Pro‐aromatic Dihydroquinazolinones – From Multigram Synthesis to Reagents for Gram‐scale Metallaphotoredox Reactions

• Published in: Chemistry, an Asian journal an Asian journal, 2024-02, Vol.19 (3), p.e202301004-n/a
• Main Authors: Tsai, Zong‐Nan, Li, Li‐Yun, Paculba, Aira Shayne, Miñoza, Shinje, Tsao, Yong‐Ting, Lin, Pei‐Shan, Liao, Hsuan‐Hung
• Format: Article
• Language: English
• Subjects: aromatization; Column chromatography; Cross coupling; Ketones; large-scale synthesis; metallaphotoredox; Ni/photoredox dual catalysis; pro-aromatic compounds; Reagents; Synthesis
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.202301004

Dihydroquinazolinone (DHQZ) has recently been harnessed as a ketone‐derived pro‐aromatic reagent extensively employed in (metalla)photoredox reactions as versatile group transfer agents. In this work, we outline a column chromatography‐free protocol for the multigram‐scale synthesis of pro‐aromatic DHQZs as well as its use in a gram‐scale nickel/photoredox dual‐catalyzed cross‐coupling in single‐batch, photoflow, and simultaneous multiple smaller batches. While the single‐batch approach leveraged moderate yields, a simple plug‐flow photoreactor also exhibited amenable productivity (up to 45 % yield) despite the use of a heterogeneous base. Meanwhile, performing the metallaphotoredox‐catalyzed reaction in multiple smaller batches in an improvised photoreactor facilitated high yields of up to 59 % and good reproducibility, implying a convenient alternative in the absence of photoflow setups. This study reports the synthesis of 2,2‐disubstituted dihydroquinazolinone (DHQZ) from diketone in a multigram scale (up to 16 grams yield). DHQZ is also applied in the detailed gram‐scale metallaphotoredox‐mediated benzoylation of aryl halides through a single batch, photoflow, and multiple smaller batches protocol.