The enantioselective formation of C–C bonds is arguably one of the most important reactions in organic chemistry. While elegant solutions have been devised for the total synthesis of several natural products, active pharmaceutical ingredients (API), and related scaffolds, efficient methods that strive towards the principles of green chemistry remain highly desirable additions to the synthetic organic toolbox. Additionally, modern strategies become increasingly challenging when the desired structures are highly strained, sterically encumbered, or contain adjacent quaternary chiral centers. In this research, the hexasubstituted ketone d,l-2,4-dimethyl-3-oxo-2,4-diphenylpentanedinitrile was chosen as a highly strained and chiral proof-of-concept substrate to evaluate the scalability of solid state photoelimination chemistry. Performing the photodecarbonylation of easily accessible alpha-chiral ketones in the solid state physically restricts the mobility of the generated radical intermediates, resulting in high regio- and enantiospecificity. Additionally, aqueous suspensions can be used, resulting in a simple filtration as the only purification step. The continuous flow HANU™ 2X 15 photoreactor, preceded by a custom inline crystallization setup, were shown to be key enabling technologies to achieve the previously problematic continuous operation and scale-up of these reactions. A solid-to-solid photochemical process was successfully optimised, resulting in a STY of 3.6 kg h⁻¹ m⁻³.

中文翻译：

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合并在线结晶和脉冲流操作以实现对映特异性固态光脱羰

C-C 键的对映选择性形成可以说是有机化学中最重要的反应之一。虽然已经为几种天然产物、活性药物成分（API）和相关支架的全合成设计了优雅的解决方案，但努力实现绿色化学原理的有效方法仍然是有机合成工具箱中非常理想的补充。此外，当所需的结构高度紧张、空间阻碍或包含相邻的四级手性中心时，现代策略变得越来越具有挑战性。在这项研究中，选择六取代酮d , l -2,4-二甲基-3-氧代-2,4-二苯基戊二腈作为高应变和手性概念验证底物，以评估固态光消除化学的可扩展性。在固态下对容易获得的α-手性酮进行光脱羰作用会在物理上限制所生成的自由基中间体的移动性，从而产生高区域特异性和对映体特异性。此外，可以使用水悬浮液，从而将简单的过滤作为唯一的纯化步骤。连续流 HANU™ 2X 15 光反应器（之前有定制的内联结晶装置）被证明是实现这些反应先前存在问题的连续操作和放大的关键技术。成功优化了固-固光化学过程，STY 达到 3.6 kg h ^-1 m ^-3。