Chemistry Reference
In-Depth Information
R
1
R
1
Y
Y
H(D)
Rh
I
L
n
X
X
H(D)
62
(R
2
=H)
63
(R
2
=H)
R
1
R
1
Y
Y
Rh
III
L
n
H(D)
Rh
III
L
n
X
X
65
64
H(D)
H
2
or D
2
Scheme 8C.26.
reductive elimination affords the cyclization product
63
(R
2
= H) and regenerates the
RhL
n
species.
As an extension of the 1,6-enyne cyclization, the enantioselective reductive carbocy-
clization of 5-alkynals
66
was also investigated. The reactions were found to proceed
smoothly in the presence of Rh(COD)
2
OTf (5 mol %), (
R
) - Cl - MeO - BIPHEP (5 mol %)
and 2-naphthoic acid (5 mol %) at 45°C and ambient pressure of hydrogen to give the
corresponding fi ve - membered - ring alcohols
67
in 63-99% yields and 91-99% ee (Scheme
8C.27) [37,38]. The proposed mechanism of this reaction is essentially identical to that
of 1,6 - enyne
62
(see Scheme 8C.26) by replacing the terminal methylene moiety with
oxygen.
8C.4. ASYMMETRIC CARBOCYCLIZATIONS
8C.4.1. Tandem 1,4 - Addition - Aldol Cyclizations
1,4-Conjugate addition of organometallic reagents to
- unsaturated carbonyl com-
pounds provides a versatile method for carbon-carbon bond formation. Thus, extensive
efforts have been made on the development of asymmetric 1,4-conjugate addition reac-
tions [39-44]. Recently, a series of catalytic tandem reductive enolate formation-aldol
cyclization processes, forming carbocycles and heterocycles have been developed [26,46-
52]. In 2003, Krische et al. reported the fi rst reductive aldol cyclization of keto-enone
68a
involving diastereo- and enantioselective carbometallation. A variety of chiral
ligands were screened, and (
R
)-BINAP was found to be the best ligand, affording
cyclized product
69a
with 88% ee in 88% yield (Scheme 8C.28) [53].
A plausible mechanism (Scheme 8C.29) was proposed based on the mechanistic
studies performed by Hayashi on the Rh-catalyzed asymmetric conjugate addition of
boronic acids to enones [54]. The observed relative stereochemistry was rationalized by
assuming
Z
- enolate formation via a Zimmerman - Traxler - type transition state [55] .
α
,
β
