Facile and Efficient Enantioselective Hydroxyamination Reaction: Synthesis of 3-Hydroxyamino-2-Oxindoles Using Nitrosoarenes
Facile and Efficient Enantioselective Hydroxyamination Reaction: Synthesis of 3-Hydroxyamino-2-Oxindoles Using Nitrosoarenes
复制标题
简便高效的对映选择性羟基化反应：使用亚硝基芳烃合成 3-羟基氨基-2-羟吲哚
DOI：
10.1002/anie.201100758
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Feng, Xiaoming
中科院分区：
文献类型：
--
作者：
Shen, Ke;Liu, Xiaohua;Feng, Xiaoming
Nitroso compounds are interesting reagents that are used in synthetic organic chemistry mainly because of their application in functional group transformations.[1–2] Nitrosoarenes have been widely recognized as an attractive electrophile in catalytic asymmetric nitroso aldol reactions. Organocatalysts having hydrogen-bond donors such as amide or hydroxy groups were used to control the regioselectivity of the nitroso aldol reaction through hydrogen bonding to nitrogen or oxygen atoms of the nitrosoarene.[2] Usually, the aminoxylation reaction of carbonyl compounds proceeds to give αoxygenated compounds as the major products because of the higher basicity of the hydrogen bond between the nitrogen and the hydrogen atoms compared with that between the oxygen and hydrogen atoms.[3] In contrast, only a few contributions on the enantioselective hydroxyamination reaction through the electrophilic attack on the nitrogen group of the nitrosoarene have been reported to give α-amino compounds; the reports focused on α-branched aliphatic aldehydes,[4] enolates,[5a] cyclic ketones,[5b] and α-cyanopropionates.[6] However, it is still a challenge to control the chemoand enantioselectivity of the products by other methods, owing to the high reactivity of nitrosoarene. Oxindoles constitute an important structural motif in the library of natural products and biologically active drugs. Recently, Barbas and co-workers developed an asymmetric aminoxylation reaction of N-protected 3-substituted-2-oxindoles, thus delivering the desired O adducts (Figure 1a).[3b] The hydroxyamination reaction of oxindoles would provide access to optically active 3-amino oxindole derivatives,[7–8] which present common structural motifs in a variety of bioactive molecules such as NITD609 and SSR-149415, the drug candidates for the treatment of malaria and stressrelated disorders, respectively.[9] In view of this, a highly enantioselective synthesis of 3-hydroxyamino-2-oxindole is therefore considered to be in high demand. Such a reaction has been recently reported as being promoted by a cinchona alkaloid catalyst, but there is room for improvement in terms of enantioselectivity and efficiency.[7] Given our long-standing work in the development of catalysts derived from rare-earth metal/N, N’-dioxide complexes,[10] we envisioned that a rare-earth metal might coordinate with the oxygen atom of a nitrosoarene as a result of its strong oxygen affinity. The enolate would then preferentially attack the nitrogen atom of the nitroso group to provide direct access to enantioenriched hydroxyamino oxindoles (Figure 1b). Herein, we address these issues and describe a general, practical, and highly enantioselective hydroxyamination of N-unprotected 3-substituted-2-oxindoles with nitrosoarenes in up to 98% yield with 98% ee using a ScIII/N, N’-dioxide complex. Initially, owing to the importance of protecting-group-free synthetic strategies,[9d, 11] we probed the optimal reaction conditions using commercially available 3-methyl-2-oxindole (1a) and nitrosobenzene as model substrates. The hydroxyamination reaction was effectively promoted by a 1: 1 Sc (OTf) 3/L1 complex in CH3CCl3 at 308C, thus giving the N-nitroso aldol product 2 aa in 88% yield with 90% ee and trace amounts of the O-adduct 3 (Table 1, entry 1).[12] The absolute configuration of 2 aa was unambiguously determined to be R by comparision of the optical rotation with that of the known compound (Scheme 1). Ligands L2 and L3, which have less sterically hindered substituents at the phenyl ring, afforded less satisfactory results (Table 1, entries 2 and 3). Other rare-earth-metal sources, such as La (OTf) 3, Lu (OTf) 3, and Sm …
