Chemistry Reference
In-Depth Information
CN
CN
Pd(dba)
2
(5-10 mol %)
(S,R)
-JOSIPHOS
(10 mol %
)
P
Me
O
DMF, 65-90°C, 24 h
O
Ph
P
Ph
I
Fe
146
92%, 84% ee
145
(S,R)
-JOSIPHOS
Scheme 8C.49.
Pd(OAc)
2
(3 mol %)
(R)
-BINAP (6 mol %)
i
-Pr
2
NEt (3 eq)
Benzene, 40°C
OTf
+
+
O
O
O
151
148
149
150
(5.0 eq)
71%, 93% ee
7%, 67% ee
Scheme 8C.50.
A plausible mechanism was proposed to explain the high enantiopurity of the major
product
150
(
R
) and inversion of confi guration in the formation of minor product
151
(
S
), which was further refi ned by Brown et al. (Scheme 8C.51) [86,87]. As Scheme 8C.51
illustrates, the insertion of the double bond of
148
into the Ar-Pd bond of
152
yields
two diastereomeric Pd complexes
153
(via
si
- face attack) and
153
′ (via
re
- face attack).
Next, β-hydride elimination takes place to both intermediates to form π - olefi n - Pd - H
complex
154
and its diastereomer
154
′ . The π - complex
154
undergoes rapid hydropal-
ladation to give
155
, followed by β-hydride elimination and reductive elimination to
afford 2 - phenyl - 2,3 - dihydrofuran (
150
). Thus, for
154
, the hydropalladation is much
faster than the dissociation of
151
. In contrast, the π - complex
151
′ rapidly dissociates
2 - phenyl - 2,5 - dihydrofuran
(151
′) rather than undergoes hydropalladation. Accordingly,
the proposed mechanism involves a kinetic resolution process that enhances enantiose-
lectivity of
150
by selectively eliminating
153
′ through the formation of
151
′ as the minor
product.
The asymmetric intermolecular Heck reaction, involving double-bond migration, has
been extensively studied using various chiral P,N-ligands (Fig. 8C.1).
As Scheme 8C.52 exemplifi es, the reaction of
148
with 2 - carbethoxycyclhexenyl tri-
fl ate (
164
) gave 5 - cyclohexenyl - 2,3 - dihydrofuran
165
with >96% ee exclusively [88]. In
contrast, the reaction of 2,2 - dimethyl - 2,3 - dihydrofuran (
166
) with phenyl trifl ate (
149
)
afforded 2 - phenyl - 2,5 - dihydrofuran (
167
) with 98% ee, as the sole product [89,90]. The
reaction of
148
with
149
catalyzed by a Pd complex with (D-glucosamine)phosphite-
oxazoline ligand
162
gave
151
with 99% ee and 97% regioselectivity [91]. Also, the
reaction of
148
with cyclohexenyl trifl ate (
168
) catalyzed by a Pd complex with
163
gave
2 - cyclohexenyl - 2,5 - dihydrofuran (
169
) with 98% ee and 98% regioselectivity [91].
A series of PHOX ligands, for example,
157
and
158
, featuring a rigid chiral cyclo-
propyl backbone were applied to the asymmetric Heck reaction of
148
with
149
. As
