Nitrogen pronucleophiles in the phosphine-catalyzed gamma-addition reaction
Nitrogen pronucleophiles in the phosphine-catalyzed gamma-addition reaction
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DOI：
10.1021/jo970848e
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发表时间：
1997-08-22
影响因子：
3.6
通讯作者：
Dake, GR
中科院分区：
文献类型：
--
作者：
Trost, BM;Dake, GR
亲核物质与 R1-不饱和体系的碳的共轭加成是有机合成化学中的基本概念。 1 如果我们能够改变迈克尔受体的反应性，从而可以避免 1, 4 加成，而有利于其他有用的转化，那么合成设计将会发生重大改进。我们发现膦能够诱导碳和氧亲核试剂添加到炔酸酯的 4 位上，这促使我们用氮基亲核试剂测试这种新的反应范例（方程式 1）。 2, 3 尽管我们之前取得了成功，但人们担心共轭加成中氮的优异供体特性会导致不需要的迈克尔加成产物（路径 a），这与膦催化过程介导的 γ 加成相反（路径 b）。然而，我们发现，在我们的膦催化条件下，迈克尔加成过程完全被颠覆，有利于各种氮亲核试剂（包括异羟肟酸酯）所需的歧管，从而提供了进入三肽结构模拟物的入口。为了测试这些过程的可行性，使用我们的膦催化系统，2-丁酸甲酯（1）与许多氮亲核试剂反应，该系统还涉及通用酸碱催化剂（eq） 2）。例如，1与对甲苯磺酰胺与50%乙酸和50%乙酸钠的等摩尔混合物使用10%三苯基膦(tpp)在甲苯中在90℃下产生加合物2a，收率72%。 4 通过 1H NMR 谱中新烯属共振的存在，清楚地确定了化合物 2a 的结构 [(δ 6.75 (dt, J) 15.7, 5.2 Hz, 1H)； 5.94（dt，J）15.7，1.86赫兹，1H）]。使用 5% 的双齿膦双（二苯基膦）甲烷 (dppm) 或 1, 2-双（二苯基膦）乙烷 (dppe) 作为催化剂，回收率分别低得多，分别为 2%、28% 和 39%。使用较大量（15%）的1, 3-双（二苯基膦）丙烷（dppp）与乙酸乙酸钠催化1与邻苯二甲酰亚胺或四氢邻苯二甲酰亚胺3的缩合，分别产生88%和57%（81% brsm）的化合物2b和2c。
The conjugate addition of nucleophilic species to the-carbon of R,-unsaturated systems is a fundamental concept in synthetic organic chemistry. 1 A significant improvement in synthetic design would occur if we could alter the reactivity of Michael acceptors so that 1, 4 addition could be circumvented in favor of other useful transformations. Our discovery of phosphine’s ability to induce addition of carbon and oxygen pronucleophiles to the 4-position of alkynoates led us to test this new reactivity paradigm with nitrogen-based nucleophiles (eq 1). 2, 3 Despite our previous successes, a fear existed that the excellent donor properties of nitrogen in conjugate additions would result in undesired Michael addition products (path a), as opposed to γ-addition mediated by the phosphine-catalyzed process (path b). However, we have found that under our phosphine-catalyzed conditions Michael addition processes are entirely subverted in favor of the desired manifold with a variety of nitrogen nucleophiles, including hydroxamic acid esters, providing an entry into tripeptide structural mimics.In order to test the feasibility of these processes, methyl 2-butynoate (1) was reacted with a number of nitrogen pronucleophiles using our phosphine catalysis system, which also involves a general acid-base catalyst (eq 2). For example, an equimolar mixture of 1 with p-toluenesulfonamide with 50% acetic acid and 50% sodium acetate using 10% triphenylphosphine (tpp) in toluene at 90 C produced the adduct 2a in 72% yield. 4 The structure of compound 2a is clearly established by the presence of the new olefinic resonances in the 1H NMR spectrum [(δ 6.75 (dt, J) 15.7, 5.2 Hz, 1H); 5.94 (dt, J) 15.7, 1.86 Hz, 1H)]. The use of 5% of the bidentate phosphines bis (diphenylphosphino) methane (dppm) or 1, 2-bis (diphenylphosphino) ethane (dppe) as catalyst led to a much lower recovery of 2, 28% and 39%, respectively. The use of a larger amount (15%) of 1, 3-bis (diphenylphosphino) propane (dppp) with acetic acidsodium acetate catalyzed the condensation of 1 with phthalimide or tetrahydrophthalimide 3 yielding compounds 2b and 2c in 88% and 57%(81% brsm), respectively.