Selective intermolecular amination of C-H bonds at tertiary carbon centers.
Selective intermolecular amination of C-H bonds at tertiary carbon centers.
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DOI：
10.1002/anie.201304238
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发表时间：
2013-10-18
期刊：
影响因子：
--
通讯作者：
Du Bois J
中科院分区：
文献类型：
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作者：
Roizen JL;Zalatan DN;Du Bois J
通过叔C2 H4键的分子间胺化制备四取代胺衍生物仍然是方法开发中的突出挑战，因为这种技术对简化合成具有吸引力（图1）。[1，2]虽然存在少量的报道，其中已经证明了该反应，但几乎所有的实施例都需要超化学计量的底物。[3]由于最近的见解，通过机制的研究，我们现在报告的一般方法叔C-H中心的选择性胺化。[4]该反应操作简单，耐受大多数常见的官能团，并提供易于释放的受保护的胺。不同氮源对产物选择性的影响也被强调沿着与暗示空间效应作为位点选择性的主要决定因素的机理研究。我们最近提供的证据表明，四羧酸二铑催化剂[Rh 2（esp）2][5]在进行C-H胺化反应条件下，经历竞争性单电子氧化，生成红色的混合价Rh 2 +/Rh 3+二聚体。[4，6]偶然地，该物质在反应条件下被tBuCO 2 H还原，tBuCO 2 H是用于驱动胺化事件的高价碘氧化剂的副产物。[4a]我们对这一过程的理解导致了反应条件的修改，包括PhMe 2CCO 2 H，一种羧酸添加剂，作为一种有效的还原剂，并提供了改进的催化剂周转数在分子间胺化反应的苄基底物。[4a然而，将这些条件应用于苯甲酸异戊酯1（1.0当量）的氧化仅除去少量所需的胺2（图2）。对1的氧化的仔细分析已经揭示，尽管2的产率低，但氮源2，2，2-三氯乙氧基磺酰胺（TcesNH 2）被大量消耗。[8]TcesNH 2的低质量回收表明烷氧基磺酰胺的亚甲基中心可能发生氧化。出于这个原因，我们研究了替代磺酰胺衍生物，包括芳基和酚基试剂。用[Rh 2（esp）2]（1 mol%）、PhI（OAc）2和PhMe 2CCO 2 H（0.5当量）进行的反应的结果表明，当使用芳氧基磺酰胺试剂时，催化剂转换数（TON）增加（图2）。[9]其中，由2，6-二氟苯酚制备的氨基磺酸盐DfsNH 2已被证明是最佳的。经验研究表明，MgO和5分子筛的包含物进一步提高了催化剂TON，如初始底物浓度为1.0 μ M。[10-12]反应
The preparation of tetrasubstituted amine derivatives through intermolecular amination of tertiary CÀH bonds remains an outstanding challenge in methods development given the allure of such a technology for streamlining synthesis (Figure 1).[1, 2] While there exist a small number of reports in which this reaction has been demonstrated, almost all examples require superstoichiometric amounts of substrate.[3] Owing to recent insights gained through mechanistic studies, we now report a general method for the selective amination of tertiary C–H centers.[4] The reaction is operationally simple, tolerant of most common functional groups, and delivers a protected amine that is easily liberated. The influence of different nitrogen sources on product selectivity is also highlighted along with mechanistic studies that implicate steric effects as a principal determinant of site selectivity.We have recently provided evidence that the dirhodium tetracarboxylate catalyst,[Rh2 (esp) 2],[5] when subjected to C–H amination reaction conditions, undergoes competitive one-electron oxidation to a red, mixed-valent Rh2+/Rh3+ dimer.[4, 6] Fortuitously, this species is reduced under the reaction conditions by tBuCO2H, a byproduct of the hypervalent iodine oxidant used to drive the amination event.[4a] Our understanding of this process has resulted in a modification of the reaction conditions to include PhMe2CCO2H, a carboxylic acid additive that serves as an effective reducing agent and offers improved catalyst turnover numbers in intermolecular amination reactions of benzylic substrates.[4a, 7] Application of these conditions to the oxidation of isoamylbenzoate 1 (1.0 equiv), however, furnishes only a small amount of the desired amine 2 (Figure 2). Careful analysis of the oxidation of 1 has revealed that the nitrogen source, 2, 2, 2-trichloroethoxysulfonamide (TcesNH2), is largely consumed in spite of the poor yield of 2.[8] The low mass recovery of TcesNH2 suggests that oxidation of the methylene center of the alkoxysulfonamide may be occurring. For this reason, we have examined alternative sulfonamide derivatives, including aryl-and phenolic-based reagents. Results from reactions performed with [Rh2 (esp) 2](1 mol%), PhI (OAc) 2, and PhMe2CCO2H (0.5 equiv) demonstrate enhanced catalyst turnover numbers (TONs) when aryloxysulfonamide reagents are employed (Figure 2).[9] Of these, the sulfamate prepared from 2, 6-difluorophenol, DfsNH2, has proven optimal. Empirical studies reveal that the inclusion of both MgO and 5 molecular sieves further improves catalyst TONs, as does an initial substrate concentration of 1.0 m.[10–12] The reaction