Organic Letters
Letter
protonic solvent MeOH was not effective for this annulation
(Table 1, entries 5 and 7 vs entry 8). It was noteworthy that
the moisture in the solvent can significantly deteriorate the
cyclization efficiency (Table 1, entry 5 vs entry 9). In addition,
other factors such as the stoichiometry of reagents and reaction
temperature were also investigated (Table 1, entries 10 and
11), revealing that 1.5 equiv of MDF and 70 °C were the best
conditions for the desired transformation. Therefore, the
condition of entry 5 in Table 1 was eventually chosen for the
preparative runs described hereafter.
In order to evaluate the functional group tolerance and
substrate scope of this methodology, a large variety of
structurally and electronically diverse aryl nitriles were
examined under the optimized reaction conditions as collected
in Scheme 2. In addition, the research results revealed that
94%−98%). Notably, the 4-iodobenzonitrile (2i) also ex-
hibited satisfying efficiency when increasing the loading of
MDF (1) to 2.0 equiv. Three versatile synthons of the SuFEx
chemistry resident in the aryl nitriles remained intact during
this annulation reaction, including aryl fluorosulfate (OSO2F,
3l), ethenesulfonyl fluoride (ESF, 3m), and aryl sulfonyl
fluoride (ArSO2F, 3n). Besides, the position of substituents on
the aromatic rings exhibited little influence on the efficiency.
The steric hindered nitrile (2r) accomplished its trans-
formation with comparable yield to its para- or meta-
substituted analogues (3r vs 3b and 3o). To our delight, the
multisubstituted nitriles were also smoothly converted to their
oxazole products under the identical conditions (3t−3w).
Considering the optical ability of polycyclic molecules and
applications of oxazole skeleton in fluorescent materials,1 2-
naphthalene nitrile and 9-anthracene nitrile were also tested
and furnished their final products 3x and 3y with isolated
yields of 81% and 82%, respectively. The heteroaromatic
substrates containing O, S, and N atoms also turned out to be
suitable starting materials, resulting in good to excellent yields
(3z−3ab, 77%−99% yields). The Ts-protected indole moiety
was compatible with this reaction system as well, albeit a
moderate yield of 3ac was obtained. Remarkably, a scale-up
reaction of MDF (1) and benzonitrile (2a) was also conducted
providing 96% isolated yield of target product 3a, which
demonstrated the excellent practicability of our developed
method for construction of 4-sulfonylfluoride-substituted
oxazoles.
a,b
Scheme 2. Substrate Scope Using Aryl Nitriles
The subsequent exploration demonstrated that this catalytic
system was also suitable for cyclizing allylic, propargylic, and
aliphatic nitriles with MDF (1), generating the corresponding
poly-substituted SO2F-functionalized oxazoles (Scheme 3, 5a−
Scheme 3. Scope of Converting Allylic, Propargylic, and
a,b
Aliphatic Nitriles to Oxazoles
a
Reaction conditions: aryl nitrile (2, 0.5 mmol, 1.0 equiv), MDF (1,
137 mg, 0.75 mmol, 1.5 equiv), Rh2(OAc)4 (2 mol %, 4.5 mg) and
b
anhydrous CHCl3 (4.0 mL), reflux (70 °C), 12 h. Isolated yields.
c
d
The reaction was conducted on a 5 mmol scale (2a, 516 mg). MDF
a
(1, 182 mg, 1.0 mmol, 2.0 equiv) was used.
Reaction conditions: nitrile (4, 0.5 mmol, 1.0 equiv), MDF (1, 137
mg, 0.75 mmol, 1.5 equiv), Rh2(OAc)4 (2 mol %, 4.5 mg) and
b
anhydrous CHCl3 (4.0 mL), reflux (70 °C), 12 h. Isolated yields.
c
most of the substrates afforded their corresponding cyclization
products in high to excellent yields, regardless of the nitriles
functionalized with electron-donating (methyl, phenyl, and
ether group) or electron-withdrawing (halogen, ester group,
trifluoromethyl, and trifluoromethoxy) substituents on the
aromatic rings. Note that the transformation proceeded
smoothly without any obvious influence caused by electronic
factors (e.g., 3d vs 3k and 3r vs 3s). In addition, this reaction
system provided an effective synthesis of silicon ether and
sulfonyl fluoride simultaneously containing oxazole molecule
(3e), which can be an interesting unit for polymer chemistry.
The halogen substituents were well-accompanied and delivered
expected products with excellent yields (3f−3h, yields of
MDF (1, 274 mg, 3.0 equiv) and Rh2(OAc)4 (5 mol %, 11 mg) were
used.
5g) in pleasing yields (76%−97%). The reactions of allylic
nitriles adjacent to long aliphatic chain (4a) or phenyl (4b)
both worked well with 100% retention of E-configuration. In
addition, the 5-methoxy-2-(phenylethynyl)oxazole-4-sulfonyl
fluoride (5c) was readily accessible in quantitative yield by
using propargylic nitrile (4c) as the cyclization partner. As for
alicyclic nitrile 4f, the steric hindrance of cyclohexane structure
frustrated the anticipated transformation obviously, leading to
only a 76% yield of oxazole 5f. Besides, the nitrile 4g
containing two reaction sites was also successfully bifunction-
C
Org. Lett. XXXX, XXX, XXX−XXX