Chemistry Reference
In-Depth Information
8D.3. INTERMOLECULAR CARBONYL - ENE REACTION
This topic has already been discussed in the series
Catalytic Asymmetric Synthesis
,
Second Edition, 2000. Therefore, signifi cant and successful examples of asymmetric
catalytic ene reactions developed mainly after 2000 are described.
8D.3.1. Chiral Ti Catalysts
Asymmetric ene reaction catalyzed by chiral Lewis acid is one of the most effi cient
methodologies for atom economical carbon-carbon bond formation [7]. The fi rst cata-
lytic enantioselective version with aromatic aldehydes or chloral using a chiral BINOL-
Al complex is reported by Yamamoto et al. [17]. The enantioselective version of simple
and atom economic reactions has been intensively investigated since 1989. Mikami and
Nakai reported BINOL-Ti (
1
) - catalyzed “ glyoxylate - ene ” reaction. A variety of chiral
Ti catalysts have been screened for the carbonyl-ene reaction. The best result was
obtained with the BINOL-Ti (
1
) prepared
in situ
in the presence of MS 4A from
TiX
2
(O
i
Pr)
2
(X = Cl or Br: Mikami et al. [18]; X = O
i
Pr: Keck et al. [19]; TiF
4
: Carreira
et al. [20] ) and optically pure BINOL or 6 - Br - BINOL (Scheme 8D.2 ). The solidifi ed
BINOL - Ti (
1
) can also be employed as the most catalytically active, stable and storable
catalyst for months (or even years) [21].
X
OH
OH
TiCl
2
(O
i
Pr)
2
+
X
(10 mol % each)
Wet MS 4A
CH
2
Cl
2
, r.t., 1 h
O
OH
BINOL-Ti
1
+
Ph
H
2
Me
Ph
CO
2
Me
CH
2
Cl
2
, -30°C
X = H 97% ee (82%)
X = Br >99% ee (82%)
Scheme 8D.2.
After Mikami and coworkers developed BINOL-Ti catalysts for various asymmetric
carbonyl-ene reactions with high catalytic activity and enantioselectivity, various asym-
metric carbonyl-ene and related carbonyl addition reactions by BINOL-Ti catalysts have
been reported. We had better summarize here the relationship between BINOL-TiX
2
(X = O
i
Pr or halides) precatalysts and the “active BINOL-Ti catalyst (
1
) ” (Scheme
8D.3), which has not been structurally determined yet by X-ray analysis. In the presence
of dry (
<
0.2 wt % H
2
O) MS 4A (NaA zeolite), the dehalogenation reaction of TiCl
2
(O
i
Pr)
2
