Pilkington Rowan L, Kössler Rosa, Molloy Jesse, Bräse Stefan, Priebbenow Daniel L
Medicinal Chemistry Theme, Monash Institute of Pharmaceutical Sciences, Monash University Parkville VIC 3052 Australia
Institute of Biological and Chemical Systems (IBCS-FMS), Karlsruhe Institute of Technology Kaiserstraße 12 76131 Karlsruhe Germany.
Chem Sci. 2025 Oct 8. doi: 10.1039/d5sc06269a.
Siloxycarbene intermediates induced the visible light irradiation of acylsilanes undergo highly efficient benzoin-type click reactions with pyruvate derivatives. This process requires no reagents other than visible light, proceeds with high efficiency and is tolerant of a wide range of functional groups. Pyruvate esters, thioesters, amides, nitriles and phosphonates were all identified as suitable electrophiles including those tethered to complex drug or biomolecule scaffolds. The visible-light induced carbon-carbon bond forming process was scalable using both batch and flow methodologies, accompanied by diversification studies on the corresponding addition products. Mechanistic insights into siloxycarbene reactivity were also obtained by DFT analysis.
硅氧基卡宾中间体在可见光照射下促使酰基硅烷与丙酮酸衍生物发生高效的安息香型点击反应。该过程除可见光外无需其他试剂，反应高效进行且对多种官能团具有耐受性。丙酮酸酯、硫酯、酰胺、腈和膦酸酯均被确定为合适的亲电试剂，包括那些连接到复杂药物或生物分子支架上的亲电试剂。使用间歇式和连续流方法，可见光诱导的碳 - 碳键形成过程都具有可扩展性，并伴随着对相应加成产物的多样化研究。通过密度泛函理论（DFT）分析，还获得了关于硅氧基卡宾反应活性的机理见解。
