Bi(OTf)3-Catalyzed Intramolecular Amination of Triazenylaryl Allylic Alcohols: A Stereoselective, High-Yield Synthesis of (E)-3-Alkenyl 2H-indazoles

Abstract An efficient Bi(OTf)3-catalyzed synthesis of 3-alkenyl-2-pyrrolidine-2H-indazoles from triazenylaryl allylic alcohols via the intramolecular direct amination process is reported. Compared with the dodecyl benzenesulfonic acid (DBSA)-catalyzed method, the new method is more efficient and gives greater yields and functionality tolerance. Additionally, the 3-alkenyl-2-pyrrolidine-2H-indazoles can be transformed to a series of new products under different reaction conditions. GRAPHICAL ABSTRACT


RESULTS AND DISCUSSION
Initially, we treated the substrate 1a with BF 3 .OEt 2 (5 mol%) in CH 2 Cl 2 , leading to the formation of the desired 2H-indazoles 2a in 64% yield (Table 1, entry  1). Upon treating the substrate 1a with CuBr (5 mol%) in CH 2 Cl 2 , the starting material was recovered in 95% yield and a trace of the desired 2H-indazole compound was obtained (entry 2). To our delight, further examination on InCl 3 and FeCl 3 resulted in improved yields of 71% and 74%, respectively (entries 3 and 4). Using BiCl 3 as the Lewis acid catalyst, the yield of the desired product 2a decreased to 13% (entry 5). When the reaction was carried out using Bi(OTf) 3 as the catalyst in CH 2 Cl 2 , the yield increased to 94%. Thus the best result was obtained when the reaction was carried out in CH 2 Cl 2 at room temperature using Bi(OTf) 3 as the catalyst (entry 6).
With the optimized conditions in hand, a variety of triazenylaryl allylic alcohols 1 were examined, and the results are summarized in Table 2. Compared with catalyst DBSA, Bi(OTf) 3 gave greater yields in most cases, as indicated by the last two columns of Table 2. Particularly, the formerly inadaptable substrates 1c and 1d were successfully converted to the corresponding 2H-indazoles (Table 2, 66-68%, entries 2 and 3). The electron property at the aryl triazene moiety significantly influenced the outcome of the reaction: The yields of the 2H-indazoles increased sharply from trace to 95% as stronger electron-withdrawing groups (entries 1-4, Table 2) were directed to the aryl triazene motif. The electronic identity of the benzyl alcohol substituents also influenced the yield of the transformation: The yield surged to 90%, when using OCH 3 (entry 5) instead of H (entry 4) on the benzyl alcohol moiety for the substrates 1e and 1f. Substrates with electron-donating substituents such as CH 3 (90%, entry 12), OCH 3 (92-96%, entries 13 and 14), and dimethyl Bi(OTf) 3

(5) 94
a All reactions were carried out with 3-aryl triazenylaryl allylic alcohol 1a (0.5 mmol) and catalyst in DCM (2 mL) at room temperature for 12 h. b Yield of the isolated product after flash column chromatography.
b Yield of the isolated product of Bi(OTf) 3 -catalyzed reaction after flash column chromatography. Bi(OTf) 3 in dicholoromethane (DCM) for 12 h, substrates with ester, cyano, and naphthyl groups were all converted to the corresponding 3-alkenyl-2-pyrrolidine-2H-indazoles in good to excellent yields (Scheme 2).
On the basis of these mentioned results, a plausible reaction mechanism for this process is depicted in Scheme 3. The interaction between the hydroxy group of triazenylaryl allylic alcohol 1=triazene cinnamyl alcohol 3 and the Lewis acid Bi(OTf) 3 led to the activation of the hydroxy and formed the intermediate cation 4=5, which lost HOBi(OTf) 2 to form allylic carbocation 6. Intramolecular nucleophilic attack of allylic carbocation 6 by nitrogen on the triazene motif provided the intermediate cation 7, which underwent deprotonation to generate the product 3-alkenyl-2pyrrolidine-2H-indazole 2.

Bi(OTf) 3 -CATALYZED SYNTHESIS OF 2H-INDAZOLES
intramolecular direct amination process using Bi(OTf) 3 catalysis in DCM has been developed. Additionally, the 3-alkenyl-2-pyrrolidine-2H-indazoles can be further transformed to a series of new products under different reaction conditions. Scheme 3. Plausible reaction mechanism for this reaction. Further investigations of the reaction mechanism and synthetic applications are under way.

EXPERIMENTAL
Typical Procedure for the Synthesis of 3-Alkenyl-2-pyrrolidine-2H-indazoles 2 from Triazenylaryl Allylic Alcohols 1 Bi(OTf) 3 (17 mg, 0.025 mmol) was added to a solution of triazenylaryl allylic alcohol 1 (0.5 mmol) in DCM (2 mL). The reaction mixture was stirred at room temperature for 12 h. Ethyl acetate and water were added, and the resulting mixture was extracted with ethyl acetate. The organic fractions were dried over Na 2 SO 4 , concentrated in vacuo, and purified by silica-gel chromatography to provide the 3-alkenyl-2-pyrrolidine-2H-indazoles 2.

FUNDING
We are thankful for financial support from the National Nature Science Foundation of China (21272003), as well as the Science Foundation of Zhejiang Sci-Tech University (Grant Nos. 1206820-Y and 1206821-Y).

SUPPORTING INFORMATION
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