Catalytic asymmetric synthesis of quaternary carbons bearing two aryl substituents. Enantioselective synthesis of 3-alkyl-3-aryl oxindoles by catalytic asymmetric intramolecular Heck reactions
Catalytic asymmetric synthesis of quaternary carbons bearing two aryl substituents. Enantioselective synthesis of 3-alkyl-3-aryl oxindoles by catalytic asymmetric intramolecular Heck reactions
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DOI：
10.1021/ja034525d
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发表时间：
2003-05-21
影响因子：
15
通讯作者：
Weiss, MM
中科院分区：
文献类型：
--
作者：
Dounay, AB;Hatanaka, K;Weiss, MM
已开发出涉及三个连续钯 (0) 催化反应的实用序列，用于合成高对映体纯度的 3-烷基-3-芳基吲哚。 Heck环化前体10和11a-k是通过2'-三氟甲磺酸基-(,Z)-2-甲锡烷基-2-丁烯酰苯胺9与芳基或杂芳基碘化物的化学选择性Stille交叉偶联一步生成的。该序列的关键催化不对称 Heck 环化步骤使用源自 Pd(OAc)(2) 的 Pd-BINAP 催化剂以高产率和高对映选择性 (71-98% ee) 进行，构建含有二芳基取代的全碳季碳中心的羟吲哚。可以通过这种方式在羟吲哚的 C3 处引入多种芳基和杂芳基取代基，包括具有相当大空间体积的取代基（表 4）。迄今为止遇到的唯一限制是含有邻硝基或碱性胺官能团的芳基取代基和庞大的N-烷基-7-氧吲哚基。在C2处具有邻-(N-乙酰基-N-苯甲基氨基)苯基取代基的布烯内酯22的不对称Heck环化以高产率和高对映选择性提供了类似于1:1的酰胺阻转异构体23和24的混合物。这些阻转异构体是在 22 在 80 ℃ 下进行 Heck 环化时直接形成的，因为它们在此温度下仅发生很小程度的热互变。
A practical sequence involving three consecutive palladium(0)-catalyzed reactions has been developed for synthesizing 3-alkyl-3-aryloxindoles in high enantiopurity. The Heck cyclization precursors 10 and 11a-k are generated in one step by chemoselective Stille cross-coupling of 2'-triflato-(,Z)-2-stannyl-2-butenanilide 9 with aryl or heteroaryl iodides. The pivotal catalytic asymmetric Heck cyclization step of this sequence takes place in high yield and with high enantioselectivity (71-98% ee) with the Pd-BINAP catalyst derived from Pd(OAc)(2) to construct oxindoles containing a diaryl-substituted all-carbon quaternary carbon center. A wide variety of aryl and heteroaryl substituents, including ones of considerable steric bulk, can be introduced at C3 of oxindoles in this way (Table 4). The only limitations encountered to date are aryl substituents containing ortho nitro or basic amine functionalities and the bulky N-alkyl-7-oxindolyl group. Asymmetric Heck cyclization of butenalide 22 having an o-(N-acetyl-N-benzylamino)phenyl substituent at C2 provided a similar to1:1 mixture of amide atropisomers 23 and 24 in high yield and high enantioselectivity. These atropisomers are formed directly upon Heck cyclization of 22 at 80 degreesC, as they interconvert thermally to only a small extent at this temperature.