Chemistry Reference
In-Depth Information
O
R
RMgBr,
7
(5 mol %)
O
R
1
Z
t
BuOMe, -75
°
C
R
1
Z
Me
Cy
2
86-99% ee
P
Br
Cu
R = Et, Me,
n
Bu; Z = OMe, OEt
Fe
Ph
2
2
7
Scheme 8A.2.
O
R
3
O
R
3
MgBr, CuBr•SMe
2
Ligand
8
,tBuOMe,-75
°
C
R
1
SR
2
R
1
SR
2
Up to 96%
ee
Me
R
1
=
n
-Pent,
n
-Bu,
n
-Pr, Et,
Me, Ph, BnO(CH
2
)
3
R
2
=Me,Et
R
3
= Et, Me,
i
-B u,
i
-Pr,
n
-Bu,
n
-Pr
PCy
2
PPh
2
Fe
8
( R,S)
-Josiphos
Scheme 8A.3.
diastereoselective and enantioselective route to both
syn
- and
anti
- 1,3 - dimethyl arrays
and deoxypropionate chains (Scheme 8A.3 [12] ).
Compared with asymmetric 1,4-conjugate additions, the conjugate addition to
extended Michael acceptors requires additional control of the regioselectivity. Recently,
using reversed Josiphos ligand
9
, Feringa et al. [13] developed a highly enantioselective
1,6-asymmetric conjugate additions (up to 97% ee) to
- unsaturated esters, provid-
ing valuable multifunctional building blocks. They also proposed a catalytic cycle as
shown in Scheme 8A.4 .
Besides the above ferrocenyl ligands, Taniaphos with CuBr·SMe
2
was also proved to
be highly effective in the conjugate addition of allylic electrophiles with Grignard
reagents (Scheme 8A.5) [14]. In this reaction, aliphatic allylic bromides were shown to
be excellent substrates, which provided almost exclusively the branched products with
up to 98% ee.
In 2006, through the asymmetric conjugate additions of Grignard reagents associated
with Cu(OTf)
2
catalyst and a chiral diaminocarbene ligand, Alexakis and coworkers
[15] found an effi cient way to create enantioselectively all-carbon quaternary centers.
In this system, there is no need to use specially activated trisubstituted enones (Scheme
8A.6 ).
The fact that free Cu-salts usually show high activity in the conjugate additions
of Grignard reagents even at
α
,
β
,
γ
,
δ
80°C led to the realization that tight binding of Cu
ions by bidentate ligands might still be active in this reaction. Privileged bidentate
phosphine Tol-BINAP was proved to be an effi cient ligand by Loh, who developed a
highly effi cient CuI - Tol - BINAP - catalyzed asymmetric conjugate addition of MeMgBr
to
−
-unsaturated esters using simple reaction procedures with up to 99% ee (Scheme
8A.7 ) [16] .
α
,
β
