Angewandte
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Chemie
Table 2: Scope of the 7-azabenzonorbornadienes.[a]
it is readily available and the N-atom could stabilize the
cation generated in the rearrangement (Scheme 2; for details,
see the Supporting Information). Using a catalyst system
consisting of [Cp*Rh(CH3CN)3](SbF6)2 (5 mol%) and
NaOAc (1.0 equiv) in CH3CN gave a promising 70% of the
product 3a. The structure of 3a was determined by single-
crystal X-ray diffraction,[16] which is consistent with the
involvement of a Wagner–Meerwein-type rearrangement in
the reaction sequence. Changing the solvent to CH2Cl2 led to
nearly quantitative yield. However, lowering the RhIII catalyst
loading to 0.5 mol% decreased the yield considerably owing
to low conversion. Next, a survey of possible additives showed
that the addition of AgOAc (20 mol%) was optimal, and the
product could be isolated in 82% yield, which highlights the
efficiency of the system.
With the optimized reaction conditions in hand, the
generality of this reaction was explored (Table 1, all cases
tested are shown).[10] To our delight, N-phenoxyacetamides
bearing both electron-withdrawing and electron-donating
substituents at different positions reacted smoothly with
substrate 2a. The corresponding products were isolated in 52–
95% yield using 0.5 mol% catalyst in majority of cases. For
unsymmetrical substrates, such as meta-substituted and meta,
para-disubstituted N-phenoxyacetamides, the reactions
[a] Reactions were carried out using 1a (0.24 mmol), 2 (0.2 mmol), [Rh]
(0.5 mol%), NaOAc (1.0 equiv), and AgOAc (20 mol%) in CH2Cl2
(0.5 mL) at 608C for 12 h. [b] 5.0 mol% catalyst loading.
dienes with a completely substituted benzene ring, as well as
benzannulated substrates were also all tolerated, affording
the corresponding products 3p–r. Moreover, changing the
protecting group to mesyl (Ms), and tert-butyloxycarbonyl
(Boc) gave the products 3s and 3t in good yield. However,
using the olefin with acetyl (Ac) on the N-atom only gave
trace product as a result of the low conversion. The reaction
with 7-oxabenzonorbornadiene as the partner gave a complex
reaction mixture, possibly owing to the reduced stabilization
of the rearranged cation by the oxygen rather than nitrogen
atom. Further, the tosyl group in 3a could be removed
smoothly, affording the product 4 in 75% yield [Eq. (1)].
À
showed excellent selectivity for the C H bond with less
steric hindrance, delivering products 3g–j in moderate to
good yields. Additionally, ortho-substituted and benzannu-
lated substrates were tolerated, giving the corresponding
products 3k and 3l.
On the basis of these results, we further investigated the
scope of the 7-azabenzonorbornadienes 2. As shown in
Table 2, 7-azabenzonorbornadienes with both electron-donat-
ing and electron-withdrawing groups on the arene performed
well, affording the corresponding products (3m–o) in yields
between 54% and 87%. In addition, 7-azabenzonorborna-
To gain insight into the mechanism, a series of experi-
ments was performed (Scheme 3). A stable cyclometalated
RhIII complex A was obtained upon treatment of substrate 1a
with [RhCp*Cl2]2. This species (2.0 mol%) was shown to be
an active catalyst for the coupling of 1a with 2a, giving 3a in
83% yield (Scheme 3a). However, a stoichiometric reaction
of complex A with 2a failed to afford any of the desired
product 3a, suggesting that product formation requires an
Table 1: Scope of the N-phenoxyacetamides.[a]
À
additional species generated from the C H activation step
(Scheme 3b). Indeed, the stoichiometric reaction with HOAc
as the additive afforded the product 3a in 71% GC yield.
These results suggested that the intermediate A is most likely
involved in the catalytic cycle, and that HOAc, generated in
the formation of rhodacycle, is essential for product forma-
tion. Next, 1a was subjected to the Rh-catalyzed reaction in
CH2Cl2/D2O (5:1) in the presence of 2a for a short time and
no deuterium incorporation was observed in either residual
1a or product 3a. This result illustrates that the cyclometa-
lation step is irreversible under the reaction conditions (see
the Supporting Information). No kinetic isotope effect was
observed (KIE, kH/kD = 1.0) for two separate parallel reac-
tions with 1a and 1a–d5 at room temperature, suggesting that
[a] Reactions were carried out using 1 (0.24 mmol), 2a (0.2 mmol), [Rh]
(0.5 mol%), NaOAc (1.0 equiv), and AgOAc (20 mol%) in CH2Cl2
(0.5 mL) at 608C for 12 h. [b] 2.0 or 5.0 mol% catalyst loading, see the
Supporting Information.
À
the C H bond cleavage is likely not involved in the rate-
determining step.[11] Moreover, the reaction of 1a with 2a was
2
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Angew. Chem. Int. Ed. 2016, 55, 1 – 5
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