Angewandte
Chemie
À
Scheme 1b. As a continuation of our interest in the C H bond
functionalization with metal–carbenes, we herein report
III
À
a Rh -catalyzed C H bond activation of N-phenoxyaceta-
mides with N-tosylhydrazones or diazo compounds (Sche-
me 2c). This reaction explores the oxidizing directing group,
À
which contains an N O bond and has recently been devel-
oped by Liu, Lu, and co-workers.[16] The reaction provides an
efficient and mild method for the synthesis of ortho-alkenyl
phenols[17] with good yields and broad substrate scope.
At the outset of this study, N-phenoxyacetamide (1a) and
N-tosylhydrazone (2a) were used as the substrates to
optimize the reaction conditions. Thus, 1a (1 equiv) and 2a
(1 equiv) were treated with [Cp*RhCl2]2 (1.0 mol%), Cs2CO3
(1 equiv), and CsOAc (1 equiv) in toluene at 908C for 16 h. To
our delight, the expected product 3a was obtained in 23%
yield under the initial conditions (Table 1, entry 1). Screening
Table 1: Optimization of the reaction conditions.[a]
Scheme 3. Scope of N-tosylhydrazones. Reaction conditions: 1a
(0.30 mmol), 2a–r (0.30 mmol), [Cp*RhCl2]2 (2.5 mol%), LiOtBu
(1.0 equiv), and NaOAc (1.0 equiv) in toluene (3 mL) at 908C for 16 h.
[a] Reaction was conducted at 1008C.
Entry
Base
Additive
Solvent
Yield [%][b]
1
2
3
4
Cs2CO3
Cs2CO3
Cs2CO3
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
CsOAc
CsOAc
CsOAc
CsOAc
NaOAc
CsOAc
none
NaOAc
KOAc
AgOAc
toluene
MeCN
23
trace
trace
63
56
68
72
83
80
0
products in good to excellent yields, while the reaction with
electron-rich substrates was sluggish under the standard
conditions and an elevated reaction temperature was required
(Scheme 3, 3 f, 3h, and 3n). The N-tosylhydrazone 2e, which
bears an ortho substitutent, was a poor substrate for this
reaction, and the corresponding product 3e was obtained in
only 14% yield. The decreased yield of product 3e presum-
ably resulted from steric hindrance. It is notable that multiply
substituted and polycyclic aromatic substrates 2m and 2n,
respectively, were also tolerated to give the corresponding
products 3m and 3n in 71% and 66% yields, respectively. A
heteroaryl-bearing N-tosylhydrazone also worked well in the
reaction, but gave the corresponding product in a diminished
yield (Scheme 3, 3o). It should be noted that this method is
not restricted to the synthesis of terminal olefins; trisubsti-
tuted olefins, such as 3p, 3q, and 3r, were also prepared in
good yields under the same reaction conditions.[19]
(CH2Cl)2
toluene
toluene
toluene
toluene
toluene
toluene
toluene
5
6[c]
7[c]
8[c]
9[c]
10[c]
[a] Reaction conditions: 1a (0.20 mmol), 2a (0.20 mmol), [Cp*RhCl2]2
(1.0 mol%), base (1 equiv), and additive (1 equiv) in solvent (2 mL) at
908C for 16 h. [b] Yields of isolated products. [c] [Cp*RhCl2]2 (2.5 mol%)
was used.
of solvents indicated that toluene was optimal, while the other
two solvents, MeCN and (CH2Cl)2, only afforded trace
amount of the desired product (Table 1, entries 2 and 3).
When Cs2CO3 was replaced with LitOBu, the yield increased
to 63% (Table 1, entry 4).[18] Replacing CsOAc with NaOAc
gave a comparable yield (Table 1, entry 5). Product 3a was
obtained with an improved yield when the catalyst loading
was increased to 2.5 mol% (Table 1, entry 4 vs. entry 6).
Finally, other acetate additives were examined, showing that
NaOAc was suitable for this reaction (Table 1, entry 8). No
product formation was observed when AgOAc was employed
as the additive (Table 1, entry 10).
With the optimized conditions established, the scope of
the N-tosylhydrazones was first examined. A variety of aryl
ketone N-tosylhydrazones with meta or para substituents on
the aromatic ring were reacted smoothly with N-phenoxya-
cetamide, affording the desired ortho-alkenyl phenols in good
to excellent yields (3b–d, f–l). N-Tosylhydrazones with
electron-deficient substituents on the aryl moiety were
suitable for this transformation, affording the corresponding
Next, the scope of N-phenoxyacetamides was examined in
this reaction (Scheme 4). The methyl-substituted substrates
1b–d afforded the corresponding products 3s–u in good
yields, regardless of the position of the substituents on the
aromatic ring. Notably, in the case of a meta-substituted
À
substrate, 3t was isolated as the sole product, in which the C
H bond activation occurred in para position to the methyl
group, thus suggesting that the direct ortho alkenylation
occurs at the less-hindered site.[16] However, when N-(3-
bromophenoxy)acetamide (1h) was subjected to the reaction,
two regioisomers were isolated (Scheme 4, 3y:3y’ = 3:1). The
reaction does not seem to be sensitive to the electronic effects
of the substituents (Scheme 4, 3v–x).
Encouraged by the successful coupling of N-tosylhydra-
zones with N-phenoxyacetamide, we then proceeded to
extend this transformation to diazoesters. However, when
Angew. Chem. Int. Ed. 2014, 53, 1364 –1367
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1365