Phosphine-Catalyzed Rauhut-Currier Domino Reaction: A Facile Strategy for the Construction of Carbocyclic Spirooxindoles Skeletons
Phosphine-Catalyzed Rauhut-Currier Domino Reaction: A Facile Strategy for the Construction of Carbocyclic Spirooxindoles Skeletons
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膦催化的 Rauhut-Currier 多米诺反应：构建碳环螺吲哚骨架的简便策略
DOI：
10.1002/asia.201300650
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发表时间：
2013-09-01
影响因子：
4.1
通讯作者：
Huang, You
中科院分区：
文献类型：
--
作者：
Hu, Chongchong;Zhang, Qinglong;Huang, You
Spirocyclic oxindoles are privileged building blocks that occur frequently in many natural products and biologically active molecules.[1, 2] Their derivatives could also be used as versatile synthetic intermediates, with simple and flexible synthetic routes that allow the production of large chemical libraries of potential bioactive molecules.[3] For example, the most notable oxindole derivatives Paraherquamide A (see Figure 1),[4] isolated from cultures of Pennicillium paraherquei, has displayed potent antiparasitic activity and antinematodal properties.[5] As a result, numerous synthetic strategies have been developed to gain access to different varieties of heteroatom spirooxindole scaffolds,[6] especially for the preparation of spiro-azaheterocycles [7] and spiro-oxaheterocycles.[8] In contrast, few efforts so far have been focused on the strategy for spiro-fused carbocyclic frameworks (see Scheme 1).[9] In most cases, both the catalysts and substrates are not easily prepared, and the applicability of these methodologies is further limited by poor chemoselectivity. Therefore, a convenient and efficient method for the construction of functionalized carbocyclic spirooxindoles skeleton is in great demand.The Rauhut–Currier (RC) reaction is an efficient method that creates a new CÀC bond.[10] As part of our interest in tandem and domino reactions, our group has successfully constructed cyclohexene and heterocyclic compounds through intermolecular RC domino reaction.[11] Using these pioneering studies and our studies on phosphine-catalyzed domino reactions as a basis, we found the diverse reactivity of conjugated diene and realized a tunable intermolecular RC domino reaction leading to two distinct bicyclic skeletons.[12] In further investigations, we realized the construction of monocyclic skeletons with conjugated diene.[13] Inspired by these studies, we envisaged that if the reaction is carried out using conjugated diene and an exocyclic double bond, there is a possibility to obtain functionalized spirofused carbocyclic skeletons. Herein, we reported a phosphine-catalyzed RC domino reaction between conjugated diene and methyleneindolinones for the construction of highly functionalized spirooxindoles skeletons. This strategy led to molecules containing three chiral centers, one of them a quaternary carbon center, in a single step. We initiated the investigation between conjugated diene [14](1a) and methyleneindolinones [7d](2a) using PBu3 as the catalyst in CHCl3 (4 mL) at room temperature. The reaction proceeded smoothly and afforded the desired product in moderate yield. The result inspired us and demonstrated that our design is feasible. In the screening of phosphine catalysts, the more nucleophilic catalyst PMe3 led to lower yield, and no product was obtained when using less nucleophilic catalysts, such as PPh3, PPh2Et, LBBA-1,
