Tandem Radical‐Addition–Aldol‐Type Reaction of an α,β‐Unsaturated Oxime Ether
Tandem Radical‐Addition–Aldol‐Type Reaction of an α,β‐Unsaturated Oxime Ether
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DOI：
10.1002/ange.200502263
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发表时间：
2005-09
影响因子：
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通讯作者：
Masafumi Ueda;H. Miyabe;H. Sugino;O. Miyata;T. Naito*
中科院分区：
文献类型：
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作者：
Masafumi Ueda;H. Miyabe;H. Sugino;O. Miyata;T. Naito*
产率为97%，没有形成其它区域异构体（路径B或c）。这是第一个涉及四个亲电位置的共轭肟醚的区域选择性自由基加成的例子。通过粗产物的1H NMR光谱分析发现3a的非对映体纯度不低于97.5：2.5 dr。通过将加合物3a转化为真实的g-氨基酸4，确定新形成的立构中心处的绝对构型为S。[11]该反应的立体化学优先性可以合理化如下。关于（E）-1的构象，方案1中所示的反式（磺酰基和羰基）和顺式（羰基和C= C键）平面旋转异构体应优于其它旋转异构体。因此，烷基自由基加成到re（底部）面是有利的，推测是由于与磺酰基的轴向氧的空间相互作用。[6c]与此形成鲜明对比的是，使用二乙基锌作为自由基引发剂时没有形成乙基化产物3a（表1，条目2）。[12]在将仲烷基加成到（E）-1中时观察到高的非对映选择性和良好的化学产率（表1，条目3和4）。用体积大的叔丁基自由基获得较低的化学产率，但反应仍以高dr（> 97.5：2.5;表1，条目5）进行。这些观察结果表明，三乙基硼烷作为一种有效的试剂，用于捕获中间体烯胺自由基，形成硼烯胺2。
in 97% yield without formation of other regioisomers (paths b or c). This is the first example of a regioselective radical addition to a conjugated oxime ether that involves four electrophilic positions. The diastereomeric purity of 3a was found to be no less than 97.5: 2.5 dr by 1H NMR spectroscopic analysis of the crude product. The absolute configuration at the newly formed stereocenter was determined to be S by converting the adduct 3a into the authentic g-amino acid 4.[11] The stereochemical preference of this reaction can be rationalized as follows. With regard to the conformation of (E)-1, the anti (sulfonyl and carbonyl groups) and s-cis (carbonyl group and C= C bond) planar rotamer shown in Scheme 1 should be favored over other rotamers. Therefore, the alkyl-radical addition to the re (bottom) face is favored, presumably resulting from steric interactions with the axial oxygen of the sulfonyl group.[6c] In marked contrast, the ethylated product 3a was not formed with the use of diethylzinc as a radical initiator (Table 1, entry 2).[12] The high diastereoselectivities and good chemical yields were observed in the addition of secondary alkyl radicals to (E)-1 (Table 1, entries 3 and 4). A lower chemical yield was attained with a bulky tert-butyl radical, but the reaction still proceeded with high dr (> 97.5: 2.5; Table 1, entry 5). These observations indicate that triethylborane acts as an effective reagent for trapping the intermediate enaminyl radical to form the boryl enamine 2.