tion of acyclic nitroalkenes and achieved up to the 98% enantioselectivities (Scheme
8A.20 ) [30] .
In 2005, Hoveyda et al. also reported the catalytic asymmetric conjugate addition of
dialkylzinc reagents to acyclic nitroalkenes using peptide-based ligand, leading to prod-
ucts with quaternary carbon stereogenic centers with up to 98% ee (Scheme 8A.21) [31].
