Hossian Asik, Manna Manash Kumar, Manna Kartic, Jana Ranjan
Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, West Bengal, India.
Org Biomol Chem. 2017 Aug 9;15(31):6592-6603. doi: 10.1039/c7ob01466j.
Over the past few decades, an impressive array of C-H activation methodology has been developed for organic synthesis. However, due to the inherent inertness of the C-H bonds (e.g. ∼110 kcal mol for the cleavage of C(aryl)-H bonds) harsh reaction conditions have been realized to overcome high energetic transition states resulting in a limited substrate scope and functional group tolerance. Therefore, the development of mild C-H functionalization protocols is in high demand to exploit the full potential of the C-H activation strategy in the synthesis of a complex molecular framework. Although, electron-rich substrates undergo electrophilic metalation under relatively mild conditions, electron-deficient substrates proceed through a rate-limiting C-H insertion under forcing conditions at high temperature. In addition, a stoichiometric amount of toxic silver salt is frequently used in palladium catalysis to facilitate the C-H activation process which is not acceptable from the environmental and industrial standpoint. We report herein, a Pd(ii)-catalyzed decarboxylative C-H acylation of 2-arylpyridines with α-ketocarboxylic acids under mild conditions. The present protocol does not require stoichiometric silver(i) salts as additives and proceeds smoothly at ambient temperature. A novel decarbonylative C-H acylation reaction has also been accomplished using aryl glyoxals as acyl surrogates. Finally, a practical C-H acylation via a dehydrogenative pathway has been demonstrated using commercially available benzaldehydes and aqueous hydroperoxides. We also disclose that acetonitrile solvent is optimal for the acylation reaction at room temperature and has a prominent role in the reaction outcome. Control experiments suggest that the acylation reaction via decarboxylative, decarbonylative and dehydrogenative proceeds through a radical pathway. Thus we disclose a practical protocol for the sp C-H acylation reaction.
在过去几十年中，已开发出一系列令人印象深刻的用于有机合成的C-H活化方法。然而，由于C-H键固有的惰性（例如，芳基C-H键的裂解需要约110 kcal/mol），为了克服高能过渡态，需要苛刻的反应条件，这导致底物范围和官能团耐受性有限。因此，迫切需要开发温和的C-H官能化方案，以充分发挥C-H活化策略在复杂分子骨架合成中的潜力。尽管富电子底物在相对温和的条件下会发生亲电金属化，但缺电子底物在高温强制条件下通过限速的C-H插入反应进行。此外，在钯催化中经常使用化学计量的有毒银盐来促进C-H活化过程，从环境和工业角度来看，这是不可接受的。我们在此报告，在温和条件下，钯（II）催化2-芳基吡啶与α-酮羧酸的脱羧C-H酰化反应。本方案不需要化学计量的银（I）盐作为添加剂，在室温下反应顺利进行。还使用芳基乙二醛作为酰基替代物完成了一种新型的脱羰C-H酰化反应。最后，使用市售的苯甲醛和氢过氧化物水溶液证明了通过脱氢途径进行的实用C-H酰化反应。我们还发现，乙腈溶剂对于室温下的酰化反应是最佳的，并且在反应结果中起着重要作用。对照实验表明，通过脱羧、脱羰和脱氢进行的酰化反应是通过自由基途径进行的。因此，我们公开了一种实用的sp C-H酰化反应方案。
