Chemistry Reference
In-Depth Information
-unsaturated carbonyl compounds has been well established [40-
42,57-59]. Also, the trapping of Zn enolates with aldehydes [40,58,60] and acetals/ketals
(oxocarbenium ions) [62] has been reported. However, the use of ketones to trap Zn
enolates was reported to have failed in the absence of a strong Lewis acid [61]. Never-
theless, the tandem conjugate addition-aldol cyclization of diethylzinc with ketones,
esters, and nitriles was found to proceed in the presence of a catalytic amount of
Cu(OTf)
2
- P(OEt)
3
to give the corresponding products
75
,
76
, and
77
, respectively, in
excellent yields (Scheme 8C.31 ) [62] .
compounds to
α
,
β
O
HO
R
Me
Et
2
Zn (150 mol %)
Cu(OTf)
2
(2.5 mol %)
P(OEt)
3
(5 mol %)
Et
n
O
OZnLn
75
E
E
R
R
E=ketone
Dichloromethane
Et
74
O
O
n
n
O
NH
2
R
R
n
= 1, 2
Et
Et
n
n
76
77
E = ester
E = nitrile
Scheme 8C.31.
To demonstrate the feasibility of the enantioselective variant of this reaction, enone-
dione
78
was subjected to conditions of Scheme 8C.31, but using Feringa's chiral phos-
phoramidite ligand [63] in place of P(OEt)
3
[62]. The reaction gave a mixture of two
diastereomers:
79
(80% ee) and
epi
- 79
(98% ee) in a 2.3:1 ratio and nearly quantitative
yield (Scheme 8C.32 ) [62] .
Et
2
Zn (150 mol %)
Cu(OTf )
2
(2.5 mol %)
Feringa ligand (5 mol %)
Ph
O
Ph
O
Ph
O
OH
OH
O
Et
Et
O
Ph
P
N
Toluene, -40°C
O
Ph
Me
Me
Me
O
78
79
80% ee
epi
-79
98% ee
99% combined yield, 2.3:1 dr
Feringa ligand
Scheme 8C.32.
8C.4.2. Reductive Aldol Cyclizations
In 2001, Chiu et al. reported that a phosphine-stabilized copper hydride complex, [(Ph
3
P)
CuH]
6
(Stryker's reagent), effectively promoted tandem reductive aldol cyclizations of
keto-enones [64]. Following up this fi nding, Lam and Joensuu looked for a catalytic
process and found that a catalytic amount of Cu(OAc)
2
· H
2
O with an achiral diphosphine
