Angewandte
Chemie
+
ꢀ
(
A -O ) initially attacks the alkyne p system of R-(+)-2a to
give the gold enol ether C and subsequently the a-oxo gold
[
14]
carbene B. The role of this gold carbene B was assessed in
a control experiment (Scheme 3). We postulate that a subse-
quent attack of the methoxy group at the carbene carbon
atom generates the oxonium species D, which has two axial
Scheme 3. A viable route involving a gold carbene intermediate.
presence of 8-methylquinoline oxide (0.5 equiv), the desired
dihydroisobenzofuran 4a was obtained as the major product
in 49% yield together with side products 7a (23%) and 9
(
21%). These results suggest that the organic oxide facilitates
Scheme 4. Chirality transfer in the cycloaddition reaction.
the generation of the gold carbene B through a stabilization
effect.
We prepared enantiomerically enriched (R)-(+)-2a
94.1% ee) and examined its gold-catalyzed cycloaddition
hydrogen atoms to minimize steric hindrance. Species D is
expected to form the gold enolate species E through a ketone/
enol equilibrium. In species E, there is a concurrent attack of
the ketone moiety at the carbocation center as the methoxy
group leaves from the same center; this process is likely to
occur because of a stable five-membered-ring transition state.
[
12]
(
with 8-methylquinoline oxide. The reaction delivered the 1,3-
dihydroisobenzofuran (R)-(ꢀ)-4a (78%, 93.9% ee) with
complete chirality transfer (Table 2, entry 1). This product
[13]
was determined to have the R absolute configuration,
which corresponds to retention of the original configuration.
The chirality transfer was also highly effective for the 4-
Such a front-on S 2 attack has been reported once previously
N
[15]
for a gold-catalyzed cycloaddition reaction.
elimination of AuL is expected to give (R)-(ꢀ)-4a with
Finally, the
+
a Z alkene functionality.
Encouraged by the success of the transformation with 8-
methylquinoline N-oxide, we sought new cycloaddition reac-
tions with an a-diazoester. No reaction occurred between
acetal 1a and ethyl diazoacetate (2 equiv) with [LAu](NTf2)
Table 2: Chirality-transfer experiments.
[
16]
(
L = PtBu (o-biphenyl); 5 mol%) in CH Cl (288C, 24 h);
2
2
2
instead, the a-diazoester decomposed completely to give
alkene 10 (93%; Table 3, entry 1).
Entry Ether (ee [%])
t [h] Product (yield [%], ee [%])
ꢀ
The NTf2 anion enhances the decomposition of the diazo
1
2
Ar=Ph, (+)-2a (94.1)
Ar=4-FC H , (+)-2c (85.3)
18 (ꢀ)-4a (78, 93.9)
20 (ꢀ)-4c (75, 83.0)
compound to alkene 10. With relatively acidic [LAu](SbF ),
6
6
4
ethyl 4-methoxy-1-naphthoate (5a) was obtained in 63%
yield in CH Cl (288C, 18 h; Table 3, entry 2). The yield of
2
2
3
Ar=4-MeOC H , (+)-2b (87.1) 20 (ꢀ)-4b (77, 75.2)
6
4
naphthalene derivative 5a was further improved to 75% in
(+)-7b (9, 33.6)
[
a]
Table 3: Gold-catalyzed cycloaddition with a diazo compound.
fluorophenyl derivative (R)-(+)-2c (85.3% ee), which was
converted into (R)-(ꢀ)-4c with 83% ee (Table 2, entry 2). In
contrast, a small loss of chirality was notable for the 4-
methoxyphenyl derivative (R)-(+)-2b (87.1% ee), which
gave (R)-(ꢀ)-4b with 75.2% ee (Table 2, entry 3). In this
case, we also obtained (R)-(+)-7b in 9% yield, albeit with low
enantioselectivity (33.6% ee); this side product is reported to
have the S configuration as a result of inversion of the
Entry Catalyst
Solvent
T
T
Compound
(yield [%] )
[
b]
[8C] [h]
1
2
3
[LAuCl]/AgNTf2 CH Cl
[LAuCl]/AgSbF
[LAuCl]/AgSbF
28
28
70
18
18
1a (91), 10 (93)
5a (63), 10 (18)
7.0 5a (75), 10 (trace)
2
2
2
[9a]
configuration, as shown by intermediate II in Equation (3).
6
CH
Cl
2
The cross-over experiment in Equation (4) supports an
intramolecular alkoxy shift; we postulate a plausible mech-
anism in Scheme 4. We envisage that 8-methylquinoline oxide
6
DCE
[
a] L=PtBu (o-biphenyl), [1a]=0.10m. [b] Product yields after purifica-
2
tion by silica-gel column chromatography are reported.
Angew. Chem. Int. Ed. 2013, 52, 7559 –7563
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7561