Enantioselective tandem radical reactions: vicinal difunctionalization in acyclic systems with control over relative and absolute stereochemistry.
Enantioselective tandem radical reactions: vicinal difunctionalization in acyclic systems with control over relative and absolute stereochemistry.
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DOI：
10.1002/chin.200205026
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发表时间：
2001-08
影响因子：
15
通讯作者：
M. Sibi;Jian-xie Chen
中科院分区：
文献类型：
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作者：
M. Sibi;Jian-xie Chen
自由基与烯烃加成后，加合物自由基可以被多种试剂捕获，例如烯丙基锡烷、CO、CdC、CdX 等，为形成多个 CC 键提供方便的方案。 1 这种类型的串联加成捕获反应对于在一次操作中建立两个 CC 键很有吸引力。加成和捕获步骤都可以是分子内或分子间的，并且串联的分子内和分子间自由基反应已经以各种创造性和有用的方式进行了测序。 2 已经报道了对映选择性自由基反应 3，其中 R4 或 β5 与羰基建立了立体化学。然而，目前还没有涉及非环系统的串联分子间加成-分子间捕获反应的例子，其中手性在β-和R-中心同时建立并控制绝对和相对立体化学。 6 这项工作报道了第一个例子，通过亲核自由基加成到烯醇酯 1 上，然后用烯丙基锡烷 2 捕获，以高度立体控制形成两个 CC 键 (eq 1)。此外，还描述了影响这些系统中 1, 2-非对映选择性 7 的因素。我们的工作始于将亲核异丙基自由基加成到肉桂酸酯 5 上，并使用手性路易斯酸用烯丙基锡烷捕获中间自由基。 （等式 2，表 1）。我们之前已经确定，双恶唑啉 6 与 Mg (II) 和 Zn (II) 盐是非常适合进行共轭自由基加成的手性路易斯酸。 5 使用化学计量量的 MgI2/6 在 78℃下与 5 进行加成/捕获反应，以优异的收率和高非对映选择性和对映选择性得到 7（条目 1）。产物7的相对立体化学被确定为抗（见下文）。将催化剂负载量减少至 30 mol% 导致
Following addition of a radical to an alkene, the adduct radical can be trapped by a variety of reagents, for example, allyl stannane, CO, CdC, CdX, and so forth, providing convenient protocols for the formation of multiple CC bonds. 1 Tandem addition-trapping reactions of this type are attractive for the establishment of two CC bonds in a single operation. Both the addition and trapping steps can be either intra-or intermolecular, and tandem intra-and intermolecular radical reactions have been sequenced in a variety of creative and useful ways. 2 Enantioselective radical reactions3 where stereochemistry has been established either R4 or β5 to a carbonyl group have been reported. However, at present there are no examples of tandem intermolecular addition-intermolecular trapping reactions involving acyclic systems where chirality is established at both β-and R-centers with control over both absolute and relative stereochemistry. 6 This work reports the first examples where two CC bonds are formed (eq 1) with high stereocontrol by nucleophilic radical addition to an enoate 1 followed by trapping with allyl stannane 2. Additionally, factors which influence 1, 2-diastereoselectivity7 in these systems are also described.Our work began with the addition of nucleophilic isopropyl radical to cinnamate 5 and trapping of the intermediate radical with allylstannane using a chiral Lewis acid (eq 2, Table 1). We have previously established that bisoxazoline 6 with Mg (II) and Zn (II) salts are very competent chiral Lewis acids for conjugate radical additions. 5 Addition/trapping reaction with 5 using a stoichiometric amount of MgI2/6 at-78 C gave 7 in excellent yield and high diastereo-and enantioselectivity (entry 1). The relative stereochemistry for the product 7 was established as anti (vide infra). Reducing the catalyst loading to 30 mol% led to