Chemistry Reference
In-Depth Information
8C.5.2. Asymmetric Intramolecular Heck Reactions
The intramolecular asymmetric Heck reaction has found numerous applications in
organic syntheses, as mentioned above. Among those applications, the synthesis of opti-
cally active oxindoles bearing a quaternary asymmetric center has been extensively
studied, mainly because enantiopure oxindoles can serve as versatile intermediates or
synthons in the total synthesis of a variety of natural products [69,75,76]. The reaction
of (
E
) -
- unsaturated - 2 - iodoanilide
110
was carried out using Pd
2
(dba)
3
- (
R
) - BINAP as
catalyst and Ag
3
PO
4
or 1,2,2,6,6-pentamethylpiperidine (PMP) as HI scavenger in
N
,
N
-
dimethylacetamide (DMA), to give oxindoles (
S
) - or (
R
) -
111
in good yield and fairly
good enantioselectivity under cationic or neutral conditions (Scheme 8C.40). It should
be noted that a dramatic switching in the direction of asymmetric induction was observed
between these two conditions even though the same chiral ligand, (
R
) - BINAP, was used
in both reactions. This was the fi rst example that achieved fairly good enantioselectivity
under neutral conditions.
α
,
β
O
N
Pd
2
(dba)
3
-CHCl
3
(5 mol %)
(R)
-BINAP (12 mol %)
Ag
3
PO
4
(2 eq)
DMA, 80°C
O
O
O
(
S
)-
111
81%, 71% ee
N
O
I
Pd
2
(dba)
3
-CHCl
3
(5 mol %)
(R)
-BINAP (12 mol %
)
PMP (5 eq)
DMA, 110°C
O
O
N
110
O
O
(
R
)-
111
77%, 66% ee
Scheme 8C.40.
In the same manner, the reactions of a series of
N
- cycloalkenoyl - 2 - iodoanilides,
N
-
cycloalkenylmethyl - 2 - iodoaniline, and cycloalkenylmethyl 2 - iodophenyl ether were
investigated, and results are shown in Scheme 8C.41 [76]. It is worthy of note that the
cationic conditions with Ag
3
PO
4
are detrimental to the enantioselectivity in the reactions
of
N
-cycloalkenoyl-2-iodoanilides, while neutral conditions with PMP do not give appre-
ciable asymmetric induction in the reaction of
N
- cycloalkenylmethyl - 2 - iodoaniline and
cycloalkenylmethyl 2-iodophenyl ether. Thus, this reaction appears to be highly sensitive
to the matching or mismatching of the functional groups in substrate and reaction
conditions.
To optimize both enantioselectivity and regioselectivity of the reaction, new chiral
ligands and modifi ed substrates have been developed in the past 10 years. For example,
Guiry and Kiely prepared aryl trifl ate
116
to investigate the regio- and enantioselectivity
in the formation of oxindole
117
catalyzed by Pd(0) complex with oxazoline-based
aminophosphine ligand
119
under cationic conditions (Scheme 8C.42) [77]. Excellent
