An intensified and scalable continuous flow process is presented for the hydroxylation of enolizable tertiary ketones. The procedure relies on molecular oxygen, metal-free conditions and a low toxicity solvent (DMSO). The reaction is optimized on the microfluidic scale with a model ketone substrate (isobutyrophenone) and next extended to a small library of structurally diverse enolizable ketones. High conversion and selectivity are achieved under extremely short residence time. A DFT computational study provides insights on the mechanism and selectivity on various substrates. The scalability of the hydroxylation step is next assessed in a commercial pilot scale continuous flow SiC reactor, hence providing up to 12.5 kg per day of industrially relevant α-ketols with applications ranging from Type I radical photoinitiators to intermediates for the preparation of active pharmaceutical ingredients.

Details of the Corning® Advanced-Flow™ G1 SiC reactor (Courtesy of Corning®) utilized for the intensified continuous flow hydroxylation of tertiary ketones with molecular oxygen.

提出了一种增强的和可扩展的连续流动方法，用于可烯醇化的叔酮的羟基化。该程序依赖于分子氧，无金属条件和低毒性溶剂（DMSO）。使用模型酮底物（异丁苯酮）在微流体规模上优化反应，然后将其扩展到结构多样的可烯化酮的小型文库中。在极短的停留时间下即可实现高转化率和选择性。DFT计算研究提供了对各种底物的机理和选择性的见解。接下来，在商业中试规模的连续流SiC反应器中评估羟基化步骤的可扩展性，因此可提供多达12个。

康宁®Advanced-Flow™G1 SiC反应器（由康宁提供）的详细信息，该反应器用于增强叔酮与分子氧的连续流动羟基化。