Chemistry Reference
In-Depth Information
mechanism of the addition steps, the tandem conversions could be divided into anionic
and radical processes.
In 1997, the fi rst metal
-
catalyzed asymmetric tandem conjugate addition reaction of
organozinc reagents to
-unsaturated aldehydes was reported by Feringa and cowork-
ers [159]. Since then, the asymmetric tandem conjugate additions was extended from
aldehydes to acetals, ketals, ortho-esters, ketones, esters, and nitriles [160,161]. As
shown in Scheme 8A.86, Krische and coworkers used ketones as electrophiles in copper-
catalyzed conjugate addition reactions. When enones including pendant ketone, ester,
and nitrile moieties as substrates reacted with organozinc reagents in the presence of
catalytic Cu(OTf)
2
and ligand
15
, the reaction afforded cyclized products in excellent
yields and enantioselectivities. These investigators also achieved a high level of stereo-
chemical control for the creation of three contiguous stereogenic centers in a single
manipulation [162]. This reaction was effected by rhodium catalyst with phenylboronic
acid in the presence of excess of water, which was effective for the construction of fi ve -
and six-membered-ring products. Particularly high enantioselectivity was observed for
methyl-substituted enone precursors (up to 95% ee).
α
,
β
O
O
O
H
1.2 mol % Cu(OTf)
2
2.4 mol %
15
Toluene,-30°C
H
O
OH
PCC
+Me
2
Zn
+
CHO
Me
Me
Ph
Ph
O
Ph
O
Ph
OH
O
2.5 mol % Cu(OTf)
2
5 mol %
15
OH
Et
Et
O
O
+
PN
1.5equiv ZnEt
2
,
toluene,-40
°
C
99%yield
O
Me
Me
O
Ph
O
2.3
:
1d.r.
Me
80% ee
98% ee
O
15
O
O
Me
2.5 mol %[{Rh(cod)Cl}
2
]
7.5 mol %(R)-binap
2 equiv PhB(OH)
2
5equiv H
2
O
dioxane(0.1M),95°C
O
Me
Me
Me
OH
(C)
n
(C)
n
Ph
n= 1,2
69~88% yield
94~95% ee
Scheme 8A.86.
Hoveyda and coworkers [163] developed peptidic compounds
26
and
28
as chiral
ligands for the copper-catalyzed asymmetric conjugate addition of dialkylzinc reagents
to α , β-unsaturated ketones. The scope of this reaction was subsequently expanded with
the use of alkyl halides and tosylates to give complex molecules with consecutive ste-
reocenters. For example, when the zinc enolate, which was formed by the conjugate
additions of dimethylzinc to cycloheptenone, was treated with 4-iodo-1-butene in the
presence of Cu(OTf)
2
and ligand
26
at −30°C, the desired products were obtained in
high yields and good ee values (Scheme 8A.87).
Morken and coworkers reported the fi rst rhodium-catalyzed asymmetric conjugate
reaction in 2000 [164]. This reaction mediated by [Rh (cod) Cl]
2
and (
R
) - BINAP gave
