Chiral phosphoric acid catalyzed enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes:: Cooperative effect of 3 Å molecular sieves
Chiral phosphoric acid catalyzed enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes:: Cooperative effect of 3 Å molecular sieves
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DOI：
10.1002/anie.200800770
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Akiyama, Takahiko
中科院分区：
文献类型：
--
作者：
Itoh, Junji;Fuchibe, Kohei;Akiyama, Takahiko
吲哚与硝基烯烃的Friedel-Crafts烷基化反应[1]是制备吲哚生物碱等生物活性化合物的最重要的碳-碳键形成反应之一。[2]虽然已经报道了几种手性催化剂，包括salen/AlCl络合物，[3a]双（磺酰胺）化合物，[3b]含硫脲结构，[3c，f]和Zn II或Cu II-双恶唑啉络合物，[3d，e，g]，但对映选择性并不总是令人满意的。近年来，新的布朗斯特酸催化剂被开发出来并用于许多不对称反应中，[4]并且由（R）-联二醇（联二醇= 2，2 '-二羟基-1，1'-联萘）衍生的手性磷酸作为对映选择性反应的通用有机催化剂已经被广泛研究。[5-7]迄今为止报道的大多数磷酸催化反应涉及亚胺或亚胺鎓离子亲电体，然而，存在包括羰基化合物[8a，B，9 h，j]氮杂环丙烷[8 c]或硝酮作为亲电体的分散实例。[8d]手性磷酸催化剂对其他亲电试剂的应用是令人期望的，并且通过使用手性磷酸将亲核试剂对映选择性加成到硝基烯烃上以前还没有报道。本文描述了第一个手性磷酸催化的吲哚[9]与硝基烯烃的傅-克烷基化反应，以优异的对映选择性得到傅-克加合物（方案1）。在苯/1，2-二氯乙烷（1：1）体系中，手性磷酸（R）-3对吲哚1a与硝基烯烃2a（2当量）的Friedel-Crafts烷基化反应具有最好的对映选择性。虽然该体系导致形成具有良好对映选择性的Friedel-Crafts加合物4a，
The enantioselective Friedel–Crafts alkylation [1] of indoles with nitroalkenes is one of the most important carbon–carbon bond-forming reactions for the preparation of biologically active compounds such as indole alkaloids.[2] Although several chiral catalysts, including salen/AlCl complexes,[3a] bis (sulfonamide) compounds,[3b] thiourea-contaning structures,[3c, f] and ZnII or CuII–bisoxazoline complexes,[3d, e, g] have been reported for the reaction, the enantioselectivities are not always satisfactory. The development of more efficient catalysts is required.Recently, novel Brønsted acid catalysts were developed and used in a number of asymmetric reactions,[4] and the chiral phosphoric acids derived from (R)-binol (binol= 2, 2’-dihydroxy-1, 1’-binaphthyl) have been extensively studied as versatile organocatalysts for enantioselective reactions.[5–7] Most of the phosphoric acid catalyzed reactions reported so far involve imine or iminium ion electrophiles, however, there are scattered examples that include carbonyl compounds [8a, b, 9h, j] aziridines,[8c] or nitrones as electrophiles.[8d] The application of chiral phosphoric acid catalysis to other electrophiles is desirable, and the enantioselective addition of a nucleophile to a nitroalkene by using a chiral phosphoric acid has not previously been reported. We describe herein the first chiral phosphoric acid catalyzed Friedel–Crafts alkylation of indoles [9] with nitroalkenes to afford Friedel–Crafts adducts in excellent enantioselectivities (Scheme 1). Chiral phosphoric acid (R)-3 provided the best enantioselectivity in the Friedel–Crafts alkylation of indole 1a with nitroalkene 2a (2 equiv) in benzene/1, 2-dichloroethane (1: 1) at À358C. Although the system resulted in the formation of Friedel–Crafts adduct 4a with good enantioselectivity, the